Exploring adolescent girls and young women's PrEP-user profiles: qualitative insights into differentiated PrEP delivery platform selection and engagement in Cape Town, South Africa.

INTRODUCTION: Adolescent girls and young women (AGYW), a priority population for HIV prevention in Africa, show high interest but difficulty in sustained effective use of pre-exposure prophylaxis (PrEP). With ongoing PrEP scale-up focused on increasing access, it is important to understand what influences AGYW's choice of PrEP delivery platforms. METHODS: The POWER implementation study in Cape Town provided PrEP between 2017 and 2020 to AGYW (16-25 years) from four differentiated delivery platforms: mobile clinic, government facility, courier delivery or community-based youth club. Healthcare providers at government and mobile clinics provided PrEP (initiation and refills) as part of comprehensive, integrated sexual and reproductive health services. Courier and youth club platforms provided light-touch PrEP refill services incorporating rapid HIV self-testing. We conducted in-depth interviews with a purposive sample of AGYW who had ≥3 months of PrEP-use and accessed ≥2 PrEP delivery platforms. The thematic analysis explored AGYW's preferences, decision-making and habits related to PrEP access to inform market segmentation. RESULTS: We interviewed 26 AGYW (median age 20) PrEP-users between November 2020 and March 2021. AGYW PrEP-users reported accessing different services with, 24 accessing mobile clinics, 17 courier delivery, 9 government health facilities and 6 youth clubs for their PrEP refills. Qualitative findings highlighted four potential behavioural profiles. The "Social PrEP-user" preferred PrEP delivery in peer spaces, such as youth clubs or adolescent-friendly mobile clinics, seeking affirmation and social support for continued PrEP use. The "Convenient PrEP-user" favoured PrEP delivery at easily accessible locations, providing quick (courier) or integrated contraception-PrEP refill visits (mobile and government clinic). The "Independent PrEP-user" preferred PrEP delivery that offered control over delivery times that fit into their schedule, such as the courier service. The "Discreet PrEP-user" highly valued privacy regarding their PrEP use (courier delivery) and avoided delivery options where unintentional disclosure was evident (youth club). Comfort with HIV self-testing had minimal influence on PrEP delivery choice. CONCLUSIONS: Market segmentation of AGYW characterizes different types of PrEP-users and has the potential to enhance tailored messaging and campaigns to reach specific segments, with the aim of improving sustained PrEP use and HIV prevention benefits.

A decision support tool has similar high PrEP uptake and increases early PrEP persistence in adolescent girls and young women in South Africa: results from a randomized controlled trial.

INTRODUCTION: African adolescent girls and young women (AGYW) have high rates of HIV acquisition and are a priority population for HIV pre-exposure prophylaxis (PrEP). PrEP implementation has been limited by AGYW's low perceived HIV risk and provider demands. A decision support tool (DST) with information about PrEP could improve clients' risk perception, knowledge about PrEP, informed decision-making and motivation to use PrEP based on their risk, facilitating PrEP delivery in primary healthcare (PHC) clinics. METHODS: We designed MyPrEP, a client-facing DST about PrEP and HIV prevention, with youth-friendly information and images. The impact of the MyPrEP tool was assessed among HIV-negative women aged 18-25 years presenting to a PHC clinic in Johannesburg, South Africa from March 2019 to 2020. AGYW were randomized by day to the DST or a general health website as the control condition. A clinician blinded to DST versus control allocation provided standard of care counselling about PrEP, offered PrEP, administered a questionnaire and conducted sexually transmitted infection testing. The primary outcome was PrEP initiation and the secondary outcome was PrEP persistence at 1 month, determined by pharmacy dispensation records. RESULTS: Of 386 AGYW screened, 353 were randomized (DST n = 172, control n = 181) with a median age of 21 years (interquartile range [IQR] 20, 23) and 56% (199/353) attending the clinic for HIV testing, 46% (164/353) using contraception, 15% (53/353) using condoms consistently and 37% (108/353) with a curable sexually transmitted infection. PrEP was initiated by 97% in the DST group and 94% in the control group (OR 1.79; 95% confidence interval, CI = 0.79-1.53), of whom two-thirds planned to continue PrEP until they decided if they liked PrEP. At 1 month, PrEP persistence was 19% in the DST and 10% in the control group (OR 1.97, 95% CI 1.08-3.69). Ninety-nine percent randomized to the DST reported satisfaction with MyPrEP. CONCLUSIONS: Among AGYW attending a South African PHC clinic, PrEP uptake was >90% with two-fold higher PrEP persistence at 1 month in those randomized to use the MyPrEP DST. Given the need for strategies to support PrEP implementation and improve low PrEP persistence among African AGYW, a PrEP DST warrants further evaluation.

