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HIV status may influence survival from non-small cell lung cancer (NSCLC). Among NSCLC patients in the Bronx, NY, we assessed (1) associations of CD4 count, CD4/CD8 ratio and HIV viral load (VL) with survival and (2) prognostic factors among persons living with HIV (PLWH). We compared survival from NSCLC diagnosis (2004-2017) between HIV-negative persons (HIV-, n=2,881) and PLWH (n=88) accounting for clinical and sociodemographic factors. HIV-survival was also compared with PLWH, dichotomized by CD4 (

Despite availability of effective antiretroviral therapy (ART), many HIV patients still have a detectable viral load (VL). Predictive factors of detectable VL are not well documented. This study was done at two large multidisciplinary HIV outpatient clinics at the Centre hospitalier de l'Université de Montréal (CHUM) and the McGill University Health Centre (MUHC). This is a retrospective case-control study of patients treated between 2016 and 2018. Cases had a VL ≥50 copies/mL in 2018. Controls had an undetectable VL from 2016 to 2018. Matching was based on gender and year of HIV diagnosis. Primary objective was to identify predictive factors of detectable VL. Secondary objectives included to identify predictive factors of virologic failure, low persistent viremia, and viral blip. A forward stepwise model selection by the Akaike Information Criterion of the conditional logistic regression was used to identify predictive factors. Two hundred cases were identified and matched with 200 controls. The cohort was mostly male (68.0%) with a median age of 54 years (21-83 years). Among cases, viral blip was the most common type of detectable VL (43.0%). The strong predictive factors for a detectable VL were adherence to ART and seeking health care services. Asylum seekers were less at risk of detectable VL. Adherence to ART was the only strong predictive factor for virologic failure. Three main predictive factors of detectable VL were identified in two ambulatory clinic hospitals in Montreal. Ascertaining these factors will allow for identification of patients more at risk of detectable VL.

Given the large numbers of people with HIV (PWH) with Medicaid coverage, it is important to understand the patient experience with Medicaid. Understanding experiences with and attitudes around the program have important policy and clinical implications. The objective was to understand the patient perspective of PWH in Virginia, who transitioned to Medicaid in 2019 due to Medicaid expansion. English-speaking PWH who gained Medicaid due to Medicaid expansion in 2019 were recruited at one Virginia Ryan White HIV/AIDS Program clinic. The goal was to enroll33% of those who newly were on Medicaid for 2019. Participants were surveyed about demographic characteristics, and semistructured interviews were performed. Descriptive analyses were performed for cohort characteristics. Using qualitative description and an open coding strategy, codebooks were generated for the interviews and themes were identified. The cohort (

Background: The monthly dapivirine vaginal ring provides partial protection against HIV, and a longer duration ring may reduce user burden and improve adherence. We examined acceptability and prefe...

Introduction The high cost of viral load (VL) testing limits its use for antiretroviral treatment (ART) adherence support. A low-cost lateral flow urine tenofovir (TFV) rapid assay predicts PrEP breakthroughs but has not yet been investigated in HIV treatment. We therefore evaluated its utility in a pilot cross-sectional study of TFV-containing ART recipients at increased risk of virologic failure. Methods Participants who had a treatment interruption ≥30 days or had ≥1 episode of viremia (VL≥400 copies/mL) in the previous year were recruited from a public health setting in Cape Town, South Africa. Self-reported adherence data were collected, the urine TFV assay performed, and concurrent TFV-diphosphate (DP) analysed in dried blood spots. VL testing was done concurrently and, if viremic, genotypic HIV drug resistance testing performed. Results Of 48 participants, 18 (37.5%) had virologic failure (VL>400 copies/mL) at the time of the study including 16 of 39 receiving efavirenz (EFV), 2 of 6 receiving protease inhibitors (PI) and 0 of 3 receiving dolutegravir (DTG). Resistance testing succeeded in 17/18, of which 14 had significant mutations compromising ≥2 agents of the current EFV-based regimen. Of these 14, all had detected urine TFV. Urine TFV was undetectable in 2 out of 3 without regimen-relevant resistance; p=0.02. Conclusion In participants on EFV-based regimens returning to care, virologic failure was largely due to viral resistance, where detectable urine TFV had 100% sensitivity (14/14 participants) in predicting resistance. Conversely, when undetectable, the urine-based assay could be used to preclude participants with poor adherence from undergoing costly HIV drug resistance testing.

