Community-based delivery and monitoring of antiretroviral therapy (ART) for HIV has the potential to increase viral suppression for individual- and population-level health benefits. However, the cost-effectiveness and budget impact are needed for public health policy. We used a mathematical model of HIV transmission in KwaZulu-Natal, South Africa, to estimate population prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 2020 to 2060 for two scenarios: 1) standard clinic-based HIV care and 2) five-yearly home testing campaigns with community ART for people not reached by clinic-based care. We parameterised model scenarios using observed community-based ART efficacy. Using a health system perspective, we evaluated incremental cost-effectiveness and net health benefits using a threshold of $750/DALY averted. In a sensitivity analysis, we varied the discount rate; time horizon; costs for clinic and community ART, hospitalisation, and testing; and the proportion of the population receiving community ART. Uncertainty ranges (URs) were estimated across 25 best-fitting parameter sets. By 2060, community ART following home testing averted 27.9% (UR: 24.3–31.5) of incident HIV infections, 27.8% (26.8–28.8) of HIV-related deaths, and 18.7% (17.9–19.7) of DALYs compared to standard of care. Adolescent girls and young women aged 15–24 years experienced the greatest reduction in incident HIV (30.7%, 27.1–34.7). In the first five years (2020–2024), community ART required an additional $44.9 million (35.8–50.1) annually, representing 14.3% (11.4–16.0) of the annual HIV budget. The cost per DALY averted was $102 (85–117) for community ART compared with standard of care. Providing six-monthly refills instead of quarterly refills further increased cost-effectiveness to $78.5 per DALY averted (62.9–92.8). Cost-effectiveness was robust to sensitivity analyses. In a high-prevalence setting, scale-up of decentralised ART dispensing and monitoring can provide large population health benefits and is cost-effective in preventing death and disability due to HIV.

Introduction With recent approvals of long-acting (LA) HIV pre-exposure prophylaxis (PrEP) in the form of injectable cabotegravir and the dapivirine ring, programmes need to consider how to optimize the delivery of PrEP methods, including by leveraging lessons from the past decade of oral PrEP delivery.Discussion Framed around differentiated service delivery building blocks, the major considerations for the delivery of LA PrEP are how to reach the populations who would most benefit from PrEP, where to locate PrEP services, how to reduce the user burden of accessing and continuing with PrEP, and how to integrate PrEP with other services. Demand creation for LA PrEP and education about new LA PrEP options should be co-developed with communities and be positively framed. Client-facing clinical decision support tools provide information about HIV prevention and PrEP options in non-technical ways and can support their informed decision-making about PrEP. Training for providers is needed to increase their ability to ask about sexual and drug use behaviours in a non-judgmental and comfortable manner as part of risk assessment, discuss harm reduction strategies and counsel about available PrEP options that fit clients' circumstances and needs. PrEP adherence support should include supportive counselling and be tailored to address an individual's particular barriers and needs. Reminders through text messaging or calls can foster PrEP persistence, given the narrow the window around dosing for injectable cabotegravir. Strategies are needed to expand PrEP delivery options, including telePrEP, pharmacy-based PrEP, key population-led services and mobile venues. Integrated delivery models are needed which include sexually transmitted infection testing and treatment, contraception for cis-women not desiring to become pregnant, PrEP for pregnant women in high HIV prevalence settings, and gender-affirming hormones and support for transgender persons.Conclusions The outcome of expanding PrEP options through LA PrEP formulations is to increase PrEP coverage, adherence, persistence and effectiveness by offering a choice of PrEP that meets the needs of persons who would benefit from PrEP. The lessons learned from the delivery of oral PrEP about demand creation, informed client decision-making, provider training, adherence support and service delivery model are relevant to the delivery of LA PrEP and integration with other services.

