Design Strategy of the Sabes Study: Diagnosis and Treatment of Early HIV Infection Among Men Who Have Sex With Men and Transgender Women in Lima, Peru, 2013–2017

Design Strategy of the Sabes Study: Diagnosis and Treatment of Early HIV Infection Among Men Who... Abstract The Sabes Study evaluated a treatment-as-prevention intervention among cisgender men who have sex with men and transgender women in Lima, Peru—populations disproportionately affected by the human immunodeficiency virus (HIV) epidemic. The intervention was designed to prevent onward transmission of HIV by identifying HIV-negative high-risk individuals, testing them monthly for the presence of HIV, and then rapidly treating those who became HIV-positive. The main outcome of interest was the development of a model predicting the population-level impact of early detection of HIV infection and immediate initiation of antiretroviral therapy in this population. From July 2013 to September 2015, a total of 3,337 subjects were screened for HIV; 2,685 (80.5%) were negative, and 2,109 began monthly testing. We identified 256 individuals shortly after HIV acquisition, 216 of whom were enrolled in the treatment phase of the study. All participants were followed for 48 weeks (follow-up ended in 2017) and were then referred to the Peruvian Ministry of Health to continue receiving free HIV care and treatment. Initial findings from this intervention demonstrate that it is possible to recruit high-risk individuals, screen them for HIV, continue to test those who are initially HIV-negative in order to identify incident cases shortly after acquisition, and then rapidly link them to health care. acquired immunodeficiency syndrome, diagnosis, disease transmission, epidemics, HIV, HIV infection, Peru, sexual minorities Despite the dramatic increase in global access to human immunodeficiency virus (HIV) treatment and prevention interventions, HIV epidemics among men who have sex with men (MSM) and transgender women (TW) have continued to expand in many countries, including those in Latin America (1, 2). In the Americas, MSM and TW represent the subpopulations with the largest proportion of new HIV infections per year (1, 3, 4). An analysis of 15 Latin American countries demonstrated that MSM were 33 times more likely to be HIV-infected than heterosexual men in the general population (3). Globally, TW are almost 50 times more likely to be HIV-infected than adults of reproductive age (4), with an estimated HIV prevalence of 30% in Peru (5). Existing HIV prevention interventions for MSM and TW (e.g., consistent condom use, serosorting, HIV testing and counseling, and individual-level behavioral interventions to reduce risk behavior) have shown varying degrees of effectiveness, but it is becoming increasingly clear that these strategies are not sufficient to end the epidemic (6). Biomedical strategies, such as the use of antiretroviral therapy (ART) by HIV-negative individuals as preexposure prophylaxis (PrEP) (7), are efficacious in preventing HIV acquisition. However, barriers to programmatic implementation of PrEP in limited-resource settings include concerns about cost, effectiveness, and risk compensation (8). In addition, use of ART for treatment rather than for PrEP will likely be prioritized, and regulatory approvals for ART as PrEP can delay in-country implementation. For example, although initial studies of PrEP were conducted in Peru, it was not approved there until April 2016 (9) and thus was unavailable during our study. ART for subjects with established HIV infection prevented onward HIV transmission by up to 96% (10). Two observational studies including HIV-discordant MSM couples found that, following the provision of ART to the infected partner, there were no documented HIV transmissions despite almost 40,000 acts of condomless anal intercourse (11, 12). There has been little research on the efficacy of treatment as prevention (TasP) among TW specifically. Hypothetically, early ART initiation could markedly reduce HIV transmission during acute and recent infection when plasma and genital/rectal HIV viral loads are high. It is estimated that up to 22% of onward transmissions among MSM in Peru occur during acute infection (13). The potential benefit of such a strategy may be high—modeling studies predict that transmission during the acute infection period could account for up to one-half to two-thirds of new infections among MSM (14). Based on these and other results, the World Health Organization (WHO) has recommended providing ART to all HIV-infected persons regardless of CD4-positive cell count for the benefit of that individual and to prevent onward transmission (i.e., TasP) (15). TasP offers advantages over other prevention interventions that reduce population-level HIV incidence only if their uptake reaches high coverage among HIV-negative individuals. TasP strategies generally focus on treatment of persons diagnosed using yearly (or less frequent) serological testing. We sought to assess whether TasP efficacy could be improved in high-risk populations through earlier HIV detection and rapid initiation of treatment. The Sabes Study (“¿Sabes?” in Spanish means “Do you know?”) sought to optimize a “seek, test, treat, and retain” strategy (16) to reduce HIV transmission through reduction of high-risk sexual behaviors and early initiation of ART in Peruvian MSM and TW with acute or recent HIV infection. Our hypothesis was that intervening early, especially during acute infection, through the provision of ART would markedly reduce HIV transmission in this population. Here we outline the methods of the study and provide details on participant recruitment. In the Sabes Study, we sought to evaluate the following specific activities: Testing for HIV frequently and treating newly diagnosed HIV-infected MSM and TW. By increasing HIV testing frequency and coverage, we sought to identify HIV infection shortly after acquisition and to initiate behavioral and ART interventions early to reduce onward HIV transmission. Quantifying the impact of timing of early ART initiation on HIV viral load in plasma, semen, and rectal secretions. These data will be used to model the potential benefits of early ART in reducing onward transmission among MSM and TW populations. Analyzing HIV phylogenetic data and linked questionnaire data in order to assess sexual networks and their relationship to alcohol and drug use. We are sequencing HIV from plasma collected shortly after HIV acquisition and conducting phylogenetic analysis; clusters of highly related sequences may indicate onward HIV transmission shortly after HIV acquisition (i.e., prior to the development of sequence diversity) (14). Further analysis integrating phylogenies with geospatial and behavioral data from monthly questionnaires (alcohol and drug use, sexual behaviors, and meeting sexual partners at social venues (e.g., bars)) may provide insights into drivers of onward transmission. Modeling with both deterministic and agent-based methods to assess network dynamics and the potential population-level impact of our TasP interventions. We are developing HIV epidemic models incorporating study data to model the impact of 2 intervention components: increased testing frequency and earlier treatment initiation. Our models may reveal additional special considerations that underlie transmission dynamics in MSM and TW. METHODS Sabes was a multisite study that investigated the feasibility and benefits of incorporating frequent testing for acute and recent HIV infection and rapid linkage to care at community testing and treatment sites in Lima, Peru. Study sites There were 4 research sites in the Sabes Study; 3 were part of HIV research organizations (2 from the Health and Education Civil Association (IMPACTA) and 1 from Asociación Vía Libre), and 1 was a community-based organization, Epicentro. The Alberto Barton Health Center (Callao, Peru), a Ministry of Health clinic that offers services to MSM and TW, also referred a small number of participants. Study population Persons who were male at birth, who reported having had sex with a male partner in the past 12 months, and who were ≥18 years of age were eligible for participation. In addition, they must have been unaware of their HIV status and have been at high risk for acquiring HIV because 1) they were a partner of a person with newly diagnosed acute or recent HIV infection; 2) they were seeking HIV testing because they had symptoms of acute retroviral syndrome; or 3) they reported high-risk sexual behavior, defined as any of the following (17): a) no condom use during anal intercourse in the last 6 months; b) anal intercourse with more than 5 male sex partners during the