Substantial Risk Of HIV Infection Research Articles

Long-acting antiretroviral therapy in low-income and middle-income countries: considerations for roll-out.

Long-acting ART (LA-ART) in low-income and middle-income countries (LMICs) may address specific issues that affect people living with HIV (PWH) and people at substantial risk of HIV infection. We reviewed products in use and under consideration in LMICS, current and anticipated challenges for implementation, and offer strategies for effective rollout. Factors to consider for effective implementation of LA-ART in LMICs are: managing co-conditions (pregnancy) and comorbidities (TB and hepatitis B); medication access, both cost and supply-related; and health systems delivery mechanisms for products. LA-ART present promising new alternatives in LMICs. Although they may tackle certain adherence concerns and systemic issues, which impact delivery of services, significant obstacles remain before their widespread implementation in people that require them most, particularly in countries most affected by HIV. We offer best practices from prior experiences and implementation studies for effective coordination of multiple stakeholders, critical for effective rollout.

Preferences for pre-exposure prophylaxis delivery among HIV-negative pregnant and breastfeeding women in Zambia: evidence from a discrete choice experiment.

Pregnant and breastfeeding women at substantial risk for HIV infection in sub-Saharan Africa can benefit from biomedical interventions such as pre-exposure prophylaxis (PrEP). We estimated the benefit that pregnant and breastfeeding women may derive from PrEP service delivery in order to guide PrEP roll-out in the target population in Zambia. Between September and December 2021, we conducted a discrete choice experiment (DCE) among a convenient sample of 389 pregnant and breastfeeding women not living with HIV in Lusaka, Zambia. Women aged 18 years or older, with a documented negative HIV result in their antenatal card responded to a structured questionnaire containing 12 choice sets on service delivery attributes of PrEP: waiting time at the facility, travel time to the facility dispensing PrEP, location for PrEP pick-up, health care provider attitude and PrEP supply at each refill. Mixed logit regression analysis was used to determine the participant's willingness to trade off one attribute of PrEP for the other at a 5% significance level. Willingness to wait (WTW) was used to determine the relative utility derived from each attribute against waiting time. Waiting time at the facility, travel time to the facility, health care provider attitude and amount of PrEP supply at each refill were important attributes of PrEP service delivery (all p < 0.01). Participants preferred less waiting time at the facility (β = -0.27, p < 0.01). Women demonstrated a strong preference for a 3-months' supply of PrEP (β = 1.69, p < 0.01). They were willing to wait for 5 h at the facility, walk for more than an hour to a facility dispensing PrEP, encounter a health care provider with a negative attitude in order to receive PrEP enough for 3 months. Patient-centered approaches can help to inform the design and implementation of PrEP services among pregnant and breastfeeding women. In this study, we found that a reduction in clinic visits-including through multi-month dispensing of PrEP-could improve uptake of services in antenatal and postnatal settings.

Exploring factors hindering the uptake of HIV pre-exposure prophylaxis by potential users in Namibia.

Pre-exposure prophylaxis (PrEP) is recommended for people who are at substantial risk of HIV infection, in conjunction with other HIV prevention tools and strategies. Unfortunately, the uptake of PrEP among potential users in Namibia's Okongo district is low. The objective of this study was to explore and describe the factors that hinder the uptake of HIV PrEP by potential users at the Okongo District Hospital in Namibia. A qualitative exploratory, descriptive and contextual design was used. The study sought to understand the factors hindering uptake of HIV PrEP by potential users in the peri-urban setting of Okongo District Hospital, Namibia. Purposive sampling was used to select participants for this study, with qualitative data being gathered from semi-structured interviews with 20 potential PrEP users. The data were analysed using qualitative thematic analysis. Participants reported numerous factors hindering uptake, including level of understanding, non-compliance on the part of the health department, distances, and attitudes. Additionally, participants maintained that health workers do not put enough effort into educating patients in the different hospital departments about PrEP, and sometimes there is insufficient stock of the medicine, both of which hinder PrEP uptake. Despite the PrEP rollout, multiple obstacles continue to hinder PrEP uptake, especially in the outskirts of Okongo district. This study recognises that there is a need to work hand in hand with the support systems of both potential users.

