HIV Prevention Tools Across the Pregnancy Continuum: What Works, What Does Not, and What Can We Do Differently?

Abstract

Purpose of Review

Multiple tools exist to support the primary prevention of HIV in pregnant and postpartum women; however, there are opportunities to enhance their use and impact. This review summarizes the current status of HIV prevention tools and existing gaps and opportunities to improve their use along the pregnancy care continuum.

Recent Findings

HIV screening efforts have steadily improved with close to universal screening of pregnant women in several East and Southern African countries. Strategies to implement partner testing through the distribution of HIV self-test kits are promising though linkage to care remains challenging. Syphilis screening rates are increasing though detection of other sexually transmitted infections could benefit from improved diagnostic capacity. Male and female condoms are rarely used and are often not the optimal tool of choice during pregnancy. Oral pre-exposure prophylaxis (PrEP) is a promising tool, although barriers such as the need for daily adherence, side effects, and stigma may limit its use. There is a growing pipeline of PrEP agents with alternative delivery platforms that might suit women’s preferences better and supports the notion that choice is vital to improving HIV prevention coverage during the pregnancy-postpartum continuum.

Summary

Clear guidance on which tools to use and how to use them, safety data supporting their use, and surveillance data documenting the scale and effectiveness of the tools will be imperative in establishing a path to more impactful prevention efforts among pregnant and postpartum women.

Introduction

We have developed systems to identify and treat pregnant women with HIV and prevent HIV in their infants; however, we have missed opportunities to establish a clear prevention pathway for the uninfected and at risk. Women of childbearing age continue to be disproportionately affected by HIV and, in high HIV prevalence settings (such as East and Southern Africa), account for nearly 50% of new HIV infections [1, 2]. Moreover, HIV incident infections in pregnancy contribute to 25% of infections in infants [3]. Few women of childbearing age routinely seek primary care services before pregnancy; thus, antenatal care is a vital entry point into the healthcare system to leverage for HIV prevention [4]. Entry points along the continuum of care in pregnancy include pregnancy diagnosis, delivery at the health facility, and postpartum care. Each entry point is an opportunity for providers to test women for HIV, assess their risk for HIV acquisition if uninfected, and provide HIV prevention tools based on risk.

However, linking pregnant women to HIV prevention tools is challenging, and often these prevention tools remain unused by pregnant women [5]. The reasons for this are multiple and complex. They include the difficulty of assessing HIV risk, caution among policymakers (and perhaps women) due to concern about the safety of prevention tools, and the lack of clearly defined metrics that show a clear path to impact. This paper explores opportunities to streamline the HIV prevention pathway in pregnancy. Based on the latest evidence and our experiences in the field, primarily in sub-Saharan Africa, we review what’s working, what’s not, and current and future opportunities to optimize HIV prevention tools across the pregnancy care continuum.

Determining HIV Status and Assessing HIV Risk

Screening pregnant women for HIV during their first antenatal care encounter is the natural first step in the HIV prevention cascade. Since the early 2000s, HIV testing rates in East and Southern Africa have steadily increased, with over 90% of pregnant women screened in most countries in this region [6, 7]. The factors contributing to the success of HIV screening in these settings are well-documented and include:

• High antenatal care attendance (data from the UNICEF data warehouse shows that over 90% of pregnant women attend at least one antenatal care visit in these countries).

• Well-funded and politically supported PMTCT campaigns with clear evaluation metrics [7].

• The introduction of rapid HIV antibody tests ensuring same-day result availability, and

• The introduction of provider-initiated (including mandatory and opt-out approaches) vs. voluntary counseling and testing [8].

Three important areas to address to improve antenatal engagement of women for HIV prevention are increased attention to West and Central Africa, accessing women who do not attend antenatal clinic at other venues, and encouraging earlier antenatal attendance. Testing rates have been comparatively lower in West and Central Africa for multiple reasons, including a lack of awareness of PMTCT programs, poor antenatal care attendance, and socioeconomic disparities among women [7]. While we are edging closer toward universal screening of pregnant women, women who do not attend antenatal care and are potentially at higher risk for HIV infection constitute a pivotal gap in attaining this goal [9]. Additionally, we are not screening most pregnant women early enough — in the first trimester of pregnancy [10]. Early screening is encouraged because of the persistent risk of HIV acquisition throughout pregnancy and early postpartum and to ensure women benefit from prevention tools earlier in pregnancy [11, 12]. However, only an estimated 25% of women attend antenatal care in the first trimester in sub-Saharan Africa [13]. Additionally, women are less likely to participate in pre-conception care in low-resource settings [14–16]. Early gaps in the pregnancy care continuum might benefit from alternative healthcare delivery models that engage women at the community level [9, 17].

