From declining PrEP to PrEP initiation as "first nature" - what changes PrEP initiation decisions among young, Black MSM.

Young Black men who have sex with men (YBMSM) bear a disproportionate burden of HIV, and HIV pre-exposure prophylaxis (PrEP) uptake has been slow. Decisions regarding PrEP initiation change in different life contexts over time. Our YBMSM cohort study found about 1/3 of those who initially declined PrEP subsequently changed and initiated PrEP care. This study explores the process of their PrEP decision changes. The study interviewed participants who initially voiced strong and clear reservations about PrEP, but subsequently started PrEP 1-14 months later. In "review/renew" follow-up interviews, participants reviewed their past statements from a time they declined PrEP, and renew their understanding regarding perspective and behavioral change. Analyzing the data with a positive deviance framework, we found that shifting the decisional balance in favor of PrEP initiation only required change in some areas. There were not consistent factors that prevented or facilitated PrEP uptake. Instead, YBMSM initiated PrEP while maintaining an array of substantial reservations. PrEP initiation discussions should be viewed by health practitioners as a longitudinal process, and routine PrEP offers should be made over time. To optimally facilitate PrEP use among YBMSM, the diverse benefits of PrEP should be emphasized rather than focusing on allaying all concerns.

Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV.

BACKGROUND: Dolutegravir (DTG) monotherapy results in virologic failure and the development of DTG resistance. Here, we evaluated virologic outcomes of patients switched to DTG functional mono- or dual therapy with a non-cytosine nucleoside analog (NA). METHODS: This retrospective, single center study included treatment-experienced patients switched to regimens containing ≥ 2 antiretrovirals between 8/13/13-11/22/14 who were later found to be on DTG functional mono- or dual therapy with a non-cytosine NA based on historical genotypes. Eligible patients were either suppressed or viremic at baseline and had ≥ 2 HIV-1 RNA measurements at least 4 weeks apart following switch. Demographics, laboratory values and clinical parameters were extracted from the charts of all eligible patients during study treatment until 12/31/2018 and were summarized using descriptive statistics. The primary endpoint was the proportion of patients with HIV-1 RNA < 50 copies/mL following switch. RESULTS: Of 70 patients switched to DTG functional mono- or dual therapy, 39 were eligible; 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG functional dual therapy with a non-cytosine NA. Historical genotypes indicated that all had an M184V/I, and 23 (59%) had an M184V/I and ≥ 1 additional NA mutation. The median duration of follow-up on study treatment was 50 weeks (range 12-244). Following switch, 32/39 (82%) patients achieved or maintained an HIV-1 RNA < 50 copies/mL and 7 (18%) had persistent HIV-1 RNA ≥ 50 copies/mL. Five viremic patients were found to be on functional dual therapy with DTG plus a non-cytosine NA and 2 were on DTG functional monotherapy. Five of these patients had post-switch genotypes ordered as a part of routine clinical care and there was no evidence of treatment-emergent resistance. Five were switched to a different DTG-containing regimen and achieved HIV-1 RNA < 50 copies/mL, 1 was switched to a non-DTG containing regimen and achieved HIV-1 RNA < 50 copies/mL and 1 was lost-to-follow up at week 36. CONCLUSIONS: In this real-world cohort, the majority of whom had virus with the M184V/I and ≥ 1 additional NA mutation, switching to DTG functional mono-or dual therapy with a non-cytosine NA resulted in persistent HIV-1 RNA ≥ 50 copies/mL in 18%. None with post-switch genotypes developed treatment-emergent resistance.

Pre-exposure Prophylaxis Uptake and Discontinuation Among Young Black Men Who Have Sex With Men in Atlanta, Georgia: A Prospective Cohort Study.