Factors associated with HIV pre-exposure prophylaxis use among Asian men who have sex with men in Sydney and Melbourne, Australia: a cross-sectional study

Asian-born MSM are a priority population as Australia aims to end HIV transmission, but they reported additional barriers to access PrEP and other HIV prevention methods. This study investigates factors associated with PrEP use among Asian MSM in Sydney and Melbourne, Australia, to inform strategies to improve PrEP uptake in this population. This was a sub-analysis of a community-based cross-sectional survey conducted from March to June 2021. We recruited participants online in Sydney and Melbourne, Australia. Univariable and multivariable logistic regression analyses were performed to identify the factors associated with PrEP use in the last six months and lifetime. Latent class analyses were used to identify subgroups of Asian MSM sharing similar characteristics related to their risk practices for HIV. Overall, 870 Asian MSM were included: 288 Oceanian-born Asian MSM and 582 Asian-born MSM. Three latent classes were identified: 1) Asian-born MSM who recently arrived in Australia with limited English, were less likely to use PrEP and at higher risk of HIV infection (e.g., had condomless anal sex with a casual sex partner in the last six months) (4.6%); 2) Asian MSM who were at lower risk of HIV infection and less likely to use PrEP (69.3%) and; 3) Asian MSM who were at substantial risk of HIV infection and more likely to use PrEP (26.1%). Compared to Oceanian-born Asian MSM, those who were born in Southeast Asia (adjusted odds ratio (aOR)=0.5, 95% confidence interval (CI) 0.3-0.7) and South Asia (aOR=0.4, 95% CI 0.2-0.8) were less likely to ever use PrEP. Compared to Oceanian-born Asian MSM, those who were born in Southeast Asia (aOR=0.4, 95% CI 0.3-0.7), Northeast Asia (aOR=0.5, 95% CI 0.3-0.8) and South Asia (aOR=0.4, 95% CI 0.2-0.7) were less likely to use PrEP in the last six months. To end HIV transmission in Australia, it will be necessary to develop strategies to improve PrEP access for the significant minority of Asian-born MSM who are at substantial risk of HIV infection. EPFC and JJO are supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grant (EPFC: GNT1172873 and JJO: GNT1193955). CKF is supported by an Australian National Health and Medical Research Council (NHMRC) Leadership Investigator Grant (GNT1172900).

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.

Awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among sexually active adults in Malawi: results from the 2020 Malawi population-based HIV impact assessment

BackgroundThe World Health Organization recommends Pre-Exposure Prophylaxis (PrEP) for all populations at substantial risk of HIV infection. Understanding PrEP awareness and interest is crucial for designing PrEP programs; however, data are lacking in sub-Saharan Africa. In Malawi, oral PrEP was introduced in 2018. We analyzed data from the 2020 Malawi Population-based HIV Impact Assessment (MPHIA) to assess PrEP awareness and factors associated with PrEP interest in Malawi.MethodsMPHIA 2020 was a national cross-sectional household-based survey targeting adults aged 15 + years. Oral PrEP was first described to the survey participants as taking a daily pill to reduce the chance of getting HIV. To assess awareness, participants were asked if they had ever heard of PrEP and to assess interest, were asked if they would take PrEP to prevent HIV, regardless of previous PrEP knowledge. Only sexually active HIV-negative participants are included in this analysis. We used multivariable logistic regression to assess sociodemographic factors and behaviors associated with PrEP interest. All results were weighted.ResultsWe included 13,995 HIV-negative sexually active participants; median age was 29 years old. Overall, 15.0%, 95% confidence interval (CI): 14.2–15.9% of participants were aware of PrEP. More males (adjusted odds ratio (aOR): 1.3, 95% CI: 1.2–1.5), those with secondary (aOR: 1.5, 95% CI: 1.2-2.0) or post-secondary (aOR: 3.4, 95% CI: 2.4–4.9) education and the wealthiest (aOR: 1.6, 95% CI: 1.2-2.0) were aware of PrEP than female, those without education and least wealthy participants, respectively. Overall, 73.0% (95% CI: 71.8–74.1%) of participants were willing to use PrEP. Being male (aOR: 1.2; 95% CI: 1.1–1.3) and having more than one sexual partner (aOR: 1.7 95% CI: 1.4–1.9), were associated higher willingness to use PrEP.ConclusionsIn this survey, prior PrEP knowledge and use were low while PrEP interest was high. High risk sexual behavior was associated with willingness to use PrEP. Strategies to increase PrEP awareness and universal access, may reduce HIV transmission.

