Pre-exposure Prophylaxis Trials Research Articles

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

Antiretrovirals and Weight Change: Weighing the Evidence.

Body weight is influenced by an interplay of individual and environmental factors. In people with HIV (PWH), weight is also influenced by disease status with loss accompanying disease progression that is reversed with effective antiretroviral therapy (ART). Weight changes in comparative ART trials differ by regimen, with greater gains observed with the integrase strand transfer inhibitors (INSTIs) dolutegravir and bictegravir, particularly when co-administered with tenofovir alafenamide fumarate (TAF), compared to regimens that include agents such as tenofovir disoproxil fumarate (TDF) that attenuate weight gain. We review weight changes in major randomized trials of pre-exposure prophylaxis (PrEP) and initial and switch HIV therapy, highlighting the challenges to assessing the role of ART in weight change. This examination forms the basis for a model that questions assumptions regarding an association between INSTI and TAF and excessive weight gain and calls for more careful consideration of these data when making HIV treatment decisions.

Likelihood-based inferences for active-arm trial with counterfactual incidence based on recency assay

Abstract Objectives The approach of using HIV recency assay to estimate the counterfactual incidence rate is being used as the primary efficacy method in a few ongoing large-scale HIV pre-exposure prophylaxis (PrEP) trials, and the current available approach for the inference is based on the Wald method that leverages the asymptotic distribution of the estimators. One issue with the Wald test is that it does not work well when the number of HIV infections are small in the active arm, and it fails to work when there are zero HIV infections. As future long-acting PrEP products are becoming more efficacious, it is very likely that a small or zero number of infections will be observed in HIV prevention trials, especially for subgroup analyses or interim analyses, hence there is a pressing need to develop inference methods that work under such scenarios. Methods It is well known that when the sample size is small to moderate, likelihood ratio tests are more reliable than Wald tests in terms of actual error probabilities coming close to matching nominal levels. In this manuscript we derive the likelihood ratio test and the likelihood-based confidence intervals for HIV prevention trials based on recency assays. Results Compared with the Wald test, the proposed method works when there are zero infections. Additionally, unlike the Wald test, the p-value from the likelihood ratio test is an increasing function with respect to the number of infections, which is a desirable property as otherwise it will cause confusions. Conclusions For HIV PrEP trials based on recency assay, the likelihood-based p-value and confidence interval can be preferable to the Wald based inference methods when the number of HIV infections is expected to be small.

Peer PrEP referral + HIV self-test delivery for PrEP initiation among young Kenyan women: study protocol for a hybrid cluster-randomized controlled trial

BackgroundOral HIV pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective, but uptake remains low in Africa, especially among young women who are a priority population for HIV prevention services. HIV self-testing (HIVST) has been proven to increase HIV testing in diverse populations but has been underutilized to support linkage to HIV prevention services. Most young women who initiate PrEP in Africa do so through informal peer referral. We wanted to test a model of formalized peer referral enhanced with HIVST delivery among young Kenyan women.MethodsThe Peer PrEP Trial is a two-arm hybrid effectiveness-implementation cluster-randomized controlled trial being conducted in central Kenya. Eligible participants (i.e., peer providers, n = 80) are women (≥ 16–24 years) refilling or initiating PrEP at public healthcare clinics who can identify at least four peers who could benefit from PrEP and not enrolled in another HIV study. Peer providers will be 1:1 randomized to (1) formal peer PrEP referral + HIVST delivery, where they will be encouraged to refer four peers (i.e., peer clients, ≥ 16–24 years) using educational materials and HIVST kits (two per peer client), or (2) informal peer PrEP referral, where they are encouraged to refer four peer clients using informal word-of-mouth referral. In both arms, peer providers will deliver a standard PrEP referral card with information on nearby public clinics delivering PrEP services. Peer providers will complete surveys at baseline and 3 months; peer clients will complete surveys at 3 months. Our primary outcome is PrEP initiation among peer clients, as reported by peer providers at 3 months. Secondary outcomes include PrEP continuation (any refilling), HIV testing (past 3 months), sexual behaviors (past month), and PrEP adherence (past month) among peer clients, as reported by both peer providers and clients at 3 months. Implementation outcomes will include participants’ perceived acceptability, appropriateness, and feasibility of the intervention as well assessments of the intervention’s fidelity and cost.DiscussionEvidence from this trial will help us understand how HIVST could support health systems by facilitating linkage to PrEP services among young women who could benefit in Kenya and similar settings.Trial registrationClinicalTrials.gov NCT04982250. Registered on July 29, 2021.