Association of sexual relationship power with PrEP persistence and other sexual health outcomes among adolescent and young women in Kenya and South Africa.

Introduction: Gendered power inequalities impact adolescent girls' and young women's (AGYW) sexual and reproductive health (SRH) outcomes. We investigated the influence of sexual relationship power on AGYW's SRH outcomes, including HIV pre-exposure prophylaxis (PrEP) persistence. Methods: The POWER study in Kisumu, Kenya, and Cape Town and Johannesburg, South Africa provided PrEP to 2,550 AGYW (aged 16-25). AGYW's perceived power in their primary sexual relationship was measured among the first 596 participants enrolled using the Sexual Relationship Power Scale's (SRPS) relationship control sub-scale. Multivariable regression was used to test for (1) key sociodemographic and relationship characteristics associated with relationship power; and (2) the association of relationship power with SRH outcomes including PrEP persistence. Results: In this cohort, the mean SRPS score was 2.56 (0.49), 542 (90.9%) initiated PrEP; 192 (35.4%) persisted with PrEP at 1 month of which 46 (24.0% of 192) persisted at 6 months. SRPS were significantly lower among AGYW who cohabited with their sex partner (-0.14, 95% CI: -0.24 to -0.04, p = 0.01), or had ≥1 sex partner (-0.10, 95% CI: -0.19 to -0.00, p = 0.05). AGYW with lower SRPS were more likely to not know their partner's HIV status (aOR 2.05, 95% CI: 1.27 to 3.33, p < 0.01), but SRPS was not associated with PrEP persistence, STI infection, condom, or hormonal contraception use. Discussion: AGYW's reasons for initiating PrEP and reasons for continuously using PrEP may be different. While low relationship power was associated with perceived HIV vulnerability, AGYW's PrEP persistence may be influenced by more than relationship power.

COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave.

Appropriate interpretation of various diagnostic tests for COVID-19 is critical, yet the association among rapid antigen tests, reverse transcription (RT)-PCR, and viral culture has not been fully defined. To determine whether rapid antigen testing correlates with the presence and quantity of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in ambulatory adults, 626 adult participants were enrolled in a cross-sectional diagnostic study. Each participant had two anterior nasal swabs obtained for rapid antigen and RT-PCR testing and SARS-CoV-2 viral culture. The primary outcomes were the presence and quantification of SARS-CoV-2 growth in VeroE6-ACE2-TMPRSS2 cells in asymptomatic and symptomatic ambulatory adults. In this cross-sectional study of 626 adult outpatients, the sensitivity of a single positive antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with RT-PCR at a cycle threshold CT less than 30 was 66.7% in asymptomatic and 90.7% in symptomatic participants. Among symptomatic participants a with a CT less than 30, a single antigen test had a positive agreement of 90.7% (95% confidence interval [CI], 84.8% to 94.8%). There was 100% negative agreement as all 425 RT-PCR-negative participants had a negative antigen test. A positive antigen test in symptomatic adults with COVID-19 has a strong correlation with replication-competent SARS-CoV-2. Rapid antigen test results may be a suitable proxy for infectiousness. IMPORTANCE Do rapid antigen test results correlate with replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., infectious) virus? In this cross-sectional diagnostic study of 626 adults, the sensitivity of the antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with reverse transcription (RT)-PCR at a CT of less than 30 was 66.7% in asymptomatic participants and 90.7% in symptomatic participants. A positive antigen test may be an appropriate surrogate for identifying replication-competent virus in symptomatic individuals with COVID-19.

Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study.

BACKGROUND: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing. METHODS: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture. RESULTS: Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, virus growth and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with culture positivity (relative risk=7.61, 95% CI: 3.01-19.22), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, the presence of N antigen remained strongly associated (adjusted relative risk=7.66, 95% CI: 3.96-14.82) with culture positivity, regardless of COVID-19 symptoms. CONCLUSIONS: Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset. N antigen testing is a strong predictor of viral infectiousness and may be a more suitable biomarker, rather than absence of symptoms or viral RNA, to discontinue isolation within two weeks from symptom onset.

Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron.

New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population.

Provider perspectives on service delivery modifications to maintain access to HIV pre-exposure prophylaxis during the COVID-19 pandemic: qualitative results from a PrEP implementation project in Kenya.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID-19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID-19 pandemic. METHODS: Since 2017, the Partners Scale-Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May-Aug 2020) and again after some decline in COVID-19 rates (Nov-Jan 2021). We analysed data using inductive memo-writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME). RESULTS: We interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n = 20) and Western (n = 20) Kenya. About half (n = 19) were female, with a median age of 32 (IQR: 29-34) and 2.3 years of experience delivering PrEP (IQR: 2-3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple-month PrEP refills, intensifying phone-based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical-room PrEP dispensing, pre-packing PrEP and task-shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides. CONCLUSIONS: COVID-19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post-pandemic.

Qualitative Analysis Using Social Maps to Explore Young Women's Experiences With Social Support of their Oral PrEP Use in Kenya and South Africa.

ABSTRACT: Daily oral pre-exposure prophylaxis (PrEP) adherence is challenging. We explored African adolescent girls and young women's (AGYW) perceptions of the social influencers of their PrEP use and the social influencers' PrEP knowledge and support (six focus group discussions; 33 South African and Kenyan AGYW) in the Prevention Options for Women Evaluation Research demonstration project. Participants completed a social mapping exercise indicating strength and direction of influence of members in their social networks. Mothers and counselors were identified as positive influencers and most influential by >50% of participants, sex partners were labeled negative influencers or both positive and negative, and best friends were mostly positive influencers. HIV- and PrEP-related stigma were the major reasons influencers were identified as negative. Participants wanted their social networks to be better educated about PrEP by someone other than the AGYW themselves (e.g., clinic staff) and to support their PrEP use. To improve PrEP adherence, community- and peer-based PrEP sensitization and delivery interventions should be evaluated.

Accuracy of 2 Rapid Antigen Tests During 3 Phases of SARS-CoV-2 Variants.

Importance: Variants of SARS-CoV-2 have sequence variations in the viral genome that may alter the accuracy of rapid diagnostic tests. Objective: To assess the analytical and clinical accuracy of 2 rapid diagnostic tests for detecting SARS-CoV-2 during 3 phases of variants. Design, Setting, and Participants: This diagnostic study included participants aged 18 years or older who reported onset of COVID-19-like symptoms within the prior 5 days and were tested at multiple COVID-19 testing locations in King County, Washington, from February 17, 2021, to January 11, 2022, during 3 distinct phases of SARS-CoV-2 infection (pre-Delta, Delta, and Omicron). Interventions: Two anterior nasal swab specimens were collected from each participant-1 for onsite testing by the SCoV-2 Ag Detect Rapid Self-Test and 1 for reverse transcriptase-polymerase chain reaction (RT-PCR) testing. Main Outcomes and Measures: The analytical limit of detection of the 2 rapid diagnostic tests (SCoV-2 Ag Detect Rapid Self-Test and BinaxNOW COVID-19 Ag Card) was assessed using Omicron (B.1.1.529/BA.1), Delta (B.1.617.2), and a wild-type (USA-WA1/2020) variant. Diagnostic sensitivity and specificity of clinical testing for the rapid antigen tests were compared with that of RT-PCR testing. Results: A total of 802 participants were enrolled (mean [SD] age, 37.3 [13.3] years; 467 [58.2%] female), 424 (52.9%) of whom had not received COVID-19 vaccination and presented a median of 2 days (IQR, 1-3 days) from symptom onset. Overall, no significant differences were found in the analytical limit of detection or clinical diagnostic accuracy of rapid antigen testing across SARS-CoV-2 variants. The estimated limit of detection for both rapid nucleocapsid antigen tests was at or below a 50% tissue culture infectious dose of 62.5, and the positive percent agreement of the SCoV-2 Ag Detect Rapid Self-Test ranged from 81.2% (95% CI, 69.5%-89.9%) to 90.7% (95% CI, 77.9%-97.4%) across the 3 phases of variants. The diagnostic sensitivity increased for nasal swabs with a lower cycle threshold by RT-PCR, which correlates with a higher viral load. Conclusions and Relevance: In this diagnostic study, analytical and clinical performance data demonstrated accuracy of 2 rapid antigen tests among adults with COVID-19 symptoms across 3 phases of SARS-CoV-2 variants. The findings suggest that home-based rapid antigen testing programs may be an important intervention to reduce global SARS-CoV-2 transmission.