Among HIV-negative women, the WHO encourages validated screening tools to evaluate a woman’s risk for HIV. Risk for HIV is assessed based on clinical and behavioral factors (i.e., sexually transmitted diseases, condom use, and number of sexual partners) and the local HIV burden [5, 18]. Risk scoring tools for women in East and Southern Africa exist [19, 20], but there has only been one validated for pregnant women in this region [18]. However, screening tools can often appear obtrusive and be challenging to implement in busy clinics. Group counseling and self-screening options might be alternative approaches that allow women to assess their risk better and inform decision-making around the use of prevention tools.

Once women are identified to be at risk (ideally self-identified at risk and requesting HIV prevention tools), multiple HIV prevention tools may be useful. These include risk reduction counseling, partner testing and linkage to care, screening and management of sexually transmitted infections (STIs), male and female condoms, and pre-exposure prophylaxis (PrEP) [5]. Risk reduction counseling includes various messaging strategies targeting individuals, couples, or groups and aims to reduce behavior that increases one’s risk of acquiring HIV [21]. Partner testing and screening for STIs (described below) can help women better assess their risk before using HIV prevention tools.

Partner Testing and Linkage to Care

In the early 2000s, the United Nations proposed a strategy to prevent primary infection in young women, incorporating knowledge of partner HIV status as a critical component [22]. The WHO subsequently endorsed two approaches for increasing male partner awareness of HIV status in 2012: (1) couples HIV testing and counseling involving disclosure of HIV status at the same time and (2) partner testing — the independent testing of male partners after testing the woman [23]. In practice, couples counseling and testing is challenging to implement. Men are unlikely to attend antenatal care, and the current healthcare system and cultural contexts do not encourage them to do so [24, 25].

While there are a growing number of national policies integrating partner testing into antenatal care guidelines, heterosexual men represent a substantial gap in testing efforts [26, 27]. Research shows that strategies to implement partner testing, such as partner notification where the woman invites her partner for clinic-based testing through verbal and written messages, have yielded minimal increases in testing coverage [28]. Home-based testing strategies, while promising, are sometimes limited by cost and unavailability of partners when the health worker visits women and their partners at home [29]. Women distributing HIV self-tests to their partners at home appears most promising and has increased partner testing uptake in recent studies [30•, 31, 32]. Ultimately, presenting women with multiple options to test their partners is important to cater to their diverse needs [33, 34]. As partner testing efforts as scaled up, this can play an essential role in helping women make more informed decisions about taking PrEP [35]. However, more work is needed to effectively link partners to treatment of HIV positive, and prevention services (e.g., vertical male medical circumcision), if HIV negative [36, 37].

Screening and Management of Sexually Transmitted Infections

The WHO recommends STI screening and treatment in pregnant women, emphasizing syphilis, which causes genital ulcers and increases HIV transmission [5, 38]. Given the additional benefits to the mother and infant beyond HIV prevention, the WHO launched a global action plan for eliminating mother-to-child transmission of syphilis in 2007 with the aim of 95% coverage of syphilis testing and treatment among pregnant women [39]. Several countries adopted universal antenatal syphilis screening programs using rapid on-site syphilis testing to accelerate maternal treatment and prevention of newborn complications of syphilis [39, 40]. As of 2016, 47% of pregnant women worldwide were screened for syphilis, and 76% of those with syphilis detected were treated [41].

