Patterns of PrEP continuation and coverage in the first year of use: a latent class analysis of a programmatic PrEP trial in Kenya.

INTRODUCTION: Effective PrEP use is critical for impact, but data are limited on common patterns of continuation and coverage among persons using PrEP in real-world settings. METHODS: Data are from the Partners Scale-Up Project, a programmatic stepped-wedge cluster-randomized trial to integrate PrEP delivery in 25 Kenyan public health facilities conducted between February 2017 and December 2021. We evaluated PrEP continuation using visit attendance and pharmacy refill records, and computed medication possession ratio to define coverage during the first year of use. Latent class mixture models were used to identify and characterize membership to different PrEP continuation patterns. Multinomial logistic regression was used to examine the association between group trajectories and demographic and behaviour characteristics. RESULTS: Overall, 4898 persons initiated PrEP, 54% (2640) were female, mean age was 33 years (standard deviation 11) and 84% (4092) had partners living with HIV. PrEP continuation was 57%, 44%, and 34% at 1, 3, and 6 months, respectively. Four unique trajectories of PrEP coverage were identified: (1) one-fourth (1154) exhibited consistent high coverage throughout the year with 93%, 94%, 96%, and 67% continuing PrEP at months 1, 3, 6, and 12, respectively; (2) 13% (682) showed high coverage trajectory throughout 6 months but coverage rapidly declined thereafter (94%, 93%, 63%, and 10% continued at months 1, 3, 6, and 12, respectively); (3) 18.9% (918) exhibited moderate coverage trajectory with 91% of clients refilling PrEP at month 1 but nearly all dropped-off thereafter (37%, 5%, and 4% continued at months 3, 6, and 12, respectively); and (4) 43.8% (2144) exhibited immediate discontinuation trajectory, in which nearly all did not have any subsequent PrEP refill. Overall, being female, older age, having partners living with HIV or of unknown HIV status were statistically associated with better PrEP continuation trajectories compared to the immediate discontinuation trajectory (p <0.05 for all). CONCLUSIONS: In this analysis of a real-world PrEP implementation programme in Kenya, we found four distinct patterns of PrEP continuation, with one-third of users exhibiting consistent high continuation throughout 12 months and two-fifths with immediate discontinuation patterns. These data may help guide tailored interventions to support PrEP continuation in this setting.

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.

Using an on-site modular training approach to amplify prep service delivery in public health facilities in Kenya.

Delivery of oral PrEP, a potent HIV prevention intervention, has begun within public health systems in many countries in Africa. Training as many health providers as possible expeditiously is necessary to efficiently and rapidly scale up PrEP delivery among at risk populations and thereby realize the greatest impact of PrEP. We designed and implemented an innovative on-site modular training approach delivered in five two-hour modules. The modules could be covered in two consecutive days or be broken across several days enabling flexibility to accommodate health provider work schedules. We assessed knowledge gain comparing pre-and post-training test scores and determined monthly PrEP uptake for six months following the training intervention. We also evaluated the cost of this training approach and conducted key informant interviews to explore acceptability among health providers. Between January 2019 and December 2020, 2111 health providers from 104 health facilities were trained on PrEP. Of 1821 (83%) providers who completed both pre- and post-tests, 505 (28%) were nurses, 333 (18%) were HIV counsellors, 276 (15%) were clinical officers and 255 (14%) were lay providers. The mean score prior to and after training was 58% and 82% respectively (p <0.001). On average, health facilities initiated an average of 2.7 (SD 4.7) people on PrEP each month after the training, a number that did not decline over six months post-training (p = 0.62). Assuming Ministry of Health costs, the costs per provider trained was $16.27. Health providers expressed satisfaction with this training approach because it enabled many providers within a facility receive training. On-site modular training is an effective approach for improving PrEP education for health workers in public health facilities, It is also acceptable and low-cost. This method of training can be scaled up to rapidly amplify the number of health workers able to offer PrEP services.

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.

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.

"I Just Decided to Stop:" Understanding PrEP Discontinuation Among Individuals Initiating PrEP in HIV Care Centers in Kenya.

BACKGROUND: Preexposure prophylaxis (PrEP) discontinuation rates in clinical trials and demonstration projects have been well characterized; however, little is known about discontinuation in routine public health settings in sub-Saharan Africa. Understanding discontinuation in nonstudy settings is important for establishing expectations for PrEP continuation in national programs and for facilitating effective PrEP scale-up. METHODS: We conducted in-depth interviews with 46 individuals who had initiated PrEP at 25 HIV comprehensive care clinics (CCCs) in central and western Kenya and whose clinic records indicated they had discontinued. RESULTS: Many of our study participants discontinued PrEP when their perceived risk decreased (eg, hiatus or end of a sexual relationship or partner known to be living with HIV became virally suppressed). Others reported discontinuation due to side effects, daily pill burden, preference for condoms, or their partner's insistence. Participant narratives frequently described facility level factors such as stigma-related discomforts with accessing PrEP at CCCs, inconvenient clinic location or operating hours, long wait times, and short refill dates as discouraging factors, suggesting actionable areas for improving PrEP access and continuation. CONCLUSION: Clients frequently make intentional decisions to discontinue PrEP as they weigh different prevention options within the context of complex lives. Many clients will decide to discontinue PrEP when perceiving themselves to be at reduced risk and PrEP counseling must include provisions for addressing seasons of risk. PrEP will not be the right prevention method for everyone, or forever. Expanding PrEP access points and increasing sex-positive messaging may facilitate PrEP being a better option for many.

