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Gonçalves, Paloma; Barreto, Jorge; Santos, Menilita; Leal, Silvania; Marcelino, José; Abecasis, Ana; Palladino, Claudia; Taveira, Nuno
doi: 10.1097/qad.0000000000003866pmid: 38349224
Objectives:To characterize the genetic diversity and drug resistance profiles of people with HIV-1 failing ART in Cape Verde (CV).Design:Cross-sectional study conducted between January 2019 and December 2021 in 24 health centres on the islands of Santiago and São Vicente.Methods:The HIV-1 pol gene was sequenced in individuals with a detectable viral load. HIV-1 genetic diversity was determined by phylogenetic analysis. Drug resistance mutation patterns and resistance phenotypes were estimated using the Stanford algorithm.Results:Viral load was detected in 73 of 252 (29%) enrolled participants and sequencing data were produced for 58 (79%) participants. CRF02 AG strains predominated (46.5%), followed by subtype G (22.4%). Most patients (80%) had mutations conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) (67%), nucleoside reverse transcriptase inhibitors (55%), integrase inhibitors (10%) and/or protease inhibitors (7%) used in Cape Verde, a significant increase compared with a study conducted in 2010–2011. The most common mutations were M184V/I (43%), K103N/S (36%) and G190A/S (19%). NNRTI resistance was associated with younger age and exposure to two or more drug regimens.Conclusion:The HIV-1 epidemic in Cape Verde is mainly driven by CRF02_AG and subtype G. Resistance to NNRTIs and/or NRTIs is highly prevalent and resistance to LPV/r and DTG is emerging. Our results support the use of DTG-based first-line ART and protease inhibitor-based regimens for patients with virological failure, but emerging resistance to LPV/r and DTG is a concern. Continued monitoring of drug resistance is essential to ensure adequate healthcare for PWH in Cape Verde.
Shivakoti, Rupak; Giganti, Mark J.; Lederman, Michael M.; Ketchum, Rachel; Brummel, Sean; Moisi, Daniela; Dadabhai, Sufia; Moodley, Dhayendre; Violari, Avy; Chinula, Lameck; Owor, Maxensia; Gupta, Amita; Currier, Judith S.; Taha, Taha E.; Fowler, Mary Glenn; ,
Duncan, Maggie C.; Omondi, F. Harrison; Kinloch, Natalie N.; Lapointe, Hope R.; Speckmaier, Sarah; Moran-Garcia, Nadia; Lawson, Tanya; DeMarco, Mari L.; Simons, Janet; Holmes, Daniel T.; Lowe, Christopher F.; Bacani, Nic; Sereda, Paul; Barrios, Rolando; Harris, Marianne; Romney, Marc G.; Montaner, Julio S.G.; Brumme, Chanson J.; Brockman, Mark A.;
Gianella, Sara; Anderson, Christy; Chaillon, Antoine; Wells, Alan; Porrachia, Magali; Caballero, Gemma; Meneses, Milenka; Lonergan, Joseph; Woodworth, Brendon; Gaitan, Noah C.; Rawlings, Stephen A.; Muttera, Leticia; Harkness, Liliana; Little, Susan J.;
Crowell, Trevor A.; Ritz, Justin; Zheng, Lu; Naqvi, Asma; Cyktor, Joshua C.; Puleo, Joseph; Clagett, Brian; Lama, Javier R.; Kanyama, Cecilia; Little, Susan J.; Cohn, Susan E.; Riddler, Sharon A.; Collier, Ann C.; Heath, Sonya L.; Tantivitayakul, Pornphen;
Sullivan, Edith V.; Zahr, Natalie M.; Zhao, Qingyu; Pohl, Kilian M.; Sassoon, Stephanie A.; Pfefferbaum, Adolf
doi: 10.1097/qad.0000000000003894pmid: 38537080
Objective:With aging, people with HIV (PWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables.Design:Mixed cross-sectional/longitudinal data were acquired over 15 years in 141 PWH and 102 age-range matched controls, 25–80 years old.Methods:Multimodal structural MRI data were quantified for seven total and regional WMH volumes. Static posturography acquired with a force platform measured sway path length separately with eyes closed and eyes open. Statistical analyses used multiple regression with mixed modeling to test contributions from non-MRI and nonpath data on sway path-WMH relations.Results:In simple correlations, longer sway paths were associated with larger WMH volumes in PWH and controls. When demographic, physiological, and HIV-related variables were entered into multiple regressions, the sway-WMH relations under both vision conditions in the controls were attenuated when accounting for age and two-point pedal discrimination. Although the sway-WMH relations in PWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for five of the seven regions in the eyes-open condition.Conclusion:The constellation of age-related increasing instability while standing, degradation of brain white matter integrity, and peripheral pedal neuropathy is indicative of advancing fraility and liability for falls as people age with HIV infection.
