Low selection of HIV PrEP refills at private pharmacies among clients who initiated PrEP at public clinics: findings from a mixed-methods study in Kenya.

BACKGROUND: In Africa, the delivery of HIV pre-exposure prophylaxis (PrEP) at public healthcare clinics is challenged by understaffing, overcrowding, and HIV-associated stigma, often resulting in low PrEP uptake and continuation among clients. Giving clients the option to refill PrEP at nearby private pharmacies, which are often more convenient and have shorter wait times, may address these challenges and improve PrEP continuation. METHODS: This mixed methods study used an explanatory sequential design. At two public clinics in Kiambu County, Kenya, clients ≥ 18 years initiating PrEP were given the option to refill PrEP at the clinic where they initiated for free or at one of three nearby private pharmacies for 300 Kenyan Shillings (~ $3 US Dollars). The providers at these pharmacies (pharmacists and pharmaceutical technologists) were trained in PrEP service delivery using a prescribing checklist and provider-assisted HIV self-testing, both with remote clinician oversight. Clients were followed up to seven months, with scheduled refill visits at one, four, and seven months. The primary outcomes were selection of pharmacy-based PrEP refills and PrEP continuation. Following pilot completion, 15 in-depth interviews (IDIs) with clients who refilled PrEP were completed. We used descriptive statistics and thematic analysis to assess study outcomes. RESULTS: From November 2020 to November 2021, 125 PrEP clients were screened and 106 enrolled. The majority (59%, 63/106) of clients were women and the median age was 31 years (IQR 26-38 years). Over 292 client-months of follow-up, 41 clients (39%) refilled PrEP; only three (3%) at a participating pharmacy. All clients who completed IDIs refilled PrEP at clinics. The reasons why clients did not refill PrEP at pharmacies included: a preference for clinic-delivered PrEP services (i.e., pre-existing relationships, access to other services), concerns about pharmacy-delivered PrEP services (i.e., mistrust, lower quality care, costs), and lack of knowledge of this refill location. CONCLUSIONS: These findings suggest that clients who initiate PrEP at public clinics in Kenya may have already overcome barriers to clinic-delivered PrEP services and prefer PrEP access there. To reach new populations that could benefit from PrEP, a stand-alone model of pharmacy-delivered PrEP services may be needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04558554 [registered: June 5, 2020].

Longitudinal assessment of bacterial vaginosis prior to and during incident pregnancy: an observational study in Kenyan adolescent girls and young women.

OBJECTIVE: To determine bacterial vaginosis (BV) status at multiple time points among adolescent girls and young women (AGYW) and assess the impact of pregnancy on their BV status. DESIGN: Longitudinal cohort study. SETTING: Thika, Kenya. PARTICIPANTS: AGYW aged 16-20 years enrolled prior to first sex or reporting only a single lifetime partner. MAIN OUTCOME MEASURES: The primary outcome was relative risk (RR) of BV during pregnancy compared with before pregnancy by analysing longitudinal trends in BV over time. BV risk was estimated using Poisson regression models. RESULTS: A total of 121 AGYW became pregnant in the parent cohort and had BV results before, during or after pregnancy. Point prevalence of BV was 11.0% at visits >12 months pre-pregnancy, 13.0% at 3-12 months pre-pregnancy, 22.1% at <3 months pre-pregnancy and 13.4% during pregnancy. Compared with visits during pregnancy, RR of BV was 1.65 (95% CI: 1.00 to 2.71; p=0.05) at visits <3 months pre-pregnancy, 0.97 (95% CI: 0.62 to 1.52; p=0.90) at visits 3-12 months pre-pregnancy and 0.82 (95% CI: 0.44 to 1.53; p=0.53) at visits 12 months pre-pregnancy. An adjusted analysis including age, income, residence, date of first sex, recent sexual activity and positive sexually transmitted infection test resulted in small changes in risk estimates, with adjusted RR of BV of 1.66 (95% CI: 1.04 to 2.67; p=0.04) at visits <3 months pre-pregnancy compared with visits during pregnancy. CONCLUSIONS: BV risk during pregnancy was lower than during the immediate pre-pregnancy period. Hormonal changes in pregnancy may reduce BV.

Higher rates of mental health screening of adolescents recorded after provider training using simulated patients in a Kenyan HIV clinic: results of a pilot study.