Facilitating Next-Generation Pre-Exposure Prophylaxis Clinical Trials Using HIV Recent Infection Assays: A Consensus Statement from the Forum HIV Prevention Trial Design Project.

Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases.

2059. Estimated Background HIV Diagnosis Rates among People Who Could Benefit from Pre-Exposure Prophylaxis (PrEP) at the Metropolitan Statistical Area (MSA) level in the United States, 2012-2019

Abstract Background Identifying areas of high background HIV diagnosis rates (bHIV) is critical for future PrEP trials using counterfactual study designs to estimate efficacy and to facilitate effective implementation of HIV prevention interventions. In this study, we used a multiple data source model to estimate bHIV between 2012 and 2019 in people who could benefit from PrEP (PWBP) but are not taking PrEP to identify with greater precision areas of high HIV transmission at the Metropolitan Statistical Area (MSA) level. We compared bHIV in PWBP in PURPOSE2 (NCT04925752) trial sites to those in the DISCOVER trial (NCT02842086) to demonstrate how this approach can inform site selection in future PrEP clinical trials and support delivery of PrEP interventions. Methods Number of new HIV diagnoses, number of individuals with a PrEP indication, and person-time on PrEP or after HIV diagnosis (obtained from published surveillance data) and pharmacy claims data (IQVIA PharMetrics Plus) were used to calculate estimated bHIV in a multivariate Poisson regression model for PWBP in 108 MSAs and across states between 2012 and 2019. Results Overall, bHIV among PWBP decreased from 4.42 per 100 person-years (PY) (95% CI 4.38 – 4.47) in 2012 to 3.14 per 100 PY (95% CI 3.10 – 3.17) in 2019. However, bHIV among PWBP in MSAs with PURPOSE2 trial sites were consistently higher (from 4.69 per 100 PY [95% CI 4.56 – 4.81] in 2012 to 3.58 per 100 PY [95% CI 3.49 – 3.67] in 2019) compared to areas with DISCOVER-only sites (from 3.77 per 100 PY [95% CI 3.53 – 4.01] in 2012 to 2.83 per 100 PY [95% CI 2.63 – 3.03] in 2019; Figure 1A). Within states, we identified specific localities with high bHIV among PWBP, such as in Illinois where state level HIV diagnosis rate was 2.65 per 100 PY [95% CI 2.50 – 2.80] but as high as 6.04 per 100 PY [95% CI 5.67 - 6.40] in the MSA with a PURPOSE2 site (Figure 1B). Figure:Estimated background HIV diagnosis rates (bHIV) in people who could benefit from PrEP by MSAs selected by DISCOVER/PURPOSE2 trials (A) from 2012 to 2019 and (B) in 2019 in the US. Conclusion We found considerable variation in bHIV at the MSA level among PWBP who are not taking PrEP, including a concentration of MSAs in the Southeastern US with high rates of new HIV diagnosis. Our methodology for leveraging existing surveillance data to identify areas of high bHIV with greater precision may provide a valuable approach to support future counterfactual clinical trial designs and prioritize resources for delivery of PrEP services. Disclosures Melanie de Boer, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Jason Yuan, n/a, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Juan Yang, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Lillian Brown, MD, PhD, Gilead Sciences: Stocks/Bonds Carlo Hojilla, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Christoph C. Carter, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|Gilead Sciences: Stocks/Bonds Moupali Das, MD, Gilead Sciences: Employee|Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|Gilead Sciences: Stocks/Bonds Li Tao, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds|Gilead Sciences: Stocks/Bonds.

Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention.

Preventing new HIV infections remains a global challenge. Young women continue to bear a disproportionate burden of infection. Oral pre-exposure prophylaxis (PrEP), offers a novel women-initiated prevention technology and PrEP trials completed to date underscore the importance of their inclusion early in trials evaluating new HIV PrEP technologies. Data from completed topical and systemic PrEP trials highlight the role of gender specific physiological and social factors that impact PrEP uptake, adherence and efficacy. Here we review the past and current developments of HIV-1 prevention options for women with special focus on PrEP considering the diverse factors that can impact PrEP efficacy. Furthermore, we highlight the importance of inclusion of female scientists, clinicians, and community advocates in scientific efforts to further improve HIV prevention strategies.

The Prevalence, Incidence, and Risk Factors for HIV Among Female Sex Workers-A Cohort Being Prepared for a Phase IIb HIV Vaccine Trial in Dar es Salaam, Tanzania.

A cohort of female sex workers (FSWs) was established to determine HIV prevalence and incidence, and associated factors in preparation for a phase IIb HIV vaccine and pre-exposure prophylaxis trial (PrEPVacc). A cohort of FSWs in Dar es Salaam, Tanzania. FSWs aged 18-45 years were recruited using a respondent-driven sampling method. Social demographic data, HIV risk behavioral assessments, and blood samples for testing of HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) infections were collected at baseline and then at 3, 6, 9, and 12 months. Poisson regressions were used to estimate the prevalence ratios for factors associated with HIV prevalence and to estimate the 12-month HIV incidence rate. Between October and December 2018, a total of 773 FSWs were screened for eligibility and 700 were enrolled. The baseline prevalence of HIV, syphilis, HBV, and HCV was 7.6%, 1.2%, 1.7%, and 1.0%, respectively. HIV prevalence was associated with older age, using illicit drugs, and being infected with syphilis, HBV, or HCV. Attendance at 12 months was 80% (562/700). Twenty-one FSWs seroconverted during follow-up, giving a 12-month HIV incidence rate of 3.45 per 100 person-years at risk (95% CI; 2.25-5.28/100 person-years at risk). The HIV incidence rate was higher among FSWs aged 18-24 years, FSWs who used drugs, and those diagnosed with syphilis, HBV, or HCV. The high HIV incidence rate and retention rate among FSWs enrolled into the cohort demonstrate that this population is suitable for participation in HIV prevention trials.

Modeling the Probability of HIV Infection over Time in High-Risk Seronegative Participants Receiving Placebo in Five Randomized Double-Blind Placebo-Controlled HIV Pre-Exposure Prophylaxis Trials: A Patient-Level Pooled Analysis.

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.

Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19.

BackgroundRecruitment into randomized trials of hydroxychloroquine (HCQ) for prevention of COVID-19 has been adversely affected by a widespread conviction that HCQ is not effective for prevention. In the absence of an updated systematic review, we conducted a meta-analysis of randomized trials that study the effectiveness of HCQ to prevent COVID-19.MethodsA search of PubMed, medRxiv, and clinicaltrials.gov combined with expert consultation found 11 completed randomized trials: 7 pre-exposure prophylaxis trials and 4 post-exposure prophylaxis trials. We obtained or calculated the risk ratio of COVID-19 diagnosis for assignment to HCQ versus no HCQ (either placebo or usual care) for each trial, and then pooled the risk ratio estimates.ResultsThe pooled risk ratio estimate of the pre-exposure prophylaxis trials was 0.72 (95% CI: 0.58–0.90) when using either a fixed effect or a standard random effects approach, and 0.72 (95% CI: 0.55–0.95) when using a conservative modification of the Hartung-Knapp random effects approach. The corresponding estimates for the post-exposure prophylaxis trials were 0.91 (95% CI: 0.72–1.16) and 0.91 (95% CI: 0.62–1.35). All trials found a similar rate of serious adverse effects in the HCQ and no HCQ groups.DiscussionA benefit of HCQ as prophylaxis for COVID-19 cannot be ruled out based on the available evidence from randomized trials. However, the “not statistically significant” findings from early prophylaxis trials were widely interpreted as definite evidence of lack of effectiveness of HCQ. This interpretation disrupted the timely completion of the remaining trials and thus the generation of precise estimates for pandemic management before the development of vaccines.