Evidence for a relationship between polysubstance use, depression, and adherence to antiretroviral therapy (ART) is limited. The objectives of this study were to examine the associations of depression, illicit drug and alcohol use with adherence to ART. People living with HIV (PLHIV) from the Miami Adult Studies on HIV (MASH) cohort were asked about the number of doses of their ART medication missed to assess adherence to ART. Harmful alcohol drinking was evaluated using the Alcohol Use Disorders Identification Test and illicit substance use assessed with self-report and urine screen. The Center for Epidemiologic Studies Depression Scale was used to assess depression symptoms. Of 391 PLHIV, 16.6% missed at least one dose (Range 1–5) in the past four days. Cocaine/crack, opiate use and depression were significantly independently associated with a bigger mean number of doses missed. The mean number of doses missed was significantly bigger among participants who used alcohol in combination with cocaine/crack, marijuana, and tobacco compared to non-users. In conclusion, polysubstance use increased risk for poor ART adherence among PLHIV. The use of cocaine/crack or opiates individually, and depressive symptoms also promote poor adherence to ART. An integrated approach is needed to address substance disorders and depression in order to achieve better ART adherence.

Introduction Dapivirine (DPV), formulated as vaginal ring, demonstrated HIV risk reduction. MTN-026 explored DPV, formulated as rectal gel, for safety, pharmacokinetics, and acceptability. Methods HIV-uninfected men and women aged 18-45 years were enrolled at United States and Thailand sites and randomized 2:1 to receive DPV 0.05% or placebo gel via rectal applicator. A single dose phase was followed by 7 observed daily doses. Plasma, and fluid and tissue from both rectum and cervix were collected at baseline and after the final dose over 72 hours for pharmacokinetics, ex-vivo HIV-1 biopsy challenge, histology, and flow cytometry. Results 28 participants were randomized; 2 terminated early; 9 were female and 19 male; 12 were white, 11 Asian, 4 black and 1 other race/ethnicity. Mean age was 28.5 and 34.2 years in the DPV and placebo arms, respectively. Thirty adverse events occurred (all Grade 1 or 2, except one unrelated Grade 3) without study arm differences. DPV rectal tissue concentrations (median [interquartile range]) 0.5-1 and 2 hours after a single dose were 256 ng/gm (below limit of quantitation [BLQ], 666) and BLQ (BLQ, 600), respectively, then BLQ (BLQ, BLQ) from 24-72 hours; concentrations following multiple doses were similar. The largest median DPV plasma concentrations were 0.33 ng/mL (0.15, 0.48) after one dose and 0.40 (0.33, 0.49) after seven doses. Conclusions The DPV rectal gel was acceptable and without safety concerns. While DPV plasma concentrations were similar to the vaginal ring, rectal tissue concentrations were well below vaginal ring tissue concentrations, suggesting need for reformulation.

The Combination HIV Antiretroviral Rectal Microbicide-3 (CHARM-03) study was a randomized, open-label, crossover Phase 1 safety and pharmacokinetic (PK) study of oral maraviroc (MVC) and MVC 1% gel. At a single site, healthy HIV-uninfected men and women were enrolled and randomized to an open label crossover sequence of eight consecutive daily exposures to MVC 300 mg dosed orally, MCV 1% gel dosed rectally, and MVC 1% gel dosed vaginally. Male participants received oral and rectal dosing and female participants received oral, rectal, and vaginal dosing. Assessments were undertaken at baseline and following each 8-day period and included collection of plasma, rectal/cervical tissue (CT), and rectal/endocervical/vaginal fluids. Eleven men and nine women were enrolled. Two participants withdrew from the study before receiving study product. There were 25 adverse events, of which 24 were Grade 1 (G1) and one was G2 (unrelated). After eight doses, MVC was quantifiable in all samples following oral, rectal, or vaginal product administration. The highest drug concentrations in plasma, rectal tissue (RT), and CT were associated with oral, rectal, and vaginal drug delivery, respectively. There were significant reductions in tissue drug concentrations when rectal and cervical biopsies were incubated in media before tissue processing for PK (p

Long-acting delivery modalities of HIV pre-exposure prophylaxis (PrEP), such as subdermal implants, are in development. To facilitate end-user uptake and sustained use, it is critical to understand potential consumers' and physician prescribers' preferences about, interest in, and relative importance of different implant features. The ordered identification of these key attributes allows implant developers to incorporate this feedback into product design, which theoretically improves acceptability, feasibility, and user experience with the device. In this study, n = 75 PrEP-prescribing physicians and n = 143 men having sex with men (MSM) at risk for HIV completed web-based surveys that directly compared the importance of eight to nine different implant features, respectively. Conjoint analysis determined the importance of these features, relative to each other. Implants presented in the study were well received, with a majority of physicians and MSM indicating that they were likely to recommend or use them. The implant was perceived as unique, reliable, and convenient, as well as able to deliver better compliance. The attributes most critical to the adoption of the implant among physicians and MSM were (1) the chance of becoming infected with HIV while on implant treatment, (2) the length of protection and size of the implant, and (3) the side effect advantages over current PrEP oral pill treatment. Some concerns about the implant included side effects and the product's safety (among MSM) and the cost or insurance coverage level for the implant (both physicians and MSM). There was also some resistance to the implantation procedure itself.

