Oral Pre-exposure Prophylaxis Research Articles

Modeled estimates of HIV-serodifferent couples in tuberculosis-affected households in four sub-Saharan African countries.

Household-based tuberculosis (TB) contact evaluation may be an efficient strategy to reach people who could benefit from oral pre-exposure prophylaxis (PrEP) because of the epidemiological links between HIV and TB. This study estimated the number of HIV serodifferent couples in TB-affected households and potential HIV acquisitions averted through their PrEP use in 4 TB-HIV high-burden countries. We conducted a model-based analysis set in Ethiopia, Kenya, South Africa, and Uganda using parameters from population-based household surveys, systematic literature review and meta-analyses, and estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We parameterized the nonlinear relationship between the proportion of serodifferent couples among people living with HIV and population-level HIV prevalence using Markov chain Monte Carlo methods. We integrated all parameters in a mathematical model and propagated uncertainty using a Monte Carlo approach. We estimated the HIV prevalence among adults aged 15-49 living in TB-affected households to be higher than in the general population in all 4 countries. The proportion of serodifferent couples among all couples in TB-affected households was also higher than in the general population (South Africa: 20.7% vs. 15.7%, Kenya: 15.7% vs. 5.7%, Uganda: 14.5% vs. 6.0%, Ethiopia: 4.1% vs. 0.8%). We estimated that up to 1,799 (95% UI: 1,256-2,341) HIV acquisitions in South Africa could be prevented annually by PrEP use in serodifferent couples in TB-affected households, 918 (95% UI: 409-1,450) in Kenya, 686 (95% UI: 505-871) in Uganda, and 408 (95% UI: 298-522) in Ethiopia. As couples in TB-affected households are more likely to be serodifferent than couples in the general population, offering PrEP during household TB contact evaluation may prevent a substantial number of HIV acquisitions.

Experiences of oral pre-exposure prophylaxis use among heterosexual men accessing sexual and reproductive health services in South Africa: a qualitative study.

South African men face a substantial burden of HIV and are less likely to test for HIV and initiate antiretroviral therapy if tested positive and more likely to die from AIDS-related causes than women. In addition to condoms and circumcision, guidelines provide for the use of daily oral pre-exposure prophylaxis (PrEP) as an HIV prevention intervention for any men who recognize their need and request PrEP. However, heterosexual men have not been a focus of PrEP programmes, and since its introduction, there is limited literature on PrEP use among men in South Africa. This study explores the experiences, motivators and barriers to oral PrEP use among heterosexual men accessing primary healthcare services in South Africa. This study forms part of a mixed-methods implementation science study aimed at generating evidence for oral PrEP introduction and conducted in primary healthcare clinics in South Africa since 2018. Men aged ≥15 years who initiated oral PrEP and enrolled in a parent cohort study were purposefully invited to participate in an in-depth interview (IDI). Between March 2020 and May 2022, 30 men participated in IDIs exploring their motivators for PrEP use, and experiences with accessing health services. Interviews were audio recorded, transcribed and analysed thematically. The final analysis included 28 heterosexual men (18-56 years old). Motivations to initiate PrEP included fear of acquiring HIV, self-perceived vulnerability to HIV and mistrust in relationships; health systems factors which motivated PrEP use included the influence of healthcare providers, educational materials and mobile services. Perceived reduction in HIV vulnerability and changing proximity to partners were reasons for PrEP discontinuation. Side effects, daily-pill burden and stigma were noted as challenges to PrEP use. Health system barriers to PrEP use included limited PrEP availability, school and work demands, and inconsistent mobile clinic schedules. Our study reports on the experiences of heterosexual men accessing oral PrEP in real-world settings and contributes to the limited literature among this population. We highlight multiple levels which could be strengthened to improve men's PrEP use, including individual support, education among partners and communities, and addressing health system barriers to access.

Impact of simplified HCV diagnostic strategies on the HCV epidemic among men who have sex with men in the era of HIV oral pre-exposure prophylaxis in Taiwan: a modelling study.

Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.

Risk Compensation After Initiation of Daily Oral Pre-exposure Prophylaxis Among Sexual and Gender Minorities in Nigeria.

Pre-exposure prophylaxis (PrEP) use may be associated with risk compensation. We enrolled and provided PreP to sexual and gender minorities (SGM) in Abuja, Nigeria between April 2018 and May 2019. Behavioral information and samples for urogenital and anorectal Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmitted infections (STIs) were collected at baseline. Blood samples for PrEP assay and self-reported adherence were collected at three-monthly follow-up visits. STIs were detected using Aptima Combo2 assay. We estimated the odds ratios (ORs) of PCR-diagnosed bacterial STIs and self-reported behavioral outcomes (condomless anal intercourse [CAI] and concurrent sexual relationships) with conditional logistic regression. Of 400 SGM who initiated PrEP, 206 were eligible for analysis, and had a median age of 24 years (IQR 22-27). In multivariable analysis, participants in the PrEP period had decreased odds of CAI (adjusted OR: 0.49, 95% CI 0.28, 0.84). PrEP use was not associated with risk compensation.

HIV pre-exposure prophylaxis uptake, retention and adherence among female sex workers in sub-Saharan Africa: a systematic review

ObjectiveTo evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA).DesignSystematic review and meta-analysis.Data...

No observed bidirectional effect between tenofovir diphosphate concentrations and gender-affirming hormone concentrations among transgender persons switching from tenofovir disoproxil fumarate/emtricitabine to tenofovir alafenamide/emtricitabine for HIV pre-exposure prophylaxis.

Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT. The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre-exposure prophylaxis. Thirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT. There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT.

Expectations of preventative benefits and risk behaviors in a randomized trial evaluating oral HIV preexposure prophylaxis candidates

ABSTRACT When participants enrolled in an HIV prevention trial hold a preventive misconception (PM) – expectations that experimental interventions will confer protection from HIV infection – they may engage in behaviors that increase their risk of acquiring HIV. This can raise ethical concerns about whether those enrolled in the trial understand the nature of participation and their safety. Consequently, we systematically evaluated the prevalence of PM and its association with risk behaviors in a trial examining three candidate regimens for oral HIV pre-exposure prophylaxis in which all participants received at least one antiretroviral agent. Overall, trial participants exhibited relatively high preventive expectations that may be associated with an increase in risk behaviors among men who have sex with men. In addition, we identified substantial site variability in PM that necessitates future research to uncover its source. This will allow appropriate measures to be taken to mitigate PM and help ensure that participants have an accurate understanding of the potential risks and benefits of trial participation throughout the course of a trial.

Frequent chlamydia and gonorrhoea but very infrequent syphilis among men who have sex with men using HIV pre-exposure prophylaxis in West Africa

ObjectivesAlthough oral pre-exposure prophylaxis (PrEP) for HIV is being rolled out in West Africa, data on sexually transmitted infections (STIs) in PrEP users are scarce. We assessed the prevalence, incidence...

Discordance Between HIV Risk Perception, Sexual Behavior, and Pre-exposure Prophylaxis Adherence Among Young Sexual and Gender Minorities in the United States

