This cross-sectional study is embedded within a large, ongoing Unitaid-funded implementation study (Project PrEP), which is evaluating the introduction of PrEP (including new PrEP methods) in primary healthcare settings through integrated HIV prevention and SRH services, with a focus on girls and young women 15─24 years. The project is implemented in eight fixed Department of Health facilities and four linked mobile clinics in four areas of South Africa: Tshwane (peri-urban area) in Gauteng, Gqeberha (peri-urban area) and Mthatha (rural area) in the Eastern Cape, and eThekwini (urban area) in Kwa Zulu Natal. These sites have been supported by Project PrEP to provide integrated, youth-friendly SRH services since 2018. Sites were selected to participate in Project PrEP based on the incidence of HIV and teenage pregnancy in their surrounding communities, as well as their proximity to learning institutions which serve young people. The first phase of the project supported the introduction of oral PrEP in South Africa and has been described elsewhere (9). The second phase is ongoing and has introduced the new PrEP methods dapivirine vaginal ring (DVR), since August 2023, and injectable cabotegravir (CAB-LA) since April 2024. Project service points within participating sites provide integrated HIV prevention and SRH services according to local guidelines, including HIV testing, PrEP, contraception, STI screening and management, with screening and linkage to gender-based-violence and mental health services provided. Clients known to be living with HIV and taking antiretroviral therapy are generally seen at other service points in the clinic, as are clients who are known to be pregnant, who are seen at service points providing antenatal care.

This study utilized routine programme monitoring and evaluation data from women and men ≥15 years accessing SRH and HIV prevention services through Project PrEP, at their point of entry to project services. Data encompassed client demographics and socio-behavioural characteristics, documented in clinic files by the consulting healthcare provider. Data on pregnancy, contraception use, presence of STI signs and symptoms and STI treatment in the preceding three months were also documented. Additionally, data on the provision and results of rapid point-of-care HIV testing, pregnancy screening, syphilis testing, HBV testing, the initiation of PrEP and the provision of contraception were recorded. HIV testing was provided to consenting clients, following a two-step serial testing algorithm aligned with national HIV Testing Service guidelines (10), with two positive rapid test results confirming an HIV positive status, and a single negative rapid test confirming an HIV negative status. Pregnancy testing was conducted using a point-of-care (POC) urine human chorionic gonadotropin (hCG) test. In line with national PrEP guidelines (11), clients initiated on oral PrEP underwent baseline laboratory testing for hepatitis B surface antigen (HBsAg) and those pregnant or ≥30 years had their renal function assessed through a baseline serum creatinine and estimated glomerular filtration rate at the time of PrEP initiation. Furthermore, clients seeking services who, based on the clinician's assessment, had symptoms of syphilis, may have been exposed to syphilis, or were from a vulnerable population group (i.e., men who have sex with men, sex workers and their clients, adolescent girls and young women accessing SRH services, pregnant women, mobile workers) underwent syphilis screening using a Rapid Plasma Reagin (RPR) test conducted at local laboratories. Results from laboratory-based testing for Hepatitis B and syphilis were generally available within three days, through an online laboratory results system that could be accessed by the attending clinician. Clients received their laboratory results at their next visit or were recalled to the clinic for treatment or clinical care by the attending clinician if required. Clients with STI symptoms were treated on the same day according to a syndromic management approach (12), and asymptomatic clients on the day they returned for their results if positive for syphilis. Clients testing positive for HIV were initiated on antiretroviral treatment (ART) by the attending nurse, or referred for initiation within the same clinic, on the day of testing. Clients testing positive for HBsAg were referred for further evaluation and management by the doctor at the clinic.

We conducted a cross-sectional, descriptive analysis of routinely collected data from clients accessing clinical services for the first time at project sites between June 2023 and March 2024. To examine the association between independent variables and the binary dependent variables HIV, syphilis, and HBV test results, while holding other variables constant, we fit multivariable firth's logistic regression models. Given the pronounced imbalance in HIV status (195 HIV-positive vs. 9,219 HIV-negative), syphilis status (168 positive vs. 3,136 negative), and hepatitis B status (32 positive vs. 3,218 negative), Firth's penalized logistic regression was used to correct for bias in maximum likelihood estimates that can arise under such conditions and prevent overfitting (13). Statistical significance was assessed at a p-value cutoff of 0.05. Data were analysed using Stata statistical software, version 18.0 (14).