Background Increasing the number of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) providers expands PrEP access to more eligible patients to help end the HIV epidemic. Previous studies have noted providers perceive financial barriers as a limitation to prescribing PrEP. Objective Describe PrEP medication access and affordability in patients seen at a multidisciplinary PrEP clinic. Method We conducted a single-center, retrospective, cohort study of adults initiating tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in the Vanderbilt PrEP Clinic between 9/1/2016 and 3/31/2019 with prescriptions filled by Vanderbilt Specialty Pharmacy. Data were gathered from the electronic health records and pharmacy claims. We evaluated three different time periods: initial evaluation to PrEP initiation, prescription of PrEP to insurance approval, and insurance approval to initiation. Treatment initiation was considered delayed when >7 days from initial evaluation, and reasons for delay were recorded. Continuous variables are presented as median (interquartile range, IQR) and categorical variables are presented as percentages. Results We included 63 patients; most were male (97%), White (84%), commercially insured (94%) with a median age of 38 years (IQR 29—47). Primary indication for PrEP was men who have sex with men at high risk for acquiring HIV (97%). Median time from initial appointment to treatment initiation was 7 days (IQR 4—8). Treatment delays occurred in 25% of patients and were mostly driven by patient preference (50%). Insurance prior authorization was required in 27% of patients; all were approved. Median total out-of-pocket medication costs for the entire study period were $0 (IQR $0 – $0). Most patients (86%) used manufacturer copay cards. Conclusion In this cohort of mostly commercially insured men, the majority were able to access PrEP with low out-of-pocket costs facilitated by manufacturer assistance. Though generalizability beyond this population is limited, these results contradict perceived financial barriers to PrEP access.

Introduction Youth aged 13–29 years represent 23% of the population but account for 40% of new HIV diagnoses, with risk peaking at ages 22–23 years. We assessed sexual behaviors, PrEP knowledge and attitudes among patients of 6 School-Based-Health-Centers (SBHCs) located in Northern Manhattan and the Bronx. Method 667 patients, aged 13–19 years, completed a survey in the SBHCs waiting rooms between 10/2018 – 4/2019 Results Of the survey respondents attending SBHCs, 32% reported ever having heard of PrEP and, upon learning of PrEP, 67% stated that would be very likely (35%) or somewhat likely (32%) to take PrEP if it was offered to them free of charge. Discussion Youth of color are disproportionately infected by HIV throughout the US. Efforts are needed to educate adolescents on the benefits of PrEP, SBHCs are well situated to reduce barriers in providing PrEP directly to those who would benefit from its protection..

The Microbicide Trials Network-017 study was undertaken to characterize the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic profile of the reduced-glycerin (RG) 1% tenofovir (RG-TFV) gel compared to oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). The study was a Phase 2, three-period, randomized sequence, open-label, expanded safety and acceptability crossover study. In each 8-week study period, HIV-1-uninfected participants were randomized to RG-TFV rectal gel daily or RG-TFV rectal gel before and after receptive anal intercourse (RAI) (or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. A mucosal substudy was conducted at sites in the United States and Thailand. Samples were collected to evaluate PK and ex vivo biopsy challenge with HIV-1. A total of 195 men who have sex with men and transgender women were enrolled in the parent study and 37 in the mucosal substudy. As previously reported, both products were found to be safe and acceptable. Systemic TFV concentrations were significantly higher following oral exposure and daily rectal administration compared to RAI-associated product use (p

It is unknown whether antiretroviral (ARV) drugs in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus. Immediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high-performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis. Twelve WLHIV were on protease inhibitors, six on non-nucleoside reverse inhibitors, and two on integrase strand inhibitors with optimized backbone. Mean birth weight of HIV-exposed neonates was significantly lower than unexposed neonates (3,075 g vs. 3,498 g, p = .01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium-chain acylcarnitines. Placental metabolism may be altered in WLHIV, possibly associated with ARV exposure. The lower birth weight among neonates of WLHIV suggests the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.