PurposeIn the United States, youth experience suboptimal HIV pre-exposure prophylaxis (PrEP) adherence. One common idea posits that this is due to their developing decision-making skills. However, quantitative evidence of this assumption is limited. We therefore examined whether individual decision-making factors, such as HIV risk perception and sexual behavior, predicted PrEP adherence in a national trial of young sexual and gender minorities (YSGMs). MethodsIn 2019–2021, the Adolescent Medicine Trials Network for HIV Interventions 142 study enrolled 225 PrEP users (ages 16–24) throughout the country. Regression models estimated the associations between HIV risk perception (using a modified Perceived HIV Risk Scale), sexual behavior (condomless anal sex in ≤ 3 months), and self-reported oral PrEP adherence (≥4 pills in the past week) at the same time point (baseline) and longitudinally (3 months). ResultsBaseline risk perception (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.82, 1.04) and condomless anal sex (RR: 1.10, 95% CI: 0.97, 1.25) were not associated with PrEP adherence at the same time point and did not predict 3-month adherence (RR: 0.97, 95% CI: 0.85, 1.11; RR: 1.05, 95% CI: 0.93, 1.19, respectively). Baseline risk perception was not associated with condomless anal sex at either time point (baseline RR: 1.16, 95% CI: 0.94, 1.43; 3-month RR: 1.07, 95% CI: 0.90, 1.28). DiscussionIn this national trial of YSGM, HIV risk perception and condomless anal sex did not predict PrEP adherence. Targeting individual-level perceptions and behaviors will likely insufficiently address youth's suboptimal PrEP use. Future research should identify YSGM-specific adherence drivers and train providers to recognize such motivations.

Understanding Attitudes of Postpartum Cisgender Women Toward Integration of HIV Prevention Services into Routine Prenatal and Postpartum Sexual Health Discussions.

Oral pre-exposure prophylaxis (PrEP) is an effective, user-controlled method for HIV prevention. However, awareness, uptake, and adherence to PrEP remain low among cisgender women (CGW). The prenatal and postpartum periods present an opportunity for delivery of comprehensive sexual health services that include HIV prevention education and services. However, little is known about postpartum CGW's attitudes toward integration of HIV prevention education and services into obstetric care in the US. We conducted semistructured interviews with 20 postpartum CGW in the Bronx, NY from July to November 2022 to explore their experiences with prenatal and postpartum sexual health care, examine their attitudes toward integration of HIV prevention services into obstetric sexual health care, and identify components of future implementation strategies. Transcripts were analyzed thematically using a framework approach. Among CGW interviewed, fewer than half reported prior knowledge of PrEP. Ten participants preferred long-acting injectable PrEP relative to six who preferred daily oral PrEP. Most participants reported no discussion of sex with their provider during pregnancy, and when discussions occurred, they focused on permission or prohibition of sexual activity. Participants described a reliance on providers to lead prenatal sexual health discussions. Even when not perceived as personally relevant, most respondents valued education on HIV prevention and PrEP services. In the postpartum period, sexual health discussions were similarly limited despite participants describing complex experiential sexual health concerns. This study supports the potential for integration of HIV prevention education and services into routine prenatal and postpartum sexual health discussions in an area of high HIV prevalence in the US.

Exploring Attitudes Toward Pre-Exposure Prophylaxis for HIV Prevention Prior to Implementation Among Female Sex Workers in Malaysia: Results from a Qualitative Study.

Pre-exposure prophylaxis (PrEP) is an effective method for prevention of HIV transmission. Female sex workers (FSW) in Malaysia are at substantially increased risk of acquiring HIV compared to the general female population, yet little is known about this population's current HIV prevention practices or acceptance of PrEP. This study aims to inform the culturally relevant implementation of PrEP through the qualitative exploration of (1) the potential need for PrEP in this population and (2) the factors that determine FSW willingness to use oral PrEP. In-depth, semi-structured interviews (n = 30) were conducted with FSW in English, Malay, or Tamil. Transcribed and translated interviews were analyzed using a grounded theory approach. FSW express positive interest in PrEP but prefer it as a supplement to condoms, not a replacement. Perceived challenges to PrEP use include cost, adherence, and side effects. The findings suggest that in combination with condom use, PrEP may be an acceptable method of HIV prevention. Effective PrEP rollout may also include condom promotion using a peer-driven model, cost subsidies, and sex work harm reduction and empowerment components.

