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In two parallel pilot studies, we implemented a combination adherence intervention of patient-centered counselling and adherence supporter training, tailored to support HIV treatment (i.e., antiretroviral therapy) or prevention (i.e., pre-exposure prophylaxis, or PrEP) during pregnancy and breastfeeding. Using a mixed-methods approach, we evaluated the intervention's acceptability. We investigated engagement, satisfaction, and discussion content via survey to all 151 participants assigned to the intervention arm (51 women living with HIV, 100 PrEP-eligible women without HIV). We also conducted serial in-depth interviews with a subgroup (n = 40) at enrollment, three months, and six months. In the quantitative analysis, the vast majority reported high satisfaction with intervention components and expressed desire to receive it in the future, if made available. These findings were supported in the qualitative analysis, with favorable comments about counselor engagement, intervention content and types of support received from adherence supporters. Overall, these results demonstrate high acceptability and provide support for HIV status-neutral interventions for antiretroviral adherence. [ABSTRACT FROM AUTHOR]

Background Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART). Methods We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months. Results Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22–30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15–34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16–43%) infants in the POC group vs 7 (19%; 6–32%) in the SOC group (RR: 1.56;.7–3.50). Conclusions POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes. Clinical Trials Registration This trial is registered at https://clinicaltrials.gov (NCT02682810). [ABSTRACT FROM AUTHOR]

Background People who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention. Methods Participants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention. Results The intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%). Conclusions Viral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention. [ABSTRACT FROM AUTHOR]

Background: Persistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men.Methods: ART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells.Results: We did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes.Conclusions: Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) requires lifelong daily oral therapy. While patient characteristics associated with suboptimal ART adherence and persistence have been described in cohorts of HIV-infected persons, these factors are poor predictors of individual medication taking behaviors. We aimed to create and test instruments for the estimation of future ART adherence and persistence for clinical and research applications. Following formative work, a battery of 148 items broadly related to HIV infection and treatment was developed and administered to 181 HIV-infected patients. ART adherence and persistence were assessed using electronic monitoring for 3 months. Perceived confidence in medication taking and self-reported barriers to adherence were strongest in predicting non-adherence over time. Barriers to adherence (e.g., affordability, scheduling) were the strongest predictors of non-adherence, as well as 3- and 7-day non-persistence. A ten-item battery for prediction of these outcomes (www.med.unc.edu/ncaidstraining/adherence/for-providers) and a 30-item battery reflective of underlying psychological constructs can help identify and study individuals at risk for suboptimal ART adherence and persistence. [ABSTRACT FROM AUTHOR]

Background: Regimen selection for highly treatment-experienced patients is complicated. Methods: Using a web-based utility, study team members reviewed antiretroviral (ARV) history and resistance data and recommended individual ARV regimens and nucleoside reverse transcriptase inhibitor (NRTI) options for treatment-experienced participants consisting of 3–4 of the following agents: raltegravir (RAL), darunavir (DRV)/ritonavir, tipranavir (TPV)/ritonavir, etravirine (ETR), maraviroc (MVC), and enfuvirtide (ENF). We evaluated team recommendations and site selection of regimen and NRTIs. Associations between baseline factors and the selection of a complex regimen (defined as including four ARV agents or ENF) were explored with logistic regression. Results: A total of 413 participants entered the study. Participants initiated the first or second recommended regimen 86% of the time and 21% of participants started a complex regimen. In a multivariable model, ARV resistance to NRTI (odds ratio [OR] = 2.2), non-nucleoside reverse transcriptase inhibitor (NNRTI, OR = 6.2) or boosted protease inhibitor (PI, OR = 6.6), prior use of integrase strand transfer inhibitor (INSTI, OR = 25), and race–ethnicity (all P ≤ 0.01) were associated with selection of a complex regimen. Black non-Hispanic (OR = 0.5) and Hispanic participants from the continental US (OR = 0.2) were less likely to start a complex regimen, compared to white non-Hispanics. Conclusions: In this multi-center trial, we developed a web-based utility that facilitated treatment recommendations for highly treatment-experienced patients. Drug resistance, prior INSTI use, and race–ethnicity were key factors in decisions to select a more complex regimen. [ABSTRACT FROM AUTHOR]

Background: The relationship between efavirenz use and suicidality is not well-defined. Objective: To compare time to suicidality with efavirenz-containing versus efavirenz-free antiretroviral regimens for initial treatment of HIV. Design: Participant-level data were analyzed from 4 AIDS Clinical Trials Group, antiretroviral-naive studies conducted from 2001 to 2010. Within each study, participants were randomly assigned to an efavirenz-containing (n = 3241) or efavirenz-free (n = 2091) regimen. (ClinicalTrials.gov: NCT00013520 [A5095], NCT00050895 [A5142], NCT00084136 [A5175], and NCT 00118898 [A5202]) Setting: AIDS Clinical Trials Group sites; 74% of participants enrolled in the United States. Patients: Antiretroviral-naive participants. Intervention: Efavirenz versus efavirenz-free regimens. Measurements: Suicidality was defined as suicidal ideation or attempted or completed suicide. Groups were compared with a hazard ratio and 95% CI estimated from a Cox model, stratified by study. Results: Seventy-three percent of participants were men, the median age was 37 years, and 32% had documented psychiatric history or received psychoactive medication within 30 days before entering the study. Median follow-up was 96 weeks. Suicidality incidence per 1000 person-years was 8.08 (47 events) in the efavirenz group and 3.66 (15 events) in the efavirenz-free group (hazard ratio, 2.28 [95% CI, 1.27 to 4.10]; P = 0.006). Incidence of attempted or completed suicide was 2.90 (17 events) and 1.22 (5 events) in the efavirenz and efavirenz-free groups, respectively (hazard ratio, 2.58 [CI, 0.94 to 7.06]; P = 0.065). Eight suicides in the efavirenz group and 1 in the efavirenz-free group were reported. Limitation: There was not a standardized questionnaire about suicidal ideation or attempt. Efavirenz was open-label in 3 of 4 studies. Conclusion: Initial treatment with an efavirenz-containing antiretroviral regimen was associated with a 2-fold increased hazard of suicidality compared with a regimen without efavirenz. [ABSTRACT FROM AUTHOR]

Background: People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use.Methods: This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18-45 years (updated to 18-60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12-24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new participants.Findings: Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4-1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0-1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4-2·1; incidence rate difference -1·0 per 100 person-years, 95% CI -2·1 to 1·1). No severe adverse events due to the intervention were recorded.Interpretation: This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered.Funding: US National Institutes of Health. [ABSTRACT FROM AUTHOR]