Beyond barriers: The role of preexposure prophylaxis in the prevention of human immunodeficiency virus in women

Abstract

Preventive measures for human immunodeficiency virus infection have greatly evolved with the approval of preexposure prophylaxis. Despite their effectiveness, a significant gap exists in the initiation and adherence to these preventive measures among cisgender women. This review aims to highlight available implementation models to increase preexposure prophylaxis use and adherence in this population. A narrative review was conducted to identify studies focusing on preexposure prophylaxis use among cisgender women. Ultimately, 15 studies were included and categorized based on their intervention type: behavioral, health clinic, community, pharmacy, technology, or mobile. This review identified several intervention models that improved preexposure prophylaxis use and adherence among cisgender women. Behavioral interventions, such as preexposure prophylaxis-trained nurses and combined counseling with short message service reminders, significantly improved adherence. Health clinic-based interventions demonstrated the importance of regular follow-up and the potential for improved adherence through injectable preexposure prophylaxis. Community interventions highlighted the effectiveness of referral systems and technology-driven approaches, including mHealth interventions and real-time electronic adherence monitoring, to promote preexposure prophylaxis uptake and adherence. Implementing diverse interventions may considerably improve adherence and reduce the human immunodeficiency virus transmission rates in this population.

Keywords

Preexposure prophylaxis human immunodeficiency virus women prevention antiretroviral

Introduction

Preventive measures for human immunodeficiency virus (HIV) infection have greatly evolved since the approval of preexposure prophylaxis (PrEP).¹ PrEP is highly effective in reducing the risk of contracting HIV when adherent to therapy. Within the scope of HIV infection, a greater number of studies have assessed men living with HIV/AIDS. In 2021, 81% of new HIV diagnoses were among men.² At the end of 2016, women, both adults and adolescents, constituted approximately one-quarter of all individuals diagnosed with and living with HIV in the United States.³ In 2022, 39 million people were reportedly living with HIV globally, with 53% being women and girls. Additionally, of the total new diagnoses in 2022 worldwide, 46% were attributed to women and girls.⁴ Although there is a large gap between the number of women and men living with HIV, there are limited resources for the use of PrEP in women, despite the risks associated with developing HIV infection. Unfortunately, many people and healthcare providers lack an understanding of the value of these prevention methods, as shown by a lack of initiation. According to data from AIDSVu, women comprised only 8% of PrEP users, whereas men accounted for 92%, despite women representing 19% of new HIV diagnoses that year.⁵ However, according to the UNAIDS Global AIDS Update, approximately 470,000 women and 260,000 men were using PrEP globally in 2021.⁶ Although the number of cases of PrEP initiation is rising, there is still a drastic need to increase the number of women initiating these preventive treatments to minimize the risk of HIV-related complications, such as increased risk of cervical cancer, opportunistic infections, other sexually transmitted infections (STIs), gynecologic issues, and fetal transmission.⁷ This need is particularly urgent in low-income countries where the incidence of HIV infection is high. In 2021, only approximately 42% of districts within sub-Saharan Africa could provide HIV prevention programs for adolescent girls and young women (AGYW) despite this population being three times more likely to acquire HIV than their male peers in 2022.⁴ There has been a drastic increase in the number of STI cases within the United States. The Department of Health and Human Services reported more than 2.5 million new cases of chlamydia, gonorrhea, and syphilis in 2021.⁸ Specifically, 50% of this increase has been observed among people aged over 65 years, many of whom are women. Older adults are less likely to be tested and generally have additional comorbid conditions that may obscure the symptoms of new STIs or HIV infection.⁹ It is necessary to analyze the disparities encountered by women due to the lack of data evaluating PrEP initiation and adherence. When taken as prescribed, PrEP can reduce the risk of developing HIV through sex by approximately 99% and by at least 74% among IV drug users.¹⁰ The currently approved options for oral PrEP include emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide. However, female individuals at birth are not eligible to receive emtricitabine/tenofovir alafenamide, leaving only a limited options. Injectable PrEP interventions, such as long-acting cabotegravir, demonstrated a 79% reduction in the risk of HIV contraction and are available to cisgender females.¹¹ Recent studies have highlighted the promising potential of twice-yearly lenacapavir for HIV prevention in women. The PURPOSE 1 trial, which compared twice-yearly lenacapavir with once-daily oral emtricitabine/tenofovir alafenamide or emtricitabine/tenofovir disoproxil fumarate, found no incident cases of HIV infection among the 2134 women and adolescent girls in the lenacapavir group, whereas the emtricitabine/tenofovir disoproxil fumarate group reported 16 cases and the emtricitabine/tenofovir alafenamide group reported 39 cases. Additionally, the trial revealed that lenacapavir was well-tolerated with a favorable safety profile, indicating its effectiveness and potential as a preferred HIV prevention method for women.¹² Innovations in long-acting prevention and treatment have the potential to shift the story of HIV from stigma and dependency to empowerment and healthy living. However, it took South Africa a decade to match the number of individuals initiated on oral PrEP with that in the United States. Currently, over 7 million people need PrEP access, falling short of the global target of 10.6 million individuals using it consistently.^13,14 There is an urgent need to develop better methods for distributing PrEP to reduce these disparities and achieve greater global equity. Although this review aims to encompass methods used globally, we acknowledge that women’s rights and access to healthcare, including access to PrEP, vary significantly by country and region. These disparities undeniably shape the barriers women face in accessing sexual and reproductive health services. The purpose of this narrative review was to highlight the implementation models available for increasing PrEP use, access, and adherence among women worldwide.