"Now that PrEP is reducing the risk of transmission of HIV, why then do you still insist that we use condoms?" the condom quandary among PrEP users and health care providers in Kenya.

Communication around condom use in the context of PrEP services presents a potential conundrum for patients and providers. Within the Partners Scale-Up Project, which supports integration of PrEP delivery in HIV care clinics, we interviewed 41 providers and 61 PrEP users and identified themes relating to condom messaging and use. Most providers counselled PrEP initiators to always use both PrEP and condoms, except when trying to conceive. However, others reported contexts and rationales for not emphasizing condom use. Providers reported that PrEP users were sometimes confused, even frustrated, with their insistence on using condoms in addition to PrEP. PrEP users generally regarded PrEP as a more feasible and desirable HIV prevention method than condoms, enabling increased sexual pleasure and conception, and reducing the conflict and stigma associated with condom use. Innovative approaches to condom counselling in PrEP programs are needed.

PrEP rollout in Africa: status and opportunity.

Following recommendations by the World Health Organization in 2015, and key clinical trials, countries in sub-Saharan Africa, the region with the highest burden of human immunodeficiency virus (HIV), developed policies that incorporate pre-exposure prophylaxis (PrEP) into national HIV-prevention strategies. By the end of 2019, more than one third of people receiving PrEP globally were in Africa. Crucial understandings gained from early rollout among at-risk populations, such as HIV-serodiscordant couples, adolescent girls and young women, female sex workers, and men who have sex with men, include the importance of strategies for maintaining persistent adherence to PrEP and novel approaches to making PrEP services accessible, simplified and efficient. This Perspective will discuss the current status of these programs and how to further widen their implementation.

HIV-1 self-testing to improve the efficiency of pre-exposure prophylaxis delivery: a randomized trial in Kenya.

BACKGROUND: The introduction of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus-1 (HIV-1) prevention in Africa presents new challenges for health systems that are already overburdened because PrEP delivery requires frequent clinic visits (generally every 3 months) for HIV-1 testing and PrEP refills. HIV-1 self-testing (HIVST) has the potential to improve the efficiency of PrEP delivery by decreasing the number of clinic visits. Here, we describe the rationale and design of a randomized, noninferiority trial designed to test the effectiveness and safety of using HIVST to support PrEP delivery in Kenya. METHODS: The JiPime-JiPrEP (Kiswahili for 'Test Yourself, PrEP Yourself') study is a three-arm randomized trial taking place in Thika, Kenya. Participants (n = 495) are eligible for enrollment if they are at least 18 years old, HIV-1 seronegative, and have been taking PrEP for 1 month. Three distinct participant types will be enrolled: men (n = 165) and women (n = 165) who are in mutually disclosed HIV-1 serodiscordant relationships, and women (n = 165) who are at HIV-1 risk and not in a known serodiscordant relationship. Participants in each of these subpopulations will be 1:1:1 randomized to: 1) the standard of care, with quarterly clinic visits; 2) oral HIVST, with biannual clinic visits plus oral HIVSTs to use at the quarters between those visits; or 3) blood-based HIVST, with biannual clinic visits plus blood-based HIVSTs. All participants will complete quantitative surveys and provide blood samples for the objective measurement of PrEP adherence at baseline, 6 months, and 12 months. The primary outcomes are PrEP adherence, PrEP continuation, and HIV-1 testing, measured at 6 months and secondarily at 12 months. DISCUSSION: The findings from this trial can help to understand how HIVST-a new HIV-1 testing technology-can support health systems in sub-Saharan Africa. Additionally, the findings can inform policy aimed at improving the efficiency of PrEP implementation and scale-up in Kenya. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03593629 . Retrospectively registered on 20 July 2018.

The Incremental Cost of Delivering PrEP as a Bridge to ART for HIV Serodiscordant Couples in Public HIV Care Clinics in Kenya.