South Africa introduced the "diagnose and treat" universal HIV treatment program in September 2016. This program enables all identified HIV-positive patients to immediately start first-line antiretroviral therapy (ART). However, the presence of drug-resistant (DR) viruses in the drug-naive population complicates the choice of ART. We used next-generation sequencing (NGS) to determine the prevalence and diversity of HIV DR mutations in patients entering HIV treatment programs in northern South Africa. RNA was isolated from plasma of drug-naive HIV-1-infected patients. Using reverse transcriptase polymerase chain reaction, the HIV-1

BACKGROUND The World Health Organization (WHO) 2019 antiretroviral treatment guidelines recommend use of optimal treatment regimens in all populations. Dolutegravir-based regimens are the preferred first-line and second-line treatment in infants and children with HIV 4 weeks of age and above. There is an urgent need for optimal pediatric formulations of dolutegravir as single-entity (SE) and fixed-dose combination (FDC) to ensure correct dosing and adherence for swallowing and palatability. This article outlines the chronology of dolutegravir pediatric formulation development as granules and conventional and dispersible tablets in a total of 5 pharmacokinetic studies evaluating the relative bioavailability of dolutegravir SE and FDC formulations in healthy adults. METHODS The relative bioavailability studies were 2-part, Phase I, open-label, randomized studies in healthy adults. Dolutegravir SE study compared conventional dolutegravir 50 and 25 mg with equivalent conventional 10-mg and dispersible 5-mg tablets, respectively. Subsequently, dolutegravir FDC study compared adult FDC of abacavir/dolutegravir/lamivudine and adult FDC of dolutegravir/lamivudine with their respective pediatric FDC formulations, taken as dispersion immediately or swallowed whole. RESULTS As observed in previous studies, dolutegravir administered as dispersion (granules/dispersible tablets) showed relatively higher bioavailability compared with conventional tablets. The bioavailability of dolutegravir dispersible tablets (both SE and FDC) was approximately 1.6-fold higher when compared with conventional tablets. In addition, the bioavailability of abacavir/lamivudine was not impacted by dispersible formulation. CONCLUSIONS These studies demonstrate the successful development of pediatric dolutegravir-containing formulations as SE and FDC that permit pediatric dosing in line with WHO recommendations.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) requires continued use at an effective dosage to reduce HIV incidence. Data suggest early PrEP drop-off among many populations. We sought to describe PrEP use over the first year among racial and ethnic minority patients in the US. SETTING: Racial and ethnic minority patients initiating PrEP at a federally qualified health center in Chicago, IL METHODS: Using electronic health records, we determined the adherence (≥6 weekly doses) trajectories over the first year of PrEP use and compared baseline and time-varying patient characteristics. RESULTS: From 2,159 patients, we identified three PrEP use trajectories. Sustained use was the most common (40%) trajectory, followed by short use (30%) and declining use (29%). In adjusted models, younger age, Black race, as well as gender, sexual orientation, insurance status at baseline, and neighborhood were associated with trajectory assignment; within some trajectories, insurance status during follow-up was associated with odds of monthly adherence (≥6 weekly doses). CONCLUSION: Among racial and ethnic minorities, a plurality achieved sustained PrEP persistence. Access to clinics, insurance, and intersectional stigmas may be modifiable barriers to effective PrEP persistence; in addition, focus on younger users and beyond gay, cismale populations are needed.

Data that inform preexposure prophylaxis (PrEP) implementation for women involved in criminal justice (WICJ) systems are scarce. In a survey of PrEP attitudes, acceptability, and barriers across the criminal justice system, incarcerated women (n = 48) were more likely than WICJ on probation (n = 125) to be eligible for PrEP (29% vs. 15%; p = .04) and willing to take PrEP if offered (94% vs. 78%; p = .01). In multivariate models, PrEP eligibility directly correlated with being incarcerated (adjusted odds ratio [aOR] 4.81, 95% confidence interval [CI] 1.76–13.1) and inversely correlated with Hispanic/Latina ethnicity (aOR 0.31; 95% CI 0.10–0.96). Recent partner violence exposure was associated with PrEP eligibility (aOR 3.29; 95% CI 1.54–7.02) and discordant risk perception (aOR 2.36; 95% CI 1.18–4.70). Findings demonstrate high potential for PrEP for all WICJ, though implementation efforts will need to address partner violence.

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Background A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection. Objective To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy. Design Detailed investigation of virologic and immunologic characteristics. Setting Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts. Patient A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication. Measurements Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing. Results No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4+ T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. Limitations Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved. Conclusion Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection. Primary funding source National Institutes of Health and Bill & Melinda Gates Foundation.

ObjectivesLong-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics.Study designWe enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrelconcentrations between antiretroviral regimens. We considered a minimum serum etonogestrelconcentration of90 pg/mLadequate for ovulation suppression.ResultsWe collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion.ConclusionsUnlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations.ImplicationsThe findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.

