Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro modelPerna, Angelica; Carleo, Maria A.; Mascolo, Silvia; Guida, Alessandra; Contieri, Marcella; Sellitto, Carmine; Hay, Eleonora; De Blasiis, Paolo; Lucariello, Angela; Guerra, Germano; Baldi, Alfonso; De Luca, Antonio; Maggi, Paolo; Esposito, Vincenzo
doi: 10.1097/qad.0000000000003455pmid: 36504092
Objective:Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens.Design:In-vitro model of adipogenesis.Methods:We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARɣ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment.Results:Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF.Conclusion:Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.
Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIVSukumaran, Luxsena; Kunisaki, Ken M.; Bakewell, Nicholas; Winston, Alan; Mallon, Patrick W.G.; Doyle, Nicki; Anderson, Jane; Boffito, Marta; Haddow, Lewis; Post, Frank A.; Vera, Jaime H.; Sachikonye, Memory; Sabin, Caroline A.
doi: 10.1097/qad.0000000000003462pmid: 36541572
Background:People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk.Methods:We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ (relatively low levels of inflammation). Ten-year cardiovascular disease (CVD) risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression.Results:Of the 312 participants included [70% living with HIV, median (interquartile range; IQR) age 55 (51–60) years; 82% male; 91% white], 36, 130, and 146 were in the ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ cluster, respectively. The median (IQR) QRISK scores were 9.3% (4.5–14.5) and 10.2% (5.5–16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK [5.8% (1.0–10.7) and 3.1% (0.3–5.8)] scores were higher, respectively, for those in the ‘gut/immune activation’ and ‘neurovascular’ clusters compared to those in the reference cluster.Conclusions:People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV.
Single-center experience evaluating and initiating people with HIV on long-acting cabotegravir/rilpivirineHill, Lucas A.; Abulhosn, Kari K.; Yin, Jeffrey F.; Bamford, Laura P.
doi: 10.1097/qad.0000000000003446pmid: 36730069
Objective:To describe our experience evaluating and initiating individuals on long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) and evaluate factors associated with starting LAI CAB/RPV and reasons for not starting.Design:We conducted a retrospective single-center study at the UC San Diego Owen Clinic.Methods:We included all individuals who expressed interest in treatment with LAI CAB/RPV between April 2021 and June 2022 who had a definitive decision made on starting LAI CAB/RPV.Results:In total, 383 individuals were included with 201 (52.5%) initiating LAI CAB/RPV. Those who initiated LAI CAB/RPV were younger (P = 0.02) and were more likely to be on a two-drug regimen or first-generation integrase inhibitor regimen and less likely to be on a protease inhibitor or multiclass regimen. The most common reasons for not starting LAI CAB/RPV were inconsistent clinic attendance or difficulty being contacted and patient choice not to start. Of those who had a proviral DNA resistance test as workup for LAI CAB/RPV (n = 135), 18.5% had a resistance mutation identified that may have impacted the activity of LAI CAB/RPV.Conclusion:Despite novel challenges over half of our cohort initiated LAI CAB/RPV. Evaluating for potential non-nucleoside reverse transcriptase inhibitor resistance is an important part of the workup for LAI CAB/RPV and proviral DNA resistance testing can be an additional tool to identify potential resistance.
Characteristics and clinical manifestations of monkeypox among people with and without HIV in the United States: a retrospective cohortChastain, Daniel B.; Motoa, Gabriel; Ortiz-Martínez, Yeimer; Gharamti, Amal; Henao-Martínez, Andrés F.
doi: 10.1097/qad.0000000000003449pmid: 36729995
Objectives:To compare characteristics and clinical manifestations of monkeypox (MPX) between people with and without HIV in the United States.Design:Retrospective cohort study using TriNetX, a federated research network.Methods:Patients 18 years and older with MPX were identified based on the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code B04 and divided into two groups: people with HIV (PWH) and people without HIV. Differences in baseline characteristics, clinical manifestations, and all-cause healthcare utilization were examined between groups. Outcomes were reported before and after propensity score matching.Results:Of 322 cases of MPX included, 29% (n = 93) were PWH. Baseline characteristics were similar, but PWH were more likely to identify as Black or African American persons (24% vs. 11%, P = 0.0303) or as Hispanic or Latino persons (24% vs. 11%, P = 0.0345) and more likely to report lifestyle factors affecting health status. Rash and rectal pain were more common in PWH (25% vs. 11%, P < 0.01, and 25% vs. 10%, P < 0.001, respectively). In addition, PWH had higher rates of anal or rectal abscesses (11% vs. 0%, P < 0.0001), phimosis (11% vs. 0%, P < 0.0001), and pneumonia (11% vs. 0%, P < 0.0001). More PWH required urgent care visits (53% vs. 29%, P < 0.0001) and hospitalizations (11% vs. 4%, P = 0.0314), but not emergency department visits (42% vs. 58%, P = 0.0085).Conclusion:PWH had higher rates of clinical manifestations and required greater utilization of healthcare resources for any reason compared with those without HIV.