last 6 months; c) self-identification as a sex worker; d) diagnosis of a sexually transmitted infection during the last 6 months or at screening; or e) being a sexual partner of an HIV-infected man or TW in the last 6 months. Definition of acute and recent HIV infections Acute HIV infection was operationally defined as a positive plasma HIV RNA test in a person with a negative third-generation HIV antibody test. Recent HIV infection was diagnosed by means of a positive third-generation rapid HIV test (confirmed by a separate enzyme immunoassay) with a documented negative third-generation HIV-antibody or HIV-RNA test in the previous 3 months. Study design The Sabes Study included 3 sequential steps: 1) identify HIV-negative subjects, 2) rescreen these subjects for incident HIV infection, and 3) if acute/recent infection is identified, enroll those subjects in a randomized study of immediate initiation of ART versus deferred initiation (Figure 1). Figure 1. View largeDownload slide CONSORT diagram for participants in the Sabes Study, Lima, Peru, 2013–2017. ART, antiretroviral therapy; CONSORT, Consolidated Standards of Reporting Trials; HIV, human immunodeficiency virus; MSM, men who have sex with men; TW, transgender women. Figure 1. View largeDownload slide CONSORT diagram for participants in the Sabes Study, Lima, Peru, 2013–2017. ART, antiretroviral therapy; CONSORT, Consolidated Standards of Reporting Trials; HIV, human immunodeficiency virus; MSM, men who have sex with men; TW, transgender women. Step 1: Screen to identify HIV-negative individuals All persons voluntarily visiting a participating clinic were asked about recent sexual activity, HIV risk factors, and their main reason for visiting the clinic. In addition, peer educators visited previously identified social venues (e.g., saunas, adult movie theaters, sex-work areas, discotheques, bars, beauty parlors, sporting events) to provide information about HIV and sexually transmitted infection prevention and to refer potential participants to study sites. Finally, a number of participants from the 2011 Peruvian Biobehavioral Survey (18) were invited to join the Sabes Study. MSM and TW were assessed for eligibility prior to HIV testing. To enroll in step 1, each participant had to be willing and able to provide informed consent for participation, including HIV testing, and to be recontacted if testing indicated acute or recent HIV infection, or to continue to be retested if the initial test result was negative (step 2). If testing indicated acute or recent HIV infection, the participant was asked to enroll in a randomized study of immediate versus deferred ART (step 3). TW who reported the use of estrogens or antiandrogens in the last 3 months were not eligible, because use of these drugs could impair provision of semen specimens collected as part of the protocol for HIV-infected participants (step 3). Persons with any physical, medical, occupational, or other condition that, in the judgment of the investigators, would interfere with or serve as a contraindication to protocol adherence or assessment of safety were excluded from participation. HIV screening was conducted on whole blood using Alere Determine HIV-1/2 (Alere Inc., Waltham, Massachusetts), a point-of-care third-generation HIV antibody test. Blood samples that were negative for HIV antibodies were pooled and tested for HIV RNA with a nucleic acid amplification test using a Liat HIV Quant Assay (IQuum, Inc., Marlborough, Massachusetts). Positive pools were deconvoluted to identify HIV-positive samples, using a fourth-generation HIV enzyme immunoassay (Bio-Rad Laboratories, Hercules, California) or HIV RNA tests. The Abbott RealTime HIV-1 test (Abbott Laboratories, Lake Bluff, Illinois) was used to confirm HIV infection. Participants completed a structured computer-assisted self-interview on demographic factors, sexual behavior, social venue attendance, drug and alcohol use, and stigma and coping. All participants were also tested for syphilis using a rapid plasma reagent test (RPR QuickTest; Stanbio Laboratory, Boerne, Texas). Positive results were confirmed by means of a Treponema pallidum particle agglutination assay (TPHA Test Kit DR0530; Oxoid Microbiology Products Ltd., Basingstoke, United Kingdom). Participants with acute or recent HIV, as defined in this study, were invited to participate in step 3. Persons found to have established HIV infections (>3 months since acquisition) were referred to local health-care providers to receive the local standard of care or to participate in other studies if available. HIV-negative subjects were invited to continue their participation in step 2. Step 2: Enroll HIV-negative subjects from step 1 for monthly HIV testing MSM and TW found to have no HIV infection in step 1 were given free condoms, lubricant, and standard risk-reduction counseling. They were asked to visit the study center monthly for a 2-year period for HIV retesting and to complete a computer-assisted self-interview questionnaire on social venue attendance, substance use, and sexual behaviors. Participants diagnosed with acute or recent HIV infection were invited to participate in step 3. HIV-positive persons identified more than 3 months after their last negative HIV RNA test were not eligible, because infection within the past 3 months could not be unambiguously determined in these individuals. They were referred to appropriate facilities to receive the local standard of care or to participate in other available studies. Step 3: Enroll subjects with early HIV infection in immediate or deferred ART Persons with acute or recent HIV infection diagnosed in steps 1 or 2 were enrolled in a 48-week randomized study of immediate ART versus deferred ART. An additional 12 subjects with recent HIV infection were enrolled directly in step 3 from the Alberto Barton Health Center. All newly diagnosed HIV-positive participants were linked to care at study clinics as quickly as possible, either by referral after diagnosis of recent infection by point-of-care assays or through peer health navigators who contacted patients shortly after laboratory diagnosis of acute infection. Consenting volunteers were administered a structured computer-assisted interview questionnaire on drug use history (19); alcohol-use disorders (20); health status (21); anxiety and depression (22); social support, stigma, and disclosure; and medical care (hospitalization and emergency room use, access to care, and barriers to care). Participants were randomized one-to-one using blocks of 2 or 4 to start ART immediately or to defer ART initiation until 24 weeks after enrollment (when setpoint viral load is established), unless Peruvian criteria for ART initiation were met earlier (CD4-positive cell count ≤500 cells/mm3; changed from ≤350 cells/mm3 in December 2014) or their illness was diagnosed as meeting WHO clinical stage 3 or 4. Thus, all participants received ART either before or at the time they met criteria for ART initiation in Peru. The ART regimen was coformulated tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg/efavirenz 600 mg, 1 tablet taken orally daily. Participants were switched to alternate WHO-recommended regimens for intolerance or toxicity. Participants experiencing treatment failure (i.e., not achieving more than 1 log10 drop in plasma HIV RNA copies per mL after 16 weeks of treatment; not achieving an HIV RNA level below 50 copies/mL after 24 weeks of treatment; or having an HIV RNA level greater than 400 copies/mL upon 2 consecutive measurements after having achieved an HIV RNA level below 50 copies/mL) were switched to an alternate WHO-recommended regimen based on clinical judgment and HIV genotyping when available. At 48 weeks, each participant was transferred to the Ministry of Health ART Program, which provides free HIV care and treatment. Protection of human subjects The study protocol, informed consent forms, and recruitment materials were approved by institutional review boards at the Fred Hutchinson Cancer Research Center, the Health and Education Civil Association, and the Asociación Vía Libre, in compliance with all applicable Peruvian and US federal regulations governing the protection of human subjects. All study participants provided written consent in Spanish, their native language, to participate in the study. Implementation of the study was authorized by the Peruvian National Institute of Health, and the study is registered with ClinicalTrials.gov (https://clinicaltrials.gov/; trial NCT01815580). RESULTS Step 1 Recruitment for step 1 began in July 2013 and was completed in September 2015 with the testing of 3,337 high-risk participants (Table 1). Over 93% of the subjects were