Methods

This review involved an analysis of studies focused on the use of PrEP among women, especially AGYW (aged 15–24 years). For this narrative review, a search was performed across PubMed, yielding a total of 448 studies. The search criteria included studies published between 1 January 2019 and 24 July 2024 and those published in English. The following keywords were used as search terms: “PrEP,” “HIV,” “women,” “antiretroviral,” “tenofovir,” “cabotegravir,” and “prevention.” Seven search terms were utilized, as incorporating more detailed searches resulted in the unintended exclusion of relevant articles aligned with our research objectives. The filters included sex (female), article type (clinical trial), and publication date (within past five years). Titles and abstracts were screened by all authors to identify studies that incorporated implementation models, such as behavioral interventions, health clinics, community, pharmacies, technology, or mobile. One author was responsible for mitigating discrepancies regarding included articles. For the purpose of this article, we defined implementation models as any structured approach to deliver and scale interventions aimed at increasing PrEP uptake among women. After removing 152 duplicate records, we screened articles based on their titles and abstracts. Articles were screened for their focus on PrEP, implementation models, clinical data, and inclusion of women, as shown in Figure 1.

Figure 1.

Included studies.

Results

Study selection

Of the 448 studies generated utilizing the search methodology outlined above, 296 remained for initial title evaluation after deleting duplicate entries. Subsequent screening of titles and abstracts led to the exclusion of 220 studies. Upon full-text scrutiny, 46 studies were deemed clinically irrelevant because they did not focus on PrEP or did not include an implementation model. Furthermore, these studies either did not include cisgender women and had a separate results section for cisgender women or did not include the study’s criteria. A total of 15 studies were included; the studies were classified based on intervention into behavioral intervention, health clinic, community, pharmacy, technology, or mobile.

Behavioral interventions

As shown in Table 1, five studies evaluated the effect of various behavioral interventions on PrEP use and adherence among women of varying ages.^15–18 Behavioral interventions have been found to be common among studies that aim to improve PrEP adherence due to the role of mental engagement in preventing HIV. Although HIV status has been the outcome of interest in many studies, the knowledge of healthcare workers (HCWs) can be evaluated to determine whether healthcare professionals are providing effective and transparent information to people regarding their health. A study conducted in Kenya sought to determine whether the use of standardized patient actors can improve HCW counseling for AGYW on PrEP.¹⁵ A total of 564 training cases were recorded during the study among 94 HCWs. HCWs had effective communication and interpersonal skills but lacked the ability to adhere to PrEP guidelines, due to the study’s self-reported nature limitation that was used to quantify the quality of PrEP counseling. As the study progressed, adherence to the PrEP guidelines increased considerably.

Table 1.

Clinical studies based on intervention.