However, there have been limited efforts to scale up the prevention, testing, and treatment of other asymptomatic STIs during pregnancy, such as Chlamydia trachomatis and Neisseria gonorrhea. Yet these STIs also significantly increase the risk of HIV transmission [42–46]. The mainstay of diagnosis for other STIs has primarily been syndromic — based on clinical signs and symptoms — due to fewer resources, inadequate laboratory services, and the need to deliver immediate care [47, 48]. However, syndromic management does not detect asymptomatic STIs [49] may result in misdiagnosis and subsequent overuse of antibiotics (particularly concerning due to gonorrhea antimicrobial resistance) [50], and does not allow for antimicrobial susceptibility testing and routine surveillance. Pilot studies in Botswana and South Africa demonstrate high acceptability and feasibility of molecular testing for chlamydia and gonorrhea (via the GeneXpert® platform) in antenatal care [51, 52]. Integrating improved diagnostic capacity to identify STIs in pregnancy represents an overlooked opportunity to improve HIV prevention efforts in antenatal care settings.

A recent modeling study from Botswana suggests placing point-of-care devices in high-volume antenatal sites that serve as testing hubs for low-volume sites might result in lower costs per infection averted compared to the syndromic approach [53]. However, real-world implementation studies are needed to test the effect of point-of-care deployment strategies on maternal, partner, and perinatal outcomes in antenatal care. Further, providing pregnant women with options for testing and treating their partners will be critical in preventing reinfection and reducing their HIV risk [54].

Male and Female Condoms

Male and female condoms are the only multipurpose prevention technologies (MPTs) that are currently recommended as an HIV prevention tool for pregnant and breastfeeding women [5]. MPTs protect against at least two combinations of pregnancy, HIV, or other STI. When used consistently, male condoms are an effective method to prevent transmission [55, 56]. However, pregnant women and their partners rarely use male condoms [57, 58]. It is often challenging for women to negotiate male condom use in stable partnerships and where power imbalances in relationships leave little room to share equal roles in decision-making [59–61].

Although female condoms would ideally address some of these barriers, their introduction and uptake have been slow (less than 1% of women having ever used them), with limited support at the policy level [62, 63]. Initially introduced in 1993 to provide dual protection against unintended pregnancies and sexually transmitted infections, there is still limited evidence on their effectiveness in preventing HIV transmission [64]. Additionally, cost, accessibility, male partner acceptance, and use difficulties limit uptake [62, 65]. We are yet to see convincing evidence of condoms being a viable option for prevention during pregnancy and postpartum [66, 67].

Other promising MPTs that might offer women more discreet and controllable options are in the early stages of clinical development and comprise various delivery platforms such as tablets, injections, patches, implants, and intravaginal rings [68]. The availability of multiple MPTs might help simplify access, transition, and uptake of prevention options because they cater to the changes in needs across the continuum of care in pregnancy [69, 70]. However, to fully benefit from MPTs, we will need to pay attention to how women’s needs change (e.g., a vaginal product used during pregnancy may not be desired postpartum during the healing process or when sexual frequency may increase). We also need to create opportunities to make transitions seamless (e.g., substituting a product with the same delivery mechanism and dosing frequency, such as a vaginal MPT with an HIV prevention vaginal ring).

Pre-exposure Prophylaxis Agents

The WHO endorses the use of PrEP agents in HIV-negative pregnant and breastfeeding women to reduce the risk of acquiring HIV and complement existing prevention efforts in antenatal care programs [5]. Currently approved PrEP agents include the combination drug tenofovir disoproxil fumarate/emtricitabine (TFD/FTC), an oral pill taken once daily for the duration of risk. When taken as directed, TDF/FTC can reduce HIV transmission in individuals at risk by over 90% [71–73]. Furthermore, a growing body of evidence suggests that TDF/FTC can be taken safely during pregnancy [74, 75].

Despite its efficacy and reassuring safety profile, PrEP implementation generally remains low. The barriers to PrEP at the individual, provider, system, and policy level are well-described — difficulty in evaluating one’s risk, adherence to PrEP, side effects, stigma, lack of trained providers, PrEP supply interruptions, and lack of clearly defined policies. However, recent demonstration studies in Kenya and South Africa suggest that pregnant and postpartum women might be more likely to initiate and continue PrEP than their non-pregnant or postpartum counterparts. In particular, women who had a higher perception of their risk or knew that their partner was living with HIV were more likely to initiate and continue PrEP [76•, 77•]. The motivation to initiate and continue PrEP during pregnancy and breastfeeding might reflect the need to protect infants from contracting HIV [78]. To fully benefit from PrEP, antenatal and postpartum care programs need more clearly defined strategies to identify women who need PrEP and monitor and support those on PrEP [79, 80].