Nurse-facilitated preexposure prophylaxis delivery for adolescent girls and young women seeking contraception at retail pharmacies in Kisumu, KenyaPintye, Jillian; Odoyo, Josephine; Nyerere, Bernard; Achieng, Pauline; Araka, Evelyne; Omondi, Christine; Ortblad, Katrina F.; Mugambi, Melissa L.; Baeten, Jared M.; Bukusi, Elizabeth A.
doi: 10.1097/qad.0000000000003447pmid: 36653342
Objective:We evaluated preexposure prophylaxis (PrEP) uptake, initiation, and continuation within a nurse-facilitated pharmacy-based delivery model for Kenyan adolescent girls and young women (AGYW) seeking contraception at retail pharmacies.Methods:From October 2020 to March 2021, PrEP-trained nurses were stationed at three retail pharmacies in Kisumu, Kenya. AGYW (aged 15–24 years) purchasing contraception (emergency contraception, oral contraceptive pills, injectables, implants, condoms) were counseled on PrEP, completed HIV testing, and offered a free 1-month supply of PrEP pills per national guidelines by nurses under supervision of a remote physician. We evaluated uptake among all AGYW offered PrEP. At 30 days after uptake, we evaluated PrEP use initiation and plans for continuation.Results:We enrolled 235 AGYW clients who were HIV-negative and purchasing contraception at pharmacies. Emergency contraception was the most frequently purchased contraceptive (35%). Median age was 22 years (IQR 19–23), 44% were currently in school, and 33% currently had multiple sexual partners. One-fourth (24%) exchanged sex for money or favors and 14% had sex while intoxicated in the prior 6 months. Overall, PrEP uptake was 85%; at 1 month, 82% had initiated PrEP use and 68% planned to continue use. Among those initiating PrEP, 69% were willing to pay for PrEP at retail pharmacies (median KES 150, IQR 100–200) even if available for free at public sector facilities.Conclusion:In this evaluation of nurse-facilitated PrEP delivery at pharmacies in Kenya, a substantial proportion of AGYW who purchased contraception subsequently initiated PrEP, planned to continue use, and were willing to pay for PrEP.
HIV in the Russian Federation: mortality, prevalence, risk factors, and current understanding of sexual transmissionNikoloski, Zlatko; King, Elizabeth J.; Mossialos, Elias
doi: 10.1097/qad.0000000000003441pmid: 36729857
Background:Although HIV infection in the Russian Federation was historically concentrated among marginalized populations (people who inject drugs, sex workers, MSM, and the prison population), recent evidence suggests that it has become a more generalized epidemic. The objective of our research was to explore how these trends in HIV prevalence and HIV-related mortality compare across Russia.Methods:We calculated HIV-associated mortality for both male and female individuals in each region (oblast) of the Russian Federation using data from the Russian Fertility and Mortality Database (RusFMD). Using current data on HIV prevalence, we computed the correlation between HIV prevalence and HIV-associated mortality. We also used oblast-level data to examine the associations between HIV prevalence and the risk factors most commonly associated with HIV infection.Results:Over the past 20 years, the Russian Federation has experienced a rapid increase in HIV-associated mortality in both male and female individuals. Our findings revealed significant heterogeneity, with higher rates of HIV-associated mortality reported in oblasts in the Siberian and Ural Federal Districts. There is a strong correlation (0.8) between HIV-associated mortality and virus prevalence. These findings confirm that there are regional disparities in access and adherence to antiretroviral therapy (ART), as indicated by the low correlation (−0.4) between virus prevalence and access to ART coverage. The results from our modeling analysis revealed that, in addition to the factors most commonly associated with this disease (e.g. intravenous drug use), knowledge about sexual transmission of HIV in the general population has a broad impact on its prevalence at the oblast level.Conclusion:Interventions that reduce HIV prevalence, for example, opioid substitution therapy and needle-sharing programs for people who inject drugs, as well as the increased availability of educational and preventive programs may halt the spread of HIV across the Russian Federation. Similarly, increased access to treatment could help in reducing HIV-related mortality.