Assessing Preferences for Long-Acting Injectable Pre-Exposure Prophylaxis Among Young Adult Sexual Minority Men and Transgender Women

ObjectiveOral pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. However, oral PrEP uptake is low, particularly among sexual and gender minority youth who are vulnerable to HIV infection. Alternative methods of PrEP delivery, such as long-acting injectable (LAI) PrEP may overcome barriers and be preferred. However, attitudes and preferences of younger sexual and gender minorities towards LAI PrEP have not been well studied. The purpose of this study is to describe preferences for initiating LAI PrEP among sexual and gender minority youth. MethodsWe analyzed data collected as part of an HIV prevention randomized trial from January 2022 to February 2023, using multiple regression to identify factors associated with a preference for LAI PrEP. ResultsThe study sample (N = 265) was 50% youth of color, mean age 25 years (SD=3.4, range=18–31), and primarily identified as gay (71%) and male (91%). Forty two percent had heard of LAI PrEP and 31% preferred LAI PrEP over other prevention methods. In multiple regression analysis, LAI PrEP preference was associated with identifying as White, previous PrEP experience, and perceived LAI PrEP efficacy. ConclusionsWe conclude that gaps in awareness exist for LAI PrEP, however it may be preferred over other prevention methods especially in White youth, those with PrEP experience and higher perceptions of its efficacy. More education and outreach are needed to prevent extension of existing race/ethnicity disparities in use of oral daily PrEP to LAI PrEP.

Barriers and Facilitators to Long-Acting Injectable HIV Pre-Exposure Prophylaxis Implementation in Primary Care Since Its Approval in the United States.

HIV pre-exposure prophylaxis (PrEP) is a highly effective method to mitigate the HIV epidemic, but uptake of PrEP has been slow and is associated with racial and gender disparities. Oral PrEP requires high levels of adherence to be effective, which may disadvantage certain high-risk groups. The first injectable HIV PrEP, a drug given every 2 months rather than as a daily pill, was approved by the US Food & Drug Administration in December 2021. A Family Medicine practice in a single health organization in the United States (November 2022 to February 2023). We conducted interviews with patients and key stakeholders to characterize factors affecting long-acting injectable (LAI) PrEP implementation. Data collection and analysis were guided by the Consolidated Framework for Implementation Research. Interviews were transcribed and analyzed using guided content analysis. Twenty-five patients (n = 13) and practice stakeholders (n = 12) were interviewed. Overall, stakeholders described a very low uptake of LAI PrEP. Barriers to LAI PrEP included a lack of awareness, insurance and access issues, a lack of streamlined workflow, and a trust in pills over injectables. Facilitators to LAI PrEP implementation included the absence of a pill burden, a culture of shared decision making, and pharmacy support. Although uptake has been slow, we have identified several promising strategies for improving rollout and implementation of LAI PrEP. Approaches that can bolster rollout of LAI PrEP include having an interdisciplinary care team that is supported by PrEP navigators and pharmacists and are informed by a patient-centered model of care to increase patient engagement and trust.

Perspectives on Injectable HIV Pre-Exposure Prophylaxis: A Qualitative Study of Health Care Providers in the United States.

The introduction of injectable HIV pre-exposure prophylaxis (PrEP) has the potential to significantly change the biomedical HIV prevention landscape. However, effective implementation will require health care providers to adopt, prescribe, and administer injectable PrEP within clinical settings. This study qualitatively examined challenges and benefit of injectable PrEP implementation from the perspective of health care providers. From April to August 2022, we conducted 19 in-depth interviews with current PrEP-prescribing health care providers in New York State, including 3 physician assistants, 5 physicians, and 11 nurse practitioners. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed to report semantic-level themes regarding injectable PrEP implementation. More than half of participants (61%) were aware of injectable PrEP; only 21% had experience prescribing it. Qualitative findings highlighted five themes. Three themes represented implementation challenges, including speculative concerns about side effects, appointment compliance, and practical and logistical considerations. The remaining two themes described benefits of injectable PrEP relative to oral PrEP, which included greater convenience and enhanced privacy. Findings from this qualitative study make significant applied contributions to the sparse knowledge on health care provider perspectives of injectable PrEP post-US Food and Drug Administration approval and their concerns and considerations regarding implementation in real-world clinical settings.