Background: Reduced bone mineral density (BMD) is a frequent comorbidity observed in people living with HIV (PLHIV). Objective: The aim of the study is to determine the prevalence and associated factors of reduced bone mineral density (BMD) among men with suppressed viral load taking antiretroviral therapy. Method: The study was conducted as a cross-sectional design between January to April 2019. 211 patients were included in the study. Z-score at either body site between -1.0 and -2.0 or -2 or less was defined as osteopenia or osteoporosis, respectively. Multivariate logistic regression analysis was used to evaluate the factors affecting the development of reduced BMD. Results: The mean age of the patients involved in the study was 34.8 ± 7.6. Osteoporosis was detected in 21.4% and osteopenia in 44.5% of the patients. There was a significant relationship found between HIV diagnosis time, ART usage duration, tenofovir disoproxil fumarate (TDF) use, TDF use in the past, total TDF usage time and decreased BMD. Multivariate logistic regression analysis showed that the likelihood of reduced bone marrow density was 67% lower among those with regular milk or dairy product intake compared to those without (OR=0.330; 95% CI = 0.12-0.92, p=0.033). Conclusion: There is a high prevalence of reduced BMD among PLHIV aged under 50, which is mainly confounded by HIV diagnosis time, ART usage duration and TDF usage. Although virological control has been achieved, these patients should be followed up, considering that they may have decreased BMD.

People living with HIV (PLWH) are at greater risk for severe COVID-19 and are a priority population for COVID-19 vaccination. As of June 15, 2021, 61.6% of PLWH in Oregon received ≥ 1 COVID-19 vaccine dose. Younger PLWH, Hispanic/Latinx PLWH and PLWH who inject drugs or reside in rural and frontier areas had low vaccine uptake while PLWH who were engaged in care, enrolled in the AIDS Drug Assistance Program, and vaccinated against influenza had high vaccine uptake. Greater advocacy, education, and care navigation are required to increase COVID-19 vaccine access and uptake among PLWH. Supplementary Information The online version contains supplementary material available at 10.1007/s10461-021-03570-9.

Objective In AIDS Clinical Trials Group study A5338, concomitant rifampicin, isoniazid, and efavirenz was associated with more rapid plasma medroxyprogesterone acetate (MPA) clearance compared to historical controls without tuberculosis or HIV therapy. We characterized the pharmacogenetics of this interaction. Methods In A5338, women receiving efavirenz-based HIV therapy and rifampicin plus isoniazid for tuberculosis underwent pharmacokinetic evaluations over 12 weeks following a 150-mg intramuscular injection of depot MPA. Data were interpreted with nonlinear mixed-effects modelling. Associations between individual pharmacokinetic parameters and polymorphisms relevant to rifampicin, isoniazid, efavirenz, and MPA were assessed. Results Of 62 A5338 participants in four African countries, 44 were evaluable for pharmacokinetic associations, with 17 CYP2B6 normal, 21 intermediate, and 6 poor metabolizers, and 5 NAT2 rapid, 20 intermediate, and 19 slow acetylators. There were no associations between either CYP2B6 or NAT2 genotype and MPA Cmin at week 12, apparent clearance, Cmax, area under the concentration-time curve (AUC) or half-life, or unexplained interindividual variability in clearance, and uptake rate constant or mean transit time of the slow-release fraction (P > 0.05 for each). In exploratory analyses, none of 28 polymorphisms in 14 genes were consistently associated with MPA pharmacokinetic parameters, and none withstood correction for multiple testing. Conclusions Study A5338 suggested that more frequent depot MPA dosing may be appropriate for women receiving rifampicin, isoniazid, and efavirenz. The present results suggest that knowledge of CYP2B6 metabolizer or NAT2 acetylator status does not inform individualized DMPA dosing in this setting.

Background: Antiretroviral therapy (ART) non-adherence and methamphetamine use are associated with higher HIV drug resistance prevalence. How they affect drug resistance mutations accumulation is less studied. Objective: We assessed factors associated with drug resistance mutations accumulation. Methods: We evaluated HIV chronically-infected patients from a clinic-based research cohort on first-line ART regimens with genotype results within 30 days of baseline. Methamphetamine use and ART adherence were self-reported at each study visit. High ART adherence was defined as 0-5% missed doses in the last 30 days. Results: One-hundred twenty-five patients contributed 496 study visits. At baseline, 81% of patients reported high ART adherence; 90% reported no methamphetamine use in the prior 4 months, 8% used monthly or less and 2% used daily or weekly. Methamphetamine users and non-users had similarly high ART adherence (p=0.93). Adjusted incidence rate ratio (aIRR) of drug resistance mutations accumulation was 2.04 (95% CI 0.64, 6.46) for daily/weekly users and 1.71 (95% CI 0.66, 4.42) for patients with monthly or less users, compared to non-users. aIRR was 0.71 (95% CI 0.44, 1.15) with >5-10% missed ART doses and 1.21 (95% CI 0.80, 1.83) with >10% missed doses compared to 0-5% missed doses. Conclusions: We found no strong evidence for the effect of methamphetamine use and ART adherence on drug resistance mutations accumulation. Research cohort patients may have been more engaged in care and treatment adherent than non-cohort patients. Our findings suggest methamphetamine use might not lead to treatment failure among HIV patients who are otherwise engaged in care.