Background Perspectives on COVID-19 risk and the willingness and ability of persons living in refugee settlements to adopt COVID-19 prevention strategies have not been rigorously evaluated. The realities of living conditions in Ugandan refugee settlements may limit the extent to which refugees can uptake strategies to mitigate COVID-19 risk. Methods In-depth qualitative interviews were conducted between April 2021 and April 2022 to assess COVID-19 knowledge, risk perception, prevention strategy adoption including COVID-19 vaccination, and COVID-19 impact on living conditions in refugee settlements in Uganda. Interview participants included 28 purposively selected refugees who called into “Dial-COVID”, a free telephone COVID-19 information collection and dissemination platform that was advertised in refugee settlements by community health workers. Interviews were analyzed using a combination of deductive and inductive content analysis. Emerging themes were mapped onto the Theoretical Domains Framework to identify domains influencing prevention behavior. Results were synthesized to provide intervention and policy recommendations for risk mitigation in refugee settlements for COVID-19 and future infectious disease outbreaks. Results The COVID-19 pandemic detrimentally impacted economic and food security as well as social interactions in refugee settlements. Youth were considered especially impacted, and participants reported incidents of child marriage and teenage pregnancy following school closures. Participants displayed general knowledge of COVID-19 and expressed willingness to protect themselves and others from contracting COVID-19. Risk mitigation strategy uptake including COVID-19 vaccination was influenced by COVID-19 knowledge, emotions surrounding COVID-19, the environmental context and resources, personal goals, beliefs about the consequences of (non)adoption, social influences, and behavior reinforcement. Resource constraints, housing conditions, and competing survival needs challenged the adoption of prevention strategies and compliance decreased over time. Conclusions Contextual challenges impact the feasibility of COVID-19 risk mitigation strategy uptake in refugee settlements. Pre-existing hardships in this setting were amplified by the COVID-19 pandemic and related lockdowns. Targeted dispelling of myths, alignment of information across communication mediums, supporting survival needs and leveraging of respected role models are strategies that may hold potential to mitigate risk of infectious diseases in this setting. Registration details World Pandemic Research Network – 490,652.

Community‐based delivery of HIV pre‐exposure prophylaxis (PrEP) to South African adolescent girls and young women's (AGYW) could increase access but needs evaluation. We integrated PrEP services via home‐based services and pop‐up tents into existing community‐based HIV testing services (CB‐HTS) in Eastern Cape Province, South Africa.

Home-based service delivery has been used to improve access to HIV testing and antiretroviral initiation across sub-Saharan Africa, but it has yet to be leveraged to improve pre-exposure prophylaxis (PrEP) uptake. We interviewed 37 adolescent girls and young women (AGYW) in Eastern Cape, South Africa to explore why they chose to initiate PrEP or not following home-based HIV testing and referral for PrEP, and what influenced time to PrEP initiation. Participants reported that home visits provided a source of trusted information and a way to involve family members in their PrEP initiation decisions, motivating some to start PrEP. AGYW who initiated PrEP were more likely to qualitatively perceive themselves to be at high risk for HIV compared with those who never initiated PrEP. Integrating home-based HIV testing with PrEP education and referral may be a valuable way to reduce familial barriers and boost PrEP uptake among AGYW in South Africa. Trial registration: NCT03977181. Retrospectively registered on June 6, 2019.

Low perceived HIV risk is a barrier to effective pre-exposure prophylaxis (PrEP) use among African adolescent girls and young women (AGYW). Single-item risk perception measures are stigmatizing and alienating to AGYW and may not predict PrEP use. There is a need for a tool capturing domains of perceived HIV risk and salience that align with PrEP use among AGYW. This HIV PrEP study was conducted in Kampala, Uganda. We developed and piloted the 9-item “HIV Salience and Perception” (HPS) scale (range: 9–36); higher scores indicate beliefs of higher vulnerability to HIV. We administered the scale to Ugandan AGYW participating in an ongoing cohort study at enrollment, one, three and six months. PrEP dispensing was measured quarterly and adherence was measured daily via Wisepill (high adherence: ≥80

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 .

Despite demonstrated efficacy for HIV prevention, substantial challenges remain for the successful rollout of oral pre-exposure prophylaxis (PrEP), especially among adolescent girls and young women (AGYW). We characterized trajectories of PrEP adherence among 200 AGYW in South Africa and analyzed data from 22 qualitative interviews and 3 focus group discussions for explanatory purposes. Two adherence trajectory groups were identified: 52% with high early adherence that declined after month three and 48% with low adherence throughout. Adherence in the "consistently low" group was related to social support and logistical concerns, while the decrease in the "high declining" group corresponded to a change in the frequency of study visits from monthly to quarterly. PrEP support should be differentiated for those who need more frequent visits and adherence support initially versus later in PrEP use. Visits every month, when needed, should be considered for AGYW who need sustained support later into use.