identified through clinic screening of the general population of MSM and TW; the remaining 7% were identified from the 2013 Peruvian Biobehavioral Survey (18). The overall prevalence of HIV among the participants at baseline was 19.5%, although there were marked differences between the 2 source populations: 20.7% for the general screening population and only 3.1% for the biobehavioral survey population. This difference occurred because subjects were tested for HIV in the Peruvian Biobehavioral Survey and only HIV-uninfected individuals were referred for rescreening in the Sabes Study several months later. Although Silva-Santisteban et al. (5) reported higher HIV prevalence among TW than among MSM in Peru, HIV prevalences in the Sabes TW and MSM were similar (19.3% and 19.7%, respectively); thus, they were combined for this analysis. Table 1. Characteristics of the Population Screened for Step 1 of the Sabes Study, Lima, Peru, 2013–2015 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Abbreviations: HIV, human immunodeficiency virus; STI, sexually transmitted infection. a Based on risk criteria defined by Sanchez et al. (17). Table 1. Characteristics of the Population Screened for Step 1 of the Sabes Study, Lima, Peru, 2013–2015 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Abbreviations: HIV, human immunodeficiency virus; STI, sexually transmitted infection. a Based on risk criteria defined by Sanchez et al. (17). The 2 most common risk factors for study inclusion, “no condom use during last anal intercourse” and “anal intercourse with more than 5 sexual partners in the last 6 months,” were reported by 57% and 37% of participants, respectively. The main reason for visiting the clinic, “thought exposed to HIV,” was reported by 42% of the participants and by 41% of those who were HIV-negative. The next most common reason, “referred by a peer educator,” was reported by 21% of the tested subjects and 22% of those who were HIV-negative. All other reasons were mentioned by less than 3% of the tested subjects, and the distributions were similar for both the tested and HIV-negative subjects. Step 2 Of the 2,685 HIV-negative MSM and TW identified in step 1, a total of 2,109 (78.5%) enrolled in step 2 for repeated monthly HIV testing (Table 2). Follow-up for step 2 ended in May 2016, so follow-up for some of the more recently enrolled participants was truncated at less than 24 months; 256 cases of HIV infection were identified in step 2. However, because the length of the interval since their last negative test was greater than 3 months, 54 of these HIV-positive subjects could not be categorized as having recent infections and were therefore ineligible to enroll in step 3, which left 202 eligible participants. Table 2. Characteristics of Eligible and Enrolled Subjects in Step 2 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Abbreviations: AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b AUDIT score ≥8 is indicative of an alcohol-use disorder. c Postsecondary includes Peruvian higher technical education as well as college/university. Table 2. Characteristics of Eligible and Enrolled Subjects in Step 2 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Abbreviations: AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b AUDIT score ≥8 is indicative of an alcohol-use disorder. c Postsecondary includes Peruvian higher technical education as well as college/university. In general, the step 2 participants were young (44% were below age 25 years), were well-educated (60% had at least some postsecondary schooling), had only marginal incomes (65% reported monthly incomes below US$400, the customary poverty line for Peru), and identified predominantly as homosexual (49%). Almost half (42%) reported both insertive and receptive sex roles, and just over half (53%) reported drinking behavior consistent with an alcohol-use disorder (score ≥8 on the Alcohol Use Disorders Identification Test). Participants who enrolled and did not enroll differed with regard to age, education, income, sexual identity, and sexual role (Table 2). Compared with the nonenrollees, persons who enrolled in step 2 were slightly older, more educated, and more likely to self-identify as homosexual, and they differed in reported sexual role. Retention of participants in the cohort was high: After 3 months, 87% were still returning for retesting, and after 12 months this proportion was 62% (Figure 2). Figure 2. View largeDownload slide Retention of participants in the Sabes Study cohort, Lima, Peru, 2013–2016. The denominator for each quarterly data point was equal to the number of subjects who were eligible for retesting at that time of observation. This excludes subjects who became positive for human immunodeficiency virus during the previous quarters, as well as a small number of participants whose follow-up was truncated when follow-up was terminated prior to the completion of 2 years of observation. Figure 2. View largeDownload slide Retention of participants in the Sabes Study cohort, Lima, Peru, 2013–2016. The denominator for each quarterly data point was equal to the number of subjects who were eligible for retesting at that time of observation. This excludes subjects who became positive for human immunodeficiency virus during the previous quarters, as well as a small number of participants whose follow-up was truncated when follow-up was terminated prior to the completion of 2 years of observation. Step 3 A total of 256 eligible subjects with acute or recent HIV infections were identified during the study—the majority (78%) from rescreening in step 2, and the remainder from initial testing in step 1 and referral from the Alberto Barton Health Center (“Barton clinic”) (Figure 1). Forty HIV-positive subjects either declined to enroll in step 3 or were excluded from enrollment in step 3 because of health issues: 6 from step 1 and 34 from step 2. An additional 12 eligible participants were recruited from the Barton clinic and enrolled in step 3. The resulting total enrollment in step 3 was 216 persons. The enrolled population closely reflected the eligible population with regard to all of the characteristics examined (Table 3). One-third (35%) of the enrolled HIV-positive subjects had acute infections, and two-thirds (65%) had recent infections. Participants in these 2 categories were then randomized separately into treatment groups to receive ART immediately or beginning at 24 weeks (Figure 1). Table 3. Characteristics of Eligible and Enrolled Subjects in Step 3 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Abbreviations: Ab, antibody; AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b An additional 54 HIV-seropositive subjects were identified during step 2 rescreening. However, the elapsed time since their previous screening was greater than 3 months, so they could not be classified as “recently infected”; therefore, they were not eligible to enroll in step 3. c Postsecondary includes Peruvian higher technical education as well as college/university. d AUDIT score ≥8 is indicative of an alcohol-use disorder. Table 3. Characteristics of Eligible and Enrolled Subjects in Step 3 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Abbreviations: Ab, antibody; AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b An additional 54 HIV-seropositive subjects were identified during step 2 rescreening. However, the elapsed time since their previous screening was greater than 3 months, so they could not be classified as “recently infected”; therefore, they were not eligible to enroll in step 3. c Postsecondary includes Peruvian higher technical education as well as college/university. d AUDIT score ≥8 is indicative of an alcohol-use disorder. DISCUSSION Initial testing of study participants in step 1 and their enrollment in periodic retesting (step 2) was completed in September 2015. Enrollment of participants identified with acute and recent HIV infections in step 3 was completed in May 2016. Follow-up of step 3 participants was completed in April 2017. Ongoing step 3 analyses In ongoing step 3 analyses, we are engaging in the following activities. Estimation of the impact of immediate and deferred ART on the decay dynamics of HIV viral load We are measuring viral load in plasma, semen, and rectal secretions collected periodically from a subset of participants receiving immediate and deferred ART. We will use these data for modeling the impact of ART on infectivity during acute and recent HIV infection through various modes of exposure. Viral phylogenetic analysis We are mapping behavioral data (such as alcohol use) and geographic data onto phylogenetic transmission clusters to gain insights into drivers of HIV transmission