Condoms are the only currently available multipurpose prevention technology, preventing pregnancy, HIV and other STIs; they are cost effective and should be the cornerstone of any integrated prevention package (17). However, consistent use of condoms remains a challenge and was observed to be low in this population, not dissimilar to reports from other PrEP programmes (18, 19). Low use of condoms among young women has been reported to be influenced by difficulty in negotiating use, fear of being perceived as unfaithful, and wanting to please partners (20, 21); with men reporting that forgetfulness and condoms being a barrier to pleasure impede consistent use (22). Condom use has been reported to increase among young women exposed to PrEP (18, 23), highlighting the benefits that may be achieved through strengthened integration, ongoing non-judgemental counselling, and incorporation of innovative approaches such as pleasure based messaging (17).

Among women presenting for SRH services, opportunity exists to conduct pregnancy screening and provide contraceptive services. As highlighted through our study, almost half of women accessing services were not using any contraceptive at their first visit, but 17% were provided with contraception for the first time through integrated services. South Africa has a high unmet need for contraception, reported at 19% among women of reproductive age in a 2016 Demographic Health Survey (24); higher at 31% among adolescent girls and women 15─19 years and 28% among those 20─24 years of age (24, 25). There is also evidence of unintended pregnancy being high, especially in girls and young women. As shown in an analysis of the South African National HIV Prevalence, Incidence and Behaviour Survey, only a third of women reporting pregnancy in the last five years had desired the pregnancy; even lower at 10.1% among adolescent girls and women 15─19 years and 20.9% among those 20─24 years of age. Contraception use was low, particularly in younger women, with only 12.8% of those 15─19 years and 19.7% of those 20─24 years reporting using contraception (26, 27). In addition to well-known benefits relating to improved maternal and child health, contraception has been highlighted as a key, cost-effective intervention to prevent new infant HIV transmissions, even in the context of increased antiretroviral therapy (ART) coverage (28, 29). The risk of acquiring HIV during pregnancy and the postpartum period more than doubles as compared to non-pregnant women (30). A high prevalence of STIs and a high incidence of HIV have been reported among women seeking contraceptive services (31), highlighting the need and potential to address multiple health needs through integrated service provision. This project has previously reported the increased access to contraceptives that is achieved when integrated with HIV prevention services (32).

POC testing for STIs facilitates earlier diagnosis and linkage to treatment, and is acceptable and feasible in low and middle income settings (33). However, the availability and affordability of quality-assured point of care tests remain a barrier to access. The WHO recommends supply-side interventions, in conjunction with national policy updates and funding, to improve early detection and treatment, resulting in greater impact in ending the epidemics and promoting health coverage (34). Our study highlights the benefits of POC screening and testing, with almost all clients who accessed services tested for HIV, and 9% of clients testing for HIV for the first time. The high burden of syphilis identified in this study points to the impact that may be achieved through the integration of POC syphilis tests within SRH programmes. The limitations of laboratory-based testing, including the loss to follow-up observed in our analysis (indicated by the low proportion of available results), are notable. Although only currently implemented in antenatal care settings in South Africa, increased syphilis screening and treatment may be achieved with the integration of the currently available dual HIV/syphilis POC test within HIV prevention services. These tests are acceptable, feasible and more cost effective than single tests (35), although implementation data from the region, outside of antenatal care, is limited (36).

South African national guidelines recommend HBV surface antigen screening for all pregnant women during the first trimester (37) and for all clients initiating oral PrEP (11). However, this is currently conducted through laboratory-based testing, is not routinely implemented for pregnant women, and POC rapid tests are not currently available within the national health system in South Africa (38). Integrating HBV screening with HIV prevention programmes could facilitate progress towards HBV elimination efforts (39), and could be strengthened with POC testing. Scaling testing to those who may benefit has been identified as one of the greatest challenges in achieving elimination targets for viral hepatitis (40). Use of a POC HBV tests has been shown to be feasible in antenatal care settings in South Africa (41, 42). However, further implementation research on the integration of rapid POC HBV testing within HIV prevention programmes in our context may be required.