PrEP use and HIV seroconversion rates in adolescent girls and young women from Kenya and South Africa: the POWER demonstration project.

INTRODUCTION: HIV incidence remains high among African adolescent girls and young women (AGYW). The primary objective of this study is to assess pre-exposure prophylaxis (PrEP) initiation, use, persistence and HIV acquisition among African AGYW offered PrEP in order to inform PrEP scale-up. METHODS: POWER was a prospective implementation science evaluation of PrEP delivery for sexually active HIV-negative AGYW ages 16-25 in family planning clinics in Kisumu, Kenya and youth and primary healthcare clinics in Cape Town and Johannesburg, South Africa. Follow-up visits occurred at month 1 and quarterly for up to 36 months. PrEP users were defined based on the month 1 refill. PrEP persistence through month 6 was assessed using Kaplan-Meier survival analysis among AGYW with a month 1 visit, defining non-persistence as an ≥15 day gap in PrEP availability for daily dosing. PrEP execution was evaluated in a subset with PrEP supply from the prior visit sufficient for daily dosing by measuring blood tenofovir diphosphate (TFV-DP) levels. RESULTS: From June 2017 to September 2020, 2550 AGYW were enrolled (1000 in Kisumu, 787 in Cape Town and 763 in Johannesburg). Median age was 21 years, 66% had a sexual partner of unknown HIV status, and 29% had chlamydia and 10% gonorrhoea. Overall, 2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month. Of AGYW who could reach 6 months of post-PrEP initiation follow-up, 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) had a gap and restarted PrEP. TFV-DP levels indicated that 47% (91/193) took an average of ≥4 doses/week. Sixteen HIV seroconversions were observed (incidence 2.2 per 100 person-years, 95% CI 1.2, 3.5); 13 (81%) seroconverters either did not have PrEP dispensed in the study interval prior to seroconversion or TFV-DP levels indicated <4 doses/week in the prior 6 weeks. CONCLUSIONS: In this study of PrEP integration with primary care and reproductive health services for African AGYW, demand for PrEP was high. Although PrEP use decreased in the first months, an important fraction used PrEP through 6 months.  Strategies are needed to simplify PrEP delivery, support adherence and offer long-acting PrEP options to improve persistence and HIV protection.

Adaptive HIV pre-exposure prophylaxis adherence interventions for young South African women: Study protocol for a sequential multiple assignment randomized trial.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy and is recommended for populations at risk of HIV, including adolescent girls and young women (AGYW) in HIV endemic settings. However, PrEP continuation and high adherence remain challenges to its impact. Existing PrEP adherence interventions can be time- and cost-intensive. Widescale PrEP delivery will require the identification of layered PrEP support strategies for AGYW with diverse prevention needs. We describe the design of a sequential multiple assignment randomized trial (SMART) to evaluate a PrEP adherence support model using scalable, stepped interventions in AGYW in South Africa. METHODS: "PrEP SMART" is a randomized trial in Johannesburg, South Africa, enrolling AGYW who are between 18 and 25 years of age, sexually active, newly initiating PrEP, and have regular access to a mobile phone. Participants are randomized 1:1 to standard-of-care PrEP counseling with either two-way SMS or WhatsApp group adherence support. Adherence is assessed at three months using tenofovir diphosphate (TFV-DP) levels from dried blood spots collected at month 2 to categorize participants as "responders" (TFV-DP ≥500 fmol/punch) or "non-responders" (TFV-DP <500 fmol/punch). AGYW defined as 'non-responders' undergo a secondary 1:1 randomization to either quarterly drug-level feedback counseling or monthly issue-focused counseling, in addition to their first-level intervention. The primary outcome is PrEP adherence at nine months (TFV-DP ≥700 fmol/punch). We will assess the effect of our two initial interventions on TFV-DP levels among responders, assess the effect of our intensified interventions on TFV-DP levels among non-responders, and identify the optimal sequence of adherence interventions through nine months. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04038060. Registered on 30 July 2019.