Lead author, publication year	Location	Baseline population	Model/intervention	Outcome
Behavioral intervention
Larsen et al. 2022¹⁵	Kenya	n = 94 HCW	2-day training for HCWs where standardized patient actors were presented to evaluate the ability to discuss key aspects of patient counseling for PrEP.	Although HCWs demonstrated high baseline communication (95.3%) and interpersonal skills (83.7%), adherence to PrEP guidelines at baseline was suboptimal (57.6%). By the fourth case presented, improvements were noted in all domains.
Roberts et al. 2023¹⁶	South Africa, Uganda, and Zimbabwe	n = 247 HIV-negative AGYW, aged 16–21 years	Monthly counseling sessions with DLF plus optional daily SMS reminders, weekly phone or SMS check-ins, peer support clubs, “peer buddies” and additional counseling to determine adherence to dapivirine rings and oral PrEP.	49%–68% demonstrating high adherence to oral PrEP, and 73%–89% for the ring. The most popular support strategies were in-person clubs and weekly calls, followed by online clubs, additional counseling, and SMS.
Ichite et al. 2023¹⁷	Miami, USA	n = 38 HIV-negative women aged 19–44 years	6 months of combination face-to-face educational sessions and telephone follow-up among patients receiving PrEP at a publicly funded health clinic in Miami Dade County.	65% (n = 25) received full intervention.Among the 13 women who discontinued the intervention prior to 3 months (T1), the majority (77%) did so because their phones had been disconnected or their PrEP care had been self-discontinued.
Mudimu et al. 2022¹⁸	South Africa	n = 603 AGYW aged 16–25 years on PrEP for a total of 1280 months	AGYW were randomized to receive group-based community health club effective use counseling, individualized effective use counseling, or community-based PrEP dispensary.	Individualized effective use counseling increased the standard-of-care cost in PrEP delivery by 89%, group-based community health effective use counseling increased the standard-of-care cost in PrEP delivery by 11%.
Health clinic
Celum et al. 2022¹⁹	Kenya and South Africa	n = 2550 HIV-negative AGYW aged 16–25 years	Implementation of PrEP in family planning clinics with follow-up visits occurring at month 1 and quarterly for up to 36 months.	2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month.6-month follow-up: 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) individuals had a gap and restarted PrEP.
Mugwanya et al. 2019²⁰	Kenya	n = 1271 women aged 15–45 years	PrEP delivery for AGYW in FP clinics	278 (22%) initiated PrEP, and 114 (41%) returned for at least one refill visit after initiation. Continuation of PrEP use at 1, 3, and 6 months post-initiation was 41%, 24%, and 15%, respectively.
Tolley et al. 2019²¹	Zimbabwe, South Africa, and two United States phase 2 trial sites.	n = 136 (100 African, 36 US) women with a median age of 31 years	Quantitative surveys were administered at the first, fourth, and sixth injection visits. FGD were conducted after the sixth injection visit.	Most US and African participants preferred injectable PrEP over daily oral pills (56%–96% vs. 4%–25%).
Community
Medina-Marino et al. 2022²²	South Africa	n = 1164HIV-negative women aged 16–25 years	Participants completed a baseline questionnaire and were referred for PrEP services at a community-based PrEP site colocated with pop-up HTS tents.	825 (74.3%) completed a questionnaire and 806 (97.7%) were referred for community-based PrEP603 (96.6%) initiated PrEP, 59.1% initiated within 0–3 days, 25.6% within 4–14 days, and 15.3% took ≥15 days to initiate; 100% of AGYW who used pop-up HTS initiated PrEP the same day.
Velloza et al. 2022²³	South Africa and Zimbabwe	n = 427 women aged 16–25 years	Evaluated high PrEP adherence represented by intracellular plasma tenofovir diphosphate concentrations of ≥700 fmol/punch or recent PrEP adherence by plasma tenofovir ≥ 40 ng/mL at weeks 13, 26, and 52.	Any detectable level of tenofovir diphosphate was associated with a higher HIV risk (aRR of 1.15, 95% CI: 1.03–1.29, p = 0.013). Any detectable level of tenofovir in the plasma was associated with a higher HIV risk (aRR: 1.27, 95% CI: 1.09–1.49, p = 0.0022).
Fearon et al. 2019²⁴	Zimbabwe	n = 611 HIV-negative female sex workers	Seven respondent-driven sampling surveys were analyzed from the intervention sites of a pragmatic cluster-randomized trial in Zimbabwe in 2016.	There were 343 (54.7%) women reporting adherence to condoms and/or PrEP, leaving almost half uncovered.
Pharmacy
Pintye et al. 2023²⁵	Kenya	n = 235 AGYW aged 15–24 years	PrEP-trained nurses were stationed at three retail pharmacies.AGYW purchasing contraception (emergency contraception, oral contraceptive pills, injectables, implants, condoms) were counseled on PrEP, completed HIV testing, and offered a free 1-month supply of PrEP pills per national guidelines by nurses under supervision of a remote physician.	PrEP uptake was 85%; at 1 month, 82% had initiated PrEP use and 68% planned to continue use.Among those initiating PrEP, 69% were willing to pay for PrEP at retail pharmacies.
Technology based
Lavoie et al. 2023²⁶	Botswana	n = 131 HIV-negative women aged 18–24 years	Completed a survey assessing the feasibility and perceived acceptability of the mHealth peer-delivered interventions mobile technology (mHealth).	84.7% (n = 111) reported being interested if it was available to them by the facility,51.8% (n = 44) preferred a hybrid model (combination of in-person and mHealth), 30.6% (n = 26) through mobile technology, 15.3% (n = 13) in-person at the facility, and 2.4% (n = 2) in-person in the community.
Ogello et al. 2024²⁷	Kenya	n = 348 young women aged 19–22 years	A wireless real-time electronic adherence monitor holds approximately 30 PrEP tablets and every time it is opened, it records each opening with a date-and-time stamp as a proxy for pill ingestion.	95% (n = 65) participants in Kisumu and 70% (n = 121) in Thika completed 24 months of follow-up.
Celum et al. 2021²⁸	South Africa, Cape Town, and Zimbabwe	n = 451HIV-negative women aged 16–25 years	Randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular TFV-DP levels in DBS for 12 months.	At 6 months, 21% (36/179) of AGYW in the enhanced arm had high adherence (TFV-DP ≥700 fmol/punch) and 22% (40/184) in the standard adherence support arm had high adherence (adjusted OR: 0.92; 95% CI: 0.55–1.34; p = 0.76).
Mobile
Rousseau et al. 2021²⁹	South Africa	n = 1784 AGYWaged 18–24 years	Mobile health clinic: an educational area; four individual consultation rooms for point-of-care HIV and pregnancy testing and health counseling; and a PrEP and contraception dispensing room. In-depth interviews of a subset of 30 AGYW described the CMHC intervention for PrEP delivery as acceptable and accessible.	32% (n = 585) of the participants initiated PrEP on the same-day.