BACKGROUND: Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has great potential to reduce HIV incidence among young black men who have sex with men (YBMSM); however, initiation and persistence for this group remain low. We sought to understand the patterns and predictors of PrEP uptake and discontinuation among YBMSM in Atlanta, Georgia. METHODS: PrEP was offered to all participants in a prospective cohort of YBMSM aged 18-29 years not living with HIV. Time to PrEP uptake, first discontinuation, and final discontinuation were assessed using the Kaplan-Meier method. Cox proportional hazard models were used to identify predictors of uptake and discontinuation. RESULTS: After 440 person-years of follow-up, 44% of YBMSM initiated PrEP through the study after a median of 122 days. Of PrEP initiators, 69% had a first discontinuation and 40% had a final discontinuation during the study period. The median time to first PrEP discontinuation was 159 days. Factors associated with PrEP uptake included higher self-efficacy, sexually transmitted infection (STI), and condomless anal intercourse. Factors associated with discontinuation included younger age, cannabis use, STI, and fewer sex partners. HIV incidence was 5.23/100 person-years (95% confidence interval [CI], 3.40-7.23), with a lower rate among those who started PrEP (incidence rate ratio, 0.39; 95% CI, .16-.92). CONCLUSIONS: Persistent PrEP coverage in this cohort of YBMSM was suboptimal, and discontinuations were common despite additional support services available through the study. Interventions to support PrEP uptake and persistence, especially for younger and substance-using YBMSM, are necessary to achieve full PrEP effectiveness. CLINICAL TRIALS REGISTRATION: NCT02503618.

PrEP Implementation and Persistence in a County Health Department Setting in Atlanta, GA.

For marginalized populations, county health departments may be important PrEP access points; however, there are little data on successful PrEP programs at these venues outside of incentivized demonstration projects. Therefore, we implemented an open-access, free PrEP clinic at a county health department in Atlanta, GA to promote PrEP uptake among high-risk clients. The Fulton County Board of Health PrEP clinic launched in October 2015, and eligible clients who expressed interest initiated PrEP and attended follow-up visits per CDC guidelines. Clients engaged in quarterly follow-up and seen within the last 6 months were defined as "persistent", whereas clients with a lapse in follow-up of > 6 months were defined as "not persistent." Factors associated with PrEP persistence were assessed with unadjusted odds ratios. Between October 2015 and June 2017, 399 clients were screened for PrEP, almost all were eligible [392/399 (98%)]; however, 158/392 (40%) did not return to start PrEP after screening. Of 234 patients, 216 (92%) received a prescription for PrEP. As of June 2017, only 69/216 (32%) clients remained persistent in PrEP care, and the only evaluated factor significantly associated with PrEP persistence was age ≥ 30 years (OR 1.86, 95% CI 1.02, 3.42). Implementation of PrEP in the county health department setting is feasible; however, we have identified significant challenges with PrEP uptake and persistence in our setting. Further research is needed to fully understand mediators of PrEP persistence and inform interventions to optimize health department-based PrEP services.

Beyond the Biomedical: Preexposure Prophylaxis Failures in a Cohort of Young Black Men Who Have Sex With Men in Atlanta, Georgia.

Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has high biomedical efficacy; however, awareness, access, uptake, and persistence on therapy remain low among black men who have sex with men (BMSM), who are at highest risk of HIV in the United States. To date, discussions of "PrEP failure" have focused on one typology: rare, documented HIV acquisitions among PrEP users with adequate serum drug levels (ie, biomedical failure). In our cohort of HIV-negative young BMSM in Atlanta, Georgia, we continue to observe a high HIV incidence (6.2% annually at interim analysis) despite access to free PrEP services. Among 14 seroconversions, all were offered PrEP before acquiring HIV. Among these participants, we identified 4 additional typologies of PrEP failure that expand beyond biomedical failure: low PrEP adherence, PrEP discontinuation, PrEP contemplation without initiation, and PrEP refusal. We describe the 5 typologies and suggest interventions to improve PrEP effectiveness among those at highest risk.

Use of a Prospective Sex Diary to Study Anal Lubricant and Enema Use Among High Risk Men Who Have Sex With Men-Implications for Human Immunodeficiency Virus Prevention.

Longitudinal data on episodes of receptive anal intercourse (RAI), lubricant, and enema use in 41 sexually active men who have sex with men were collected using a prospective sex diary. Data on 550 episodes of RAI showed that lubricants were used in 489 (88.9%) of 550 episodes and enemas were used in 165 (30%) of 550 RAI episodes.

Efficacy, Safety, and Tolerability of Switching From Bictegravir/Emtricitabine/Tenofovir Alafenamide to Dolutegravir/Lamivudine Among Adults With Virologically Suppressed HIV: The DYAD Study.