Background: Kenyan adolescent girls and young women (AGYW) experience a dual burden of HIV and common mental disorders (CMD). HIV clinics are a key entry point for AGYW in need of integrated CMD and HIV care; however, rates of screening and referral for CMDs are low. Our objective was to test an evidence-based provider training strategy, simulated patient encounters (SPEs), on CMD service delivery for AGYW in a Kenyan HIV clinic. Methods: This pilot study was conducted in a public HIV clinic in Thika, Kenya from January to November 2021. The simulated patient encounter (SPE) implementation strategy included case script development from prior qualitative work, patient actor training, and a three-day SPE training including four standardized mock clinical encounters followed by quantitative surveys assessing provider competencies for each encounter. We abstracted medical record data related to HIV and CMDs such as HIV status, reason for visit, CMD screening test performed, and counselling or referral information. We conducted an interrupted time series analysis using abstracted HIV and CMD screening rates from AGYW ages 16-25 years visiting the clinic 7 months before and 3 months after SPE training. We used generalized linear models to assess changes in CMD screening rates after training. Results: A total of 10 providers participated in the training. Competency ratings improved across four mock encounters (mean score from 8.1 to 13.7) between first and fourth encounters. We abstracted all medical records (n = 1,154) including from 888 (76%) AGYW seeking HIV treatment, 243 (21%) seeking prevention services, and 34 (3%) seeking other services. CMD screening rates increased immediately following training from 8 to 21% [relative risk (RR) = 2.57, 95% confidence interval (CI) = 1.34-4.90, p < 0.01]. The 3 months following the SPE training resulted in an 11% relative increase in CMD screening proportion compared to the 7 months pre-SPE (RR: 1.11, 95% CI: 1.04-1.17, p < 0.01). Finally, 1% of all pre-SPE screens resulted in referral versus 5% of post-SPE screens (p = 0.07). Conclusion: The SPE model is a promising implementation strategy for improving HIV provider competencies and CMD service delivery for adolescents in HIV clinics. Future research is needed to explore effects on adolescent clinical outcomes in larger trials.

Experiences and attitudes towards Menstrual Suppression among Women with Bacterial vaginosis Randomised to Continuous Use of NuvaRing in Kenya.

Background: The contraceptive vaginal ring (NuvaRing), one of the Multipurpose Prevention Technologies (MPT) products, is effective in preventing unintended pregnancies and may contribute to reducing the frequency of Bacterial Vaginosis (BV), which is a risk factor for HIV acquisition, transmission, and shedding among women. NuvaRing may cause irregular menstruation, including menstrual suppression, which may influence women's decision on product choice, use, and acceptability. In this prospective cohort study, we assessed women's experiences with menstruation suppression following continued NuvaRing use. Methods: A total of 18 in-depth interviews were conducted using a semi-structured interview guide among purposively selected women with BV in Thika, Kenya, aged 18-40 years, who used NuvaRing continuously. All women received counseling on possibility of menstrual suppression following continuous NuvaRing use. Audio recordings were transcribed verbatim and thematically analyzed. Results: Participants who expected and were aware that menstrual suppression was a possible side effect of Nuvaring accepted its benefits, and expressed acceptance and desire to continue using NuvaRing. Participants who had not anticipated menstrual suppression expressed anxiety and fear, with some expressing desire to continue using NuvaRing but worried about unintended negative consequences. The ability to perform daily activities uninterrupted, reduced expenses on sanitary supplies, enhanced sexual pleasure and relationships, and absence of menstrual pain were benefits of menstrual suppression. Although all participants received counseling on menstrual suppression, some expressed anxiety over the possibility of unintended pregnancy. As a result, they frequented medical facilities for health check-ups and pregnancy tests, and some used combined oral contraceptives to induce menses. Conclusion: Understanding perceptions regarding menstrual suppression is crucial in offering targeted and comprehensive counseling to improve women's understanding of menstruation suppression to influence acceptance and use of NuvaRing. Additionally, improved male involvement in reproductive health concerns and women's autonomy in discussing reproductive health issues with partners is essential.

"I was just concerned about getting pregnant": Attitudes toward pregnancy and contraceptive use among adolescent girls and young women in Thika, Kenya.

BACKGROUND: Adolescent girls and young women (AGYW) have a high incidence of unplanned pregnancies, especially in low-resource settings. AGYW assess the overlapping risks of pregnancy, contraception, and STIs as they navigate relationships. Few studies have examined how AGYW consider the comparative risks of their decisions around sexual and reproductive health in this context or how risk perception influences contraceptive use. METHODS: Twenty in-depth interviews (IDIs) and 5 focus group discussions (FGDs) were conducted with a subset of sexually active AGYW enrolled in the Girls Health Study (GHS), a longitudinal cohort study in Thika, Kenya, assessing HSV-2 incidence in a cohort of AGYW aged 16-20. Interview questions were focused on perspectives and decision-making around sexual and reproductive health. Interviews were conducted in both English and Kiswahili, transcribed, and coded using inductive and deductive approaches to identify emerging themes. RESULTS: Misconceptions about long-acting reversible contraceptives (LARCs), injectables, and daily oral contraceptive pills strongly disincentivized their use among AGYW. Participants described pregnancy as undesirable, and AGYW reported prioritizing contraceptive methods that were effective and reliable in pregnancy prevention, even if not effective in preventing STI/HIV infection. Participants reported that AGYW relied heavily on emergency contraceptive (EC) pills for pregnancy prevention. CONCLUSIONS: Though the goal of avoiding unintended pregnancy was common, this did not suffice to motivate the uptake of long-term contraceptives among AGYWs. Given the convenience, cost-effectiveness, and lower perceived risk of side effects, EC pills were more likely to be accepted as a form of contraception. Understanding the reasons for AGYW's acceptance of certain contraceptive methods over others can help future interventions better target communication and counseling about contraception and influence key drivers of AGYW behavior and decision-making around sexual and reproductive health.