Dirajlal-Fargo, Sahera; Yu, Wendy; Jacobson, Denise L.; Mirza, Ayesha; Geffner, Mitchell E.; Jao, Jennifer; McComsey, Grace A.; ,
doi: 10.1097/qad.0000000000003896pmid: 38564437
The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally acquired HIV (YPHIV) have not been investigated.The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007 to 2009. For this analysis, we included YPHIV with HIV viral load 1000 c/ml or less, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or nonhigh density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide-binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log10 gut markers with log10 HOMA-IR and non-HDLc at all timepoints.HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 years (10, 14), CD4+ cell count was 762 cells/μl (574, 984); 90% had HIV RNA less than 400 c/ml. For every 10-fold higher baseline I-FABP, HOMA-IR dropped 0.85-fold at baseline and Yr2. For a 10-fold higher baseline zonulin, there was a 1.35-fold increase in HOMA-IR at baseline, 1.23-fold increase in HOMA-IR at Yr2, and 1.20-fold increase in HOMA-IR at Yr3 in adjusted models. For a 10-fold higher baseline LBP, there was a 1.23-fold increase in HOMA-IR at baseline in the unadjusted model, but this was slightly attenuated in the adjusted model. Zonulin was associated with non-HDLc at baseline, but not for the other time points.Despite viral suppression, intestinal damage may influence downstream insulin sensitivity in YPHIV.
Saberian, Chantal; Lurain, Kathryn; Hill, Lindsay K.; Marshall, Vickie; Castro, Elena M. Cornejo; Labo, Nazzarena; Miley, Wendell; Moore, Kyle; Roshan, Romin; Ruggerio, Margie; Ryan, Kerry; Widell, Anaida; Ekwede, Irene; Mangusan, Ralph; Rupert, Adam;
Colbrunn, Danielle K.; Jacks, Courtney; Curry, Scott R.; Gebregziabher, Mulugeta; Meissner, Eric G.
doi: 10.1097/qad.0000000000003884pmid: 38489581
Objective:The aim of this study was to examine outcomes of follow-up for persons with discordant fourth-generation HIV screening test results.Design:A retrospective chart review.Methods:We analyzed the electronic health record at the Medical University of South Carolina for a 10-year period spanning 2012–2022 to identify instances of discordant HIV screening test results, wherein initial antigen/antibody screening was positive, but reflex confirmatory testing for HIV-1 and HIV-2 antibodies was negative. We reviewed individual records to evaluate clinical follow-up and determine if the discordant test represented an acute HIV infection, a false-positive result, or was unresolved.Results:We identified 199 testing instances with discordant results. Most discordant results (n = 115) were subsequently determined to reflect a false-positive test, while 56 were unresolved without documented follow-up testing. Twenty-eight cases of acute HIV infection were identified of which 26 were linked to care within a month of initial testing. Two acute HIV cases were not identified in real time leading to delay in diagnosis and care. Testing done in the context of infectious symptoms and testing performed in the emergency department were associated with increased odds of a discordant test ultimately reflecting acute HIV infection.Conclusion:These results demonstrate the importance of appropriate and timely follow-up for discordant HIV screening test results.
Showing 1 to 10 of 27 Articles
Objective:HIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD.Design/methods:A nested 1 : 1 case–control study (N = 362) was conducted within a multicountry randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (<37 weeks of gestational age). The following inflammatory biomarkers were measured in plasma samples using immunoassays: soluble CD14 (sCD14) and sCD163, intestinal fatty acid-binding protein, interleukin (IL)-6, interferon γ, and tumor necrosis factor α. We fit regression models to assess associations between second trimester biomarkers (measured before ART initiation at 13–23 weeks of gestational age and 4 weeks later), treatment regimen, and PTD. We also assessed whether inflammation was a mediator in the relationship between ART regimen and PTD.Results:Persistently high interleukin-6 was associated with increased PTD. Compared with zidovudine alone, the difference in biomarker concentration between week 0 and week 4 was significantly higher (P < 0.05) for both protease inhibitor-based regimens. However, the estimated proportion of the ART effect on increased PTD mediated by persistently high biomarker levels was 5% or less for all biomarkers.Conclusion:Persistently high IL-6 during pregnancy was associated with PTD. Although protease inhibitor-based ART was associated with increases in inflammation, factors other than inflammation likely explain the increased PTD in ART-based regimens compared with zidovudine alone.