Effectiveness of a Community Empowerment Intervention to Improve Access to Pre-exposure Prophylaxis in Migrant Women Sex Workers: Protocol for a Mixed Methods Implementation Study.

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for all populations at substantial risk of HIV infection. However, at-risk women very rarely use PrEP in France-this represents a critical issue among migrant women sex workers (MWSWs). Previous studies on PrEP use among women sex workers or migrants focused on individual or social determinants of motivation. However, operational studies in real-word settings using a holistic population approach to maximize PrEP adherence among MWSWs are lacking. FASSETS (ie, "Favoriser l'Accès à la Santé Sexuelle des Travailleuses du Sexe"; English: "facilitate the access to Sexual Health in women sex workers") is a participative, multilevel, mixed methods study aiming to improve global knowledge of and access to sexual health care and PrEP among MWSWs through targeted empowerment strategies. This study comprises several phases: (1) phase 1: an initial qualitative study combining semistructured interviews, informal interviews, and participative observations will be performed among MWSWs, local community nongovernmental organizations, and institutions providing sexual reproductive health services to identify the determinants of PrEP access among MWSWs and for respondent-driven sampling (RDS); (2) phase 2: the size of the hidden MWSW population is estimated in Marseille through capture-recapture (the RDS survey will serve as "recapture"); (3) phase 3: a longitudinal cohort will be formed through RDS to represent the MWSW population with a goal of 150 inclusions-this cohort will be followed up for 12 months, and sequential questionnaires exploring medical history; knowledge of sexual health, HIV, and sexually transmitted infections; migration route; and current living conditions will be administered at inclusion (month 0) and months 3, 6, and 12 to measure the following interventional phase's outcomes; and (4) phase 4: an interventional study with community empowerment actions about sexual health and PrEP will be conducted with community health workers; standardized questionnaires and semistructured interviews, observations, and focus groups will highlight MWSWs' experiences with empowerment resources, concerns about sexual health, and especially PrEP use or uptake, and we will evaluate whether and how community-adapted empowerment actions conducted by community health workers are effective in increasing access to sexual health, prevention and screening of sexually transmitted infections, and PrEP knowledge and access among MWSWs. Recruitment commenced on March 1, 2022. We estimate the follow-up period to end on September 30, 2023. This multiphase study will provide robust evidence about the magnitude of the MWSW population in Marseille (the second largest town in France) and their current conditions of living, access to and knowledge of sexual health, and PrEP access. Using a mixed methods analysis, we will investigate whether individual and collective community health empowerment approaches can facilitate access to PrEP and its initiation, use, and adherence in this vulnerable population. DERR1-10.2196/42844.

Factors influencing the retention of clients in oral pre-exposure prophylaxis (PrEP) care at 3 months after initiation in the Omusati region of Namibia

BackgroundThe United Nations has set a target of ending the HIV/AIDS epidemic as a public health threat by 2030. The WHO recommended the use of oral pre-exposure prophylaxis (PrEP) for HIV prevention for all people at substantial risk of HIV infection in 2016. In Namibia since the adoption of PrEP in 2016, many clients have been initiated on PrEP. ObjectivesThe objectives of this study were to measure clients’ rate of PrEP retention at three months and determine factors that influence it in the Omusati region of Namibia. MethodsAn analytical cross-sectional design was used for this study. Three hundred and forty-five participants were selected for this study using a simple random sampling method. The data were collected from the Electronic Patient Monitoring System (EPMS). Chi-square tests and logistic regression were used for data analysis. ResultsThe retention rate in PrEP care at three months was 60 %. The Chi-square tests showed significant associations between age, sex, sexually transmitted infection (STI) symptoms, marital status, HIV status and viral load of partner, number of sexual partners, and retention in PrEP care at three months (p < 0.05). Logistic regression analysis revealed that females and those with STI symptoms were more likely to be retained in PrEP care, Adjusted Odds Ratio (AOR) = 2.21, 95 % CI (1.36–3.57), and AOR = 4.25, 95 % CI (1.23–14.63), respectively. Participants with HIV-negative/unknown status partners and with multiple/concurrent sexual partners were less likely to continue with PrEP, Crude Odds Ratio (COR) = 0.56, 95 % CI (0.36–0.86), COR = 0.39, 95 % CI (0.16–0.96), respectively. ConclusionThe findings of this study accentuate the need for increased provision of information on the importance of the continuation of PrEP.

