Effect of differentiated direct-to-pharmacy PrEP refill visits supported with client HIV self-testing on clinic visit time and early PrEP continuation.

INTRODUCTION: Delivery of oral pre-exposure prophylaxis (PrEP) is being scaled up in Africa, but clinic-level barriers including lengthy clinic visits may threaten client continuation on PrEP. METHODS: Between January 2020 and January 2022, we conducted a quasi-experimental evaluation of differentiated direct-to-pharmacy PrEP refill visits at four public health HIV clinics in Kenya. Two clinics implemented the intervention package, which included direct-to-pharmacy for PrEP refill, client HIV self-testing (HIVST), client navigator, and pharmacist-led rapid risk assessment and dispensing. Two other clinics with comparable size and client volume served as contemporaneous controls with the usual clinic flow. PrEP continuation was evaluated by visit attendance and pharmacy refill records, and time and motion studies were conducted to determine time spent in the clinics. Dried blood spots were collected to test for tenofovir-diphosphate (TFV-DP) at random visits. We used logistic regression to assess the intervention effect on PrEP continuation and the Wilcoxon rank sum test to assess the effect on clinic time. RESULTS: Overall, 746 clients were enrolled, 366 at control clinics (76 during pre-implementation and 290 during implementation phase), and 380 at direct-to-pharmacy clinics (116 during pre-implementation and 264 during implementation phase). Prior to implementation, the intervention and control clinics were comparable on client characteristics (female: 51% vs. 47%; median age: 33 vs. 33 years) and PrEP continuation (35% vs. 37% at 1 month, and 37% vs. 39% at 3 months). The intervention reduced total time spent at the clinic by 35% (median of 51 minutes at control vs. 33 minutes at intervention clinics; p<0.001), while time spent on HIV testing (20 vs. 20 minutes; p = 0.50) and pharmacy (8 vs. 8 minutes; p = 0.8) was unchanged. PrEP continuation was higher at intervention versus the control clinics: 45% versus 33% at month 1, 34% versus 25% at month 3 and 23% versus 16% at month 6. TFV-DP was detected in 85% (61/72) of samples, similar by the study group (83% vs. 85%). CONCLUSIONS: A client-centred PrEP delivery approach with direct-to-pharmacy PrEP refill visits plus client HIVST significantly reduced clinic visit time by more than one-third and improved PrEP continuation in public health HIV clinics in Kenya.

The Acceptability of Pharmacy-Based HPV Vaccination in Western Kenya among Pharmacy Clients and Providers.

Vaccine coverage for the human papillomavirus (HPV) remains low globally, and differentiated models of vaccine delivery are needed to expand access. Pharmacy-based models of the HPV vaccination may engage women who could benefit. We assessed the acceptability of such a model among pharmacy clients and providers at 20 private pharmacies in Kisumu County, Kenya. In questionnaires, participants (≥18 years) were asked the extent they agreed (5-point scale) with statements that assessed different acceptability component constructs outlined in the Theoretical Framework of Acceptability (TFA). From March to June 2022, 1500 pharmacy clients and 40 providers were enrolled and completed questionnaires. Most clients liked the intervention (TFA: affective attitude; 96%, 1435/1500) and did not think it would be hard to obtain (TFA: burden; 93%, 1399/1500). All providers agreed the intervention could reduce HPV infection (TFA: perceived effectiveness) and felt confident they could deliver it (TFA: self-efficacy). Among the clients who had received or were planning to receive the HPV vaccine in the future, half (50%, 178/358) preferred a pharmacy-based HPV vaccination. In this study, most Kenyan pharmacy clients and providers perceived a pharmacy-delivered HPV vaccination as highly acceptable; however, more research is needed to test the feasibility and effectiveness of this novel vaccine delivery model in Africa.

Measuring the performance of HIV self-testing at private pharmacies in Kenya: a cross-sectional study.