Population-Level Correlation Between Incidence of Curable Sexually Transmitted Infections and Human Immunodeficiency Virus (HIV)-1 Among African Women Participating in HIV-1 Pre-Exposure Prophylaxis Trials.

Highly efficacious oral pre-exposure prophylaxis (PrEP) is the global standard for human immunodeficiency virus (HIV)-1 prevention, including in clinical trials of novel PrEP agents using active-comparator designs. The analysis assessed whether incident sexually transmitted infections (STIs) can serve as a surrogate indicator of HIV-1 incidence that might occur in the absence of PrEP. We analyzed data from 3256 women randomized to placebo groups of oral and vaginal PrEP trials (MTN-003/VOICE and MTN-020/ASPIRE). Regression modeling assessed the correlation between incident individual STIs (Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, each considered separately) and incident HIV-1. Across 18 sites in 4 countries (Malawi, South Africa, Uganda, Zimbabwe), STI and HIV-1 incidences were high: HIV-1 4.9, N gonorrhoeae 5.3, C trachomatis 14.5, and T vaginalis 7.1 per 100 person-years. There was limited correlation between HIV-1 incidence and incidence of individual STIs: N gonorrhoeae (r = 0.02, P = .871), C trachomatis (r = 0.49, P = <.001), and T vaginalis (r = 0.10, P = .481). The modest association with C trachomatis was driven by country-level differences in both C trachomatis and HIV-1, with no statistically significant association within countries. Sexually transmitted infection incidence did not reliably predict HIV-1 incidence at the population level among at-risk African women participating in 2 large PrEP trials.

M2HepPrEP: study protocol for a multi-site multi-setting randomized controlled trial of integrated HIV prevention and HCV care for PWID

BackgroundOpioid use is escalating in North America and comes with a multitude of health consequences, including HIV and hepatitis C virus (HCV) outbreaks among persons who inject drugs (PWID). HIV pre-exposure prophylaxis (PrEP) and HCV treatment regimens have transformative potential to address these co-occurring epidemics. Evaluation of innovative multi-modal approaches, integrating harm reduction, opioid agonist therapy (OAT), PrEP, and HCV treatment is required. The aim of this study is to assess the effectiveness of an on-site integrated care model where delivery of PrEP and HCV treatment for PWID takes places at syringe service programs (SSP) and OAT programs compared with referring PWID to clinical services in the community through a patient navigation model and to examine how structural factors interact with HIV prevention adherence and HCV treatment outcomes.MethodsThe Miami-Montreal Hepatitis C and Pre-Exposure Prophylaxis trial (M2HepPrEP) is an open-label, multi-site, multi-center, randomized, controlled, superiority trial with two parallel treatment arms. A total of 500 persons who injected drugs in the prior 6 months and are eligible for PrEP will be recruited in OAT clinics and SSP in Miami, FL, and Montréal, Québec. Participants will be randomized to either on-site care, with adherence counseling, or referral to off-site clinics assisted by a patient navigator. PrEP will be offered to all participants and HCV treatment to those HCV-infected. Co-primary endpoints will be (1) adherence to pre-exposure prophylaxis medication at 6 months post-randomization and (2) HCV sustained virological response (SVR) 12 weeks post-treatment completion among participants who were randomized within the HCV stratum. Up to 100 participants will be invited to participate in a semi-structured interview regarding perceptions of adherence barriers and facilitators, after their 6-month assessment. A simulation model-based cost-effectiveness analysis will be performed to determine the comparative value of the strategies being evaluated.DiscussionThe results of this study have the potential to demonstrate the effectiveness and cost-effectiveness of offering PrEP and HCV treatment in healthcare venues frequently attended by PWID. Testing the intervention in two urban centers with high disease burden among PWID, but with different healthcare system dynamics, will increase generalizability of findings.Trial registrationClinicaltrials.gov NCT03981445. Trial registry name: Integrated HIV Prevention and HCV Care for PWID (M2HepPrEP). Registration date: June 10, 201.