The cost-effectiveness of Pre-Exposure Prophylaxis in HIV Prevention: Analysis from A Multicentre Intervention in Northern Nigeria

Background: Pre-exposure prophylaxis (PrEP) is recommended for people at substantial risk of acquiring HIV to prevent new infections. The Nigeria PEPFAR program through USAID funded the implementation of PrEP for Key Population (KP) groups including Men Who Have Sex with Men (MSM), People who inject drugs (PWIDS), and Female sex Workers (FSW) in July 2020. We assessed the number of new infections averted and the financial resources saved because of this intervention. Methodology: HIV-negative clients from the key population community in North- East Nigeria eligible for PrEP were enrolled over a 7-month period (July 2020 – February 2021). Eligibility criteria used include being at substantial risk for HIV infection based on a screening test administered. The person-month was calculated by using the duration the participants were retained on PrEP. The incidence 15.4/100 person-years of HIV among MSM at high risk of HIV infection in the TRUST study conducted in Nigeria was used to calculate the expected positive cases if PrEP was not provided for those enrolled using the formula (15.4/100 * X) where X is number of person-years. We compared the expected positive to the actual positive seen among KPs while on PrEP within the study period. The cost-effectiveness of being on PrEP was calculated by multiplying the standard cost per HIV infection averted ($13, 267 per HIV infection averted) by the No of HIV averted. Results: We enrolled a total of 1,197 eligible HIV-negative KPs within the study period (189 were retained for seven months, 407 for four months, 585 for 3 months, and 18 for 1 month). A total of 4722 person-months (394 person-years) were accumulated over the period of the study. Using the incidence of 15.4/100 person-years, the expected positive cases if PrEP was not provided was 61 (15.4/100 *394). With the use PrEP, no client seroconverted to be HIV positive. This means that within the 7-month period, 61 HIV infections were averted. At the cost of $13,267 per HIV infection averted for PrEP, the project saved $809,287 for averting 61 HIV infections in seven months of using PrEP among HIV-negative KPs involved in high-risk behaviors. Conclusion: This study shows that PrEP is effective in averting new infections among key population groups. Placing high-risk groups such as KPs on PrEP is cost-effective due to the money saved from new infections averted. Increased funding for proven and innovative strategies on PrEP enrolment, retention, and adherence of eligible clients should be expanded for KPs.

Long-acting injectable cabotegravir for PrEP: A game-changer in HIV prevention?

Long-acting injectable cabotegravir (CAB-LA) represents a new additional option for HIV prevention in people at substantial risk of HIV infection that may fill the gaps in pre-exposure prophylaxis (PrEP) uptake, adherence, and retention in users having difficulty with oral PrEP. Data from clinical trials demonstrated that CAB-LA was safe, highly effective, and well-accepted for HIV prevention. However, the occurrence of breakthrough HIV infections despite timely injections, HIV seroconversion timing and patterns, risk of selection and dissemination of resistance-associated mutations to integrase inhibitors, complexity of follow-up, logistical considerations, and its cost effectiveness compared with oral PrEP constitute significant issues for the integration of CAB-LA into clinical routine. These concerns need to be addressed before moving forward with large-scale implementation programmes. Pilot and implementation projects are required in the following areas: HIV testing algorithms, patient education, clinic procedures, protocols for switching and discontinuation, efficacy and safety in populations not included in clinical trials, and demedicalization processes. The development of models to increase the uptake of, adherence to, and persistence with and after CAB-LA injections will also be of paramount importance for success. Lessons learned from these projects will increase experience, staff expertise, and organizational and training capacities to support the roll-out of this new agent as part of HIV prevention programmes. CAB-LA has not yet achieved its full potential in HIV prevention, and strong commitment from all stakeholders is required to push CAB-LA as a game-changer in HIV response.