Effect of 6-Month HIV Preexposure Prophylaxis Dispensing With Interim Self-testing on Preexposure Prophylaxis Continuation at 12 Months: A Randomized Noninferiority Trial.

Importance: Daily oral HIV preexposure prophylaxis (PrEP) delivery requires quarterly clinic visits for HIV testing and drug refilling that are costly to health systems and clients. Objective: To evaluate whether 6-month PrEP dispensing supported with interim HIV self-testing (HIVST) results in noninferior PrEP continuation outcomes at 12 months compared with standard quarterly clinic visits. Design, Setting, and Participants: This randomized noninferiority trial was conducted from May 2018 to May 2021 with 12 months of follow-up among PrEP clients aged 18 years or older who were returning for their first refill at a research clinic in Kiambu County, Kenya. Intervention: Participants were randomized 2:1 to (1) 6-month PrEP dispensing with semiannual clinic visits and interim HIVST at 3 months or (2) standard-of-care (SOC) PrEP delivery with 3-month dispensing, quarterly clinic visits, and clinic-based HIV testing. Main Outcomes and Measures: Prespecified 12-month outcomes included recent HIV testing (any in past 6 months), PrEP refilling, and PrEP adherence (detectable tenofovir-diphosphate concentrations in dried blood spots). Binomial regression models were used to estimate risk differences (RDs), and a 1-sided 95% CI lower bound (LB) of -10% or greater was interpreted as noninferior. Results: A total of 495 participants were enrolled, with 329 enrolled in the intervention group and 166 enrolled in the SOC group; 330 (66.7%) were women, 295 (59.6%) were in serodifferent relationships, and the median (IQR) age was 33 (27-40) years. At 12 months, 241 individuals in the intervention group (73.3%) and 120 in the SOC group (72.3%) returned to clinic. In the intervention group, recent HIV testing was noninferior (230 individuals [69.9%]) compared with the SOC group (116 [69.9%]; RD, -0.33%, 95% CI LB, -7.44%). PrEP refilling in the intervention group (196 [59.6%]) was inconclusive compared with the SOC group (104 [62.7%]; RD, -3.25%; 95% CI LB, -10.84%), and PrEP adherence was noninferior in the intervention group (151 [45.9%]) compared with the SOC group (70 [42.2%]; RD, 4.96%; 95% CI LB, -2.46%). No HIV seroconversions were observed over the follow-up period. Conclusions and Relevance: In this analysis of secondary trial end points at 1 year, semiannual PrEP dispensing with interim HIVST resulted in noninferior recent HIV testing and PrEP adherence compared with SOC quarterly PrEP dispensing. This novel model has the potential to optimize PrEP delivery. Trial Registration: ClinicalTrials.gov Identifier: NCT03593629.

Low prevalence of bacterial vaginosis in Kenyan adolescent girls and rapid incidence after first sex.

BACKGROUND: Bacterial vaginosis is a risk factor for sexually transmitted infections, including HIV. Adult African women have a high prevalence of bacterial vaginosis, but it is not known when first bacterial vaginosis occurs. OBJECTIVE: This study aimed to describe bacterial vaginosis in younger African women, before and after first sex, and to determine the incidence of bacterial vaginosis and significant correlates of bacterial vaginosis incidence and recurrence. STUDY DESIGN: In a prospective observational cohort study enrolling adolescents with limited sexual experience, young women aged 16 to 21 years were recruited in Thika, Kenya. Eligible participants were HIV and herpes simplex virus 2 seronegative and reported 0 or 1 lifetime sexual partner. The Nugent score was determined at quarterly visits from vaginal Gram stains. The trends in bacterial vaginosis were described over time; hazard ratios were calculated using Cox regression, and relative risk of bacterial vaginosis was estimated using generalized estimating equations and Poisson regression. RESULTS: A total of 400 participants with a median age of 18.6 years (interquartile range, 16-21) were enrolled. Of note, 322 participants (80.5%) reported no history of sex, whereas 78 participants (19.5%) reported sex with 1 partner. At enrollment, bacterial vaginosis (Nugent score of ≥7) was uncommon (21/375 [5.6%]). Overall, 144 participants had bacterial vaginosis at least once, for an incidence rate of 16.5 cases per 100 person-years. Before first sex, bacterial vaginosis was present at 2.8% of visits, compared with 13.7% of visits after first sex. An adjusted model of bacterial vaginosis incidence observed that first sex was associated with more than a 2-fold increased bacterial vaginosis risk (adjusted hazard ratio, 2.44; 95% confidence interval, 1.25-4.76; P=.009). Chlamydia diagnosis (adjusted hazard ratio, 1.73; 95% confidence interval, 1.1-2.8; P=.02), and herpes simplex virus 2 seropositivity (adjusted hazard ratio, 2.88; 95% confidence interval, 1.17-7.09; P=.021) were both associated with incident bacterial vaginosis. A multivariate generalized estimating equation model, including all episodes of bacterial vaginosis, demonstrated risk factors, including first sex, sexually transmitted infections, urban residence, recent sex, and no income; the most important risk factor was first sex (adjusted relative risk, 1.92; 95% confidence interval, 1.12-3.31; P=.018). The probability of bacterial vaginosis increased with each subsequent episode; mean Nugent scores increased after each bacterial vaginosis episode. CONCLUSION: Using detailed longitudinal observation, this study found that Kenyan adolescents have almost no bacterial vaginosis before first sex and that initiation of sexual activity was the strongest risk factor for both prevalent bacterial vaginosis and incident bacterial vaginosis.