Table 1 presents an overview of clinical studies categorized by the implementation model type (e.g. behavioral intervention, health clinic, and community-based models). Each study is described by its location (country and city), baseline population (number of participants (n) and target population), the intervention or model implemented, and the reported outcomes. The table highlights the effectiveness of each model based on trial results.

AGYW: adolescent girls and young women; aRR: adjusted rate ratio; CI: confidence interval; CMHC: community-based mobile health clinic; DBS: dried blood spots; DLF: drug-level feedback; FGD: focus group discussions; FP: family planning; HCW: healthcare worker; HIV: human immunodeficiency virus; HTS: HIV testing services; OR: odds ratio; PrEP: preexposure prophylaxis; SMS: short message service; TVF-DP: tenofovir diphosphate.

Another study conducted among multiple countries in Africa used a combination of counseling, short message service (SMS) reminders, peer support, and drug-level feedback to determine adherence rates among 247 AGYW using dapivirine rings or oral PrEP.¹⁶ In total, 73%–89% of people in the study group receiving the dapivirine ring reported adherence, whereas 49%–68% of people in the oral emtricitabine/tenofovir disoproxil fumarate PrEP group reported adherence. They also concluded that in-person activities and continuous calls/SMS were the most favored support strategies among the participants.

Within the United States, a study piloted in Miami combined 6 months of data from in-person educational sessions and telephonic follow-up among cisgender women without HIV who were aged 19–44 years and received PrEP at a publicly funded clinic.¹⁷ By the end of the study, 65% of women had received the full intervention. However, among those who discontinued treatment, the majority reported failure due to device issues or discontinuation of PrEP for unknown reasons.

Another study conducted in South Africa randomized 603 AGYW on PrEP to receive community group-based behavioral programs (referred to as health clubs, group-based effective use counseling, individualized effective use counseling, or community-based PrEP dispensaries) to understand the costs associated with PrEP initiation.¹⁸ Individualized effective use counseling was associated with the highest cost, increasing the standard-of-care cost by 87%. However, other methods demonstrated only a 11% increase in the standard-of-care cost.

Behavioral interventions are useful in many disease states across healthcare, thus encouraging their use in HIV prevention.

Health clinic

Studies have been conducted throughout Africa to determine the adherence rates of PrEP in women when it is implemented and followed in health clinic settings. Table 1 presents four studies that demonstrated the relationship between clinic visits and patient PrEP adherence. In a large study in South Africa, 2550 HIV-negative AGYW aged 16–25 years were initiated on PrEP in family planning clinics who were scheduled for follow-up at 1 month and quarterly for up to 36 months.¹⁹ Ninety-four percent (n = 2397) initiated PrEP, and 31% requested a refill at 1 month. Upon further evaluation, at the 6-month time point, 20% (n = 128) of the participants continued PrEP, whereas 14% experienced treatment interruption but successfully reinitiated PrEP during this period.

Similarly, a study in Kenya evaluated PrEP adherence in AGYW aged 15–45 years in family planning clinics.²⁰ Of the 1271 women screened, 22% (278) initiated PrEP, and 41% (114) returned for at least one refill after initiation. The adherence rates decreased as the trial continued, with 24% adherence at 3 months post-initiation and only 15% at 6 months.

Oral PrEP has become increasingly popular since its approval, and injectable PrEP has also become a medication of interest because its formulation allows improved flexibility and adherence. A study conducted in Zimbabwe, South Africa, and two states within the United States compared the acceptability of oral PrEP with that of injectable PrEP. Quantitative surveys were administered among 136 women (100 African and 36 American) at the first, fourth, and sixth injection visits, followed by a focus group discussion. Both U.S. and African participants preferred dosing of injectable PrEP every 2 months over daily oral pills.²¹ The participants in this study were followed for approximately 2 years to assess their continued adherence.