in this population. This approach will allow us to determine the relative contributions of MSM and TW, with and without alcohol-use disorder (or other risk behaviors), to onward HIV transmission. Modeling the expected intervention impact at the population level The culmination of these analyses will be the development of an HIV epidemic model. We will use study data to estimate the percentage of HIV infections that are diagnosed as acute or recent and the distribution of testing intervals among MSM and TW overall. A series of deterministic models will be developed to simulate HIV transmission in Peruvian MSM and TW populations with and without our interventions, and to evaluate the public health impact of increased detection and treatment of acute and recent HIV infections on the HIV epidemic. A cost-effectiveness evaluation will provide information to inform prevention strategies such as the one we have evaluated. Association of HIV testing strategies and linkage to care using peer navigators We will assess the overall impact of study activities on increasing the frequency of HIV testing among high-risk MSM and TW. Ninety percent of participants with early HIV infection were linked to the study clinics, within a median of 6 days. This compares very favorably with linkage-to-care rates for MSM and TW from this population who are referred to HIV care in the absence of study interventions—only 45% were linked to care within 90 days after testing positive (23). Context This project has demonstrated that it is possible to reach a target population of high-risk MSM and TW, screen them for HIV, and then frequently retest those who are initially HIV-negative in order to identify incident cases shortly after HIV acquisition. Recruitment for HIV screening was accomplished through enhancing an existing platform for outreach in neighborhoods, and HIV testing was performed at clinics that are regularly visited by MSM and TW residents of Lima. Similarly, follow-up testing and treatment was performed at those same clinics. All other study activities were conducted with only slight modifications to the existing public health infrastructure within the community. Implications While current WHO guidelines call for initiation of ART at the time of HIV diagnosis, this alone does not guarantee early treatment, since most people are diagnosed years after HIV acquisition. Recent studies suggest that HIV reservoirs can be limited if treatment is begun in the weeks after HIV acquisition (24) and suggest that this would reduce onward transmission (25, 26); however, detecting infection this early remains a huge operational challenge. The Sabes Study sought to address this gap in public health practice by exploring the feasibility and impact of early HIV detection and treatment. Results to date have demonstrated the feasibility of detecting HIV infection shortly after acquisition with rapid linkage to care through community outreach and use of local clinics serving MSM and TW. Additional follow-up of these study participants has been instituted and will provide further insight into the benefits of early treatment initiation for individuals and the community. ACKNOWLEDGMENTS Author affiliations: Asociación Civil Impacta Salud y Educación (IMPACTA), Lima, Peru (Javier R. Lama, Jessica Rios); Fred Hutchinson Cancer Research Center, Seattle, Washington (Audrey Brezak, James G. Dobbins, Carolyn Bain, Angela Ulrich, Ann Duerr); Epicentro, Lima, Peru (Hugo Sanchez); Asociación Vía Libre, Lima, Peru (Robinson Cabello); and Cent de Investigación Tecnologicas, Biomedicas y Medioambientales, Universidad Mayor de San Marcos, Lima, Peru (Robert De la Grecca, Jorge Sanchez). This work was funded by the National Institute on Drug Abuse, US National Institutes of Health (grant DA032106 to A.D.). A.B. was supported by a Mary Gates Scholarship from the University of Washington (Seattle, Washington). Medication for this study was donated by Gilead Sciences (Foster City, California) and Merck & Co., Inc. (Kenilworth, New Jersey). We thank Ashley Clayton and Siavash Pasalar for developing the figures for this article. The Sabes Study Team: Carmela Ganoza, Ricardo Alfaro, Cecilia Correa, Karin Sosa, Peter Brandes, Eduardo Ruiz, Cecilia Zegarra, Manuel Villaran, Patricia Segura, Gonzalo Meneses, David Huaytalla, Daniel Alva, Karin Roca, Carlos Medrano, and Yesika Magallens. This paper was presented in abstract form (abstract P52.03) at the 2014 HIV Research for Prevention Meeting, Cape Town, South Africa, October 28–31, 2014. Conflict of interest: none declared. Abbreviations ART antiretroviral therapy MSM men who have sex with men PrEP preexposure prophylaxis TasP treatment as prevention TW transgender women WHO World Health Organization REFERENCES 1 Beyrer C , Baral SD , van Griensven F , et al. . Global epidemiology of HIV infection in men who have sex with men . Lancet . 2012 ; 380 ( 9839 ): 367 – 377 . Google Scholar CrossRef Search ADS PubMed 2 Poteat T , Scheim A , Xavier J , et al. . Global epidemiology of HIV infection and related syndemics affecting transgender people . J Acquir Immune Defic Syndr . 2016 ; 72 ( suppl 3 ): S210 – S219 . Google Scholar CrossRef Search ADS PubMed 3 Baral S , Sifakis F , Cleghorn F , et al. . Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000–2006: a systematic review . PLoS Med . 2007 ; 4 ( 12 ): e339 . Google Scholar CrossRef Search ADS PubMed 4 Baral SD , Poteat T , Strömdahl S , et al. . Worldwide burden of HIV in transgender women: a systematic review and meta-analysis . Lancet Infect Dis . 2013 ; 13 ( 3 ): 214 – 222 . Google Scholar CrossRef Search ADS PubMed 5 Silva-Santisteban A , Raymond HF , Salazar X , et al. . 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Google Scholar CrossRef Search ADS PubMed 17 Sanchez J , Lama JR , Peinado J , et al. . High HIV and ulcerative sexually transmitted infection incidence estimates among men who have sex with men in Peru: awaiting for an effective preventive intervention . J Acquir Immune Defic Syndr . 2009 ; 51 ( suppl 1) : S47 – S51 . Google Scholar CrossRef Search ADS PubMed 18 Sanchez J , Peinado J , Lama J . Study of Epidemiological Surveillance of STIs and HIV in Men Who Have Sex with Men Comparing Recruitment Methodologies: Sampling for Convenience, Sampling by Time and Space, and Participant-Led Sampling. Lima, Peru : National Multisectoral Coordinating Committee on Health ; 2011 . 19 Gavin DR , Ross HE , Skinner HA . Diagnostic validity of the drug abuse screening test in the assessment of DSM-III drug disorders . Br J Addict . 1989 ; 84 ( 3 ): 301 – 307 . Google Scholar CrossRef Search ADS PubMed 20 Saunders JB , Aasland OG , Babor TF , et al. . Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption—II . Addiction . 1993 ; 88 ( 6 ): 791 – 804 . Google Scholar CrossRef Search ADS PubMed 21 Selim AJ , Rogers W , Fleishman JA , et al. . Updated US population standard for the Veterans RAND 12-item Health Survey (VR-12) . Qual Life Res . 2009 ; 18 ( 1 ): 43 – 52 . Google Scholar CrossRef Search ADS PubMed 22 Wittchen HU , Boyer P . Screening for anxiety disorders. Sensitivity and specificity of the Anxiety Screening Questionnaire (ASQ-15) . Br J Psychiatry Suppl . 1998 ;( 34 ): 10 – 17 . 23 Primbas A , Villaran M , Duerr A . Identifying men who have sex with men and transgender women who have poor linkage to HIV care in Lima, Peru [abstract 331]. Presented at Western Regional Meeting of the American Federation for Medical Research and Participating Societies, Carmel, California , January 28–30, 2016. 24 Ananworanich J , Chomont N , Eller LA , et al. . HIV DNA set point is rapidly established in acute HIV infection and dramatically reduced by early ART . EBioMedicine . 2016 ; 11 : 68 – 72 . Google Scholar CrossRef Search ADS PubMed 25 Kroon EDMB , Phanuphak N , Shattock AJ , et al. . Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok . J Int AIDS Soc . 2017 ; 20 ( 1 ): 21708 . Google Scholar CrossRef Search ADS PubMed 26 Abu-Raddad LJ . Role of acute HIV infection in driving HIV transmission: implications for HIV treatment as prevention . PLoS Med . 2015 ; 12 ( 3 ): e1001803 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Epidemiology Oxford University Press

Design Strategy of the Sabes Study: Diagnosis and Treatment of Early HIV Infection Among Men Who Have Sex With Men and Transgender Women in Lima, Peru, 2013–2017

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Abstract