Assessing preferences for HIV pre-exposure prophylaxis (PrEP) delivery services via online pharmacies in Kenya: protocol for a discrete choice experiment.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV acquisition, but coverage remains low in high prevalence settings. Initiating and continuing PrEP via online pharmacies is a promising strategy to expand PrEP uptake but little is known about user preferences for this strategy. We describe methods for a discrete choice experiment (DCE) to assess preferences for PrEP delivery from an online pharmacy. METHODS AND ANALYSIS: This cross-sectional study is conducted in Nairobi, Kenya, in partnership with MYDAWA, a private online pharmacy retailer with a planned sample size of >400 participants. Eligibility criteria are: ≥18 years, not known HIV-positive and interested in PrEP. Initial DCE attributes and levels were developed via literature review and stakeholder meetings. We conducted cognitive interviews to assess participant understanding of the DCE survey and refined the design. The final DCE used a D-efficient design and contained four attributes: PrEP eligibility assessment, HIV test type, clinical consultation type and user support options. Participants are presented with eight scenarios consisting of two hypothetical PrEP delivery services. The survey was piloted among 20 participants before being advertised on the MYDAWA website on pages displaying products indicating HIV risk (eg, HIV self-test kits). Interested participants call a study number and those screened eligible meet a research assistant in a convenient location to complete the survey. The DCE will be analysed using a conditional logit model to assess average preferences and mixed logit and latent class models to evaluate preference heterogeneity among subgroups. ETHICS AND DISSEMINATION: This study was approved by the University of Washington Human Research Ethics Committee (STUDY00014011), the Kenya Medical Research Institute, Nairobi County (EOP/NMS/HS/128) and the Scientific and Ethics Review Unit in Kenya (KEMRI/RES/7/3/1). Participation in the DCE is voluntary and subject to completion of an electronic informed consent. Findings will be shared at international conferences and peer-reviewed publications, and via engagement meetings with stakeholders.

Online HIV prophylaxis delivery: Protocol for the ePrEP Kenya pilot study.

Background: Online pharmacies in Kenya provide sexual and reproductive health products (e.g., HIV self-testing, contraception) and could be leveraged to increase the reach of HIV pre-exposure and post-exposure prophylaxis (PrEP/PEP) to populations who do not frequently attend health facilities. To date, evidence is limited for operationalizing online PrEP/PEP delivery and the type of populations reached with this differential service delivery model. Methods: The ePrEP Kenya Pilot will deliver daily oral PrEP and PEP via MYDAWA, a private online pharmacy retailer, to clients in Nairobi for 18 months. Potential clients will obtain information about PrEP/PEP on MYDAWA's sexual wellness page and self-screen for HIV risk. Individuals ≥18 years, identified as at HIV risk, and willing to pay for a blood-based HIV self-test and PrEP/PEP delivery will be eligible for enrollment. To continue with online PrEP/PEP initiation, eligible clients will purchase a blood-based HIV self-test for 250 KES (~USD 2) [delivered to their setting of choice for 99 KES (~USD 1)], upload an image of their self-test result, and attend a telemedicine visit with a MYDAWA provider. During the telemedicine visit, providers will screen clients for PrEP/PEP eligibility, including clinical concerns (e.g., kidney disease), discuss self-test results, and complete counseling on PrEP/PEP use and safety. Providers will refer clients who self-test HIV positive or report any existing medical conditions to the appropriate services at healthcare facilities that meet their preferences. Eligible clients will be prescribed PrEP (30-day PrEP supply at initiation; 90-day PrEP supply at follow-up visits) or PEP (28-day supply) for free and have it delivered for 99 KES (~USD 1). We will measure PrEP and PEP initiation among eligible clients, PEP-to-PrEP transition, PrEP continuation, and implementation outcomes (e.g., feasibility, acceptability, and costs). Discussion: Establishing pathways to increase PrEP and PEP access is crucial to help curb new HIV infections in settings with high HIV prevalence. The findings from this study will provide evidence on the implementation of online pharmacy PrEP and PEP service delivery that can help inform guidelines in Kenya and similar settings.