Long-acting prevention tools (injectables, oral formulations, subcutaneous implants, and intravaginal rings) in the pipeline could overcome adherence difficulties with daily oral PrEP and increase the number of discreet prevention options for pregnant and postpartum women [81]. The long-acting injectable cabotegravir (CAB-LA), recently approved by the FDA for cis-gender women, is administered as an injection every 2 months. Findings from the HPTN 084 trial that resulted in regulatory approval showed that CAB-LA was more effective in reducing the risk of HIV acquisition compared to tenofovir containing daily oral PrEP [82]. Studies are ongoing to evaluate the safety of CAB-LA during pregnancy. However, findings from the trial show that residual CAB-LA was well-tolerated among participants who became pregnant and stopped taking CAB-LA per trial guidelines [83]. In 2021, the WHO recommended the intravaginal ring that releases the HIV prevention drug, dapivirine, as a monthly prevention option for cis-gender women however safety data during pregnancy is pending [84]. Other formulations, such as islatravir (as a monthly oral formulation or bi-annual subcutaneous implant) and lenacapavir (as a semiannual subcutaneous injection) are promising and still under investigation [85]. Establishing safety and efficacy data for pregnant women by ensuring their participation in ongoing clinical trials is critical to expediting access to these novel PrEP agents [81].

Conclusion and Future Directions

The primary prevention of HIV in pregnant women is a longstanding priority to eliminate vertical HIV transmission and protect women during pregnancy. Yet, primary HIV prevention in pregnancy persists as a global health challenge. Identifying optimal strategies for partner testing through the secondary distribution of HIV self-testing kits is ongoing, with few data available on partner self-testing outcomes beyond women’s self-reports and limited evidence on impact of secondary distribution approaches on HIV incidence [31, 32, 86]. Syndromic STI screening approaches that are suboptimal or inaccurate persist as the standard of care in several settings. There are limited opportunities for diagnostic STI testing beyond syphilis, despite the high burden of STIs among pregnant women in settings with high HIV prevalence [87]. HIV prevention tools, such as male and female condoms, are chronically underutilized and perhaps not the optimal tool of choice based on user experiences, relationship dynamics, and preferences among women in HIV high-burden settings [88, 89]. Oral PrEP is a promising HIV prevention tool in pregnancy with demonstrated acceptability and feasibility in Kenya and South Africa [76•, 77•]. Ongoing studies will refine and expand the suite of PrEP options to suit women’s preferences better and support the notion that choice is vital to improving HIV prevention coverage [80]. Optimizing HIV prevention tools requires clear policies and guidelines, structured implementation plans, provider training, community awareness campaigns, strong supply, and distribution logistics, monitoring and evaluation systems, and reliable funding sources [81].

While national governments have established policies recommending HIV prevention tools, including oral PrEP, safety data for the additional PrEP agents in the pipeline will be important in expediting their inclusion in relevant policies and guidelines [81]. Beyond this, guidance on how the tools should be rolled out and used informed by the growing body of implementation research evidence will be critical. For example, what algorithm can providers and women use to identify which tools to use and when and on whom? How should these tools be integrated into the clinical work-flows? While antenatal care is arguably a critical entry point and helps normalize HIV prevention because many women access antenatal care, we need to create opportunities and define approaches for other entry points in the pre-conception and postpartum period [9, 17]. We also need to ensure women benefit from prevention tools earlier in pregnancy.

The effects of HIV prevention tools used during pregnancy at a population level remain unknown due to relatively low uptake outside of research settings and lack of pregnancy-specific PrEP use tracking within national programs. Standardizing key performance indicators to measure or monitor progress would help facilitate impact evaluation. Improving the capacity to continuously monitor whether pregnant women access prevention tools and effectively use them will bolster efforts to train providers and motivate them to encourage their use. Additionally, this data will help educate the community about the benefits of HIV prevention tools along the pregnancy continuum.

Ensuring HIV-negative pregnant and postpartum women gain access to and effectively use HIV prevention tools that meet their needs is imperative in tackling the growing burden of HIV in women of reproductive age. Clear guidance on which tools to use and how to use them, safety data supporting their use, and surveillance data documenting the scale and effectiveness of the tools will be imperative in establishing a path to more impactful prevention efforts among pregnant and postpartum women.