Abstract The Sabes Study evaluated a treatment-as-prevention intervention among cisgender men who have sex with men and transgender women in Lima, Peru—populations disproportionately affected by the human immunodeficiency virus (HIV) epidemic. The intervention was designed to prevent onward transmission of HIV by identifying HIV-negative high-risk individuals, testing them monthly for the presence of HIV, and then rapidly treating those who became HIV-positive. The main outcome of interest was the development of a model predicting the population-level impact of early detection of HIV infection and immediate initiation of antiretroviral therapy in this population. From July 2013 to September 2015, a total of 3,337 subjects were screened for HIV; 2,685 (80.5%) were negative, and 2,109 began monthly testing. We identified 256 individuals shortly after HIV acquisition, 216 of whom were enrolled in the treatment phase of the study. All participants were followed for 48 weeks (follow-up ended in 2017) and were then referred to the Peruvian Ministry of Health to continue receiving free HIV care and treatment. Initial findings from this intervention demonstrate that it is possible to recruit high-risk individuals, screen them for HIV, continue to test those who are initially HIV-negative in order to identify incident cases shortly after acquisition, and then rapidly link them to health care. acquired immunodeficiency syndrome, diagnosis, disease transmission, epidemics, HIV, HIV infection, Peru, sexual minorities Despite the dramatic increase in global access to human immunodeficiency virus (HIV) treatment and prevention interventions, HIV epidemics among men who have sex with men (MSM) and transgender women (TW) have continued to expand in many countries, including those in Latin America (1, 2). In the Americas, MSM and TW represent the subpopulations with the largest proportion of new HIV infections per year (1, 3, 4). An analysis of 15 Latin American countries demonstrated that MSM were 33 times more likely to be HIV-infected than heterosexual men in the general population (3). Globally, TW are almost 50 times more likely to be HIV-infected than adults of reproductive age (4), with an estimated HIV prevalence of 30% in Peru (5). Existing HIV prevention interventions for MSM and TW (e.g., consistent condom use, serosorting, HIV testing and counseling, and individual-level behavioral interventions to reduce risk behavior) have shown varying degrees of effectiveness, but it is becoming increasingly clear that these strategies are not sufficient to end the epidemic (6). Biomedical strategies, such as the use of antiretroviral therapy (ART) by HIV-negative individuals as preexposure prophylaxis (PrEP) (7), are efficacious in preventing HIV acquisition. However, barriers to programmatic implementation of PrEP in limited-resource settings include concerns about cost, effectiveness, and risk compensation (8). In addition, use of ART for treatment rather than for PrEP will likely be prioritized, and regulatory approvals for ART as PrEP can delay in-country implementation. For example, although initial studies of PrEP were conducted in Peru, it was not approved there until April 2016 (9) and thus was unavailable during our study. ART for subjects with established HIV infection prevented onward HIV transmission by up to 96% (10). Two observational studies including HIV-discordant MSM couples found that, following the provision of ART to the infected partner, there were no documented HIV transmissions despite almost 40,000 acts of condomless anal intercourse (11, 12). There has been little research on the efficacy of treatment as prevention (TasP) among TW specifically. Hypothetically, early ART initiation could markedly reduce HIV transmission during acute and recent infection when plasma and genital/rectal HIV viral loads are high. It is estimated that up to 22% of onward transmissions among MSM in Peru occur during acute infection (13). The potential benefit of such a strategy may be high—modeling studies predict that transmission during the acute infection period could account for up to one-half to two-thirds of new infections among MSM (14). Based on these and other results, the World Health Organization (WHO) has recommended providing ART to all HIV-infected persons regardless of CD4-positive cell count for the benefit of that individual and to prevent onward transmission (i.e., TasP) (15). TasP offers advantages over other prevention interventions that reduce population-level HIV incidence only if their uptake reaches high coverage among HIV-negative individuals. TasP strategies generally focus on treatment of persons diagnosed using yearly (or less frequent) serological testing. We sought to assess whether TasP efficacy could be improved in high-risk populations through earlier HIV detection and rapid initiation of treatment. The Sabes Study (“¿Sabes?” in Spanish means “Do you know?”) sought to optimize a “seek, test, treat, and retain” strategy (16) to reduce HIV transmission through reduction of high-risk sexual behaviors and early initiation of ART in Peruvian MSM and TW with acute or recent HIV infection. Our hypothesis was that intervening early, especially during acute infection, through the provision of ART would markedly reduce HIV transmission in this population. Here we outline the methods of the study and provide details on participant recruitment. In the Sabes Study, we sought to evaluate the following specific activities: Testing for HIV frequently and treating newly diagnosed HIV-infected MSM and TW. By increasing HIV testing frequency and coverage, we sought to identify HIV infection shortly after acquisition and to initiate behavioral and ART interventions early to reduce onward HIV transmission. Quantifying the impact of timing of early ART initiation on HIV viral load in plasma, semen, and rectal secretions. These data will be used to model the potential benefits of early ART in reducing onward transmission among MSM and TW populations. Analyzing HIV phylogenetic data and linked questionnaire data in order to assess sexual networks and their relationship to alcohol and drug use. We are sequencing HIV from plasma collected shortly after HIV acquisition and conducting phylogenetic analysis; clusters of highly related sequences may indicate onward HIV transmission shortly after HIV acquisition (i.e., prior to the development of sequence diversity) (14). Further analysis integrating phylogenies with geospatial and behavioral data from monthly questionnaires (alcohol and drug use, sexual behaviors, and meeting sexual partners at social venues (e.g., bars)) may provide insights into drivers of onward transmission. Modeling with both deterministic and agent-based methods to assess network dynamics and the potential population-level impact of our TasP interventions. We are developing HIV epidemic models incorporating study data to model the impact of 2 intervention components: increased testing frequency and earlier treatment initiation. Our models may reveal additional special considerations that underlie transmission dynamics in MSM and TW. METHODS Sabes was a multisite study that investigated the feasibility and benefits of incorporating frequent testing for acute and recent HIV infection and rapid linkage to care at community testing and treatment sites in Lima, Peru. Study sites There were 4 research sites in the Sabes Study; 3 were part of HIV research organizations (2 from the Health and Education Civil Association (IMPACTA) and 1 from Asociación Vía Libre), and 1 was a community-based organization, Epicentro. The Alberto Barton Health Center (Callao, Peru), a Ministry of Health clinic that offers services to MSM and TW, also referred a small number of participants. Study population Persons who were male at birth, who reported having had sex with a male partner in the past 12 months, and who were ≥18 years of age were eligible for participation. In addition, they must have been unaware of their HIV status and have been at high risk for acquiring HIV because 1) they were a partner of a person with newly diagnosed acute or recent HIV infection; 2) they were seeking HIV testing because they had symptoms of acute retroviral syndrome; or 3) they reported high-risk sexual behavior, defined as any of the following (17): a) no condom use during anal intercourse in the last 6 months; b) anal intercourse with more than 5 male sex partners during the last 6 months; c) self-identification as a sex worker; d) diagnosis of a sexually transmitted infection during the last 6 months or at screening; or e) being a sexual partner of an HIV-infected man or TW in the last 6 months. Definition of acute and recent HIV infections Acute HIV infection was operationally defined as a positive plasma HIV RNA test in a person with a negative third-generation HIV antibody test. Recent HIV infection was diagnosed by means of a positive third-generation rapid HIV test (confirmed by a separate