Adolescent Girls and Young Women in Kenya Demonstrate Rapid STI Incidence Following First Sex: Data From a Longitudinal Cohort.

PURPOSE: Adolescent girls and young women (AGYW) are disproportionately affected by STIs. Observation of life course events can describe behavioral and biological factors associated with STI risk. METHODS: Sexually inexperienced AGYW aged 16-20 years in Kenya were followed for five years. Quarterly visits assessed for C. trachomatis (CT), N. gonorrhea (GC), and T. vaginalis (TV), bacterial vaginosis (BV), HSV-2, and HIV. Sexual activity was self-reported but amended if incongruent with results from STI, pregnancy, or any other testing. Cox regression and Generalized Estimating Equation models were used to determine hazard ratios (HRs) and relative risks (RRs) of STI. RESULTS: During follow-up, 293 of 400 participants reported sex, 163 AGYW experienced an STI, and 72 participants had multiple STIs. Among 163 participants that experienced an STI, there were a total of 259 visits where STIs were detected, 78% (n = 201) of which included CT. Cox regression found participants with BV had over two-fold higher risk of first STI acquisition (adjusted hazard ratio (aHR): 2.35; 95% confidence interval (CI) 1.43-3.88; p = .001). Increased risk for first STI episode was associated with a new partner (aHR: 3.16; 95% CI 1.59-6.28; p = .001). AGYW who did not disclose sexual activity had the highest risk (aHR: 3.60; 95% CI 1.93-6.70; p < .001). Condom use was low, with 21% reporting condom use with sex. GEE analysis of all STIs including incident, prevalent, and recurrent, confirmed these risk factors. DISCUSSION: During the critical years after first sex, AGYW with BV, new sexual partners, and those who did not disclose sexual activity were at highest risk for STI events, especially CT.

Starting to have sexual intercourse is associated with increases in cervicovaginal immune mediators in young women: a prospective study and meta-analysis.

Background: Adolescent girls and young women (AGYW) are at high risk of sexually transmitted infections (STIs). It is unknown whether beginning to have sexual intercourse results in changes to immune mediators in the cervicovaginal tract that contribute to this risk. Methods: We collected cervicovaginal lavages from Kenyan AGYW in the months before and after first penile-vaginal sexual intercourse and measured the concentrations of 20 immune mediators. We compared concentrations pre- and post-first sex using mixed effect models. We additionally performed a systematic review to identify similar studies and combined them with our results by meta-analysis of individual participant data. Results: We included 180 samples from 95 AGYW, with 44% providing only pre-first sex samples, 35% matched pre and post, and 21% only post. We consistently detected 19/20 immune mediators, all of which increased post-first sex (p<0.05 for 13/19; Holm-Bonferroni-adjusted p<0.05 for IL-1ß, IL-2, and CXCL8). Effects remained similar after excluding samples with STIs and high Nugent scores. Concentrations increased cumulatively over time after date of first sex, with an estimated doubling time of about 5 months.Our systematic review identified two eligible studies, one of 93 Belgian participants, and the other of 18 American participants. Nine immune mediators were measured in at least two-thirds of studies. Meta-analysis confirmed higher levels post-first sex for 8/9 immune mediators (p<0.05 for six mediators, most prominently IL-1α, IL-1ß, and CXCL8). Conclusions: Cervicovaginal immune mediator concentrations were higher in women who reported that they started sexual activity. Results were consistent across three studies conducted on three different continents. Funding: This research was funded by R01 HD091996-01 (ACR), by P01 AI 030731-25 (Project 1) (AW), R01 AI116292 (FH), R03 AI154366 (FH) and by the Center for AIDS Research (CFAR) of the University of Washington/Fred Hutchinson Cancer Research Center AI027757.

Low-frequency pre-treatment HIV drug resistance: effects on 2-year outcome of first-line efavirenz-based antiretroviral therapy.

OBJECTIVES: Assess the impact of pre-treatment high-frequency and low-frequency drug-resistant HIV variants on long-term outcomes of first-line efavirenz-based antiretroviral therapy (ART). DESIGN: Prospective observational study. METHODS: Participants' pre-treatment plasma RNA had two sections of HIV pol encoding reverse transcriptase sequenced (Illumina, MiSeq) using unique molecular identifiers to detect wild-type (pre-treatment drug-resistant variants less than 1% of viral quasispecies), low-frequency (1-9%) or high-frequency drug-resistant variants (10-100%). Associations between pre-treatment drug resistance and virologic outcomes over 24 months of efavirenz-based ART were assessed for the number and frequency of mutations by drug class and other resistance parameters. RESULTS: Virologic failure was detected in 30 of 352 (9%) and pre-treatment drug-resistant variants were detected in the viral quasispecies of 31 of 352 (9%) participants prescribed efavirenz-based ART. Survival analyses revealed statistically significant associations between pre-treatment drug resistance at low (P < 0.0001) and high (P < 0.001) frequencies, at oligonucleotide ligation assay (OLA) (P < 0.00001) and non-OLA (P < 0.01) codons, to a single-antiretroviral class (P < 0.00001), and a shorter time to virologic failure of efavirenz-based ART. Regression analyses detected independent effects across resistance categories, including both low-frequency (P < 0.01) and high-frequency (P < 0.001) drug-resistant variants. CONCLUSION: We observed that pre-treatment HIV drug resistance detected at low frequencies increased the risk of virologic failure over 24 months of efavirenz-based ART, but that most failures, regardless of drug-resistant variants' frequencies, were detected within a year of ART initiation. These observations suggest that when efavirenz-based ART is prescribed, screening for pre-treatment drug resistance by an assay capable of detecting low-frequency variants, including OLA, may guide clinicians to prescribe more effective ART.