Supplemental Digital Content is Available in the Text., Introduction: Recent studies project thousands of additional AIDS-related deaths because of COVID-19–related disruptions in HIV care. However, the extent to which disruptions in care have materialized since the start of the pandemic is not well understood. Methods: We use electronic health records to investigate how the pandemic has affected clinic visits, patients' antiretroviral therapy (ART) supply, and viral suppression for a cohort of 14,632 HIV clients from a large HIV clinic in Kampala, Uganda. We complement this with an analysis of electronically measured longitudinal ART adherence data from a subcohort of 324 clients. Results: Clinic visits decreased by more than 50% after a national lockdown started. The risk of patients running out of ART on a given day increased from 5% before the lockdown to 25% 3 months later (Relative Risk Ratio of 5.11, 95% confidence interval: 4.99 to 5.24) and remained higher than prelockdown 6 months later at 13% (Relative Risk Ratio of 2.60; 95% confidence interval: 2.52 to 2.70). There was no statistically significant change in electronically measured adherence or viral suppression. Conclusion: We document substantial gaps in HIV care after the start of the COVID-19 pandemic in Uganda. This suggests that measures to improve access should be explored as the pandemic persists. However, ART adherence was unaffected for the subcohort for whom we measured electronic adherence. This suggests that some clients may have stockpiles of ART tablets from previous prescriptions that allowed them to keep taking their medication even when they could not visit the clinic for ART refills.

Dolutegravir (DTG) is now a component of preferred first-line antiretroviral therapy (ART) worldwide. ADVANCE and NAMSAL were two landmark clinical trials conducted exclusively in sub-Saharan Africa, which studied the effectiveness of DTG-based first-line regimens for ART-naive individuals. In this review, we examine the data from these studies to consider the contributions of adherence and HIV drug resistance to treatment failure on DTG-based ART, as compared with efavirenz (EFV)-based ART, which has a lower genetic barrier to resistance. We also discuss the implications of virologic failure on DTG and consolidate currently available data to conclude with recommendations for virologic monitoring on DTG-based ART.

Background Out-of-facility multi-month dispensing (MMD) is a differentiated service delivery model which provides antiretroviral treatment (ART) at intervals of up to 6 monthly in the community. Limited randomized evidence investigating out-of-facility MMD is available. We evaluated participant outcomes and compared out-of-facility MMD models using data from cluster-randomized trials in Southern Africa. Setting Eight districts in Zimbabwe and Lesotho. Methods Individual-level participant data from 2 cluster-randomized trials that included stable adults receiving ART at 60 facilities were pooled. Both trials had 3 arms: ART collected 3-monthly at healthcare facilities (3MF, control); ART provided three-monthly in community ART groups (CAGs) (3MC); and ART provided 6-monthly in either CAGs or on an individual provider-patient basis (6MC). Participant retention, viral suppression and incidence of unscheduled facility visits were compared. Results Ten thousand one hundred thirty-six participants were included, 3817 (37.7%), 2893 (28.5%) and 3426 (33.8%) in arms 3MF, 3MC and 6MC, respectively. After 12 months, retention was non-inferior for 3MC (95.7%) vs. 3MF (95.0%) {adjusted risk difference (aRD) = 0.3 [95% confidence interval (CI): -0.8 to 1.4]}; and 6MC (95.1%) vs. 3MF [aRD = -0.2 (95% CI: -1.4 to 1.0)]. Retention was greater amongst intervention arm participants in CAGs versus 6MC participants not in CAGs, aRD = 1.5% (95% CI: 0.2% to 2.9%). Viral suppression was excellent (≥98%) and unscheduled facility visits were not increased in the intervention arms. Conclusions Three and 6-monthly out-of-facility MMD was non-inferior versus facility-based care for stable ART patients. Out-of-facility 6-monthly MMD should incorporate small group peer support whenever possible. Clinicaltrial registration ClinicalTrials.gov NCT03238846 and NCT03438370.