Implementation strategies for integrating pre-exposure prophylaxis for HIV prevention and family planning services for adolescent girls and young women in Kenya: a qualitative study.

INTRODUCTION: Across sub-Saharan Africa, ministries of health have proposed integrating pre-exposure prophylaxis (PrEP) for HIV prevention into family planning (FP) services to reach adolescent girls and young women (AGYW); however, evidence on effective implementation strategies is still limited. We conducted a qualitative study of integrated PrEP-FP service implementation at two FP clinics in Kisumu, Kenya. METHODS: From June 2017 to May 2020, the Prevention Options for Women Evaluation Research (POWER) study enrolled 1000 sexually active, HIV-negative AGYW age 16 to 25. Actions taken to implement PrEP were captured prospectively in 214 monitoring and evaluation documents and 15 interviews with PrEP implementers. We analysed data using conventional and directed content analysis, with the latter informed by the Consolidated Framework for Implementation Research (CFIR) and the Expert Recommendations for Implementing Change (ERIC) compilation. RESULTS: POWER deployed a variety of implementation strategies to train and educate stakeholders (e.g., having new providers shadow PrEP providers); develop stakeholder interrelationships (e.g., organizing support teams with protected time to reflect on implementation progress and make refinements); provide technical assistance; and change physical infrastructure and workflow. Although these strategies reportedly influenced contextual factors across four of the five CFIR domains, they primarily interacted with contextual factors relevant to inner setting, especially implementation climate and readiness for implementation. Overall, implementing PrEP proved easier and less labor-intensive at a private, youth-friendly clinic than a public FP clinic, largely because the baseline structural characteristics (e.g., space, workflow) and organizational mission of the former were more conducive to offering AGYW-centered care. Nevertheless, adoption of PrEP delivery among non-study staff at both sites was low, likely due to the widespread perception that PrEP was not within their scope of work. CONCLUSIONS: Some FP clinics may be "lower-hanging fruit" than others for PrEP implementation. Approaching PrEP implementation as a behavioral intervention for FP providers may help ensure that providers have the requisite capability, opportunity, and motivation to adopt the clinical innovation. In particular, PrEP implementers should assess the need for implementation strategies that support providers' clinical decision-making, establish worker expectations and accountability, and address workload constraints. TRIAL REGISTRATION: Clinical Trial Number: NCT03490058 .

The Effect of PrEP Use Disclosure on Adherence in a Cohort of Adolescent Girls and Young Women in South Africa.

Effective strategies to support PrEP adherence among adolescent girls and young women (AGYW) are needed. We examined PrEP use disclosure and its effect on adherence among 200 AGYW ages 16-25 initiating PrEP in South Africa to help inform these  strategies. We estimated the relative prevalence of high adherence (intracellular tenofovir-diphosphate concentration ≥ 700 fmol/punch) 3- and 6-months after PrEP initiation among those who disclosed vs. did not disclose their PrEP use, both overall and by age. Most AGYW disclosed to a parent (58%), partner (58%), or friend (81%) by month 6. We did not observe a strong effect of disclosure on adherence overall; however, among younger AGYW (≤ 18 years), those who disclosed to a parent were 6.8 times as likely to have high adherence at month 6 than those who did not (95% CI 1.02, 45.56). More work is needed to understand parents' roles as allies and identify ways peers and partners can motivate PrEP use for AGYW.

A one-stop shop model for improved efficiency of pre-exposure prophylaxis delivery in public clinics in western Kenya: a mixed methods implementation science study.