Efficiency of 6-month PrEP dispensing with HIV self-testing in Kenya: an open-label, randomised, non-inferiority, implementation trial.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective and is being implemented at scale at health clinics throughout sub-Saharan Africa. However, barriers to clinic-based PrEP delivery remain. We aimed to establish the efficiency of semiannual PrEP clinic visits supplemented with interim home-based HIV self-testing (HIVST) versus standard of care for HIV testing, drug refilling, and adherence among PrEP users. METHODS: This was a randomised, open-label, non-inferiority trial done at the Partners in Health and Research Development clinic in Thika, Kenya. Eligible participants were HIV-negative adults (≥18 years) at risk of acquiring HIV who had started PrEP at least 1 month before enrolment. Participants were randomly assigned (1:1:1) to 6-month PrEP dispensing plus interim blood-based HIVST (with biannual clinic visits), 6-month PrEP dispensing plus interim oral fluid-based HIVST (with biannual clinic visits), or standard of care PrEP delivery (3-month PrEP dispensing with quarterly clinic visits). The three coprimary outcomes, measured at 6 months, were HIV testing (any testing between enrolment and the 6-month visit), PrEP refilling, and PrEP adherence (detectable tenofovir diphosphate concentration in dried blood spots). All analyses were done according to the intention-to-treat principle. We used binomial regression models to estimate risk differences and one-sided 95% CIs. 6-month PrEP dispensing was considered non-inferior to standard of care if the lower limit bound of the one-sided 95% CI was greater than or equal to -10%. This study is registered with ClinicalTrials.gov, NCT03593629. FINDINGS: Between May 28, 2018, and Feb 24, 2020, 495 participants were enrolled: 165 men and 130 women in HIV serodifferent couples and 200 singly enrolled women. 166 participants were randomly assigned to the standard of care group, 163 to the 6-month PrEP dispensing plus oral-fluid HIVST group, and 166 to the 6-month PrEP dispensing plus blood-based HIVST group. At 6 months, 274 (83%) of 329 participants in the combined 6-month PrEP dispensing group had tested for HIV compared with 140 (84%) of 166 participants in the standard of care group (risk difference -1·15%, 95% CI lower bound -6·89). Among participants in the combined 6-month PrEP dispensing group, 257 (78%) participants refilled PrEP compared with 134 (81%) participants in the standard of care group (-2·60%, -8·88), and 200 (61%) participants were adherent to PrEP compared with 95 (57%) participants in the standard of care group (2·37%, -5·05). No participants acquired HIV during the study. INTERPRETATION: 6-month PrEP dispensing with HIVST for interim testing reduced the number of PrEP clinic visits in half without compromising HIV testing, retention, or adherence. FUNDING: US National Institute of Mental Health.

Examining the Use of HIV Self-Testing to Support PrEP Delivery: a Systematic Literature Review.

PURPOSE OF REVIEW: HIV self-testing (HIVST) has the potential to expand access to and uptake of HIV pre-exposure prophylaxis (PrEP) delivery. We conducted a systematic literature review to understand the evidence on HIVST use for PrEP delivery. RECENT FINDINGS: After screening 1055 records, we included eight: three randomized trials and five values and preferences studies. None measured PrEP initiation. Most studies occurred in Sub-Saharan Africa (7/8) and included different populations. One trial found that HIVST use between quarterly clinic visits as part of an adherence package with biofeedback slightly increased adherence; the other two trials found that HIVST use between or in lieu of quarterly clinic visits had no significant or non-inferior effects on adherence. HIVST to support PrEP delivery was acceptable, feasible, and preferred. HIVST use for PrEP continuation largely resulted in similar outcomes to standard-of-care delivery and was perceived acceptable and feasible. Further research is needed to optimize HIVST use within PrEP programming.

Targeted Implementation of HIV Self-Testing Increases Testing Uptake Among Partners of Index Persons Known to Have HIV in Kenya.