Background: In TANGO and SALSA, switching to dolutegravir/lamivudine (DTG/3TC) was noninferior to continuing a baseline regimen among adults who were treatment experienced, although few switched from bictegravir (B) / emtricitabine (F) / tenofovir alafenamide (TAF). Here, we present the efficacy and safety of switching to DTG/3TC as compared with continuing with B/F/TAF among adults with virologic suppression. Methods: DYAD is an open-label clinical trial that randomized adults with HIV-1 RNA <50 copies/mL and no prior virologic failure (2:1) to switch to once-daily fixed-dose DTG/3TC or maintain B/F/TAF. The primary end point is the proportion with HIV-1 RNA ≥50 copies/mL at week 48 (Food and Drug Administration Snapshot algorithm, intention-to-treat exposed population, 6% noninferiority margin). Results: Overall, 222 adults were randomized (16% women, 51% aged ≥50 years, 28% Black). At week 48, 6 (4%) with DTG/3TC and 5 (7%) with B/F/TAF had HIV-1 RNA ≥50 copies/mL (treatment difference, -2.8%; 95% CI, -11.4% to 3.1%), meeting noninferiority criteria. Through week 48, 18 participants (12 with DTG/3TC, 6 with B/F/TAF) met confirmed virologic withdrawal (CVW) criteria, and 2 of 18 had resistance: 1 with B/F/TAF developed M184M/I and G140G/S at week 12, and 1 with DTG/3TC had M184V at week 12. One participant with DTG/3TC and non-CVW developed M184V and K65R at week 12. Drug-related adverse events (AEs) and withdrawals due to AEs occurred in 31 (21%) and 6 (4%) participants with DTG/3TC and 2 (3%) and 0 participants with B/F/TAF, respectively. Conclusions: Switching to DTG/3TC was noninferior to continuing B/F/TAF among adults with virologic suppression at week 48. Drug-related AEs and withdrawals were higher in the DTG/3TC arm, which is likely consistent with the open-label nature of this switch study.

Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial.

Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies1-4. A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound5-7. Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2. The primary endpoints were safety, tolerability and pharmacokinetics, and the secondary endpoints in part 2 were antiviral activity following ART discontinuation, changes in CD4+ T cell counts and development of HIV-1 sequence mutations associated with bNAb resistance. The trial met its prespecified endpoints. The bNAb treatment was generally safe and well tolerated. In part 2, 83% of participants (10 of 12) maintained virologic suppression for the duration of antibody therapy for at least 28 weeks, and 42% of participants (5 of 12) showed virologic suppression for at least 38-44 weeks, despite the decline of serum bNAb concentrations to low or undetectable levels. In exploratory analyses, early viral rebound in two individuals correlated with baseline resistance to PGT121 and PGDM1400, whereas long-term virologic control in five individuals correlated with reduced immune activation, T cell exhaustion and proinflammatory signaling following bNAb therapy. Our data show the potential of a triple bNAb cocktail to suppress HIV-1 in the absence of ART. ClinicalTrials.gov registration: NCT03721510 .

Racial/ethnic disparities in HIV care outcomes among insured patients at a large urban sexual health clinic.

Prior studies demonstrate that non-White patients are less likely to achieve human immunodeficiency virus (HIV) suppression compared to White patients due to lack of health insurance. This study aims to determine whether racial disparities in the HIV care cascade persist among a cohort of privately and publicly insured patients. This retrospective analysis evaluated HIV care outcomes during the first year of care. Eligible patients were aged 18-65 years, treatment-naïve, and seen between 2016 and 2019. Demographic and clinical variables were extracted from the medical record. Differences in the proportion of patients achieving each HIV care cascade stage by race were evaluated using unadjusted chi-square testing. Risk factors for viral non-suppression at 52 weeks were analyzed using multivariate logistic regression. We included 285 patients; ninety-nine were White, 101 were Black, and 85 identified as Hispanic/LatinX ethnicity. Significant differences in retention in care for Hispanic/LatinX patients (odds ratio (OR): 0.214, 95% confidence interval (CI): 0.067-0.676) and viral suppression for both Black (OR: 0.348, 95% CI: 0.178, 0.682) and Hispanic/LatinX patients (OR: 0.392, 95% CI: 0.195, 0.791) compared to White patients were observed. In multivariate analyses, Black patients were less likely to achieve viral suppression compared to White patients (OR: 0.464, 95% CI: 0.236, 0.902). This study showed that non-White patients were less likely to achieve viral suppression after 1 year despite insurance and suggests that other unmeasured factors may disproportionately affect viral suppression in these patients. Interventions to identify and address these factors are needed to improve HIV care outcomes for non-White populations.