Despite high risk for HIV, South African adolescent girls and young women (AGYW) experience numerous challenges with adherence to PrEP. To better understand AGYW's motivations for PrEP and factors that impact PrEP adherence, we conducted serial in-depth interviews with 22 South African AGYW during a 12 month prospective study. Interviews explored motivations and initial experiences of PrEP use, patterns of adherence, social support, and reasons for stopping or persisting with PrEP. We also assessed drug levels as a biomarker of adherence; dried blood spots were collected at months 1, 2, 3, 6, and 12 to assess intracellular tenofovir diphosphate levels. An end-user journey analytical approach revealed themes related to behavioral and emotional aspects of use, including multilevel factors leading to divergent PrEP adherence trajectories. Our findings highlight how internal versus external motivations drive PrEP use, as well as how positive identity formation and challenges are handled, which are essential to understand AGYW in their PrEP journeys.

Accurate reporting of antiretroviral therapy (ART) uptake is crucial for measuring the success of epidemic control. Programs without linked electronic medical records are susceptible to duplicating ART initiation events. We assessed the prevalence of undisclosed ART use at the time of treatment initiation and explored its correlates among people presenting to public ambulatory clinics in South Africa. Data were analyzed from the community-based delivery of ART (DO ART) clinical trial, which recruited people living with HIV who presented for ART initiation at two clinics in rural South Africa. We collected data on socioeconomic factors, clinical factors, and collected blood as part of study screening procedures. We estimated the proportion of individuals presenting for ART initiation with viral load suppression (< 20 copies/mL) and fitted regression models to identify social and clinical correlates of non-disclosure of ART use. We also explored clinical and national databases to identify records of ART use. Finally, to confirm surreptitious ART use, we measured tenofovir (TDF) and emtricitabine (FTC) levels in dried blood spots. A total of 193 people were screened at the two clinics. Approximately 60% (n = 114) were female, 40% (n = 78) reported a prior HIV test, 23% (n = 44) had disclosed to a partner, and 31% (n = 61) had a partner with HIV. We found that 32% (n = 62) of individuals presenting for ART initiation or re-initiation had an undetectable viral load. In multivariable regression models, female sex (AOR 2.16, 95% CI 1.08-4.30), having a prior HIV test and having disclosed their HIV status (AOR 2.48, 95% CI 1.13-5.46), and having a partner with HIV (AOR 1.94, 95% CI 0.95-3.96) were associated with having an undetectable viral load. In records we reviewed, we found evidence of ART use from either clinical or laboratory databases in 68% (42/62) and detected either TDF or FTC in 60% (37/62) of individuals with an undetectable viral load. Undisclosed ART use was present in approximately one in three individuals presenting for ART initiation or re-initiation at ambulatory HIV clinics in South Africa. These results have important implications for ART resource use and planning in the region. A better understanding of reasons for non-disclosure of ART at primary health care clinics in such settings is needed.

BackgroundCommunity-based delivery of antiretroviral therapy (ART) for HIV, including ART initiation, clinical and laboratory monitoring, and refills, could reduce barriers to treatment and improve viral suppression, reducing the gap in access to care for individuals who have detectable HIV viral load, including men who are less likely than women to be virally suppressed. We aimed to test the effect of community-based ART delivery on viral suppression among people living with HIV not on ART.MethodsWe did a household-randomised, unblinded trial (DO ART) of delivery of ART in the community compared with the clinic in rural and peri-urban settings in KwaZulu-Natal, South Africa and the Sheema District, Uganda. After community-based HIV testing, people living with HIV were randomly assigned (1:1:1) with mobile phone software to community-based ART initiation with quarterly monitoring and ART refills through mobile vans; ART initiation at the clinic followed by mobile van monitoring and refills (hybrid approach); or standard clinic ART initiation and refills. The primary outcome was HIV viral suppression at 12 months. If the difference in viral suppression was not superior between study groups, an a-priori test for non-inferiority was done to test for a relative risk (RR) of more than 0·95. The cost per person virally suppressed was a co-primary outcome of the study. This study is registered with ClinicalTrials.gov, NCT02929992.FindingsBetween May 26, 2016, and March 28, 2019, of 2479 assessed for eligibility, 1315 people living with HIV and not on ART with detectable viral load at baseline were randomly assigned; 666 (51%) were men. Retention at the month 12 visit was 95% (n=1253). At 12 months, community-based ART increased viral suppression compared with the clinic group (306 [74%] vs 269 [63%], RR 1·18, 95% CI 1·07–1·29; psuperiority=0·0005) and the hybrid approach was non-inferior (282 [68%] vs 269 [63%], RR 1·08, 0·98–1·19; pnon-inferiority=0·0049). Community-based ART increased viral suppression among men (73%, RR 1·34, 95% CI 1·16–1·55; psuperiority<0·0001) as did the hybrid approach (66%, RR 1·19, 1·02–1·40; psuperiority=0·026), compared with clinic-based ART (54%). Viral suppression was similar for men (n=156 [73%]) and women (n=150 [75%]) in the community-based ART group. With efficient scale-up, community-based ART could cost US$275–452 per person reaching viral suppression. Community-based ART was considered safe, with few adverse events.InterpretationIn high and medium HIV prevalence settings in South Africa and Uganda, community-based delivery of ART significantly increased viral suppression compared with clinic-based ART, particularly among men, eliminating disparities in viral suppression by gender. Community-based ART should be implemented and evaluated in different contexts for people with detectable viral load.FundingThe Bill & Melinda Gates Foundation; the University of Washington and Fred Hutch Center for AIDS Research; the Wellcome Trust; the University of Washington Royalty Research Fund; and the University of Washington King K Holmes Endowed Professorship in STDs and AIDS.