BACKGROUND: Partners of persons living with HIV (PLHIV) are at a high risk of HIV acquisition, particularly if PLHIV are newly diagnosed or not virally suppressed. A focused partner HIV testing strategy could stimulate efficient identification of persons for pre-exposure prophylaxis (PrEP) or antiretroviral therapy (ART) programs. METHODS: We sequentially implemented 2 partner testing strategies at 2 Kenyan HIV clinics: (1) an invitation for clinic-based testing and (2) HIV self-testing (HIVST) kits distribution to index PLHIV. For each testing strategy, we enrolled approximately 150 consecutive index PLHIV with partners of unknown HIV status, not on ART, <6 months on ART, or who had detectable viral load. We compared partner engagement, testing uptake, and linkage for ART or PrEP between the 2 testing strategies. RESULTS: Of 313 index PLHIV enrolled (160 in invitation, 153 in HIVST), the median age was 32 years (interquartile range 26-40) and 76% were women. Overall, 73% of participants (229) discussed HIV testing with their partners: 76% (121) in the invitation strategy vs 71% (108) in the HIVST strategy [adjusted odds ratio (adjOR): 0.54, 95% confidence interval (CI): 0.31 to 0.97]. Overall, 52% (79) partners in the HIVST strategy tested vs 38% (60) in the invitation strategy (adjOR: 1.78, 95% CI: 1.13 to 2.78). Among partners engaged, 73% in the HIVST strategy vs 50% in the invitation tested (adjOR: 2.68, 95% CI: 1.46 to 4.96); 25% (35/139) tested positive for HIV. Eighty-nine percentage (31/35) who tested positive initiated treatment, but only 21% (20/93) who tested negative initiated PrEP. CONCLUSIONS: HIVST kit distribution to PLHIV with partners of unknown HIV status effectively increased partner testing. Only one-fifth of partners who tested negative initiated PrEP-thus innovations to link to prevention services are urgently needed.

Understanding Pre-Exposure Prophylaxis Adherence in Young Women in Kenya.

OBJECTIVE: To present detailed analyses of long-term pre-exposure prophylaxis (PrEP) use and associated behaviors and perceptions among young Kenyan women. DESIGN: Prospective, observational cohort. METHODS: The Monitoring PrEP among Young Adult women Study involved 18 to 24-year-old women at high HIV risk initiating PrEP in Kisumu and Thika, Kenya. Visits for PrEP counseling and dispensing, HIV testing, and socio-behavioral data collection occurred at Month 1 and quarterly for 2 years. PrEP adherence was measured with pharmacy refill and real-time electronic monitoring, plus tenofovir diphosphate levels in 15% of participants. HIV risk behavior and perception were assessed by self-report in weekly short message service surveys from Months 6-24. Predictors of adherence were assessed with multivariable logistic regression analysis. RESULTS: Three hundred forty-eight women (median age 21, VOICE risk score 7) were followed for 617 person-years. Pharmacy refills steadily declined from 100% (Month 0-1) to 54% (Months 22-24). Average electronically monitored adherence similarly declined from 65% (Month 0-1) to 15% (Months 22-24). Electronically monitored adherence had moderately high concordance with tenofovir diphosphate levels (67%). High average adherence (5+ doses/week) was seen at 385/1898 (20%) participant-visits and associated with low baseline VOICE risk score, >1 current sexual partner, ≤1-hour travel time to clinic, and the Kisumu site. short message service-reported behavior and risk perception were not associated with adherence. Four women acquired HIV (incidence 0.7/100 person-years). CONCLUSIONS: PrEP adherence was modest and declined over time. HIV risk was inconsistently associated with adherence; clinic access and site-level factors were also relevant. Relatively low HIV incidence suggests participants may have achieved protection through multiple strategies.

HIV risk and pre-exposure prophylaxis interest among women seeking post-abortion care in Kenya: a cross-sectional study.

INTRODUCTION: Post-abortion clinics located in regions with high HIV burden may ideal locations to integrate counselling and delivery of HIV pre-exposure prophylaxis (PrEP), aligning with normative goals for integrated delivery of HIV and reproductive health care. The objective of this study was to gauge the degree to which Kenyan women seeking care for a pregnancy loss, including induced abortion, are at risk for HIV and whether women would welcome an introduction to PrEP prior to discharge from post-abortion care. METHODS: We conducted a mixed-methods study from August 2019 to February 2020 with women ages 15 to 30 recruited sequentially as they were accessing post-abortion care at public and private facilities in Thika and Kisumu, Kenya. Data collection was through a cross-sectional survey and laboratory testing for common sexually transmitted infections (N = 200), and in-depth interviews (N = 30). Descriptive statistics summarize PrEP knowledge and referrals and a multivariable log-link binomial model estimated correlates of receiving a referral for PrEP. Qualitative data were analysed using inductive and deductive approaches. RESULTS: Among 200 HIV-negative women (median age 21.0, interquartile range 19.0 to 22.0), the prevalence of Chlamydia trachomatis was 18.2% and Neisseria gonorrhoeae was 2.0%. Half of the women scored ≥5 on a validated tool that would correspond to an expected HIV incidence of 9.5% per year. Approximately half (55.8%) of women were familiar with PrEP prior to the study and 33.3% received a referral from study staff to a clinic offering PrEP. In qualitative interviews, women expressed interest in accessing PrEP from the gynaecology ward that provided post-abortion care but they preferred alternative locations for PrEP refills. CONCLUSIONS: Kenyan women accessing post-abortion care have substantial HIV risk and were favourable about the idea of receiving support to initiate PrEP as part of care offered during post-abortion care. These settings can be integrated into national PrEP programmes as locations providing PrEP referrals and initiation.