The use of self-testing may provide further opportunity to reach partners and social networks with screening and testing services, optimising identification, and early treatment of infection to prevent transmission and reinfection. HIV self-test kits are available in South Africa, and secondary distribution has been acceptable in antenatal care settings (43). Further opportunities for integration of syphilis self-testing, when available, also exist (44).

In keeping with other implementation studies in the region (45, 46), and as reported previously for this project (9), we observed a high uptake of HIV PrEP when offered within a package of integrated prevention services. PrEP has been shown to be highly effective in preventing HIV and is a key component of combination HIV prevention and Triple Elimination efforts (7, 47). Initiatives to accelerate access to meet global prevention targets are, however, still required (48). The introduction of newer, long-acting PrEP methods has the potential to further enhance PrEP uptake and effective use for the prevention of HIV. One advantage of oral PrEP over long-acting PrEP methods, however, is its activity against HBV. Tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) within the oral PrEP combination of TDF and emtricitabine (FTC), are potent inhibitors of HBV viral replication and effective at both preventing HBV acquisition and suppressing HBV replication (39, 49). Globally, challenges with testing and treatment for chronic HBV remain, with less than 3% of people living with chronic hepatitis B globally treated in 2022 (50). Oral PrEP services thus provide an opportunity to facilitate integrated prevention interventions for both HIV and HBV, whilst improving access to treatment for people with HBV (39, 49). It has however been recommended, due to concerns about hepatitis reactivation, or “flares”, in people with chronic HBV who discontinue TDF/FTC, that there is closer follow up and monitoring of those with HBV infection who initiate TDF/FTC PrEP (49). The lack of benefit against HBV with long-acting PrEP methods could be overcome through integrated HBV screening regardless of PrEP method and ensuring availability of a choice of PrEP methods to suit different individual needs (49).

HBV vaccination has been a key success in combatting hepatitis infection, with widespread adoption of childhood immunization globally (40). In South Africa, substantial declines in hepatitis B incidence have been achieved since the inclusion of HBV vaccination for children as part of the expanded programme for immunization (EPI) since 1995 (51, 52). Whilst most programming is focused on childhood vaccination, and intensified focus and strengthening of birth dose vaccination more recently (40), there is opportunity to provide catch up vaccination to non-immune adults, especially those with HIV, who inject drugs or who may be exposed through sexual transmission, as is recommended in national guidelines (37). Within our study population, approximately half of the cases of hepatitis B identified were amongst clients born after the introduction of childhood immunization. Where HBV screening is integrated within HIV prevention programmes, additional laboratory testing would need to be conducted to confirm immunity (37), but the three dose HBV vaccination schedule can be aligned to PrEP follow up visits to facilitate integration (39).

Linkage to care and treatment for individuals diagnosed with HIV, HBV, or syphilis through SRH programmes should be prioritized and is the second pillar of triple elimination efforts. Ideally this should be provided on the same day, by the same healthcare provider and at the same service point, to facilitate integrated care. National guidelines in South Africa recommend a first line antiretroviral therapy (ART) regimen which includes TDF and lamivudine (3TC), which has the benefit of treating both HIV and hepatitis B (39, 53).

Although this study was conducted across four geographical areas of South Africa, the sampling frame did not include a representative sample of all SRH service users and the findings may not be representative of other contexts, particularly where the burden of HIV, HBV and syphilis differs. These data were collected from healthcare users who had presented for SRH and HIV prevention services and may not fully represent populations who have not accessed or experience barriers to accessing healthcare services. It is also notable that clients known to be living with HIV or who were pregnant would likely have received services at other service points in the clinic, and this data would not be representative of these populations. Incomplete laboratory results, particularly for syphilis and hepatitis B, may also have introduced bias. In addition, the lack of data on treatment outcomes for clients diagnosed with HIV, hepatitis B or syphilis and the cross-sectional study design limits analysis of outcomes and trends over time. The proposed opportunities for integration of triple elimination efforts that are discussed, are drawn from the data in our analysis and literature from the field but would be further supported by implementation research to determine their acceptability, feasibility, and cost effectiveness in specific contexts.