The early-stage comprehensive costs of routine PrEP implementation and scale-up in Zambia.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention option, but cost-effectiveness is sensitive to implementation and program costs. Studies indicate that, in addition to direct delivery cost, PrEP provision requires substantial demand creation and client support to encourage PrEP initiation and persistence. We estimated the cost of providing PrEP in Zambia through different PrEP delivery models. Taking a guidelines-based approach for visits, labs and drugs, we estimated the annual cost of providing PrEP per client for five delivery models: one focused on key populations (men-who-have-sex-with-men (MSM) and female sex workers (FSW), one on adolescent girls and young women (AGYW), and three integrated programs (operated within HIV counselling and testing services at primary healthcare centres). Program start-up and support costs were based on program expenditure data and number of PrEP sites and clients in 2018. PrEP clinic visit costs were based on micro-costing at two PrEP delivery sites (2018 USD). Costs are presented in 2018 prices and inflated to 2021 prices. The annual cost/PrEP client varied by service delivery model, from $394 (AGYW) to $655 (integrated model). Cost differences were driven largely by client volume, which impacted the relative costs of program support and technical assistance assigned to each PrEP client. Direct service delivery costs ranged narrowly from $205-212/PrEP-client and were a key component in the cost of PrEP, representing 35-65% of total costs. The results show that, even when integrated into full service delivery models, accessing vulnerable, marginalised populations at substantial risk of HIV infection is likely to cost more than previously estimated due to the programmatic costs involved in community sensitization and client support. Improved data on individual client resource usage and outcomes is required to get a better understanding of the true resource utilization, expected outcomes and annual costs of different PrEP service delivery programs in Zambia.

Loss to Follow-Up from HIV Pre-Exposure Prophylaxis Care in Men Who Have Sex with Men in West Africa.

Loss to follow-up (LTFU) from HIV pre-exposure prophylaxis (PrEP) care compromises the goal of HIV elimination. We investigated the proportion of LTFU and associated risk factors among men who have sex with men (MSM) enrolled in a PrEP demonstration project in Burkina Faso, Côte d'Ivoire, Mali, and Togo. CohMSM-PrEP, a prospective cohort study, was conducted between November 2017 and June 2021 in community-based clinics. MSM aged 18 years or older at substantial risk of HIV infection received a comprehensive prevention package, including PrEP and peer education. LTFU was defined as not returning to the clinic for six months. Associated risk factors were investigated using a time-varying Cox's model. Of 647 participants followed up for a median time of 15 months, 372 were LTFU (57.5%). LTFU was associated with younger age (adjusted hazard ratio [95% Confidence Interval]; 1.50 [1.17-1.94]), unemployment (1.33 [1.03-1.71]), depression (1.63 [1.12-2.38]), and perceiving no HIV risk with stable male partners (1.61 [1.23-2.10]). Contacting peer educators outside of scheduled visits was protective (0.74 [0.56-0.97]). Our findings show that LTFU from PrEP care in West African MSM is a major challenge to achieving HIV elimination, but that the involvement of peer educators in PrEP delivery helps to limit LTFU by providing users with adequate support.

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.

The HIV pre-exposure prophylaxis continuum of care among women who inject drugs: A systematic review

IntroductionPeople who inject drugs have a substantial risk for HIV infection, especially women who inject drugs (WWID). HIV pre-exposure prophylaxis (PrEP), a highly-effective HIV prevention drug, is uncommonly studied among WWID, and we aimed to synthesize existing knowledge across the full PrEP continuum of care in this population.MethodsWe systematically searched for peer-reviewed literature in three electronic databases, conference abstracts from three major HIV conferences, and gray literature from relevant sources.Eligibility criteria included quantitative, qualitative or mixed-methods studies with primary data collection reporting a PrEP-related finding among WWID, and published in English or Spanish between 2012 and 2021. The initial search identified 2,809 citations, and 32 were included. Data on study characteristics and PrEP continuum of care were extracted, then data were analyzed in a narrative review.ResultsOur search identified 2,809 studies; 32 met eligibility requirements. Overall, awareness, knowledge, and use of PrEP was low among WWID, although acceptability was high. Homelessness, sexual violence, unpredictability of drug use, and access to the healthcare system challenged PrEP usage and adherence. WWID were willing to share information on PrEP with other WWID, especially those at high-risk of HIV, such as sex workers.ConclusionsTo improve PrEP usage and engagement in care among WWID, PrEP services could be integrated within gender-responsive harm reduction and drug treatment services. Peer-based interventions can be used to improve awareness and knowledge of PrEP within this population. Further studies are needed on transgender WWID as well as PrEP retention and adherence among all WWID.