Where are the pregnant and breastfeeding women in new pre-exposure prophylaxis trials? The imperative to overcome the evidence gap

Pregnant and breastfeeding populations are at substantial risk of acquiring HIV in some settings, yet are underrepresented in clinical trials of new pre-exposure prophylaxis (PrEP) agents. Several PrEP formulations are in development (eg, vaginal rings, long-acting injectables, and other modalities). Pregnant and breastfeeding populations are typically excluded from initial clinical trials. We identified 14 PrEP trials of novel agents in non-pregnant or non-breastfeeding populations, and six phase 1-3 trials and open label extensions among pregnant and breastfeeding populations, that are currently ongoing or complete. A framework shift is needed to consider the ethical costs of excluding pregnant and breastfeeding populations at risk for HIV in PrEP clinical trials and promote inclusion to maximise the benefits from PrEP tools in the pipeline. Research on new PrEP agents should include pregnant and breastfeeding populations to avoid delays in reaching those who could benefit from PrEP after efficacy is established.

Combining information to estimate adherence in studies of pre-exposure prophylaxis for HIV prevention: Application to HPTN 067.

In trials of oral HIV pre-exposure prophylaxis (PrEP), multiple approaches have been used to measure adherence, including self-report, pill counts, electronic dose monitoring devices, and biological measures such as drug levels in plasma, peripheral blood mononuclear cells, hair, and/or dried blood spots. No one of these measures is ideal and each has strengths and weaknesses. However, accurate estimates of adherence to oral PrEP are important as drug efficacy is closely tied to adherence, and secondary analyses of trial data within identified adherent/non-adherent subgroups may yield important insights into real-world drug effectiveness. We develop a statistical approach to combining multiple measures of adherence and show in simulated data that the proposed method provides a more accurate measure of true adherence than self-report. We then apply the method to estimate adherence in the ADAPT study (HPTN 067) in South African women.

Overlapping needs for sexual and reproductive health and HIV prevention in women with substance use disorders.

Objectives:Women with substance use disorders have high unmet needs for HIV prevention and drug treatment and face challenges accessing care for other unique health issues, including their sexual and reproductive health.Methods:We did a cross-sectional evaluation of sexual and reproductive health behaviors and outcomes among women with substance use disorders, who were enrolled in one of two concurrent clinical trials of pre-exposure prophylaxis for HIV prevention. Descriptive analyses and bivariate logistic regression were used to assess factors driving contraceptive use, and other essential sexual and reproductive health services utilization and outcomes.Results:Among 226 women, 173 (76.5%) were of reproductive age. Most women had histories of unintended pregnancy (79.2%) or miscarriage (45.1%) and high HIV risk behaviors (53.5%). Most (61%) participants did not use any form of contraception at the time of assessment, although few (15%) reported pregnancy intentions. In bivariate models, ongoing criminal justice involvement was associated with 2.22 higher odds of not using contraception (95% confidence interval = 1.09–4.53; p = 0.03) and hazardous drinking was protective against not using contraception (odds ratio = 0.33, 95% confidence interval = 0.13–0.81; p = 0.02). Contraception use was not significantly associated with any other individual characteristics or need factors.Conclusions:This is the first study that identifies the unmet sexual and reproductive health needs of women with substance use disorders who are engaging with pre-exposure prophylaxis. We found that women accessed some health services but not in a way that holistically addresses the full scope of their needs. Integrated sexual and reproductive care should align women’s expressed sexual and reproductive health intentions with their behaviors and outcomes, by addressing social determinants of health.

Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum.

Pregnancy is a risk factor for progression from latent tuberculosis infection to symptomatic tuberculosis. However, how pregnancy influences T-cell responses to Mycobacterium tuberculosis is unknown. We measured M. tuberculosis-specific cytokines, T-cell memory markers, and overall CD4+ and CD8+ T-cell activation by flow cytometry from 49 women (18 with and 31 without HIV) who became pregnant while enrolled in a randomized controlled trial of preexposure prophylaxis for HIV. We analyzed data using COMPASS, an established statistical method for evaluating overall antigen-specific T-cell responses. Pregnant women with latent tuberculosis infection demonstrated significantly diminished M. tuberculosis-specific CD4+ cytokine responses in the third trimester (COMPASS polyfunctional score [PFS], 0.07) compared before (PFS, 0.15), during (PFS, 0.13 and 0.16), and after pregnancy (PFS, 0.14; P = .0084, Kruskal-Wallis test). Paradoxically, M. tuberculosis-specific CD8+ cytokines and nonspecifically activated T-cells increased during late pregnancy. Nonspecific T-cell activation, a validated biomarker for progression from latent tuberculosis infection to tuberculosis disease, increased in latent tuberculosis infection-positive women postpartum, compared with latent tuberculosis infection-negative women. Pregnancy-related functional T-cell changes were most pronounced during late pregnancy. Both M. tuberculosis-specific T-cell changes during pregnancy and increases in immune activation postpartum may contribute to increased risk for tuberculosis progression. NCT0557245.

Fitting a vaccine into the HIV prevention landscape.

Fitting a vaccine into the HIV prevention landscape.

HIV self-testing and oral pre-exposure prophylaxis are empowering for sex workers and their intimate partners: a qualitative study in Uganda.

IntroductionHIV self‐testing (HIVST) and oral pre‐exposure prophylaxis (PrEP) are complementary, evidence‐based, self‐controlled HIV prevention tools that may be particularly appealing to sex workers. Understanding how HIVST and PrEP are perceived and used by sex workers and their intimate partners could inform prevention delivery for this population. We conducted qualitative interviews to examine ways in which HIVST and PrEP use influence prevention choices among sex workers in Uganda.MethodsWithin a randomized trial of HIVST and PrEP among 110 HIV‐negative cisgender women, cisgender men and transgender women sex workers (NCT03426670), we conducted 40 qualitative interviews with 30 sex workers and 10 intimate partners (June 2018 to January 2020). Sex worker interviews explored (a) experiences of using HIVST kits; (b) how HIVST was performed with sexual partners; (c) impact of HIVST on PrEP pill taking; and (d) sexual risk behaviours after HIVST. Partner interviews covered (i) introduction of HIVST; (ii) experiences of using HIVST; (iii) HIV status disclosure; and (iv) HIVST's effect on sexual behaviours. Data were analysed using an inductive content analytic approach centering on descriptive category development. Together, these categories detail the meaning of HIVST and PrEP for these qualitative participants.ResultsUsing HIVST and PrEP was empowering for this group of sex workers and their partners. Three types of empowerment were observed: (a) economic; (b) relational; and (c) sexual health. (i) Using HIVST and PrEP made sex without condoms safer. Sex workers could charge more for condomless sex, which was empowering economically. (ii) Self‐testing restored trust in partners’ fidelity upon being reunited after a separation. This trust, in combination with condomless sex made possible by PrEP use, restored intimacy, empowering partnered relationships. (iii) HIVST and PrEP enabled sex workers to take control of their HIV prevention efforts and avoid the stigma of public clinic visits. In this way they were empowered to protect their sexual health.ConclusionsIn this sample, sex workers’ use of HIVST and PrEP benefitted not only prevention efforts, but also economic and relational empowerment. Understanding these larger benefits and communicating them to stakeholders could strengthen uptake and use of combination prevention interventions in this marginalized population.