INTRODUCTION: HIV self-testing (HIVST) has the potential to support daily oral pre-exposure prophylaxis (PrEP) delivery in private pharmacies, but many national guidelines have not approved HIVST for PrEP dispensing. In Kenya, pharmacy providers are permitted to deliver HIVST, but often do not have the required certification to deliver rapid diagnostic testing (RDT). We estimated the performance of provider-delivered HIVST compared to RDT, the standard of care for PrEP delivery, at private pharmacies in Kenya to inform decisions on the use of HIVST for PrEP scale-up. METHODS: At 20 pharmacies in Kisumu County, we trained pharmacy providers (pharmacists and pharmaceutical technologists) on blood-based HIVST use and client assistance (if requested). We recruited pharmacy clients purchasing sexual and reproductive health-related products (e.g. condoms) and enrolled those ≥18 years with self-reported behaviours associated with HIV risk. Enrolled clients received HIVST with associated provider counselling, followed by RDT by a certified HIV testing services (HTS) counsellor. Pharmacy providers and clients independently interpreted HIVST results prior to RDT (results interpreted only by the HTS counsellor). We calculated the sensitivity and specificity of pharmacy provider-delivered HIVST compared to HTS counsellor-administered RDT. RESULTS: Between March and June 2022, we screened 1691 clients and enrolled 1500; 64% (954/1500) were female and the median age was 26 years (IQR 22-31). We additionally enrolled 40 providers; 42% (17/40) were pharmacy owners and their median years of experience was 6 (IQR 4-10). The majority (79%, 1190/1500) of clients requested provider assistance with HIVST and providers spent a median of 20 minutes (IQR 15-43) with each HIVST client. The sensitivity of provider-delivered HIVST at the pharmacy was high when interpreted by providers (98.5%, 95% CI 97.8%, 99.1%) and clients (98.8%, 95% CI 98.0%, 99.3%), as was the specificity of HIVST in this setting (provider-interpretation: 96.9%, 95% CI 89.2%, 99.6%; client-interpretation: 93.8%, 95% CI 84.8%, 98.3%). CONCLUSIONS: When compared to the national HIV testing algorithm, provider-delivered blood-based HIVST at private pharmacies in Kenya performed well. These findings suggest that blood-based HIVST may be a useful tool to support PrEP initiation and continuation at private pharmacies and potentially other community-based delivery settings.

HPV vaccination in Kenya: a study protocol to assess stakeholders' perspectives on implementation drivers of HPV vaccination and the acceptability of the reduced dose strategy among providers.

Background: Cervical cancer is the leading cause of cancer-related deaths among Kenyan women. Persistent infection with high-risk oncogenic Human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. HPV vaccines are safe, durable, and efficacious in preventing incident HPV infections. In Kenya, despite efforts to increase HPV vaccination, coverage remains low. We sought to assess: (1) barriers and facilitators of HPV vaccination from the perspective of adolescent girls and young women (AGYW), their guardians as well as stakeholders involved in HPV vaccine delivery, and (2) the acceptability of the single dose of the HPV vaccination among healthcare providers (HCPs). Methods: Our study is nested within the KENya Single-dose HPV-vaccine Efficacy study (KEN SHE) that sought to test the efficacy of single-dose bivalent (HPV 16/18) and single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination. We are conducting this study in Kiambu, Nairobi, and Kisumu counties. In these counties, we are interviewing stakeholders (n = ∼25), selected based on their role in HPV vaccination at the county and national levels. Interviews are audio recorded and conducted in English or Swahili. The semi-structured interview guides were designed based on: (1) the Theoretical Domains Framework (TDF) for AGYW and guardians and (2) the Consolidated Framework for Implementation Research (CFIR) for other stakeholders. The Theoretical Framework of Acceptability (TFA) was leveraged to design the survey administered to HCPs (n = ∼309) involved in HPV vaccination. We will develop a codebook based on emerging codes from the transcripts and constructs from the TDF and CFIR. Emerging themes will be summarized highlighting similarities and differences between and within the different stakeholder groups and counties. Descriptive statistics and a χ2 test will be used to assess the distribution of responses between the different sites and regression analysis will be used to assess factors associated with high acceptability of the single-dose strategy while controlling for confounding variables. Discussion: Our study will describe key barriers and facilitators that affect HPV vaccination from the perspective of multiple stakeholders as well as insights on the perspective of HCPs towards the single-dose strategy to inform the designing of strategies to increase HPV vaccination uptake in Kenya and comparable settings.

Implementation and scale-up of a single-visit, screen-and-treat approach with thermal ablation for sustainable cervical cancer prevention services: a protocol for a stepped-wedge cluster randomized trial in Kenya.