These studies highlight the challenges of maintaining adherence to PrEP over time and provide insight into possible strategies for improving the continuation of HIV prevention medications.

Community

As shown in Table 1, three studies evaluated the efficacy of community health interventions in the setting of HIV-negative women on PrEP.^22–24 All studies were conducted in South Africa. One study reviewed the status of HIV-negative women aged 16–25 years using a baseline questionnaire and referred the use of PrEP at a community-based site.²² Overall, 74% (n = 825) of women included in the study completed a questionnaire, and 98% (n = 806) of them were referred to community-based PrEP, which was implemented using home-based services and pop-up tents. Of the 806 women referred, 77% (n = 624) presented to a community-based site for initiation of PrEP. By the end of the study, 97% (n = 603) of the participants who had presented for initiation of PrEP actually initiated PrEP.

Another study was conducted to review the status of 427 women currently taking tenofovir-based oral PrEP. The study aimed to evaluate PrEP adherence, measured by intracellular plasma tenofovir diphosphate concentrations of ≥700 fmol/punch, or recent PrEP adherence measured by plasma tenofovir level ≥40 ng/mL at weeks 13, 26, and 52.²³ The results revealed that any detectable level of tenofovir diphosphate was associated with increased HIV risk (adjusted rate ratio: 1.15, 95% confidence interval: 1.03–1.29; p = 0.013). A strong correlation between HIV risk factors and PrEP drug concentrations was noted; those taking PrEP were at greater risk of HIV, possibly due to engaging in at-risk behaviors or more frequent testing and detection.

A study among 611 HIV-negative female sex workers in Zimbabwe found that 55% of them adhered to condoms and/or PrEP, leaving approximately half of the population unprotected even when 94% of them were aware of the benefits of condoms.²⁴ Of the participants, 9% used PrEP daily without condom adherence, whereas 6% adhered to both. Women with steady partners were more likely to adhere to both methods.

Pharmacy

A study in Kenya evaluated PrEP adherence among AGYW in a pharmacy setting.²⁵ Among 235 participants purchasing contraception, all were counseled on PrEP, tested for HIV, and offered a free 1-month PrEP supply. The nurses collected demographic, contraceptive, and behavioral data via questionnaires. Of those tested as HIV-negative, 85% (n = 200) accepted PrEP, with higher uptake among those at high HIV risk (90% vs. 80%). Key reasons for PrEP acceptance included feeling at risk for HIV (92%) and concerns about partners having other partners (84%). Additionally, 71% (n = 166) accepted HIV self-test kits for at-home partner testing, although the fear of partner reactions was the main reason for refusal (53%). The study highlights the potential of pharmacy-based PrEP delivery for AGYW, warranting further research.

Technology

PEPFAR’s DREAMS initiative launched in 2014 across 15 countries, including Botswana, to address HIV/AIDS among AGYW.²⁶ This study examined the feasibility and acceptability of mHealth peer-delivered interventions to provide PrEP services for HIV-negative women aged 18–24 years at DREAMS-supported facilities. Among these participants, 89% owned a mobile phone, and 85% expressed interest in mHealth peer interventions. Of those indicating a preference, 52% favored a hybrid model (in-person and mHealth), 31% preferred mobile-only, 15% chose in-person support at facilities, and 2% opted for community-based in-person support. The interventions showed high acceptability, scoring 3.8/5 on the Acceptability of Intervention Measure. These findings suggest that mHealth peer interventions can enhance PrEP delivery in Botswana.

A study in Kisumu and Thika, Kenya, assessed the acceptability and feasibility of using the Wisepill device to monitor PrEP adherence among women aged 18–24 years over a period of 2 years.²⁷ The participants were randomized to SMS adherence reminder group or no reminder group. The device tracked pill-taking behavior, with data sent to a central server. High acceptability of using the Wisepill device was reported, with participants finding the device useful and expressing interest in continued use. The completion rates were 95% in Kisumu and 70% in Thika over a period of 24 months. The feasibility of using this device was high; however, it slightly varied by site. Qualitative interviews highlighted privacy, confidentiality, and ease of use, alongside some concerns about stigma. The study demonstrated the potential of real-time adherence monitoring for supporting PrEP use in sub-Saharan Africa.

A study by HPTN 082 (2016–2018) in Cape Town, Johannesburg, and Harare evaluated the uptake and persistence of PrEP as well as the impact of drug-level feedback on adherence among 451 sexually active HIV-negative women aged 16–25 years.²⁸ The participants received tenofovir-based PrEP and were followed up for 12 months with either standard or enhanced adherence support. Most of the participants initiated PrEP, and over 50% of them had uninterrupted refills at 12 months. Although detectable drug levels were common at 6 months, only one-fifth of the participants demonstrated high adherence, and drug-level feedback did not significantly improve adherence. The HIV incidence was 1% (4 women), and all of them had low or undetectable drug levels before seroconversion, with no resistance mutations. The study highlights the need for improved adherence strategies in this population.