Uptake and challenges with daily oral pre-exposure prophylaxis among men who have sex with men and transgender women, suburban Yangon, Myanmar.

Pre-exposure prophylaxis (PrEP) is effective for human immunodeficiency virus (HIV) prevention in risk groups. We assessed PrEP uptake and 12-month retention among men who have sex with men (MSM) and transgender women (TGW) in Myanmar during the coronavirus disease 2019 pandemic and a political crisis. Using prospectively collected data, we assessed the proportion of persons eligible, initiated and retained 12months on PrEP. We calculated HIV and syphilis incidence among those initiated on PrEP. Predictors of compliance to scheduled visits were assessed with fractional logistic regression. Among 652 persons screened between July and December 2020, 85.3% were eligible and 38.8% initiated PrEP. The daily pill burden was the main reason (86.5%) for refusing PrEP. A history of HIV post-exposure prophylaxis (PEP) and having an HIV-positive partner not on anti-retroviral therapy (ART) was associated with PrEP uptake (p<0.05). The 12-month retention among those initiating PrEP was 43.0%. Age ≥25y, a history of PEP and having an HIV-positive partner not on ART predicted better compliance with scheduled visits (p<0.05). HIV incidence among PrEP initiators was 3.1 per 100 person-years (95% confidence interval [CI] 1.3 to 7.4) and syphilis incidence was 17.6 per 100 person-years (95% CI 12.3 to 25.1). A PrEP program for MSM and TGW in Myanmar was implemented successfully under difficult circumstances. Alternative strategies are needed addressing PrEP uptake and retention.

Providing medication for opioid use disorder and HIV pre-exposure prophylaxis at syringe services programs via telemedicine: a pilot study

BackgroundPeople who inject drugs (PWID) are at high risk for opioid overdose and infectious diseases including HIV. We piloted PARTNER UP, a telemedicine-based program to provide PWID with medication for opioid use disorder (MOUD) with buprenorphine/naloxone (bup/nx) and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine through two syringe services programs (SSP) in North Carolina. We present overall results from this project, including participant retention rates and self-reported medication adherence.MethodsStudy participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly until program end at month 6. Participants were asked to start both MOUD and PrEP at initiation but could choose to discontinue either at any point during the study. Demographics and health history including substance use, sexual behaviors, and prior use of MOUD/PrEP were collected at baseline. Follow-up surveys were conducted at 3- and 6-months to assess attitudes towards MOUD and PrEP, change in opioid use and sexual behaviors, and for self-reported medication adherence. Participant retention was measured by completion of visits; provider notes were used to assess whether the participant reported continuation of medication.ResultsOverall, 17 persons were enrolled and started on both bup/nx and PrEP; the majority self-identified as white and male. At 3 months, 13 (76%) remained on study; 10 (77%) reported continuing with both MOUD and PrEP, 2 (15%) with bup/nx only, and 1 (8%) with PrEP only. At 6 months, 12 (71%) remained on study; 8 (67%) reported taking both bup/nx and PrEP, and 4 (33%) bup/nx only. Among survey participants, opioid use and HIV risk behaviors decreased. Nearly all reported taking bup/nx daily; however, self-reported daily adherence to PrEP was lower and declined over time. The most common reason for not continuing PrEP was feeling not at risk for acquiring HIV.ConclusionsOur study results show that MOUD and PrEP can be successfully administered via telemedicine in SSPs. PrEP appears to be a lower priority for participants with decreased continuation and adherence. Low perception of HIV risk was a reason for not continuing PrEP, possibly mitigated by MOUD use. Future studies including helping identify PWID at highest need for PrEP are needed.Trial registrationProviding Suboxone and PrEP Using Telemedicine, NCT04521920. Registered 18 August 2020. https://clinicaltrials.gov/study/NCT04521920?term=mehri%20mckellar&rank=2.