Treatment-related early discontinuations and adverse events among newly diagnosed people living with HIV initiating integrase inhibitors in a real-world setting.

BACKGROUND: Cohort studies suggest higher discontinuation rates with integrase strand transfer inhibitors (INSTIs) than are seen in clinical trials. We assessed discontinuations and adverse events (AEs) that were considered related to the initial INSTI in the first year following initiation among treatment-naïve people living with HIV (PLWH). METHODS: Newly diagnosed PLWH initiating raltegravir, elvitegravir/cobicistat, dolutegravir or bictegravir in combination with emtricitabine/tenofovir alafenamide or emtricitabine/tenofovir disoproxil fumarate between 10/2007 and 1/2020 at the Orlando Immunology Center were included. Unadjusted incidence rates (IRs) and incidence rate ratios (IRRs) were calculated for treatment-related discontinuations and AEs associated with the initial INSTI in the first year following initiation. RESULTS: Of 331 enrolled, 26 (8%) initiated raltegravir, 151 (46%) initiated elvitegravir/cobicistat, 74 (22%) initiated dolutegravir and 80 (24%) initiated bictegravir. Within the first year, treatment-related discontinuations occurred in 3 on elvitegravir/cobicistat (IR 0.02 per person-years (PPY)) and 5 on dolutegravir (IR 0.08 PPY); no treatment-related discontinuations occurred among those initiating raltegravir or bictegravir. Eleven treatment-related AEs occurred in 7 on raltegravir (IR 0.46 PPY), 100 treatment-related AEs occurred in 63 on elvitegravir/cobicistat (IR 0.72 PPY), 66 treatment-related AEs occurred in 37 on dolutegravir (IR 0.97 PPY) and 65 treatment-related AEs occurred in 34 on bictegravir (IR 0.88 PPY). Unadjusted IRRs did not reveal any significant difference between INSTIs in terms of early treatment-related discontinuations or AEs. CONCLUSIONS: In our cohort, treatment-related AEs occurred in 43% initiating INSTIs but were responsible for early discontinuation in only 2% with no treatment-related discontinuations observed among those initiating RAL or BIC.

Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks.

Background: We assessed the efficacy and safety of dolutegravir/lamivudine (DTG/3TC) in a US test-and-treat setting at a secondary 48-week time point of the multicenter, single-arm, phase IIIb STAT study. Methods: Participants were eligible adults newly diagnosed with human immunodeficiency virus (HIV)-1 and had started once-daily DTG/3TC within 14 days of diagnosis, before laboratory results were available. Antiretroviral therapy (ART) was modified if baseline testing indicated DTG or 3TC resistance, hepatitis B virus (HBV) coinfection, or creatinine clearance <30 mL/min per 1.73 m2, and these participants remained in the study. A proportion with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48 was calculated among all participants (intention-to-treat-exposed [ITT-E] missing = failure analysis) and those with available data (observed analysis). Results: At Week 48, 82% of all participants regardless of ART (107 of 131; ITT-E missing = failure) and 97% with available data (107 of 110; observed analysis) achieved HIV-1 RNA <50 copies/mL. High proportions of virologic response were seen overall, including in participants with high viral load (≥500 000 copies/mL; 89%) or low CD4+ cell count (<200 cells/mm3; 78%) at baseline. Ten participants had treatment modification (baseline HBV coinfection, n = 5; participant/proxy decision, n = 2; baseline M184V resistance mutation, adverse event [AE; rash], and pregnancy, n = 1 each) before Week 48. Two participants met confirmed virologic failure criteria. No treatment-emergent resistance was observed. Ten participants reported drug-related AEs (all grade 1-2); no serious drug-related AEs occurred. Conclusions: Results demonstrated high proportions of participants with sustained virologic suppression, no treatment-emergent resistance, and good safety over 48 weeks, supporting first-line use of DTG/3TC in a test-and-treat setting.

Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated.

Background: Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in coronavirus disease 2019 (COVID-19) vaccinees typically produces milder disease than infection in unvaccinated individuals. Methods: To explore disease attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 infection in participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination (NCT04516746). Results: We observed that AZD1222 vaccinees had an overall lower incidence and shorter duration of COVID-19 symptoms compared with placebo recipients, as well as lower SARS-CoV-2 viral loads and a shorter median duration of viral shedding in saliva. Vaccinees demonstrated a robust antibody recall response versus placebo recipients with low-to-moderate inverse correlations with virologic endpoints. Vaccinees also demonstrated an enriched polyfunctional spike-specific Th-1-biased CD4+ and CD8+ T-cell response that was associated with strong inverse correlations with virologic endpoints. Conclusion: Robust immune responses following AZD1222 vaccination attenuate COVID-19 disease severity and restrict SARS-CoV-2 transmission potential by reducing viral loads and the duration of viral shedding in saliva. Collectively, these analyses underscore the essential role of vaccination in mitigating the COVID-19 pandemic.

Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial.

HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia. We performed a two-part study consisting of a single-center, randomized, double-blind, dose-escalation, placebo-controlled first-in-human trial of the HIV-1 V2-glycan-specific antibody PGDM1400 alone or in combination with the V3-glycan-specific antibody PGT121 in 24 adults without HIV in part 1, as well as a multi-center, open-label trial of the combination of PGDM1400, PGT121 and the CD4-binding-site antibody VRC07-523LS in five viremic adults living with HIV not on antiretroviral therapy (ART) in part 2 ( NCT03205917 ). The primary endpoints were safety, tolerability and pharmacokinetics for both parts and antiviral activity among viremic adults living with HIV and not on ART for part 2 of the study. The secondary endpoints were changes in CD4+ T cell counts and development of HIV-1 sequence variations associated with PGDM1400, PGT121 and VRC07-523LS resistance in part 2. Intravenously administered PGDM1400 was safe and well-tolerated at doses up to 30 mg kg-1 and when given in combination with PGT121 and VRC07-523LS. A single intravenous infusion of 20 mg kg-1 of each of the three antibodies reduced plasma HIV RNA levels in viremic individuals by a maximum mean of 2.04 log10 copies per ml; however, viral rebound occurred in all participants within a median of 20 days after nadir. Rebound viruses demonstrated partial to complete resistance to PGDM1400 and PGT121 in vitro, whereas susceptibility to VRC07-523LS was preserved. Viral rebound occurred despite mean VRC07-523LS serum concentrations of 93 µg ml-1. The trial met the pre-specified endpoints. Our data suggest that future bNAb combinations likely need to achieve broad antiviral activity, while also maintaining high serum concentrations, to mediate viral control.

Determinants of pre-exposure prophylaxis (PrEP) persistence in a high-risk population in Central Florida.

Orlando has the second highest HIV incidence in the USA. Tenofovir disoproxil fumarate/emtricitabine is approved as pre-exposure prophylaxis (PrEP) to minimize HIV transmission. Our study describes the PrEP care continuum and factors impacting PrEP persistence during the first year of PrEP care at a sexual health clinic in Orlando. Patients initiating PrEP between 2014 and 2017 with at least 1 year of follow-up were eligible for inclusion. Demographic and clinical factors were extracted from medical records. At the end of the first year of PrEP care, patients seen within the last 6 months were defined as 'persistent' whereas patients lost to follow-up for ≥6 months were defined as 'not persistent'. We evaluated factors associated with PrEP persistence with Firth's multivariable logistic regression. Of 300 patients meeting inclusion criteria, 96% were male, 59% were ≥30 years old, 59% identified as men who have sex with men and 57% endorsed recent condomless anal intercourse. Of PrEP initiators, 133 (44.3%) were persistent in the first year, whereas 167 (55.7%) were not persistent. PrEP persistence was positively associated with age ≥30 years (OR 1.04, 95% CI 1.0 to 1.08) and negatively associated with non-white race (OR 0.33, 95% CI 0.12 to 0.83). There were no HIV seroconversions among persistent patients. In our study, younger and minority patients were less likely to persist in PrEP care and persistence was poor despite many being insured and 'high-risk'. Further research is needed to identify and address barriers that hinder PrEP persistence, specifically among younger, minority patients.