doi: 10.1097/qad.0000000000003841pmid: 38224350
Objective:The immunogenic nature of coronavirus disease 2019 (COVID-19) mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign.Design:Longitudinal observational cohort and province-wide analysis.Methods:Sixty-two participants were sampled prevaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the intact proviral DNA assay; pVL were measured using the cobas 6800 (lower limit of quantification: 20 copies/ml). The province-wide analysis included all 290 401 pVL performed in British Columbia, Canada between 2012 and 2022.Results:Prevaccination, the median intact reservoir size was 77 [interquartile range (IQR): 20–204] HIV copies/million CD4+ T-cells, compared to 74 (IQR: 27–212) and 65 (IQR: 22–174) postfirst and -second dose, respectively (all comparisons P > 0.07). Prevaccination, 82% of participants had pVL <20 copies/ml (max: 110 copies/ml), compared to 79% postfirst dose (max: 183 copies/ml) and 85% postsecond dose (max: 79 copies/ml) (P > 0.4). There was no evidence that the magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike immune response influenced pVL nor changes in reservoir size (P > 0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART.Conclusion:We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.
doi: 10.1097/qad.0000000000003882pmid: 38526550
Objective:We sought to determine if standard influenza and pneumococcal vaccines can be used to stimulate HIV reservoirs during antiretroviral therapy (ART).Design:A prospective, randomized, double-blinded, placebo-controlled, crossover trial of two clinically recommended vaccines (influenza and pneumococcal).Methods:Persons with HIV on ART (N = 54) were enrolled in the clinical trial. Blood was collected at baseline and days 2,4,7,14, and 30 postimmunizations. Levels of cellular HIV RNA and HIV DNA were measured by ddPCR. Expression of immunological markers on T cell subsets was measured by flow cytometry. Changes in unspliced cellular HIV RNA from baseline to day 7 postinjection between each vaccine and placebo was the primary outcome.Results:Forty-seven participants completed at least one cycle and there were no serious adverse events related to the intervention. We observed no significant differences in the change in cellular HIV RNA after either vaccine compared with placebo at any timepoint. In secondary analyses, we observed a transient increase in total HIV DNA levels after influenza vaccine, as well as increased T cell activation and exhaustion on CD4+ T cells after pneumococcal vaccine.Conclusion:Clinically recommended vaccines were well tolerated but did not appear to stimulate the immune system strongly enough to elicit significantly noticeable HIV RNA transcription during ART.Clinicaltrials.gov identifier: NCT02707692.
doi: 10.1097/qad.0000000000003881pmid: 38489580
Objective:To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses.Design:Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia.Methods:HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines.Results:From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23–38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+ or CD8+ T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest.Conclusion:Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.
doi: 10.1097/qad.0000000000003897pmid: 38564482
Objective:Kaposi sarcoma is a vascular tumor that affects the pulmonary system. However, the diagnosis of airway lesions suggestive of pulmonary Kaposi sarcoma (pKS) is reliant on bronchoscopic visualization. We evaluated the role of Kaposi sarcoma herpesvirus (KSHV) viral load in bronchoalveolar lavage (BAL) as a diagnostic biomarker in patients with bronchoscopic evidence of pKS and evaluated inflammatory cytokine profiles in BAL and blood samples.Design:In this retrospective study, we evaluated KSHV viral load and cytokine profiles within BAL and blood samples in patients who underwent bronchoscopy for suspected pKS between 2016 and 2021.Methods:KSHV viral load and cytokine profiles were obtained from both the circulation and BAL samples collected at the time of bronchoscopy to evaluate compartment-specific characteristics. BAL was centrifuged and stored as cell pellets and KSHV viral load was measured using primers for the KSHV K6 gene regions.Results:We evaluated 38 BAL samples from 32 patients (30 with HIV co-infection) of whom 23 had pKS. In patients with airway lesions suggestive of pKS, there was higher KSHV viral load (median 3188 vs. 0 copies/106 cell equivalent; P = 0.0047). A BAL KSHV viral load cutoff of 526 copies/106 cells had a sensitivity of 72% and specificity of 89% in determining lesions consistent with pKS. Those with pKS also had higher IL-1β and IL-8 levels in BAL. The 3-year survival rate for pKS patients was 55%.Conclusion:KSHV viral load in BAL shows potential for aiding in pKS diagnosis. Patients with pKS also have evidence of cytokine dysregulation in BAL.