Mobile

A community-based mobile health clinic (CMHC), also known as Tutu Teen Truck (TTT) in Cape Town, Africa, was established to explore the feasibility and acceptability of providing PrEP to AGYWs aged 16–25 years.²⁹ In July 2017, the TTT integrated PrEP delivery for providing comprehensive sexual and reproductive health services (SRHS). The TTT aimed to increase healthcare access by providing counseling and clinical services in schools, community centers, and public transport hubs in a private and nonjudgmental environment. The services were tailored to each individual and linked to their medical records, including HIV and STI testing and a range of contraception options.

AGYWs who self-presented at the mobile clinic were educated about the effectiveness of PrEP and offered the option to accept, delay, or refuse uptake. Point-of-care tests for HIV infection and pregnancy are conducted at every visit before dispensing PrEP. Blood and urine samples are collected for verification of eligible creatinine clearance and STI infection at baseline and 6 months as well as hepatitis B status at baseline only. These samples are sent off daily to BARC/Lancet laboratories for analysis via a courier pick-up service.

Follow-up visits were scheduled monthly and quarterly, using phone calls and WhatsApp communication for occasional reminders. The study team attended bimonthly learning and troubleshooting meetings to adapt to the PrEP delivery operations and counseling messaging. For the qualitative substudy, the study involved 30 young women from the PrEP demonstration cohort selected through quota sampling. In-depth interviews revealed that the CMHC intervention for PrEP delivery was acceptable and accessible.

Between July 2017 and October 2019, 1784 AGYWs accessed SRHS, and 32% (n = 585) of them initiated PrEP on the same day. The intervention targeted the intended population, who assessed their HIV vulnerability and self-selected PrEP initiation. However, 80% (n = 468) of the AGYW participants who initiated PrEP were unaware of their partner’s HIV status, 85% (n = 497) struggled with consistent condom use, and 49% (n = 286) tested positive for STIs. The integration of PrEP and SRHS service delivery was highly valued by AGYW. However, there were several challenges faced by the broader community, such as community riots, violence, severe weather conditions, and interrupted PrEP delivery. The study concluded that PrEP delivery from a CMHC was feasible and acceptable for young women in South Africa, but a more diverse approach is needed to effectively scale up PrEP efforts.

Discussion

Despite the approval of oral PrEP more than a decade ago, most of the data have focused on populations other than women. Prioritizing the widespread availability of PrEP, particularly for women, is crucial to ending the HIV epidemic. Compared with men, women show significantly lower levels of awareness and willingness to use PrEP.³⁰ Therefore, understanding the specific needs of women and ensuring universal access to PrEP could play a vital role in reducing HIV transmission within this population. The implementation of PrEP to ensure improved adherence in AGYW has been studied worldwide. Many individuals, especially young adults, lack regular and affordable access to healthcare providers and insurance.³¹ Community-based programs could address this issue by implementing free and rapid HIV screening, regardless of the insurance status; providing education to patients about PrEP; offering rapid PrEP initiation when eligible; and reducing the stigma surrounding HIV, HIV screening, and PrEP. Skovdal et al. reported that interventions embedded within a community that provides individualized counseling for AGYW help articulate context-specific measures for improving access to PrEP in Zimbabwe.³² A community pilot program in the United States demonstrated the cost-effectiveness and accessibility of implementing PrEP.³³ Community-based PrEP sites could be located in areas of high HIV prevalence, facilitating both HIV testing and PrEP initiation through pop-up tents. When PrEP is indicated, clients who are considered HIV-negative can meet with a clinical provider on site to review their medical history and risk factors while simultaneously undergoing rapid PrEP initiation. A study in South Africa demonstrated that 100% of AGYW who used pop-up HIV testing sites initiated PrEP on the same day, and 54.6% of AGYW returned for a medication refill within 90 days of accepting their first bottle of PrEP.