Depression Among Pregnant and Breastfeeding Persons Participating in Two Randomized Trials of the Dapivirine Vaginal Ring and Oral Pre-Exposure Prophylaxis (PrEP) in Malawi, South Africa, Uganda, and Zimbabwe.

Depression is associated with lower adherence to oral pre-exposure prophylaxis (PrEP) to prevent HIV, but data are not currently available on how depression may affect use of other HIV prevention methods including the dapivirine vaginal ring (DVR). We conducted a mixed methods study using data from the Microbicide Trials Network (MTN) 042/DELIVER (n = 558) and MTN-043/B-PROTECTED (n = 197) studies to describe the prevalence of depressive symptoms and explore how depressive symptoms may have influenced attitudes about use of the monthly DVR and once-daily oral PrEP tablet among pregnant and breastfeeding persons, respectively, in Malawi, South Africa, Uganda, and Zimbabwe. Eleven participants had high Edinburgh Postnatal Depression scores ≥ 10 in MTN-042/DELIVER (2%) and four participants (2%) in MTN-043/B-PROTECTED. In interviews with 9 participants who had high scores (6 DVR, 3 oral PrEP), those with depressive symptoms described overlapping stressors which were magnified by job loss and economic instability during the COVID-19 pandemic, and by experiences of pregnancy/postpartum. These participants experienced a lack of support from partners or family members, and conflict with partners related to trust, and infidelity. While we did not find evidence of a change in product adherence, there was a strong sense of commitment and motivation to use the study products for protection from HIV for participants themselves and their baby. Although lack of social support is usually an obstacle to adherence, in this study, the participants' lives and relationships seemed to have reinforced the need for HIV prevention and motivated women to protect themselves and their babies from HIV.

Concordance between daily diary reported PrEP intake and intraerythrocytic tenofovir diphosphate (TFV-DP) in the Amsterdam PrEP demonstration project.

We assessed the association and concordance between self-reported oral preexposure prophylaxis (PrEP) intake in a diary app and intraerythrocytic drug metabolite concentrations. AMPrEP was a prospective demonstration study providing daily and event-driven PrEP to MSM in Amsterdam, the Netherlands (2015-2020). Participants could record their PrEP intake in a diary app. Dried blood spots (DBS) were taken at 6, 12, 24, and 48 months and analysed for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations. We included TFV-DP measurements preceded by diary completion on at least 90% of days in the 6 weeks prior. We examined the association between self-reported PrEP intake (i.e. number of pills) and TFV-DP concentrations using tobit regression with a random intercept per participant. We also calculated concordance between categorized PrEP intake (i.e. <2, 2-3, 4-6 or 7 pills per week) and categorized TFV-DP concentrations (i.e. <350, 350-699,700-1249 or ≥1250 fmol/punch) using weighted Cohen's kappa. Last, we calculated concordance between self-reported recent PrEP intake (yes/no, in past 2 days) and quantifiability of FTC-TP (yes/no) using Cohen's kappa. Seven hundred and fifty-nine DBS measurements from 282 MSM were included. Self-reported PrEP intake was strongly and positively associated with TFV-DP concentration (β = 0.77, 95% CI = 0.70-0.84, P < 0.0001). Concordance between categorized PrEP intake and TFV-DP concentration was moderate (κ = 0.44, 95% CI = 0.39-0.50). Concordance between self-reported recent PrEP intake and FTC-TP quantifiability was perfect (κ = 0.83, 95% CI 0.76-0.90). Self-reported PrEP intake in a diary app is strongly correlated with actual use, and therefore reliable for comparing PrEP adherence between groups. Still, suboptimal criterion validity according to clinically relevant categories warrants caution when assessing 6-week reported adherence for individuals.

Perinatal outcomes associated with pre-exposure prophylaxis for HIV prevention during pregnancy: a systematic review and meta-analysis

The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality. We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825. Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; I2=0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; I2=0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, I2=0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA. We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy. None.

HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.