INTRODUCTION: In public clinics in Kenya, separate, sequential delivery of the component services of pre-exposure prophylaxis (PrEP) (e.g. HIV testing, counselling, and dispensing) creates long wait times that hinder clients' ability and desire to access and continue PrEP. We conducted a mixed methods study in four public clinics in western Kenya to identify strategies for operationalizing a one-stop shop (OSS) model and evaluate whether this model could improve client wait time and care acceptability among clients and providers without negatively impacting uptake or continuation. METHODS: From January 2020 through November 2020, we collected and analysed 47 time-and-motion observations using Mann-Whitney U tests, 29 provider and client interviews, 68 technical assistance reports, and clinic flow maps from intervention clinics. We used controlled interrupted time series (cITS) to compare trends in PrEP initiation and on-time returns from a 12-month pre-intervention period (January-December 2019) to an 8-month post-period (January-November 2020, excluding a 3-month COVID-19 wash-out period) at intervention and control clinics. RESULTS: From the pre- to post-period, median client wait time at intervention clinics dropped significantly from 31 to 6 minutes (p = 0.02), while median provider contact time remained around 23 minutes (p = 0.4). Intervention clinics achieved efficiency gains by moving PrEP delivery to lower volume departments, moving steps closer together (e.g. relocating supplies; cross-training and task-shifting), and differentiating clients based on the subset of services needed. Clients and providers found the OSS model highly acceptable and additionally identified increased privacy, reduced stigma, and higher quality client-provider interactions as benefits of the model. From the pre- to post-period, average monthly initiations at intervention and control clinics increased by 6 and 2.3, respectively, and percent of expected follow-up visits occurring on time decreased by 18% and 26%, respectively; cITS analysis of PrEP initiations (n = 1227) and follow-up visits (n = 2696) revealed no significant difference between intervention and control clinics in terms of trends in PrEP initiation and on-time returns (all p>0.05). CONCLUSIONS: An OSS model significantly improved client wait time and care acceptability without negatively impacting initiations or continuations, thus highlighting opportunities to improve the efficiency of PrEP delivery efficiency and client-centredness.

Integration of pre-exposure prophylaxis services into public HIV care clinics in Kenya: a pragmatic stepped-wedge randomised trial.

BACKGROUND: Successful and sustainable models for HIV pre-exposure prophylaxis (PrEP) delivery in public health systems in Africa are needed. We aimed to evaluate the implementation of PrEP delivery integrated in public HIV care clinics in Kenya. METHODS: As part of Kenya's national PrEP roll-out, we conducted a stepped-wedge cluster-randomised pragmatic trial to catalyse scale-up of PrEP delivery integrated in 25 public HIV care clinics. We selected high-volume clinics in these regions (ie, those with a high number of people living with HIV enrolled in HIV care and treatment). Clinics (each representing a cluster) were stratified by region and randomly assigned to the order in which clinic staff would receive PrEP training and ongoing technical support using numbered opaque balls picked from a bag. There was no masking. PrEP provision was done by clinic staff without additional financial support. Data were abstracted from records of individuals initiating PrEP. The primary outcome was the number of people initiating PrEP per clinic per month comparing intervention to control periods. Other outcomes included PrEP continuation, adherence, and incident HIV infections. This trial is registered with ClinicalTrials.gov, NCT03052010. FINDINGS: After the baseline period, which started in January, 2017, every month two to six HIV care clinics crossed over from control to intervention, until August, 2017, when all clinics were implementing the intervention. Of 4898 individuals initiating PrEP (27 during the control period and 4871 during the intervention period), 2640 (54%) were women, the median age was 31 years (IQR 25-39), and 4092 (84%) reported having a partner living with HIV. The mean monthly number of PrEP initiations per clinic was 0·1 (SD 0·5) before the intervention and 7·5 (2·7) after intervention introduction (rate ratio 23·7, 95% CI 14·2-39·5, p<0·0001). PrEP continuation was 57% at 1 month, 44% at 3 months, and 34% at 6 months, and 12% of those who missed a refill returned later for PrEP re-initiation. Tenofovir diphosphate was detected in 68 (96%) of 71 blood samples collected from a randomly selected subset of participants. Six HIV infections were observed over 2531 person-years of observation (incidence 0·24 cases per 100 person-years), three of which occurred at the first visit after PrEP initiation. INTERPRETATION: We observed high uptake, reasonable continuation with high adherence, frequent PrEP restarts, and low HIV incidence. Integration of PrEP services within public HIV care clinics in Africa is feasible. FUNDING: National Institute of Mental Health and Bill & Melinda Gates Foundation.

Adolescent girls and young women's PrEP-user journey during an implementation science study in South Africa and Kenya.

Successful scale-up of PrEP for HIV prevention in African adolescent girls and young women (AGYW) requires integration of PrEP into young women's everyday lives. We conducted interviews and focus group discussions with 137 AGYW PrEP users aged 16-25 from South Africa and Kenya. Individual and relational enablers and disablers were explored at key moments during their PrEP-user journey from awareness, initiation and early use through persistence, including PrEP pauses, restarts, and discontinuation. PrEP uptake was facilitated when offered as part of an integrated sexual reproductive health service, but hampered by low awareness, stigma and misconceptions about PrEP in the community. Daily pill-taking was challenging for AGYW due to individual, relational and structural factors and PrEP interruptions (intended or unintended) were described as part of AGYW's PrEP-user journey. Disclosure, social support, adolescent-friendly health counseling, and convenient access to PrEP were reported as key enablers for PrEP persistence.