Real-world efficacy and safety of switching to bictegravir/emtricitabine/tenofovir alafenamide in older people living with HIV.

ABSTRACT: Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Clinical trials of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) demonstrated potent efficacy and favorable safety in older PLWH; however, real-world data would be useful to validate these results.Retrospective cohort study.We evaluated records from PLWH aged ≥50 years at the Orlando Immunology Center who were switched to B/F/TAF between February 2018 and August 2019. Eligible patients had baseline HIV-1 RNA <50 copies/mL and 48 weeks of follow-up data. The primary endpoint was maintenance of HIV-1 RNA <50 copies/mL at Week 48. The impact of switching to B/F/TAF on drug-drug interactions (DDIs) and safety parameters were also assessed.Three-hundred and fifty patients met inclusion criteria, median age was 57 years, 20% were women, and 43% were non-White. Fifty-five percent of patients switched from integrase inhibitor-based regimens; the most common reason for switch was simplification. At Week 48, 330 (94%) patients maintained an HIV-1 RNA <50 copies/mL and 20 (6%) had an HIV-1 RNA between 50 and 400 copies/mL. One-hundred and forty potential DDIs were identified in 121 (35%) patients taking a boosting agent or rilpivirine at baseline that were resolved after switching to B/F/TAF. Treatment-related adverse events occurred in 51 (15%) patients (all Grade 1-2) and led to 8 discontinuations.In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH.

Dolutegravir/lamivudine as a first-line regimen in a test-and-treat setting for newly diagnosed people living with HIV.

OBJECTIVES: Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting. DESIGN: The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting. METHODS: Eligible adults initiated DTG/3TC 14 days or less after HIV-1 diagnosis without availability of baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance less than 30 ml/min per 1.73 m2, participants remained on study with treatment modification. Efficacy endpoints included proportions of participants with HIV-1 RNA less than 50 copies/ml at Week 24, regardless of antiretroviral regimen, among all participants (intention-to-treat exposed) and those with available HIV-1 RNA data (observed). RESULTS: Of 131 participants enrolled, 8% were female and 50% were non-white. Through Week 24, treatment was modified in eight participants [five with HBV co-infection, one with baseline M184V, one for adverse event (rash), one participant decision]. At Week 24, 78% (102/131) of all participants and 92% (102/111) of those with available data achieved HIV-1 RNA less than 50 copies/ml. Incidence of drug-related adverse events was low (7%); no drug-related serious adverse events occurred. CONCLUSION: These data demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting, with therapy adjustments for baseline resistance or HBV co-infection occurring safely via routine clinical care as needed [ClinicalTrials.gov, NCT03945981; see Supplemental Digital Content 1, video abstract (Video abstract summarizing the STAT study design and results), http://links.lww.com/QAD/C189].

Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial.

Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg-1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg-1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

Clinical outcomes of HIV-1 infected patients switched from complex multi-tablet regimens to tenofovir alafenamide based single-tablet regimens plus a boosted protease inhibitor in a real-world setting.