BACKGROUND HIV programmes world-wide currently make decisions regarding new antiretroviral therapy (ART) regimens with less side-effects and higher resistance barriers, which may improve adherence and viral suppression. Economic evaluation helps inform these decisions. METHODS We conducted an economic evaluation of three ART regimens included in the ADVANCE trial from the provider's perspective: tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG) and tenofovir disoproxil fumarate (TDF)/FTC+DTG, compared with TDF/FTC/efavirenz (EFV). We used top-down and bottom-up cost analysis with resource utilization based on trial data and adjusted to emulate routine care. We estimated the cost-effectiveness of each regimen as cost per person virally suppressed or retained and per life-year saved, at 48 and 96 weeks. RESULTS Though the DTG-based trial arms were 2% more costly than TDF/FTC/EFV, both had slightly lower cost-per-outcome ($9783 and $9929/patient virally suppressed for TDF/FTC+DTG and TAF/FTC+DTG, respectively) than TDF/FTC/EFV ($10 365). The trial cost per additional virally suppressed patient, compared with TDF/FTC/EFV, was lower in the TDF/FTC+DTG arm ($2967) compared with TAF/FTC+DTG ($3430). In routine care, cost per virally suppressed patient was estimated as similar between TDF/FTC+DTG ($426) and TDF/FTC/EFV ($424) but more costly under TAF/FTC+DTG. Similar results were seen in the cost per additional person retained across scenarios. When modelled over 20 years, TDF/FTC+DTG was more cost-effective than TAF/FTC+DTG ($10 341 vs $41 958/life-year saved). CONCLUSION TDF/FTC+DTG had similar costs per outcome as TDF/FTC/EFV in the routine care scenario but TDF/FTC+DTG was more cost-effective when modelled over 20 years.

Background Pre-exposure prophylaxis (PrEP) uptake among trans people to date has been low. Recommendations implemented in San Francisco to offer PrEP with feminizing hormones have not led to improvement of PrEP uptake in trans communities. New delivery models may be needed. The aim of this study was to examine whether a PrEP-only clinic was more likely to serve trans people at highest risk of HIV than trans-affirming primary care clinics. Methods Participants were recruited between 2017 and 2019 as part of a PrEP demonstration project in the San Francisco Bay Area. Survey data including sociodemographics, HIV-related risk behavior, barriers to PrEP, and self-reported PrEP adherence were collected at baseline, 3 months, and 6 months for all participants. Bivariable Poisson regression models were used to examine differences between participants in the primary care clinics and PrEP-only clinic delivered to participants. Results Baseline survey data were collected from 153 participants. Those with a higher number of sexual partners were significantly more likely to use the PrEP-only clinic rather than the primary care clinics. Participants with higher perceived HIV risk and those who engaged in sex work were also more likely to use the PrEP-only clinic compared with the primary care clinic. Medical mistrust was higher at baseline among participants of the PrEP-only clinic. PrEP adherence was not significantly different by delivery model. Few participants identified PrEP barriers, such as interactions with feminizing hormones, to be determinants of PrEP uptake. Conclusions A PrEP-only delivery model could improve PrEP uptake and may better meet the needs of trans people who could most benefit from PrEP.

BackgroundAdherence to antiretroviral treatment (ART) among postpartum women with HIV is essential for optimal health and prevention of perinatal transmission. However, suboptimal adherence with subsequent viremia is common, and adherence challenges are often underreported. We aimed to predict viremia to facilitate targeted adherence support in sub-Saharan Africa during this critical period.MethodsData are from PROMISE 1077BF/FF, which enrolled perinatal women between 2011 and 2014. This analysis includes postpartum women receiving ART per study randomization or country-specific criteria to continue from pregnancy. We aimed to predict viremia (single and confirmed events) after 3 months on ART at >50, >400, and >1000 copies/mL within 6-month intervals through 24 months. We built models with routine clinical and demographic data using the least absolute shrinkage and selection operator and SuperLearner (which incorporates multiple algorithms).ResultsAmong 1321 women included, the median age was 26 years and 96% were in WHO stage 1. Between 0 and 24 months postpartum, 42%, 31%, and 28% of women experienced viremia >50, >400, and >1000 copies/mL, respectively, at least once. Across models, the cross-validated area under the receiver operating curve ranged from 0.74 [95% confidence interval (CI): 0.72 to 0.76] to 0.78 (95% CI: 0.76 to 0.80). To achieve 90% sensitivity predicting confirmed viremia >50 copies/mL, 64% of women would be classified as high risk.ConclusionsUsing routinely collected data to predict viremia in >1300 postpartum women with HIV, we achieved moderate model discrimination, but insufficient to inform targeted adherence support. Psychosocial characteristics or objective adherence metrics may be required for improved prediction of viremia in this population.

Long-acting antiretroviral drugs have emerged as exciting treatment and preexposure prophylaxis (PrEP) options for people with HIV and at risk of HIV. Long-acting regimens may improve dosing convenience, tolerability and cost compared with current daily-based oral therapy. They can also circumvent stigma associated with oral therapy for both treatment and PrEP, thereby improving adherence and outcomes. Yet, multiple challenges remain, many specific to low-income and middle-income countries (LMICs), where the epidemic is most concentrated and HIV prevention and treatment options are limited. To optimize the use of long-acting formulations, key outstanding questions must be addressed. Uncertain costing, scale-up manufacturing, complex delivery systems and implementation challenges are potential barriers when considering the scalability of long-acting ARVs for global use.