Process evaluation of PrEP implementation in Kenya: adaptation of practices and contextual modifications in public HIV care clinics.

INTRODUCTION: In Africa, oral pre-exposure prophylaxis (PrEP) is largely provided via over-burdened public HIV care clinics. Successfully incorporating PrEP services into these clinics may require adaptations to practices outlined in national implementation guidelines and modifications to routine existing service delivery. We aimed to describe adaptations made by public HIV clinics in Kenya to integrate PrEP delivery into existing services. METHODS: The Partners Scale-Up Project aimed to catalyse integration of PrEP in 25 public HIV care clinics. Between May and December 2018, we conducted qualitative interviews with health providers and documented clinic observations in technical assistance (TA) reports to understand the process of PrEP service integration. We analysed 36 health provider interview transcripts and 25 TA reports to identify clinic-level adaptations to activities outlined in Kenyan Ministry of Health PrEP guidelines and modifications made to existing service delivery practices to successfully incorporate PrEP services. Identified adaptations were reported using the expanded framework for reporting adaptations and modifications (FRAME). RESULTS: All clinics (n = 25) performed HIV testing, HIV risk assessment, PrEP education and adherence counselling as stipulated in the guidelines. Most clinics initiated clients on PrEP without creatinine testing if otherwise healthy. While monthly refill appointments are recommended, a majority of clinics issued PrEP users two to three months of pills at a time. Clinics also implemented practices that had not been specified in the guidelines including incorporating PrEP-related topics into routine health talks, calling clients with missed PrEP appointments, discussing PrEP service delivery in regular staff meetings, 'fast-tracking' PrEP clients and dispensing PrEP in clinic rooms rather than at clinic-based pharmacies. PrEP initiation numbers were highest among clinics that did not require creatinine testing, conducted peer on-the-job PrEP training and those that discussed PrEP delivery in their routine meetings. Above-average continuation was observed among clinics that discussed PrEP in their routine meetings, dispensed PrEP in clinic rooms and offered PrEP at nonregular hours. CONCLUSIONS: Health providers in public HIV care clinics instituted practices and made innovative adaptations to PrEP delivery to reduce barriers for clients and staff. Encouraging clinic level adaptations to national implementation guidelines will facilitate scale-up of PrEP delivery.

Low costs and opportunities for efficiency: a cost analysis of the first year of programmatic PrEP delivery in Kenya's public sector.

BACKGROUND: In 2017, the Kenyan Ministry of Health integrated provision of pre-exposure prophylaxis (PrEP) into public HIV-1 care clinics as a key component of the national HIV-1 prevention strategy. Estimates of the cost of PrEP provision are needed to inform the affordability and cost-effectiveness of PrEP in Kenya. METHODS: We conducted activity-based micro-costing from the payer perspective to estimate both the financial and economic costs of all resources and activities required to provide PrEP in Kenya's public sector. We estimated total and unit costs in 2019 United States dollars from a combination of project expense reports, Ministry of Health training reports, clinic staff interviews, time-and-motion observations, and routinely collected data from PrEP recipient files from 25 high-volume HIV-1 care clinics. RESULTS: In the first year of programmatic PrEP delivery in 25 HIV-1 care clinics, 2,567 persons initiated PrEP and accrued 8,847 total months of PrEP coverage, accounting for 2 % of total outpatient clinic visits. The total financial cost to the Ministry of Health was $91,175, translating to an average of $10.31 per person per month. The majority (69 %) of financial costs were attributable to PrEP medication, followed by administrative supplies (17 %) and training (9 %). Economic costs were higher ($188,584 total; $21.32 per person per month) due to the inclusion of the opportunity cost of staff time re-allocated to provide PrEP and a proportional fraction of facility overhead. The vast majority (88 %) of the annual $80,811 economic cost of personnel time was incurred during activities to recruit new clients (e.g., discussion of PrEP within HIV-1 testing and counselling services), while the remaining 12 % was for activities related to both initiation and maintenance of PrEP provision (e.g., client consultations, technical advising, support groups). CONCLUSIONS: Integration of PrEP provision into existing public health HIV-1 care service delivery platforms resulted in minimal additional staff burden and low incremental costs. Efforts to improve the efficiency of PrEP provision should focus on reductions in the cost of PrEP medication and extra-clinic demand creation and community sensitization to reduce personnel time dedicated to recruitment-related activities. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT03052010 . Retrospectively registered on February 14, 2017.