Dynamic Perceived HIV Risk and Sexual Behaviors Among Young Women Enrolled in a PrEP Trial in Kenya: A Qualitative Study.

Background: In Kenya and elsewhere in sub-Saharan Africa, young women are disproportionately affected by the HIV epidemic compared to young men. The extent to which young women's self-perceptions about risk of HIV acquisition influence their sexual behaviors and use of HIV prevention methods remains unclear. We therefore conducted a qualitative study to explore these issues among young women enrolled in a pre-exposure prophylaxis (PrEP) trial.Methods: From January 2017 to January 2020, we conducted serial semi-structured in-depth interviews 50 purposively selected young women (18–24 years old) who were participating in the MPYA (Monitoring PrEP for Young Adult women) study—a randomized controlled trial in Thika and Kisumu, Kenya, assessing the impact of SMS reminders on PrEP adherence. Interviews were conducted at three time points (~1 week, 3, and 12 months after initiating PrEP). We used an inductive, content analytic approach to identify key themes related to risk perceptions, sexual behavior, and use of HIV prevention tools.Results: Around the time of enrollment, most of the 50 women interviewed reported being at high risk of HIV because of their own sexual behaviors, such as inconsistent condom use, multiple sexual partners, and transactional sex. Additionally, high risk perception was based on the behavior of their partners, such as refusing to use condoms and being unsure of their partner's HIV status. Young women's perceived risk of HIV acquisition was a key motivator for PrEP initiation and continuation. During PrEP use, participants reported feeling protected and at less risk compared to peers who were not taking PrEP. Some reported no longer using condoms because they were confident that PrEP provided enough protection. Over time, many young women reported reducing risky sexual behaviors because of the regular counseling and HIV testing they received as part of their PrEP services. This lowered risk perception was in most cases accompanied by discontinuation of PrEP.Conclusions: HIV risk perception among young women in Kenya was dynamic and influenced their use of PrEP and condoms over time, suggesting an often-deliberate approach to HIV prevention and sexual health.

High Levels of Prevention-Effective Adherence to HIV PrEP: An Analysis of Substudy Data From the EPIC-NSW Trial.

Preexposure prophylaxis (PrEP) prevents HIV infection but relies on good adherence at times of risk, termed "prevention-effective adherence." Most studies assess adherence without reference to sexual behaviur, making it challenging to determine if poor adherence coincides with HIV risk. We examined data from a behavioral substudy of a large-scale PrEP implementation trial in New South Wales, Australia. Trial participants completed optional brief quarterly surveys, reporting the number of pills taken and sexual behavior with male partners for each day of the "last full week" before each survey. Condomless sex (CLS) was defined as "higher risk" for HIV when with HIV-positive men with detectable/unknown viral loads or unknown HIV status men. Adequate PrEP protection was defined as ≥4 pills for participants assigned male sex at birth and ≥6 pills for participants assigned female sex at birth (including transgender men). Of 9596 participants dispensed PrEP, 4401 completed baseline and ≥1 follow-up survey. Participants reported on 12,399 "last full weeks": 7485 weeks (60.4%) involved CLS and 2521 weeks (33.7% of CLS-weeks) involved higher risk CLS. There were 103 weeks in which participants did not have adequate PrEP protection and had higher risk CLS: 4.1% of higher-risk CLS weeks (n = 103/2521), 1.4% of all CLS weeks (n = 103/7485), and 0.8% of all observed weeks (n = 103/12,399). In a large PrEP trial, prevention-effective adherence to PrEP was very high at 99%. Our findings illustrate the importance of measuring pill-taking and sexual behavior in the same period so that prevention-effective adherence can be better estimated.