enzyme immunoassay) with a documented negative third-generation HIV-antibody or HIV-RNA test in the previous 3 months. Study design The Sabes Study included 3 sequential steps: 1) identify HIV-negative subjects, 2) rescreen these subjects for incident HIV infection, and 3) if acute/recent infection is identified, enroll those subjects in a randomized study of immediate initiation of ART versus deferred initiation (Figure 1). Figure 1. View largeDownload slide CONSORT diagram for participants in the Sabes Study, Lima, Peru, 2013–2017. ART, antiretroviral therapy; CONSORT, Consolidated Standards of Reporting Trials; HIV, human immunodeficiency virus; MSM, men who have sex with men; TW, transgender women. Figure 1. View largeDownload slide CONSORT diagram for participants in the Sabes Study, Lima, Peru, 2013–2017. ART, antiretroviral therapy; CONSORT, Consolidated Standards of Reporting Trials; HIV, human immunodeficiency virus; MSM, men who have sex with men; TW, transgender women. Step 1: Screen to identify HIV-negative individuals All persons voluntarily visiting a participating clinic were asked about recent sexual activity, HIV risk factors, and their main reason for visiting the clinic. In addition, peer educators visited previously identified social venues (e.g., saunas, adult movie theaters, sex-work areas, discotheques, bars, beauty parlors, sporting events) to provide information about HIV and sexually transmitted infection prevention and to refer potential participants to study sites. Finally, a number of participants from the 2011 Peruvian Biobehavioral Survey (18) were invited to join the Sabes Study. MSM and TW were assessed for eligibility prior to HIV testing. To enroll in step 1, each participant had to be willing and able to provide informed consent for participation, including HIV testing, and to be recontacted if testing indicated acute or recent HIV infection, or to continue to be retested if the initial test result was negative (step 2). If testing indicated acute or recent HIV infection, the participant was asked to enroll in a randomized study of immediate versus deferred ART (step 3). TW who reported the use of estrogens or antiandrogens in the last 3 months were not eligible, because use of these drugs could impair provision of semen specimens collected as part of the protocol for HIV-infected participants (step 3). Persons with any physical, medical, occupational, or other condition that, in the judgment of the investigators, would interfere with or serve as a contraindication to protocol adherence or assessment of safety were excluded from participation. HIV screening was conducted on whole blood using Alere Determine HIV-1/2 (Alere Inc., Waltham, Massachusetts), a point-of-care third-generation HIV antibody test. Blood samples that were negative for HIV antibodies were pooled and tested for HIV RNA with a nucleic acid amplification test using a Liat HIV Quant Assay (IQuum, Inc., Marlborough, Massachusetts). Positive pools were deconvoluted to identify HIV-positive samples, using a fourth-generation HIV enzyme immunoassay (Bio-Rad Laboratories, Hercules, California) or HIV RNA tests. The Abbott RealTime HIV-1 test (Abbott Laboratories, Lake Bluff, Illinois) was used to confirm HIV infection. Participants completed a structured computer-assisted self-interview on demographic factors, sexual behavior, social venue attendance, drug and alcohol use, and stigma and coping. All participants were also tested for syphilis using a rapid plasma reagent test (RPR QuickTest; Stanbio Laboratory, Boerne, Texas). Positive results were confirmed by means of a Treponema pallidum particle agglutination assay (TPHA Test Kit DR0530; Oxoid Microbiology Products Ltd., Basingstoke, United Kingdom). Participants with acute or recent HIV, as defined in this study, were invited to participate in step 3. Persons found to have established HIV infections (>3 months since acquisition) were referred to local health-care providers to receive the local standard of care or to participate in other studies if available. HIV-negative subjects were invited to continue their participation in step 2. Step 2: Enroll HIV-negative subjects from step 1 for monthly HIV testing MSM and TW found to have no HIV infection in step 1 were given free condoms, lubricant, and standard risk-reduction counseling. They were asked to visit the study center monthly for a 2-year period for HIV retesting and to complete a computer-assisted self-interview questionnaire on social venue attendance, substance use, and sexual behaviors. Participants diagnosed with acute or recent HIV infection were invited to participate in step 3. HIV-positive persons identified more than 3 months after their last negative HIV RNA test were not eligible, because infection within the past 3 months could not be unambiguously determined in these individuals. They were referred to appropriate facilities to receive the local standard of care or to participate in other available studies. Step 3: Enroll subjects with early HIV infection in immediate or deferred ART Persons with acute or recent HIV infection diagnosed in steps 1 or 2 were enrolled in a 48-week randomized study of immediate ART versus deferred ART. An additional 12 subjects with recent HIV infection were enrolled directly in step 3 from the Alberto Barton Health Center. All newly diagnosed HIV-positive participants were linked to care at study clinics as quickly as possible, either by referral after diagnosis of recent infection by point-of-care assays or through peer health navigators who contacted patients shortly after laboratory diagnosis of acute infection. Consenting volunteers were administered a structured computer-assisted interview questionnaire on drug use history (19); alcohol-use disorders (20); health status (21); anxiety and depression (22); social support, stigma, and disclosure; and medical care (hospitalization and emergency room use, access to care, and barriers to care). Participants were randomized one-to-one using blocks of 2 or 4 to start ART immediately or to defer ART initiation until 24 weeks after enrollment (when setpoint viral load is established), unless Peruvian criteria for ART initiation were met earlier (CD4-positive cell count ≤500 cells/mm3; changed from ≤350 cells/mm3 in December 2014) or their illness was diagnosed as meeting WHO clinical stage 3 or 4. Thus, all participants received ART either before or at the time they met criteria for ART initiation in Peru. The ART regimen was coformulated tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg/efavirenz 600 mg, 1 tablet taken orally daily. Participants were switched to alternate WHO-recommended regimens for intolerance or toxicity. Participants experiencing treatment failure (i.e., not achieving more than 1 log10 drop in plasma HIV RNA copies per mL after 16 weeks of treatment; not achieving an HIV RNA level below 50 copies/mL after 24 weeks of treatment; or having an HIV RNA level greater than 400 copies/mL upon 2 consecutive measurements after having achieved an HIV RNA level below 50 copies/mL) were switched to an alternate WHO-recommended regimen based on clinical judgment and HIV genotyping when available. At 48 weeks, each participant was transferred to the Ministry of Health ART Program, which provides free HIV care and treatment. Protection of human subjects The study protocol, informed consent forms, and recruitment materials were approved by institutional review boards at the Fred Hutchinson Cancer Research Center, the Health and Education Civil Association, and the Asociación Vía Libre, in compliance with all applicable Peruvian and US federal regulations governing the protection of human subjects. All study participants provided written consent in Spanish, their native language, to participate in the study. Implementation of the study was authorized by the Peruvian National Institute of Health, and the study is registered with ClinicalTrials.gov (https://clinicaltrials.gov/; trial NCT01815580). RESULTS Step 1 Recruitment for step 1 began in July 2013 and was completed in September 2015 with the testing of 3,337 high-risk participants (Table 1). Over 93% of the subjects were identified through clinic screening of the general population of MSM and TW; the remaining 7% were identified from the 2013 Peruvian Biobehavioral Survey (18). The overall prevalence of HIV among the participants at baseline was 19.5%, although there were marked differences between the 2 source populations: 20.7% for the general screening population and only 3.1% for the biobehavioral survey population. This difference occurred because subjects were tested for HIV in the Peruvian Biobehavioral Survey and only HIV-uninfected