Cost of pre-exposure prophylaxis delivery in family planning clinics to prevent HIV acquisition among adolescent girls and young women in Kisumu, Kenya.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is increasingly being implemented in sub-Saharan Africa. Adolescent girls and young women (AGYW) in Kenya contribute more than half of all new infections among young people aged 15-24 years, highlighting the need for evidence on the cost of PrEP in real-world implementation to inform the budget impact, cost-effectiveness, and financial sustainability of PrEP programs. METHODS: We estimated the cost of delivering PrEP to AGYW enrolled in a PrEP implementation study in two family planning clinics in Kisumu county, located in western Kenya. We derived total annual costs and the average cost per client-month of PrEP by input type (variable or fixed) and visit type (initiation or follow-up). We estimated all costs as implemented in the study, and under implementation by the Kenyan Ministry of Health (MoH), both at the program volume observed and if the facilities were delivering PrEP at full capacity (scaled-MoH). RESULTS: For the costing period between March 2018 and March 2019, 615 HIV-negative women contributed 1,128 (502 initiation and 626 follow-up) visits. The average cost per client-month of PrEP dispensed per study protocol and per the MoH scenario was $28.92 and $14.52, respectively. If the MoH scaled the program so that facilities could see PrEP clients at capacity, the average cost per client-month of PrEP was $10.88. Medication costs accounted for the largest proportion of the total annual costs (48% in MoH scenario and 65% in the scaled-MoH scenario). CONCLUSIONS: Using data from a PrEP implementation program, we found that the cost per client-month of PrEP dispensed is reduced by 62% if PrEP delivery at the two clinics is scaled up by the MoH. Our findings are valuable for informing local resource allocation and budgetary cost projections for scale-up of PrEP delivery to AGYW. Additionally, previous cost-effectiveness studies have been limited by the use of fixed assumptions of the cost of PrEP per person-month. Our study provides cost estimates from practical data which will better inform cost-effectiveness and budget impact analyses.

Experiences of oral pre-exposure prophylaxis (PrEP) use disclosure among South African adolescent girls and young women and its perceived impact on adherence.

INTRODUCTION: There is limited understanding of how social dynamics impact pre-exposure prophylaxis (PrEP) adherence among adolescent girls and young women (AGYW) in generalized HIV-epidemic settings. We examined experiences of oral PrEP use disclosure to various social groups with the goal of identifying supportive relationships that can be leveraged to promote adherence. METHODS: We used qualitative methods to explore experiences disclosing PrEP use and the perceived impact of disclosure on adherence among 22 South African AGYW (16-25 years) taking daily oral PrEP. Serial in-depth-interviews (IDIs) were conducted 1-, 3-, and 12-months post-PrEP initiation. Respondents also self-reported their disclosures separately for various social groups and adherence was assessed using intracellular tenofovir-diphosphate levels. RESULTS: Qualitative respondents had a median age of 20.5 years and reported disclosing their PrEP use to friends (n = 36 total disclosures), partners, siblings, other family members (n = 24 disclosures each), and parents (n = 19 disclosures). IDI data revealed that parents and partners provided the most support to respondents and a lack of support from these groups was most often perceived as negatively affecting PrEP use. AGYW described difficulties explaining PrEP to their mothers, who believed PrEP was HIV treatment or would lead to HIV infection. Disclosure to household members was notably meaningful for AGYW (both positively and negatively). Respondents reported leveraging supportive relationships for pill reminders. For respondents who perceived a household member would be unsupportive, however, non-disclosure was less feasible and PrEP use was often stigmatized. To avoid stigma, several respondents hid or discontinued PrEP. CONCLUSIONS: While supportive relationships may facilitate PrEP use, disclosure can also lead to stigma. Counselors should support AGYW in disclosing to key people in their social networks and provide AGYW with materials that lend credibility to explanations of PrEP. Community education is necessary to alleviate PrEP-related stigma and facilitate disclosure.