BACKGROUND: In 2016, the Kenyan Ministry of Health (MOH) released guidelines that recommend preexposure prophylaxis (PrEP) for persons with substantial ongoing HIV risk, including those in HIV serodiscordant partnerships. Estimates of the costs of delivering PrEP within Kenyan public health facilities are needed for planning for PrEP scale up. METHODS: We estimated the incremental annual costs of providing PrEP to HIV uninfected partners as a time-limited "bridge" until the infected partner is virally suppressed on ART within HIV serodiscordant couples as part of routine clinic care in Thika, Kenya. Costs were collected from the Partners Demonstration Project, a prospective evaluation of integrated delivery of preexposure prophylaxis (PrEP) and antiretroviral therapy (ART) to high-risk HIV serodiscordant couples. We conducted time and motion studies to distinguish between activities related to research, routine clinical care, and PrEP delivery. Costs (2015 US dollars) were collected from the MOH perspective and divided into staff, transportation, equipment, supplies, buildings and overhead, and start-up. RESULTS: PrEP related activities conducted during the screening, enrollment, and follow-up visits took an average of 13 minutes, 51 minutes, and 12 minutes, respectively. Assuming a staff structure of 3 counselors, 1 nurse, and 2 clinicians, we estimate that 3,178 couples can be screened, 1,444 couples offered PrEP and ART, and 6,138 couples followed up annually in an average HIV care clinic. Using costs incurred by the MOH for personnel, drug, and laboratory tests, we estimate that the incremental cost of offering PrEP to HIV uninfected partners within existing ART programs is $86.79 per couple per year. Personnel and PrEP medication made up the largest portion of the costs. We estimate that the total cost to Ministry of Health of delivering integrated PrEP and ART program in public health facilities is $250.19 per HIV serodiscordant couple per year. CONCLUSIONS: Time-limited provision of PrEP to the HIV uninfected partner within HIV serodiscordant couples can be an affordable delivery model implemented in HIV care programs in Kenya and similar settings. These costs can be used for budgetary planning and cost effectiveness analyses.

Training health care providers to provide PrEP for HIV serodiscordant couples attending public health facilities in Kenya.

To catalyse national scale up of PrEP for HIV serodiscordant couples in public health facilities in Kenya, the Partners Scale-Up Project, using a two-day case-based interactive curriculum, trained health care providers working in 24 high volume facilities in central and western Kenya on PrEP service delivery. Using a standardised test with questions about PrEP and antiretroviral-based HIV prevention we assessed gain in knowledge and confidence gain by comparing pre-and post-training test scores. We explored experiences of the training through key informant interviews after clinics started delivering PrEP. Of 716 health care providers trained, 235 (32.9%) were nurses, 144 (20.2%) were clinical officers and 155 (21.7%) were HIV counsellors. There was a significant improvement between the means of pre-test and post-test scores (61.7% (SD 17.4) vs 86.4% (SD 12.7) p < 0.001). The proportion of those who reported being 'very comfortable' providing care to HIV serodiscordant couples increased from 22.8% to 67.3% (p < 0.001). Key themes that training increasing both knowledge of PrEP and confidence to deliver PrEP to HIV serodiscordant couples emerged from interviews. This short, standardised training resulted in a substantial increase in knowledge of PrEP and in the confidence of the health providers to provide PrEP to HIV serodiscordant couples. Trial registration ClinicalTrials.gov NCT03052010.

Use of a risk scoring tool to identify higher-risk HIV-1 serodiscordant couples for an antiretroviral-based HIV-1 prevention intervention.

BACKGROUND: Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) reduce HIV-1 transmission within heterosexual HIV-1 serodiscordant couples. Prioritizing couples at highest HIV-1 transmission risk for ART and PrEP would maximize impact and minimize costs. METHODS: The Partners Demonstration Project is an open-label, delivery study of integrated PrEP and ART for HIV-1 prevention among high risk HIV-1 serodiscordant couples in Kenya and Uganda. We evaluated the feasibility of using a validated risk score that weighs a combination of easily measurable factors (age, children, marital status, male circumcision status, condom use, plasma HIV-1 levels) to identify couples at highest risk for HIV-1 transmission for enrollment. Couples scoring ≥5 met the risk score eligibility criteria. RESULTS: We screened 1694 HIV-1 serodiscordant couples and enrolled 1013. Of the screened couples, 1331 (78.6 %) scored ≥5 (with an expected incidence >3 % per year) and 76 % of these entered the study. The median age of the HIV-1 uninfected partner was 29 years [IQR 26, 36] and 20 % were <25 years of age. The HIV-1 uninfected partner was male in 67 % of partnerships, 33 % of whom were uncircumcised, 57 % of couples had no children, and 65 % reported unprotected sex in the month prior to enrollment. Among HIV-1 infected partners, 41 % had plasma viral load >50,000 copies/ml. CONCLUSION: A risk scoring tool identified HIV-1 serodiscordant couples for a demonstration project of PrEP and ART with high HIV-1 risk. The tool may be feasible for research and public health settings to maximize efficiency and minimize HIV-1 prevention costs.