BACKGROUND: An important cervical cancer prevention strategy in low- and middle-income countries (LMICs) has been single-visit screen-and-treat (SV-SAT) approach, using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy to manage precancerous lesions. While SV-SAT with VIA and cryotherapy have established efficacy, its population level coverage and impact on reducing cervical cancer burden remains low. In Kenya, the estimated cervical cancer screening uptake among women aged 30-49 is 16% and up to 70% of screen-positive women do not receive treatment. Thermal ablation for treatment of precancerous lesions of the cervix is recommended by the World Health Organization and has the potential to overcome logistical challenges associated with cryotherapy and facilitate implementation of SV-SAT approach and increase treatment rates of screen-positive women. In this 5-year prospective, stepped-wedge randomized trial, we plan to implement and evaluate the SV-SAT approach using VIA and thermal ablation in ten reproductive health clinics in central Kenya. METHODS: The study aims to develop and evaluate implementation strategies to inform the national scale-up of SV-SAT approach with VIA and thermal ablation through three aims: (1) develop locally tailored implementation strategies using multi-level participatory method with key stakeholders (patient, provider, system-level), (2) implement SV-SAT approach with VIA and thermal ablation and evaluate clinical and implementation outcomes, and (3) assess the budget impact of SV-SAT approach with VIA and thermal ablation compared to single-visit, screen-and-treat method using cryotherapy. DISCUSSION: Our findings will inform national scale-up of the SV-SAT approach with VIA and thermal ablation. We anticipate that this intervention, along with tailored implementation strategies will enhance the adoption and sustainability of cervical cancer screening and treatment compared to the standard of care using cryotherapy. TRIAL REGISTRATION: NCT05472311.

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.

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.

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.

Prevalence and correlates of cervical squamous intraepithelial lesions among HIV-infected and uninfected women in Central Kenya.

INTRODUCTION: cervical intraepithelial neoplasia the precursor of cervical cancer occurs with increased frequency in women infected with human immunodeficiency virus (HIV). This study aimed at determining the prevalence and correlates of abnormal cervical cytology among HIV-infected women and compare to the uninfected women. METHODS: a cross-sectional study conducted among HIV-infected and uninfected women enrolled in a HIV study in Central Kenya. All women had baseline Pap smear examination assessed using Bethesda system. Bivariate and multivariate logistic regression methods were employed to assess the correlates of cervical squamous epithelial lesions (CSIL). RESULTS: a total 480 women had an acceptable baseline smear, 373 (78%) were HIV-infected. Median age was 30.2 years [IQR 25.4-35.5]. Overall prevalence of CSIL was 37% (176/480) with the prevalence of low grade squamous intraepithelial lesion (LSIL), atypical squamous cells undetermined significance (ASCUS), high grade squamous intraepithelial lesions (HSIL) and atypical glandular cells (AGC) were 17%, 14%, 4% and 2% respectively. HIV-infected women had a higher prevalence of CSIL at 42% as compared to HIV-uninfected women at 19%. HIV infection was the predictor associated with development of CSIL at multivariate analysis and specifically, HIV-infected women were 3 times (AOR 3.1, 95% CI: 1.8 - 5.4, p<0.005) more likely to have CSIL than HIV-uninfected women. The age 35 - 44 years was protective to developing CSIL (AOR 0.45, 95% CI: 0.24 - 0.87, p=0.018). CONCLUSION: cervical squamous epithelial lesions is a major problem among Kenyan women. HIV infection confers a higher risk to development of CSIL. Cervical cancer screening should be an established practice in HIV programs.

Antibody responses to prophylactic quadrivalent human papillomavirus vaccine at 48 months among HIV-infected girls and boys ages 9-14 in Kenya, Africa.