Abstract Background PrEP use should be aligned with periods of risk for HIV acquisition. For HIV serodiscordant couples, PrEP can be used as a bridge until the partner living with HIV takes antiretroviral therapy (ART) long enough to achieve viral suppression (the “PrEP as a Bridge to ART” strategy). However, adherence to this strategy is unknown. Methods In a demonstration project in Kenya and Uganda, HIV-uninfected partners of serodiscordant couples were advised to take PrEP until the partner living with HIV took ART for ≥ 6 months. PrEP discontinuation was then recommended unless there were concerns about ART adherence, immediate fertility intentions, or outside partners with unknown HIV/ART status. Electronic adherence monitoring and socio-behavioral questionnaire data were used in logistic regression models to explore completion of this strategy and continuation of PrEP beyond recommendations to stop its use. Results Among 833 serodiscordant couples, 436 (52%) HIV-uninfected partners completed ≥ 6 months of PrEP as a bridge to ART. Strategy completion was associated with older age (aOR per 5 years = 1.1; p = 0.008) and having fewer children (aOR = 0.9; p = 0.019). Of the 230 participants encouraged to stop PrEP according to strategy recommendations, 170 (74%) did so. PrEP continuation among the remaining 60 participants was associated with more education (aOR = 1.1; p = 0.029), a preference for PrEP over ART (aOR = 3.6; p = 0.026), comfort with managing their serodiscordant relationship (aOR = 0.6; p = 0.046), and believing PrEP makes sex safe (aOR = 0.5; p = 0.026). Conclusion Half of participants completed the PrEP as a bridge to ART strategy and the majority stopped PrEP as recommended. These findings suggest that targeting PrEP to periods of risk is a promising approach; however, tailoring counseling around aligning PrEP use and HIV risk will be important for optimal strategy implementation.

Women who have a prevention mindset may opt for concurrent use of oral pre-exposure prophylaxis (PrEP) and all forms of contraception; we therefore assessed how contraception may influence PrEP use or vice versa. We analyzed data from Kenyan and Ugandan HIV-uninfected non-pregnant women in sero-discordant partnerships who were participating in the Partners Demonstration Project. Using multivariable generalized estimating equation models, we estimated the associations between effective contraceptive use and 1) PrEP dispensation 2) high effective PrEP use. Among the 311 women (93.1% of all those followed in the Partners Demonstration Project) median age was 29 years (interquartile range [IQR] 24.0-35.0) and 115 (37.0%) reported using effective contraception at baseline. All the women initiated PrEP during the study and moderately high PrEP adherence was recorded at 73.1% of visits over an average 7.5 months following PrEP dispensation. Women (14.8%) consistently used an effective contraceptive throughout study follow-up. PrEP dispensation was more frequent among those concurrently using effective contraception, (adjusted relative risk [aRR] = 1.19; 95% confidence interval [CI] = 1.08-1.32) and contraceptive use was more common among those on PrEP (aRR = 1.63; 95% CI = 1.18-2.25). Among East African women at high risk of HIV infection, PrEP dispensation was more frequent among women using effective contraception, indicating that family planning outlets may be efficient locations to deliver PrEP.

Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV infection was demonstrated to be efficacious and safe earlier this decade from pivotal studies using oral emtricitabine-tenofovir disoproxil fumarate. Regulatory approval and normative guidance, now for almost 70 countries worldwide, has followed. Demonstration projects have shown high uptake and population-level HIV reductions, highlighting the need for simplifying delivery and reducing current barriers to access and persistence. A portfolio of additional, next-generation PrEP formulations, currently under testing, if effective, will offer users choice and likely increase coverage and impact.

In this report, we review the need for point-of-care (POC) or near real-time testing for antiretrovirals, progress in the field, evidence for guiding implementation of these tests globally, and future directions in objective antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) adherence monitoring. Two cornerstones to end the HIV/AIDS pandemic are ART, which provides individual clinical benefits and eliminates forward transmission, and PrEP, which prevents HIV acquisition with high effectiveness. Maximizing the individual and public health benefits of these powerful biomedical tools requires high and sustained antiretroviral adherence. Routine monitoring of medication adherence in individuals receiving ART and PrEP may be an important component in interpreting outcomes and supporting optimal adherence. Existing practices and subjective metrics for adherence monitoring are often inaccurate or unreliable and, therefore, are generally ineffective for improving adherence. Laboratory measures of antiretroviral concentrations using liquid chromatography tandem mass spectrometry have been utilized in research settings to assess medication adherence, although these are too costly and resource-intensive for routine use. Newer, less costly technologies such as antibody-based methods can provide objective drug-level measurement and may allow for POC or near-patient adherence monitoring in clinical settings. When coupled with timely and targeted counseling, POC drug-level measures can support adherence clinic-based interventions to ART or PrEP in near real time.

The Southern African Journal of HIV Medicine is focused on HIV/AIDS treatment, prevention and related topics relevant to clinical and public health practice. The purpose of the journal is to disseminate original research results and support high-level learning related to HIV Medicine. It publishes original research articles, editorials, case reports/case series, reviews of state-of-the-art clinical practice and correspondence.

Background: Controlled pharmacokinetic (PK) studies in United States populations have defined categories of tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) for various pre-exposure prophylaxis (PrEP) adherence targets. It is unknown how these categories perform in other populations. Therefore, we evaluated the sensitivity and specificity of these PK-derived categories compared to daily medication electronic adherence monitoring (MEMS) data among East African men and women using daily PrEP. Methods: Participants were enrolled as members of HIV serodiscordant couples as part of an open-label PrEP study in Kenya and Uganda. Blood samples were taken at quarterly visits and stored as DBS, which were analyzed for TFV-DP concentrations. Results: Among 150 samples from 103 participants, MEMs data indicated that 87 (58%) took ≥4 doses and 62 (41%) took ≥6 per week consistently over the 4 weeks prior to sample collection. Sensitivities of DBS TFV-DP levels were 62% for the ≥4 doses/week category (≥700 fmol/punch TFV-DP) and 44% for the ≥6 doses/week category (≥1050 fmol/punch TFV-DP); specificities were 86 and 94%, respectively. There were no statistically significant differences in these sensitivities and specificities by gender. Conclusion: In this sample of East African PrEP users, categories of TFV-DP concentrations developed from directly observed PrEP use among United States populations had high specificity but lower than expected sensitivity. Sensitivity was lowest when MEMS data indicated high adherence (i.e., ≥6 doses/week). PrEP studies and implementation programs should carefully consider the sensitivity and specificity of the TFV-DP levels used for adherence feedback.

Voluntary medical male circumcision (MMC) reduces risk of HIV infection, but uptake remains suboptimal among certain age groups and locations in sub-Saharan Africa. We analysed qualitative data as part of the Linkages Study, a randomized controlled trial to evaluate community-based HIV testing and follow-up as interventions promoting linkage to HIV treatment and prevention in Uganda and South Africa. Fifty-two HIV-negative uncircumcised men participated in the qualitative study. They participated in semistructured individual interviews exploring (a) home HTC experience; (b) responses to test results; (c) efforts to access circumcision services; (d) outcomes of efforts; (e) experiences of follow-up support; and (f) local HIV education and support. Interviews were audio-recorded, translated, transcribed, and summarized into "linkage summaries." Summaries were analysed inductively to identify the following three thematic experiences shaping men's circumcision choices: (1) intense relief upon receipt of an unanticipated seronegative diagnosis, (2) the role of peer support in overcoming fear, and (3) anticipation of missed economic productivity. Increased attention to the timing of demand creation activities, to who delivers information about the HIV prevention benefits of MMC, and to the importance of missed income during recovery as a barrier to uptake promises to strengthen and sharpen future MMC demand creation strategies.