The implementation of PrEP in health clinics is another method aimed at reducing HIV transmission. Currently, health clinic settings include family planning facilities, academic-based clinics, primary care clinics, gynecology practices, sexual health clinics, student health clinics, and federally qualified health centers. A study by Celum et al. in Kenya and South Africa demonstrated that the PrEP initiation rate in family planning clinics was 94%, with 31% of individuals returning for a medication refill at 1 month. Mugwanya et al. reported that 41% of people returned for at least one refill visit after initiation. The proportions of individuals who continued using PrEP at 1, 3, and 6 months post-initiation were 41%, 24%, and 15%, respectively. In the United States, approximately 40% of women can access reproductive health services, including pregnancy and family planning care.³⁴ These clinics may be the only effective way to reach and educate women about HIV prevention and care. Therefore, these are considered an ethical place to access and obtain PrEP. As the administration of PrEP evolves with the introduction of long-acting injectable options, a study by Tolley et al. revealed that most women preferred injectable PrEP over daily oral pills when administered at health clinics. This preference highlights a new, promising approach to enhancing adherence to PrEP among women. The advantages of injectable PrEP, such as increased discretion and ease of use, address some of the barriers associated with the daily oral regimen, thereby supporting better adherence and potentially improving the overall effectiveness of HIV prevention efforts among women. A recent study demonstrated the key benefits of long-acting injectable cabotegravir in preventing HIV infection among pregnant and breastfeeding women (PBW).³⁵ The findings indicate a substantial reduction in new HIV infections, with a 41.2% (19.8%–65.0%) decrease in the incidence among those receiving cabotegravir, compared with an 8.6% (4.8%–12.9%) reduction among those using oral PrEP. These data show the superior efficacy of long-acting injectable cabotegravir over oral PrEP in protecting PBW from acquiring HIV. In addition to cabotegravir, advancements in HIV medication have led to the discovery of lenacapavir, a novel first-in-class inhibitor of HIV-1 capsid function. Lenacapavir has shown efficacy at various stages of the viral life cycle and is specifically indicated for the treatment of multidrug-resistant HIV-1 infection when used in combination with optimized background antiretroviral therapy. This innovative drug represents a significant breakthrough in the management of HIV, particularly for individuals with limited treatment options due to drug resistance. Currently, two ongoing phase 3, randomized double-blind clinical trials, named PURPOSE I and PURPOSE II, are evaluating the efficacy of lenacapavir for HIV-1 PrEP.³⁶ PURPOSE I focuses on comparing the incidence of HIV infection in AGYW at high risk of HIV exposure. The trial examines the effectiveness of subcutaneous lenacapavir versus oral emtricitabine and tenofovir disoproxil fumarate for PrEP.

A third major approach to dispensing PrEP is pharmacy-based interventions. Pharmacists and pharmacy technicians have expressed strong interest in and support for screening and dispensing PrEP in the pharmacy setting.³⁷ Pintye et al. reported that the use of pharmacies to provide oral PrEP was associated with a high uptake of PrEP. Of the participants, 82% chose to initiate PrEP at the pharmacy level, and 68% continued to use it. In fact, 69% of those who took PrEP were willing to pay retail pharmacy prices for it. However, this study was nurse-driven under the supervision of a remote physician, reflecting the specific medical practice model in that country. This role could potentially be expanded to include pharmacists, who have already established patient relationships in retail pharmacy settings. Pharmacists are well-positioned to take on this responsibility due to their accessibility and frequent interactions with patients, which could enhance the continuity and reach of care. This suggests that leveraging the existing relationship between patients and retail pharmacies in the United States could have a large impact on closing the gap in utilization observed between women and men. As of 2024, pharmacists can independently prescribe PrEP for HIV prevention in 14 states. The use of pharmacy as an avenue for PrEP delivery not only increases access but also improves continuity and adherence to PrEP regimens, thus becoming a key strategy to support HIV prevention.³⁸

Intervention behaviors serve as an effective method to enhance adherence to PrEP usage. Numerous studies have demonstrated the positive impact of implementing intervention counseling to not only improve the standard of care but also increase health literacy among users. These intervention behaviors can include various approaches, such as personalized counseling sessions, motivational interviewing, and the use of digital health tools. Personalized counseling sessions provide tailored support and guidance to individuals, helping them understand the importance of PrEP and addressing any concerns or barriers they might face. Motivational interviewing, a technique that encourages individuals to explore their motivations for using PrEP and reinforces their commitment to adherence, has been particularly effective. With increasing adoption of these methods by healthcare providers, the effectiveness of PrEP as a preventive measure against HIV can be maximized, leading to improved health and well-being for at-risk populations.

Technology plays a crucial role in healthcare by improving different facets of patient care and management. Technological reminders for pill use and/or appointment attendance can greatly enhance PrEP adherence. A study conducted by Lavoie et al. demonstrated that mobile technology (mHealth) contributed to improving PrEP adherence, with 30.6% of individuals benefiting from peer-delivered interventions on mobile phones. This revealed the potential of novel delivery platforms for health services and adherence support. In another study, Ogello et al. explored the use of wireless real-time electronic adherence monitors. They utilized Medication Event Monitoring Systems caps, which are monitored pillboxes that activate and track a transmitter that emits an inaudible signal when the cap is removed or placed back onto the pill box. Approximately 95% of participants from Kisumu and 70% from Thika completed 24 months of follow-up while using the monitored pillbox. These devices not only remind patients to take their medication but also provide real-time data to healthcare providers, allowing better management of the patient’s health. The integration of these technologies into routine healthcare can significantly improve medication adherence and patient engagement. By providing timely reminders and facilitating easier communication with healthcare providers, these tools help patients manage their health more effectively. In the future, the adoption of such technologies could lead to higher adherence rates, better health outcomes, and more efficient healthcare delivery.