OBJECTIVES: HIV infected children remain at increased risk of HPV associated malignancies as they initiate sexual activity. Though they mount a vigorous immune response to the quadrivalent human papillomavirus (QHPV-6, -11,-16, and -18; Gardasil®) vaccine, durability of the immune response is uncertain. We assessed antibody responses to HPV 6, -11, -16 and -18 for up to 48 months following administration of quadrivalent human papillomavirus vaccine in HIV-infected girls and boys ages 9-14 years in Kenya. DESIGN: Of 178 girls and boys who had previously received three doses of the quadrivalent HPV vaccine, 176 enrolled into extended follow up for 4 years. HPV antibodies to -6, -11, -16 and -18 were measured at 24, 36 and 48 months after the first vaccine dose using the total immunoglobulin G immunoassay (IgG LIA). We evaluated the magnitude and trend in HPV vaccine response and the effect of plasma HIV-1 RNA on HPV vaccine response from month 24 to month 48 of follow up. RESULTS: At re-enrollment, 24 months after initial vaccination, median age of participants was 14 years (range 11-17); 167 (95%) were receiving antiretroviral therapy and 110 (66%) had plasma HIV RNA < 40 copies/mL. The rate of HPV seropositivity at 48 months was 83% for HPV-6; 80% for HPV-11; 90% for HPV-16; and 77% for HPV-18. There was a plateau in mean log10 HPV-specific antibody titer between month 24 and 48. The mean log10 HPV-type specific antibody titer for children with undetectable HIV viral load (<40) at the time of vaccination consistently remained higher for the 48 months of follow up compared to children with detectable viral load. CONCLUSION: Children with HIV infection may retain long term antibody response following HPV immunization. Further work to define whether HIV-infected children are protected from HPV acquisition with low levels of HPV antibodies is needed.

Cognitive testing of the PHQ-9 for depression screening among pregnant and postpartum women in Kenya.

BACKGROUND: African women face high rates of depression, particularly during pregnancy or postpartum or after a recent HIV diagnosis. The Patient Health Questionnaire-9 (PHQ-9) depression screening tool has been quantitatively validated and extensively used to identify depression and link individuals to care. However, qualitative work is necessary to identify important opportunities to improve PHQ-9 question comprehension and performance among Kenyan women. METHODS: We administered the Kiswahili or English PHQ-9 (based on preference) to 29 pregnant and postpartum women in Thika, Kenya. Following administration, we conducted cognitive interviews with a purposive sample of 20 women. We used analytic memos and data matrices to identify themes around scale acceptability, comprehension, and decision and response processes. RESULTS: Most participants preferred to answer the PHQ-9 in Kiswahili (N = 15; 52%). Among the 20 interview participants, 12 (60%) had scores ≥5, indicating depressive symptoms. Overall, participants found the scale acceptable as an interviewer-administered tool. Participants reported few problems related to comprehension but had difficulty answering items not relevant to their lives (e.g., "watching television") and double-barreled items (e.g., "poor appetite or overeating"). They were hesitant to endorse items related to "duties as a wife and mother" and suicidal ideation. Most participants had difficulty distinguishing between response options of "several days" and "more than half the days". CONCLUSIONS: We detected several problems related to PHQ-9 comprehension, decision processes, and response processes. We provide recommended changes to instructions and item wording to improve PHQ-9 validity among Kenyan women.

Perceptions of pregnancy occurring among HIV-serodiscordant couples in Kenya.

BACKGROUND: Among HIV serodiscordant couples, most conception involves condomless sex and may confer a period with increased HIV transmission risk if HIV viral load is not suppressed and other precautions are not used. Safer conception strategies enable HIV serodiscordant couples to attain their pregnancy goals while markedly reducing this risk. We explored the perceptions and beliefs held by HIV serodiscordant couples and health care providers concerning pregnancy among HIV serodiscordant couples in Kenya and gathered their thoughts about how these might influence use of safer conception methods. METHODS: We conducted 20 Key Informant Interviews (KIIs) with health care providers offering safer conception counseling and 21 In-Depth Interviews (IDIs) and 4 Focus Group Discussions (FGDs) with members of HIV serodiscordant couples with immediate pregnancy goals in Thika, Kenya. Data were analyzed using an inductive approach that identified two emergent themes: perceptions towards pregnancy among HIV serodiscordant couples and access to safer conception services. RESULTS: The perceptions held by the community towards couples in HIV serodiscordant relationships having children were largely negative. The participants were aware of the increased HIV transmission risk to the HIV uninfected partners while trying to become pregnant. In the community, having biological children was cherished yet the majority of the couples shied away from accessing safer conception services offered at health facilities due to stigma and lack of knowledge of the existence of such services. Some providers had limited knowledge on safer conception strategies and services and consequently discouraged HIV serodiscordant couples from natural conception. CONCLUSIONS: Negative perceptions towards HIV serodiscordant couples becoming pregnant has hindered access to safer conception services. Therefore, there is need to create a supportive environment for HIV serodiscordant couples with fertility intentions that normalizes their desire to have children and informs the community about the availability of safer conception services.