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

Background:HIV endpoint–driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.Methods:ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16–35 years, randomized to 1 of 3 contraceptives. Oral PrEP was offered onsite as part of the HIV prevention package at the South African trial sites. We measured tenofovir in plasma samples collected at the final trial visit among women reporting ongoing PrEP use. We used bivariate and multivariate logistical regression to assess demographic and sexual risk factors associated with plasma tenofovir quantification.Results:Of 260 women included, 52% were ≤24 years and 22% had Chlamydia trachomatis at enrollment. At PrEP initiation, 68% reported inconsistent/nonuse of condoms. The median duration of PrEP use was 90 days (IQR: 83–104). Tenofovir was quantified in 36% (n = 94) of samples. Women >24 years had twice the odds of having tenofovir quantified vs younger women (OR = 2.12; 95% confidence interval = 1.27 to 3.56). Women who reported inconsistent/nonuse of condoms had lower odds of tenofovir quantification (age-adjusted OR = 0.47; 95% confidence interval = 0.26 to 0.83).Conclusions:Over a third of women initiating PrEP and reporting ongoing use at the final trial visit had evidence of recent drug exposure. Clinical trials may serve as an entry point for PrEP initiation among women at substantial risk for HIV infection with referral to local facilities for ongoing access at trial end.Clinical trial number:NCT02550067.

An implementation model for scaling up oral pre-exposure prophylaxis in Kenya: Jilinde project.

Oral pre-exposure prophylaxis (PrEP) is an efficacious way to lower the risk of HIV acquisition among high-risk individuals. Despite the World Health Organization's 2015 recommendation that all persons at substantial risk of HIV infection be provided with access to oral PrEP, the rollout has been slow in many low- and middle-income countries. Initiatives for national rollout are few, and subtle skepticism persists in several countries about the feasibility of national PrEP implementation. We describe the conceptual design of the Jilinde project, which is implementing oral PrEP as a routine service at a public health scale in Kenya. We describe the overlapping domains of supply, demand, and government and community ownership, which combine to produce a learning laboratory environment to explore the scale-up of PrEP. We describe how Jilinde approaches PrEP uptake and continuation by applying supply and demand principles and ensures that government and community ownership informs policy, coordination, and sustainability. We describe the "learning laboratory" approach that informs strategic and continuous learning, which allows for adjustments to the project. Jilinde's conceptual model illustrates how the coalescence of these concepts can promote scale-up of PrEP in real-world conditions and offers critical lessons on an implementation model for scaling up oral PrEP in low- and middle-income countries.

HIV pre-exposure prophylaxis for men who have sex with men in west Africa: a multicountry demonstration study

HIV pre-exposure prophylaxis (PrEP) data in men who have sex with men (MSM) in west Africa are essential to guide its large-scale implementation. We assessed the uptake of event-driven and daily PrEP, HIV incidence, and changes over time in sexual behaviours and prevalence of bacterial sexually transmitted infections (STIs) in MSM in Burkina Faso, Côte d'Ivoire, Mali, and Togo. We did a prospective cohort study from Nov 20, 2017, to April 14, 2020, in four community-based clinics in Abidjan (Côte d'Ivoire), Bamako (Mali), Lomé (Togo), and Ouagadougou (Burkina Faso). Participants were MSM aged 18 years or older at substantial risk of HIV infection. Participants could choose between event-driven (2+1+1 dosing) and daily oral PrEP (tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg), switch regimen, and discontinue or restart PrEP. We compared HIV incidence in this study with that of the same cohort before the availability of PrEP (CohMSM). Statistical analysis included the Kaplan-Meier method and mixed-effects regression models. This study is registered with ClinicalTrials.gov, NCT03459157. We followed up 598 participants for a total of 743·6 person-years. At enrolment, 445 (74%) of 598 participants chose event-driven PrEP and 153 (26%) of 598 chose daily PrEP. 60 (13%) of 445 and 65 (42%) of 153 participants switched PrEP regimen at least once (p<0·0001). 159 participants (27%) were lost to follow-up. Overall HIV incidence was 2·3 per 100 person-years (95% CI 1·3-3·7; adjusted incidence rate ratio 0·21, 95% CI 0·12-0·36 compared with CohMSM). Adherence was optimal in 802 (41%) of 1946 measures with event-driven PrEP and in 394 (71%) of 554 measures with daily PrEP (p<0·0001). Coverage of sex acts with PrEP only and PrEP and condom decreased during follow-up (p=0·039 if PrEP only; p=0·0025 if PrEP and condom). The frequency of condomless anal sex remained stable (p=0·96). The number of male sexual partners (p<0·0001) and number of sex acts with casual male partners (p=0·0014 for 1-4 sex acts in previous 4 weeks; p=0·030 for ≥5 sex acts) decreased. The prevalence of gonorrhoea, chlamydia, and syphilis remained stable. PrEP availability helped prevent HIV infection and did not lead to an increase in risky sexual behaviours or other STIs. PrEP should be urgently implemented in west Africa. Retention in care and PrEP adherence require special attention to ensure PrEP reaches its full prevention potential. ANRS and Expertise France. For the French translation of the abstract see Supplementary Materials section.