Overall, health clinics, pharmacies, and community-based PrEP delivery methods are considered feasible and beneficial for both healthcare providers and individuals interested in PrEP, especially women, in terms of improving adherence. The integration of technology further enhances the promise of better access and consistent use of PrEP, offering women a reliable means to protect themselves from HIV. Technological aids, such as mobile health (mHealth) applications and real-time electronic adherence monitors, can significantly boost adherence by providing reminders and facilitating communication with healthcare providers. These innovations ensure that women can adhere to their PrEP regimens, thereby enhancing the effectiveness of HIV prevention efforts. However, the success of these initiatives depends on adequate funding and meticulous planning for public rollout. Sustainable financial support is crucial for developing, implementing, and maintaining these programs. Moreover, careful attention to detail in program design and execution is necessary to address potential challenges and ensure that the programs reach those most in need.

In addition to funding and planning, legislative support is essential. Expanding the scope of practice for healthcare providers, including pharmacists, through supportive legislation can enhance the quality of care offered to AGYW. This legal backing may enable healthcare providers to offer comprehensive and accessible PrEP services, addressing the unique needs of this demographic and improving overall public health outcomes. In summary, the combination of clinical, pharmaceutical, and community-based PrEP delivery, augmented by technological advancements, holds great promise for improving adherence among women. With adequate funding, careful planning, and legislative support, these programs can significantly enhance HIV prevention efforts and provide better care for women at risk.

Study limitations

This systematic review had limitations that should be considered when interpreting the findings. First, the majority of the included studies were conducted in specific geographic regions, primarily in African countries and the United States. This may limit the generalizability of the results to other regions with different sociocultural and healthcare contexts. Second, the variability in healthcare systems, level of HIV prevalence, and access to PrEP and post-exposure prophylaxis (PEP) services could affect the applicability of the intervention models reviewed. Transitioning to the varying study designs implemented across the included studies poses a major challenge. The studies varied widely in their sample sizes, follow-up durations, and specific intervention components, which could influence the reported outcomes. Finally, the review may have excluded relevant studies that were not indexed in PubMed or published in languages other than English, leading to potential publication bias. Despite these limitations, this review provides valuable insights into the various intervention models that can enhance PrEP and PEP use and adherence among cisgender women.

Conclusion

The scarcity of systematic reviews on women’s PrEP usage highlights a critical gap in research and implementation efforts. It is crucial to address this gap, especially given the disparities in awareness and willingness to use PrEP between the two sexes. Prioritizing universal access to tailored PrEP interventions for women could significantly reduce HIV transmission within this demographic in the future.

Community-based programs show promise in enhancing PrEP access and adherence among women, particularly among vulnerable groups such as AGYW. These initiatives not only bridge healthcare gaps but also destigmatize HIV prevention. The integration of PrEP services into existing healthcare settings, such as family planning clinics, offers significant potential for reaching women who lack access to comprehensive SRHS. Sustained efforts to expand PrEP provision and education within healthcare systems are vital for achieving meaningful progress in HIV prevention among women, emphasizing the importance of inclusive and effective PrEP delivery strategies.

Footnotes

Acknowledgments

Not applicable.

Author contributions

Alex Dang: Conception or design of the work; acquisition, analysis, or interpretation of data for the work; drafting of the work or critical review of the work for important intellectual content; and final approval of the version submitted.

Hillary Debs: Conception or design of the work; acquisition, analysis, or interpretation of data for the work; drafting of the work or critical review of the work for important intellectual content; and final approval of the version submitted.

Amber Vu: Conception or design of the work; acquisition, analysis, or interpretation of data for the work; drafting of the work or critical review of the work for important intellectual content; and final approval of the version submitted.

Johnny Ruiz: Conception or design of the work; acquisition, analysis, or interpretation of data for the work; drafting of the work or critical review of the work for important intellectual content; and final approval of the version submitted.

Melissa E Badowski: Conception or design of the work; acquisition, analysis, or interpretation of data for the work; drafting of the work or critical review of the work for important intellectual content; and final approval of the version submitted.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Data availability statement

Not applicable.

Declaration of conflicting interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical considerations

Ethical approval was not required.

Funding

No funding source was provided for this research.

ORCID iD

Melissa E Badowski

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