BACKGROUND: Multi-tablet regimens (MTRs) are associated with increased adverse events and non-adherence. Single tablet regimens (STRs) plus boosted protease inhibitors (PIs) are a simplification option for MTR-treated patients; however, data is needed to validate this therapeutic strategy. METHODS: This retrospective analysis included all HIV-1 infected patients seen at a single center from March 2016 to December 2017 who were switched from twice-daily (BID) regimens or regimens containing â€‹≥ â€‹3 pills daily to elvitegravir/cobicistat/emtricitabine/tenofovir-alafenamide (E/C/F/TAF) plus darunavir (DRV) or rilpivirine/emtricitabine/tenofovir-alafenamide (RPV/F/TAF) plus DRV boosted with ritonavir or cobicistat (DRV/r-c). Eligible patients had baseline HIV-1 RNA<200 copies/mL and were followed for 48 weeks. The primary endpoint was HIV-1 RNA≥50 copies/mL at Week 48. Adherence and safety data were recorded throughout the study. RESULTS: Of 61 patients included, median age was 53 years, the median number of pills taken daily (range) was 5 (3-9), 80% were taking BID regimens, 97% had baseline HIV-1 RNA<50 copies/mL, 56 (92%) were switched to E/C/F/TAF plus DRV and 5 (8%) to RPV/F/TAF plus DRV/r-c. At Week 48, 2 patients (3%) had HIV-1 RNA≥ 50 copies/mL, both were treated with E/C/F/TAF plus DRV and neither had evidence of treatment-emergent resistance. Fifty-nine (97%) had an HIV-1 RNA<50 copies/mL. Adverse drug reactions (ADRs) occurred in 3/61 (5%) (all Grade 2) leading to 3/61 (5%) ADR-related discontinuations. CONCLUSION: In this real-world cohort of MTR-treated patients, switching to a TAF-based STR plus boosted PI maintained virologic control in 97% and was well-tolerated, supporting potential use of this strategy for regimen simplification.

Clinical outcomes of once-daily darunavir in treatment-experienced patients with darunavir resistance-associated mutations through 48 weeks of treatment.

Darunavir (DRV) is approved for once-daily use in patients with no DRV resistance-associated mutations (RAMs) and twice-daily use in those with DRV RAMs. Several studies suggest that once-daily DRV retains efficacy in the setting of 1-2 DRV RAMs whereas three or more DRV RAMs are needed for DRV resistance. There are few data to support the long-term use of once-daily DRV in patients with DRV RAMs. This observational study evaluated 48-week clinical outcomes of 22 treatment-experienced patients with ≥1 DRV RAMs switched to once-daily DRV between 2014 and 2017. The primary endpoint was HIV-1 RNA <50 copies/ml at week 48. Safety parameters were analyzed throughout the study. The median age of the sample was 53 years, 18 (82%) had baseline HIV-1 RNA <50 copies/ml, and the median number of historical DRV RAMs was 2. At week 48, 20 (91%) had HIV-1 RNA < 50 copies/ml, and 2 (9%) had HIV-1 RNA of 82 and 59,637 copies/ml and reported non-adherence. No adverse drug reactions were observed through week 48. Once-daily DRV maintained virologic control in patients with ≥1 historical DRV RAMs and was safe and well-tolerated. Further data are needed to validate this as a viable treatment option in this population.

Contrasting Self-Perceived Need and Guideline-Based Indication for HIV Pre-Exposure Prophylaxis Among Young, Black Men Who Have Sex with Men Offered Pre-Exposure Prophylaxis in Atlanta, Georgia.

Despite high HIV incidence among young black men who have sex with men (YBMSM), pre-exposure prophylaxis (PrEP) uptake in this group is low. In a cohort of HIV-negative YBMSM in Atlanta, GA, all participants were offered PrEP as standard of care with free clinician visits and laboratory testing. We explored self-perceived need for PrEP among 29 in-depth interview participants by asking about reasons for PrEP uptake or refusal and factors that may lead to future reconsideration. Self-perceived need was compared to US Center for Disease Control and Prevention guidance for clinical PrEP indication using behavioral data and laboratory testing data. Self-perceived need for PrEP consistently underestimated clinical indication, primarily due to optimism for choosing other HIV prevention strategies, such as condom use, abstinence, or monogamy. Many participants cited consistent condom use and lack of sexual activity as reasons for not starting PrEP; however, follow-up survey data frequently demonstrated low condom use and high levels of sexual activity in the period after the interview. Study participants endorsed perceptions that PrEP is only for people with very high levels of sexual activity. Only one participant perceived incident sexually transmitted infection (STI) to be an indication for PrEP, despite the fact that several of the participants had a history of an STI diagnosis. These findings point to an opportunity for clinician intervention at diagnosis. Disconnect between self-perceived and guidance-based PrEP indications, as well as other factors such as medical mistrust or difficulty with access, may contribute to low PrEP uptake among YBMSM. A better understanding of the ways in which these issues manifest may be one tool for clinicians to support PrEP uptake.