Quadrivalent HPV vaccine in HIV-1-infected early adolescent girls and boys in Kenya: Month 7 and 12 post vaccine immunogenicity and correlation with immune status.

INTRODUCTION: In sub-Saharan Africa, a generation of HIV-1-infected children is approaching the age of sexual debut and becoming at risk for HPV infection and its sequelae. We assessed safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in HIV-1-infected adolescents. METHODS: In an open-label trial among Kenyan, HIV-1-infected adolescents aged 9-14 years, we administered the qHPV vaccine at 0, 2 and 6 months and measured antibody titers to HPV-16, 18, 6 and 11 at month 7 and 12 post-vaccination. Measures of immunogenic response from HIV-1-negative historical cohorts from Africa and HIV-1 positive adolescent cohorts from the USA were used for comparison. RESULTS: We enrolled 100 girls and 80 boys with a median age of 12 years and median baseline CD4 cell count of 684 (IQR 478, 935) cells/µL. One hundred and fifty four (86%) were receiving antiretroviral therapy for a median of 4.5 (IQR 2.3, 6.3) years; 110 (71%) had <400 copies of plasma HIV-1 RNA/mL. Of 189 enrolled children, 179 received all three doses. Two hundred and eighty five (64%) of 445 adverse events were injection site reactions; none were greater than grade 2. Of 6 Serious Adverse Events (SAEs), none were considered vaccine related. Seroconversion to HPV-18, 16, 11, 6 at month 7 occurred in 93.3%, 98.3%, 97.2% and 99.6% of vaccine recipients; similar rates have been reported in historical controls. The mean log10 HPV antibody titer measured at month 7 increased with each log10 increase in CD4 by 1.4 (95% CI: 1.1-1.7) for HPV-18; 1.2 (0.9-1.4) for HPV-16; 1.1 (0.8-1.3) for HPV-11; 0.7 (0.5-1.0) for HPV-6 (all p < 0.0001). CONCLUSION: Almost all Kenyan HIV-1-infected adolescents mounted an immune response comparable to other immunized populations. HPV antibody titers were higher in those with preserved CD4 cell counts. Longer term-follow up will determine sustainability of the immune response. ClinicalTrials.gov number, NCT00557245.

Effect of Depression on Adherence to Oral PrEP Among Men and Women in East Africa.

BACKGROUND: Low adherence can undermine the efficacy of daily oral pre-exposure prophylaxis (PrEP). Mental health conditions, particularly depression, could be associated with low PrEP adherence, especially for women. SETTING: We analyzed data from 1013 Kenyan and Ugandan HIV-uninfected participants in the Partners Demonstration Project, an open-label study of PrEP delivered to HIV-uninfected members of serodiscordant couples. METHODS: Participants completed quarterly visits over 2 years and were encouraged to use PrEP until their partners living with HIV had ≥6 months of antiretroviral therapy use (when viral suppression was expected). PrEP adherence was measured daily with electronic medication event monitoring system caps and dichotomized into low (<80% of expected bottle openings) and high adherence. Depression was assessed annually using the 16-item Hopkins Symptom Checklist screening tool; scores >1.75 indicate "probable depression." The association between probable depression and PrEP adherence was assessed separately for men and women using generalized estimating equations and marginal structural models. RESULTS: At enrollment, 39 (11.7% of 334) women and 64 (9.4% of 679) men reported symptoms indicating probable depression, and these proportions decreased during follow-up (P < 0.001 for women and men). Probable depression was significantly associated with low PrEP adherence among women (adjusted risk ratio = 1.77; 95% confidence interval: 1.14 to 2.77; P = 0.01); there was no association between depression and adherence among men (P = 0.50). Marginal structural models and sensitivity analyses confirmed these findings. CONCLUSIONS: Depression was relatively uncommon in this population and was an independent risk factor for low PrEP adherence among women. For PrEP programs targeting African women, integration of depression screening may improve PrEP effectiveness.