individuals were referred for rescreening in the Sabes Study several months later. Although Silva-Santisteban et al. (5) reported higher HIV prevalence among TW than among MSM in Peru, HIV prevalences in the Sabes TW and MSM were similar (19.3% and 19.7%, respectively); thus, they were combined for this analysis. Table 1. Characteristics of the Population Screened for Step 1 of the Sabes Study, Lima, Peru, 2013–2015 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Abbreviations: HIV, human immunodeficiency virus; STI, sexually transmitted infection. a Based on risk criteria defined by Sanchez et al. (17). Table 1. Characteristics of the Population Screened for Step 1 of the Sabes Study, Lima, Peru, 2013–2015 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Characteristic Subjects Tested HIV-Negative Subjects HIV-Positive Subjects No. % of Sample No. % of HIV-Negative Subjects No. Prevalence, % Total study population 3,337 100.0 2,685 100.0 652 19.5  General screening population 3,109 93.2 2,464 91.8 645 20.7  Biobehavioral survey population 228 6.8 221 8.2 7 3.1 Inclusion risk factor(s)a  No condom use during last anal sex 1,887 56.6 1,512 56.3 375 19.9  Anal sex with >5 partners in last 6 months 1,219 36.5 983 36.6 236 19.4  Self-identified as a sex worker 628 18.8 528 19.6 100 15.9  Sex partner of HIV-positive male 195 5.8 151 5.6 44 22.6  Syphilis diagnosed in last 6 months 120 3.6 90 3.4 30 25.0 Main reason for visit to testing clinic  Thought exposed to HIV 1,415 42.4 1,088 40.5 327 23.1  Referred by a peer educator 699 21.0 583 21.7 116 16.6  Routine STI screening 665 19.9 567 21.1 98 14.7  Got a new partner 92 2.8 75 2.8 17 18.5  Diagnosed with an STI 63 1.9 46 1.7 20 31.7  Felt sick 42 1.3 24 0.9 17 40.5  Acute HIV infection symptoms 73 2.2 44 1.6 29 39.7  Other reasons 88 2.6 68 2.5 20 22.7  No response 200 6.0 190 7.1 10 5.0 Abbreviations: HIV, human immunodeficiency virus; STI, sexually transmitted infection. a Based on risk criteria defined by Sanchez et al. (17). The 2 most common risk factors for study inclusion, “no condom use during last anal intercourse” and “anal intercourse with more than 5 sexual partners in the last 6 months,” were reported by 57% and 37% of participants, respectively. The main reason for visiting the clinic, “thought exposed to HIV,” was reported by 42% of the participants and by 41% of those who were HIV-negative. The next most common reason, “referred by a peer educator,” was reported by 21% of the tested subjects and 22% of those who were HIV-negative. All other reasons were mentioned by less than 3% of the tested subjects, and the distributions were similar for both the tested and HIV-negative subjects. Step 2 Of the 2,685 HIV-negative MSM and TW identified in step 1, a total of 2,109 (78.5%) enrolled in step 2 for repeated monthly HIV testing (Table 2). Follow-up for step 2 ended in May 2016, so follow-up for some of the more recently enrolled participants was truncated at less than 24 months; 256 cases of HIV infection were identified in step 2. However, because the length of the interval since their last negative test was greater than 3 months, 54 of these HIV-positive subjects could not be categorized as having recent infections and were therefore ineligible to enroll in step 3, which left 202 eligible participants. Table 2. Characteristics of Eligible and Enrolled Subjects in Step 2 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Abbreviations: AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b AUDIT score ≥8 is indicative of an alcohol-use disorder. c Postsecondary includes Peruvian higher technical education as well as college/university. Table 2. Characteristics of Eligible and Enrolled Subjects in Step 2 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Characteristic Eligible HIV-Negative Enrolled HIV-Negative P Valuea No. % No. % Total 2,685 100.0 2,109 100.0 Age group, years <0.01  18–24 1,169 43.5 897 42.4  25–34 1,024 38.1 795 37.6  ≥35 488 18.2 416 19.9  No response 4 <0.2 1 <0.1 Education <0.01  No secondary 168 6.3 126 6.0  Partial or complete secondary 877 32.7 643 30.5  Postsecondaryc 1,621 60.4 1,329 63.0  No response 19 0.7 11 0.5 Monthly income 0.50  <$400 1,746 65.0 1,386 65.7  $400–$799 288 10.7 236 11.2  ≥$800 80 3.0 66 3.1  No response 571 21.3 421 20.0 Sexuality and gender identity <0.01  Homosexual male 1,326 49.4 1,091 51.7  Bisexual male 810 30.2 624 29.6  Heterosexual male 116 4.3 80 3.8  Transgender female 414 15.4 302 14.3  No response 19 0.7 12 0.6 Sexual role <0.01  Insertive 759 28.3 566 26.8  Receptive 782 29.1 618 29.3  Both 1,125 41.9 913 43.3  No response 19 0.7 12 0.6 AUDIT scoreb 0.29  0–7 971 36.2 775 36.8  8–15 885 33.0 691 32.8  ≥16 533 19.9 407 19.3  No response 296 11.0 236 11.2 Abbreviations: AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b AUDIT score ≥8 is indicative of an alcohol-use disorder. c Postsecondary includes Peruvian higher technical education as well as college/university. In general, the step 2 participants were young (44% were below age 25 years), were well-educated (60% had at least some postsecondary schooling), had only marginal incomes (65% reported monthly incomes below US$400, the customary poverty line for Peru), and identified predominantly as homosexual (49%). Almost half (42%) reported both insertive and receptive sex roles, and just over half (53%) reported drinking behavior consistent with an alcohol-use disorder (score ≥8 on the Alcohol Use Disorders Identification Test). Participants who enrolled and did not enroll differed with regard to age, education, income, sexual identity, and sexual role (Table 2). Compared with the nonenrollees, persons who enrolled in step 2 were slightly older, more educated, and more likely to self-identify as homosexual, and they differed in reported sexual role. Retention of participants in the cohort was high: After 3 months, 87% were still returning for retesting, and after 12 months this proportion was 62% (Figure 2). Figure 2. View largeDownload slide Retention of participants in the Sabes Study cohort, Lima, Peru, 2013–2016. The denominator for each quarterly data point was equal to the number of subjects who were eligible for retesting at that time of observation. This excludes subjects who became positive for human immunodeficiency virus during the previous quarters, as well as a small number of participants whose follow-up was truncated when follow-up was terminated prior to the completion of 2 years of observation. Figure 2. View largeDownload slide Retention of participants in the Sabes Study cohort, Lima, Peru, 2013–2016. The denominator for each quarterly data point was equal to the number of subjects who were eligible for retesting at that time of observation. This excludes subjects who became positive for human immunodeficiency virus during the previous quarters, as well as a small number of participants whose follow-up was truncated when follow-up was terminated prior to the completion of 2 years of observation. Step 3 A total of 256 eligible subjects with acute or recent HIV infections were identified during the study—the majority (78%) from rescreening in step 2, and the remainder from initial testing in step 1 and referral from the Alberto Barton Health Center (“Barton clinic”) (Figure 1). Forty HIV-positive subjects either declined to enroll in step 3 or were excluded from enrollment in step 3 because of health issues: 6 from step 1 and 34 from step 2. An additional 12 eligible participants were recruited from the Barton clinic and enrolled in step 3. The resulting total enrollment in step 3 was 216 persons. The enrolled population closely reflected the eligible population with regard to all of the characteristics examined (Table 3). One-third (35%) of the enrolled HIV-positive subjects had acute infections, and two-thirds (65%) had recent infections. Participants in these 2 categories were then randomized separately into treatment groups to receive ART immediately or beginning at 24 weeks (Figure 1). Table 3. Characteristics of Eligible and Enrolled Subjects in Step 3 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Abbreviations: Ab, antibody; AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b An additional 54 HIV-seropositive subjects were identified during step 2 rescreening. However, the elapsed time since their previous screening was greater than 3 months, so they could not be classified as “recently infected”; therefore, they were not eligible to enroll in step 3. c Postsecondary includes Peruvian higher technical education as well as college/university. d AUDIT score ≥8 is indicative of an alcohol-use disorder. Table 3. Characteristics of Eligible and Enrolled Subjects in Step 3 of the Sabes