Use of fertility awareness methods as a component of safer conception for women in HIV-serodifferent relationships in Kenya.

BACKGROUND: For couples affected by HIV, and serodifferent couples in particular, pregnancy desire is often juxtaposed against the risk of HIV transmission between the couple and the potential neonate leading to thinking about measures to minimize risk of HIV transmission. We assess the use of fertility awareness methods [FAM] and evaluate the drivers of alignment between indicators of fertility and sexual behavior among HIV-serodifferent couples desiring pregnancy. METHODS: HIV-serodifferent couples from Thika, Kenya were enrolled into an open-label pilot evaluation of safer conception strategies. Women responded to daily 7-item short message service [SMS] surveys on FAM and sexual activity. Menstrual cycles were categorized as having condomless sex aligned, not aligned, or partially aligned to the predicted peak fertility. We used binomial logit models with generalized estimating equations to assess alignment between condomless sex during peak fertility days and FAM results. We used Cox proportional hazards to compare pregnancy incidence among months with sex and peak fertility aligned and mis-aligned. RESULTS: A total of 6929 SMS surveys across 252 menstrual cycles of 65 women were included. Reporting "sticky" cervical mucus (adjusted odds ratio [aOR]: 2.25, 95% confidence interval [95% CI]: 1.30, 3.90) and positive ovulation prediction kit [OPK] result (aOR: 2.07, 95% CI: 1.11, 3.86) were associated with increased likelihood of alignment of condomless sex during peak fertility. Pregnancy incidence was statistically similar among periods with sex aligned and not aligned with peak fertility. CONCLUSIONS: Among women engaged in a comprehensive safer conception program, a moderate percentage of women aligned condomless sex and predicted peak fertility days at least once. While FAM, particularly cervical mucus and OPK, are an inexpensive option for couples to consider using as a component of their safer conception strategies, antiretroviral-based strategies remain important to minimize risk.

Effect of SMS reminders on PrEP adherence in young Kenyan women (MPYA study): a randomised controlled trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV acquisition. However, adherence among young women (aged 18-24 years) has been challenging. SMS reminders have been shown to improve adherence to antiretroviral therapy in some contexts, including in combination with real-time adherence monitoring. We aimed to determine the effect of SMS reminders on PrEP adherence among young women in Kenya over a 2-year period. METHODS: The monitoring PrEP among young adult women (MPYA) study was an open label randomised controlled trial involving young adult women at high risk of HIV in Thika and Kisumu, Kenya. Participants were recruited from colleges, vocational institutions, informal settlements, and community-based organisations supporting young women. Women had to be aged 18-24 years and at high risk of HIV acquisition (defined as a VOICE risk score of 5 or higher, or being in a serodiscordant relationship). Study staff randomly assigned participants (1:1) to receive either SMS reminders (SMS reminder group) or no reminders (no SMS reminder group). Study group assignment was known to trial staff but masked to investigators. Reminders were initially sent daily and participants could switch to as-needed reminders (ie, sent only if they missed opening the monitor as expected) after 1 month. Study visits occurred at 1 month, 3 months, and then quarterly (ie, every 3 months). The primary outcome was PrEP adherence over 24 months measured with a real-time electronic monitor and assessed by negative binomial models adjusted for the study site and quarter among participants who collected PrEP. This trial is registered with ClinicalTrials.gov, NCT02915367. FINDINGS: Of 642 women initially approached, 348 eligible women were enrolled between Dec 21, 2016, and Feb 5, 2018. Participants were randomly assigned to either the SMS reminder group (n=173) or the no SMS reminder group (n=175). The median age was 21 years (IQR 19-22) and 228 (66%) of the 348 participants reported condomless sex in the month before baseline. 24 (14%) of the 173 participants assigned to receive daily SMS reminders later opted for as-needed reminders. 69 291 (97%) of 71 791 SMS reminders were sent as planned. Among participants collecting PrEP (thus potentially suggesting a desire for HIV protection), electronically monitored adherence averaged 26·8% over 24 months and was similar by study group (27·0% with SMS, 26·6% without SMS, adjusted incidence rate ratio 1·16 [95% CI 0·93-1·45], p=0·19). There were no serious adverse events related to trial participation; five social harms occurred in each study group, primarily related to PrEP use. INTERPRETATION: SMS reminders were ineffective in promoting PrEP adherence among young Kenyan women. Given the overall low adherence in the trial, additional interventions are needed to support PrEP use in this population. FUNDING: US National Institute of Mental Health.