Comparison of short messaging service self-reported adherence with other adherence measures in a demonstration project of HIV preexposure prophylaxis in Kenya and Uganda.

OBJECTIVE: Short messaging service (SMS) can collect adherence data on a frequent basis and is relatively anonymous, and therefore could potentially reduce recall and social desirability biases prevalent in other self-reported measures. METHODS: We compared SMS self-reported adherence with three self-reported adherence questions (rating of ability to adhere, frequency of doses taken, percentage of doses taken) and two objective adherence measures [electronic adherence monitoring (EAM) and plasma tenofovir levels] using data from HIV-uninfected members of serodiscordant couples enrolled in a preexposure prophylaxis demonstration project in Kenya and Uganda. RESULTS: Of 373 enrolled participants, 256 (69%) were male and median age at enrolment was 29 years (26, 35). Fifty-two percent were from Kenya and median education at enrolment was 10 years (7,12). Overall, median adherence was 90, 75, 85, 94 and 79%, respectively, for self-report by SMS, rating, frequency, percentage and EAM adherence. Spearman's correlation coefficient between SMS and interviewer-administered self-reported measures was 0.18 for rating and frequency, 0.22 for percentage and 0.14 for EAM (all P < 0.001). The estimated difference in average adherence between SMS and self-reported rating, frequency, percentage adherence and EAM was 8.1 (P < 0.001), 0.3 (P = 0.81), -5.2 (P < 0.001) and 9.5 (P < 0.001), respectively. Area under the receiver-operating curve assessing the ability of SMS self-report to discriminate between detectable and undetectable tenofovir was 0.51. CONCLUSION: Our study found low correlation between SMS self-report and other self-reported and objective adherence measures and did not discriminate between detectable and undetectable plasma tenofovir levels. Future use of SMS self-report should explore alternative means for reducing potential biases.

Feasibility and acceptability of HIV self-testing among pre-exposure prophylaxis users in Kenya.

INTRODUCTION: HIV testing is key to the delivery of pre-exposure prophylaxis (PrEP): testing HIV-uninfected at-risk persons is the first step for PrEP initiation and ongoing HIV testing is an essential part of PrEP delivery. Thus, novel and cost-effective HIV-testing approaches to streamline delivery of PrEP are urgently needed. Within a demonstration project of PrEP for HIV prevention among high-risk HIV serodiscordant couples in Kenya (the Partners Demonstration Project), we conducted a pilot evaluation of HIV self-testing. METHODS: Clinic visits were scheduled quarterly and included in-clinic HIV testing using fingerstick rapid HIV tests and refills of PrEP prescriptions. HIV oral fluid self-test kits were provided for participants to use in the two-month interval between scheduled quarterly clinic visits. Acceptability of HIV self-testing was assessed using both quantitative and qualitative methods. RESULTS: We found that 222 of 226 (98%) HIV-uninfected persons who were offered accepted self-testing. Nearly all (96.8%) reported that using the self-testing kit was easy. More than half (54.5%) reportedly did not share the HIV results from self-testing with anyone and almost all (98.7%) the participants did not share the HIV self-testing kits with anyone. Many participants reported that HIV self-testing was empowering and reduced anxiety associated with waiting between clinic HIV tests. CONCLUSION: HIV self-testing was highly acceptable and may therefore be a feasible strategy to efficiently permit routine HIV testing between PrEP refills.

The Effect of Human Immunodeficiency Virus Prevention and Reproductive Health Text Messages on Human Immunodeficiency Virus Testing Among Young Women in Rural Kenya: A Pilot Study.

BACKGROUND: More than half of human immunodeficiency virus (HIV)-infected individuals in Kenya are unaware of their status, and young women carry a disproportionate burden of incident HIV infections. We sought to determine the effect of an SMS intervention on uptake of HIV testing among female Kenyan college students. METHODS: We conducted a quasi-experimental study to increase HIV testing among women 18 to 24 years old. Four midlevel training colleges in Central Kenya were allocated to have their study participants receive either weekly SMS on HIV and reproductive health topics or no SMS. Monthly 9-question SMS surveys were sent to all participants for 6 months to collect data on HIV testing, sexual behavior, and HIV risk perception. We used multivariate Cox proportional hazards regression to detect differences in the time to the first HIV test reported by women during the study period. RESULTS: We enrolled 600 women between September 2013 and March 2014 of whom 300 received weekly SMS and monthly surveys and 300 received only monthly surveys. On average, women were 21 years of age (interquartile range, 20-22), 71.50% had ever had sex and 72.62% had never tested for HIV. A total of 356 women reported testing for HIV within the 6 months of follow-up: 67% from the intervention arm and 51% from the control arm (hazard ratio, 1.57; 95% confidence interval, 1.28-1.92). CONCLUSIONS: Use of weekly text messages about HIV prevention and reproductive health significantly increased rates of HIV testing among young Kenyan women and would be feasible to implement widely among school populations.