Study, Lima, Peru, 2013–2016 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Characteristic Eligible HIV-Positive Enrolled HIV-Positive P Valuea No. % No. % Screened population 256 100.0 216 100.0 0.68  Step 1 screening 42 16.4 36 16.7  Step 2 rescreeningb 202 78.5 168 77.8  Barton clinic screening 12 5.1 12 5.6 Timing of infection 0.38  Acute (RNA-positive; Ab-negative) 87 34.0 71 32.9  Recent (Ab-positive; last Ab-negative test <90 days prior) 169 66.0 145 67.1 Age group, years 0.82  18–24 125 48.8 104 48.2  25–34 98 38.3 84 38.9  ≥35 27 10.6 22 10.2  No response 6 2.3 6 2.8 Education 0.24  No secondary 13 5.1 9 4.2  Partial or complete secondary 63 24.6 52 24.1  Postsecondaryc 180 70.3 155 71.8 Monthly income 0.93  <$400 173 67.6 148 68.5  $400–$799 33 12.9 29 13.4  ≥$800 6 2.3 5 2.3  No response 44 17.2 34 15.7 Sexuality and gender identity 0.55  Homosexual male 144 56.3 123 56.9  Bisexual male 73 28.5 60 27.8  Heterosexual male 6 2.3 4 1.9  Transgender female 33 12.9 29 13.4 Sexual role 0.06  Insertive 35 14.1 26 12.0  Receptive 83 32.4 69 31.9  Both 137 53.5 121 56.0 AUDIT scored 0.45  0–7 98 38.3 85 39.4  8–15 78 30.5 66 30.6  ≥16 51 19.9 47 21.8  No response 29 11.3 18 8.3 Abbreviations: Ab, antibody; AUDIT, Alcohol Use Disorders Identification Test; HIV, human immunodeficiency virus. a 2-sided P value (χ2 test). P values were calculated on nonmissing data. b An additional 54 HIV-seropositive subjects were identified during step 2 rescreening. However, the elapsed time since their previous screening was greater than 3 months, so they could not be classified as “recently infected”; therefore, they were not eligible to enroll in step 3. c Postsecondary includes Peruvian higher technical education as well as college/university. d AUDIT score ≥8 is indicative of an alcohol-use disorder. DISCUSSION Initial testing of study participants in step 1 and their enrollment in periodic retesting (step 2) was completed in September 2015. Enrollment of participants identified with acute and recent HIV infections in step 3 was completed in May 2016. Follow-up of step 3 participants was completed in April 2017. Ongoing step 3 analyses In ongoing step 3 analyses, we are engaging in the following activities. Estimation of the impact of immediate and deferred ART on the decay dynamics of HIV viral load We are measuring viral load in plasma, semen, and rectal secretions collected periodically from a subset of participants receiving immediate and deferred ART. We will use these data for modeling the impact of ART on infectivity during acute and recent HIV infection through various modes of exposure. Viral phylogenetic analysis We are mapping behavioral data (such as alcohol use) and geographic data onto phylogenetic transmission clusters to gain insights into drivers of HIV transmission in this population. This approach will allow us to determine the relative contributions of MSM and TW, with and without alcohol-use disorder (or other risk behaviors), to onward HIV transmission. Modeling the expected intervention impact at the population level The culmination of these analyses will be the development of an HIV epidemic model. We will use study data to estimate the percentage of HIV infections that are diagnosed as acute or recent and the distribution of testing intervals among MSM and TW overall. A series of deterministic models will be developed to simulate HIV transmission in Peruvian MSM and TW populations with and without our interventions, and to evaluate the public health impact of increased detection and treatment of acute and recent HIV infections on the HIV epidemic. A cost-effectiveness evaluation will provide information to inform prevention strategies such as the one we have evaluated. Association of HIV testing strategies and linkage to care using peer navigators We will assess the overall impact of study activities on increasing the frequency of HIV testing among high-risk MSM and TW. Ninety percent of participants with early HIV infection were linked to the study clinics, within a median of 6 days. This compares very favorably with linkage-to-care rates for MSM and TW from this population who are referred to HIV care in the absence of study interventions—only 45% were linked to care within 90 days after testing positive (23). Context This project has demonstrated that it is possible to reach a target population of high-risk MSM and TW, screen them for HIV, and then frequently retest those who are initially HIV-negative in order to identify incident cases shortly after HIV acquisition. Recruitment for HIV screening was accomplished through enhancing an existing platform for outreach in neighborhoods, and HIV testing was performed at clinics that are regularly visited by MSM and TW residents of Lima. Similarly, follow-up testing and treatment was performed at those same clinics. All other study activities were conducted with only slight modifications to the existing public health infrastructure within the community. Implications While current WHO guidelines call for initiation of ART at the time of HIV diagnosis, this alone does not guarantee early treatment, since most people are diagnosed years after HIV acquisition. Recent studies suggest that HIV reservoirs can be limited if treatment is begun in the weeks after HIV acquisition (24) and suggest that this would reduce onward transmission (25, 26); however, detecting infection this early remains a huge operational challenge. The Sabes Study sought to address this gap in public health practice by exploring the feasibility and impact of early HIV detection and treatment. Results to date have demonstrated the feasibility of detecting HIV infection shortly after acquisition with rapid linkage to care through community outreach and use of local clinics serving MSM and TW. Additional follow-up of these study participants has been instituted and will provide further insight into the benefits of early treatment initiation for individuals and the community. ACKNOWLEDGMENTS Author affiliations: Asociación Civil Impacta Salud y Educación (IMPACTA), Lima, Peru (Javier R. Lama, Jessica Rios); Fred Hutchinson Cancer Research Center, Seattle, Washington (Audrey Brezak, James G. Dobbins, Carolyn Bain, Angela Ulrich, Ann Duerr); Epicentro, Lima, Peru (Hugo Sanchez); Asociación Vía Libre, Lima, Peru (Robinson Cabello); and Cent de Investigación Tecnologicas, Biomedicas y Medioambientales, Universidad Mayor de San Marcos, Lima, Peru (Robert De la Grecca, Jorge Sanchez). This work was funded by the National Institute on Drug Abuse, US National Institutes of Health (grant DA032106 to A.D.). A.B. was supported by a Mary Gates Scholarship from the University of Washington (Seattle, Washington). Medication for this study was donated by Gilead Sciences (Foster City, California) and Merck & Co., Inc. (Kenilworth, New Jersey). We thank Ashley Clayton and Siavash Pasalar for developing the figures for this article. The Sabes Study Team: Carmela Ganoza, Ricardo Alfaro, Cecilia Correa, Karin Sosa, Peter Brandes, Eduardo Ruiz, Cecilia Zegarra, Manuel Villaran, Patricia Segura, Gonzalo Meneses, David Huaytalla, Daniel Alva, Karin Roca, Carlos Medrano, and Yesika Magallens. This paper was presented in abstract form (abstract P52.03) at the 2014 HIV Research for Prevention Meeting, Cape Town, South Africa, October 28–31, 2014. Conflict of interest: none declared. Abbreviations ART antiretroviral therapy MSM men who have sex with men PrEP preexposure prophylaxis TasP treatment as prevention TW transgender women WHO World Health Organization REFERENCES 1 Beyrer C , Baral SD , van Griensven F , et al. . Global epidemiology of HIV infection in men who have sex with men . 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Presented at Western Regional Meeting of the American Federation for Medical Research and Participating Societies, Carmel, California , January 28–30, 2016. 24 Ananworanich J , Chomont N , Eller LA , et al. . HIV DNA set point is rapidly established in acute HIV infection and dramatically reduced by early ART . EBioMedicine . 2016 ; 11 : 68 – 72 . Google Scholar CrossRef Search ADS PubMed 25 Kroon EDMB , Phanuphak N , Shattock AJ , et al. . Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok . J Int AIDS Soc . 2017 ; 20 ( 1 ): 21708 . Google Scholar CrossRef Search ADS PubMed 26 Abu-Raddad LJ . Role of acute HIV infection in driving HIV transmission: implications for HIV treatment as prevention . PLoS Med . 2015 ; 12 ( 3 ): e1001803 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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American Journal of EpidemiologyOxford University Press

Published: Aug 1, 2018

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