"Yes, I'm interested in taking PrEP!": PrEP interest among women respondents to the European community-based survey "Flash! PrEP in Europe".

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for all populations at substantial risk of HIV infection, including women. However, data regarding PrEP interest among women is lacking, particularly in Europe. Factors associated with interest in using PrEP were assessed among women respondents to the Flash! PrEP in Europe (FPIE) survey. This community-based cross-sectional study, conducted in 12 European countries, aimed to assess PrEP knowledge and interest. “High objective risk” (HOR) was assessed using established risk criteria following EACS and CDC guidelines. Factors associated with interest in using PrEP were assessed in univariable and multivariable logistic regression models. Among 678 women, 12.5% (n = 85) were considered at HOR, 46.8% (n = 317) indicated prior PrEP knowledge and 18.0% (n = 122) reported interest in using PrEP. Among women at HOR, 40.0% (n = 34) were interested in PrEP. Factors significantly associated with PrEP interest in the final multivariable model were: younger age (18–29 years) (aOR 1.91[95CI: 1.07; 3.41]), bad self-perceived financial status (1.84[1.09; 3.11]), migrant status (south to north) (2.87[1.05; 7.89]), single or dating relationship status (1.93[1.23; 3.03]), sexual abuse history (1.86[1.17; 2.97]), “rather high”/ “high” self-perceived HIV risk (3.21[1.32; 7.81]), and HOR (2.49[1.42; 4.35]). These results show that women at HOR and those who perceived themselves to be at high risk are interested in using PrEP. There is a critical need for targeted information and improved access to PrEP to increase uptake of this HIV prevention tool to meet PrEP interest among women.

Lamivudine/Tenofovir Disoproxil Fumarate is an Appropriate PrEP Regimen.

Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC) or lamivudine (3TC) is recommended as an additional prevention option for persons at substantial risk of HIV infection by both the World Health Organization (WHO) and the US President's Emergency Plan for AIDS Relief (PEPFAR). The WHO and PEPFAR consider 3TC clinically interchangeable with FTC for PrEP given comparable pharmacologic equivalence, resistance and toxicity patterns, and indirect clinical trial evidence from TDF-containing studies. Globally, FTC/TDF has been widely used in clinical trials, open-label extension studies and demonstration projects. Thus, most PrEP efficacy and safety data are based on FTC/TDF use in heterosexual women and men, men who have sex with men, and people who inject drugs. However, generic 3TC/TDF is less expensive than FTC/TDF, is already available in supply chains for HIV drugs, and has 60-70% of the global adult market share, making it particularly appealing in settings with limited availability or affordability of FTC/TDF. Compelling indirect evidence suggests that scaling up use of 3TC/TDF is potentially cost saving for HIV programs in settings where restricting drug choice to FTC/TDF would delay PrEP implementation. Guideline committees and public health decision-makers in countries should encourage flexibility in PrEP drug selection, support off-label use of 3TC/TDF, and approve use of generic formulations to decrease the cost of PrEP medications and accelerate PrEP delivery through the public and private sectors.

Emerging evidence from a systematic review of safety of pre-exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading?

IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre‐exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from http://www.clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)‐based oral PrEP safety in pregnant and breastfeeding HIV‐uninfected women.Results and discussionWe identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP‐exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV‐uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.