The preexposure prophylaxis revolution; from clinical trials to programmatic implementation.

PURPOSE OF REVIEW: An investment in preexposure prophylaxis (PrEP) delivery must have public health impact in reducing HIV infections. Sustainable delivery of PrEP requires policy, integration of services, and synergy with other existing HIV prevention programs. This review discusses key policy and programmatic considerations for implementation and scale up of PrEP in Africa. RECENT FINDINGS: PrEP delivery has been delayed by concerns about adherence and delivery in 'real world' settings. Demonstration projects and clinical service delivery models are providing evidence of PrEP effectiveness with an impact much higher than that found in randomized clinical trials. Data confirm that PrEP uptake, adherence, and retention has been high, more so by persons who perceive themselves at high risk for HIV infection, and PrEP is well tolerated. PrEP delivery is more than dispensation of a pill and programs should address other risk drivers, which differ by population. In Africa, barriers to PrEP uptake and adherence include stigma among MSM and low HIV risk perception among young women. Additional data have provided insight into optimal points of service delivery, provider training requirements and quality assurance needs. Of the 2 million new HIV infections in 2014, 70% were in Africa. PrEP use is not lifelong, and use limited to periods of risk may be both effective and cost-effective for the continent. SUMMARY: HIV prevention programs should determine strategies to identify those at substantial risk for HIV infection, formulate and deliver PrEP in combination with interventions that target social drivers of HIV vulnerability specific to each population. Policy guidance for optimal combination of interventions and service delivery avenues, clinical protocols, health infrastructure requirements are required. Cost-effectiveness and efficiency data are essential for policy guidance to navigate ethical questions over use of antiretroviral therapy for HIV-negative individuals when treatment coverage has not been attained in many parts of Africa. Countries need to invest in purposeful advocacy at both local and global forums. Failure to implement PrEP will be a failure to protect future generations.

Willingness of Kenyan HIV-1 serodiscordant couples to use antiretroviral-based HIV-1 prevention strategies.

INTRODUCTION: Antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) have demonstrated efficacy as new human immunodeficiency virus-1 (HIV-1) prevention approaches for HIV-1 serodiscordant couples. METHODS: Among Kenyan HIV-1 serodiscordant heterosexual couples participating in a clinical trial of PrEP, we conducted a cross-sectional study and used descriptive statistical methods to explore couples' willingness to use antiretrovirals for HIV-1 prevention. The study was conducted before July 2011, when studies among heterosexual populations reported that ART and PrEP reduced HIV-1 risk. RESULTS: For 181 couples in which the HIV-1-infected partner had a CD4 count ≥350 cells per microliter and had not yet initiated ART (and thus did not qualify for ART under Kenyan guidelines), 60.2% of HIV-1 infected partners (69.4% of men and 57.9% of women) were willing to use early ART (at CD4 ≥350 cells per microliter) for HIV-1 prevention. Among HIV-1 uninfected partners, 92.7% (93.8% of men and 86.1% of women) reported willingness to use PrEP. When given a hypothetical choice of early ART or PrEP for HIV-1 prevention, 52.5% of HIV-1-infected participants would prefer to initiate ART early and 56.9% of HIV-1-uninfected participants would prefer to use PrEP. CONCLUSIONS: Nearly 40% of Kenyan HIV-1-infected individuals in known HIV-1 serodiscordant partnerships reported reservations about early ART initiation for HIV-1 prevention. PrEP interest in this PrEP-experienced population was high. Strategies to achieve high uptake and sustained adherence to ART and PrEP for HIV-1 prevention in HIV-1 serodiscordant couples will require responding to couples' preferences for prevention strategies.