OBJECTIVE This study evaluated body mass index (BMI) and weight changes in people living with human immunodeficiency virus (HIV-1; PLWH) initiated on single-tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/FTC/TAF) or bictegravir/FTC/TAF (BIC/FTC/TAF). METHODS Electronic medical records (EMR) data for treatment-naive or virologically suppressed adults with HIV-1 who initiated treatment with DRV/c/FTC/TAF or BIC/FTC/TAF (index date) were obtained from Decision Resources Group's EMR (7/17/2017-3/1/2020). Inverse probability of treatment weighting was used to account for differences in baseline characteristics between the two cohorts. BMI and weight changes from pre-index to 3, 6, 9, and 12 months following the index date were compared using weighted mean differences (MDs). The time until an increase in BMI or weight ≥5% or ≥10% was compared using weighted hazard ratios (HRs). RESULTS The weighted DRV/c/FTC/TAF and BIC/FTC/TAF cohorts comprised 1,116 and 1,134 PLWH, respectively (mean age=∼49 years, females: ∼28%). Larger increases in BMI and weight from pre-index to each post-index time points were observed in PLWH initiating BIC/FTC/TAF vs DRV/c/FTC/TAF (12 months: MD in BMI =1.23 kg/m2, p

Antiretroviral options for neonates (younger than 28 days) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the "4-in-1" fixed-dose pediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates.The PETITE study is an ongoing phase I/II, open-label, single-arm, 2-stage trial conducted in South Africa. In stage 1, term neonates exposed to HIV on standard antiretroviral prophylaxis (nevirapine ± zidovudine) received single dose(s) of the 4-in-1 formulation, followed by intensive pharmacokinetic sampling and safety assessments. At each PK visit, blood was drawn after an observed dose at 1, 2, 4, 8, and 12 hours postdose. In this study, we have reported the planned interim pharmacokinetic and safety analysis after completion of the single-dose administration.Sixteen neonates, with a median (range) birth weight of 3130 g (2790-3590 g), completed 24 pharmacokinetic visits. The 4-in-1 formulation imposed relatively high doses of abacavir [8.6 mg/kg (6.6-11.4)] and lamivudine [4.3 mg/kg (3.3-5.7)] but lower doses of lopinavir [11.5 mg/kg (8.8-15.2)]. The geometric means (GM, 90% CI) AUC0-12 of abacavir, lamivudine, and lopinavir were 29.87 (26.29-33.93), 12.61 (10.72-14.83), and 3.49 (2.13-5.72) µg.h/mL, respectively. Lopinavir GM AUC0-12 was below the predefined target (20-100 µg.h/mL), and ritonavir concentrations were only detectable in 4 of the 120 (3%) samples. No adverse events were related to study drugs. No neonate had difficulty swallowing the 4-in-1 formulation.The high doses of abacavir and lamivudine (in mg/kg) and AUCs were safe, and the formulation was well tolerated; however, lopinavir/ritonavir exposures were extremely low, preventing its use in neonates use in neonates. Alternative pediatric solid antiretroviral formulations must be studied in neonates.

Background: The HIV-1 pandemic is undoubtedly the major public-health crisis of our time. The extensive research on HIV has deepened our understanding of its pathogenesis and transmission dynamics. Some new entity molecules have been approved by the FDA for HIV treatment but till now protective vaccine remains elusive. Scientists are targeting many important proteins of HIV-1; gp41, gp120, CCR5 coreceptor, integrase, reverse transcriptase and protease. Few compounds are used as nucleotide analogues to stop HIV replication. Altogether, these compounds and their derivatives specifically block HIV entry and DNA replication. Using ADMET studies, people are working on these compounds to reduce toxicity and increase potency. Objective: Our main aim is to discuss the Pharmacokinetics properties of 23 important FDA antiretroviral drugs used for the treatment of HIV-1 infections. Methods: We have searched literature related to pharmacokinetics properties in PubMed, Google Scholar search engine. Conclusion: Here, we have reviewed the pharmacokinetic properties such as absorption, bioavailability, distribution, metabolism, and excretion, of important 23 FDA approved drugs. The drugs namely Fuzeon, Selzentry, Complera, Epivir, Retrovir, Emtriva, Ziagen, Edurant, Intelence, Pifeltro, Sustiva, Viramune, Isentress, Genvoya, Tivicay, Reyataz, Prezista, Lexiva, Invirase, Aptivus etc. are classified into five major classes: fusion inhibitors, Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), Integrase Strand transfer inhibitors (INSTIs) and Protease inhibitors (PIs). This Review may helpful for the future development of potent antiretroviral drugs with improved pharmacokinetic properties.