HIV Pre-Exposure Prophylaxis Uptake Among High-Risk Population in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

Abstract

Globally, 38.4 million people are affected by the human immunodeficiency virus (HIV) pandemic, and more than 2.5 million new HIV infections occur yearly. HIV pre-exposure prophylaxis (PrEP) has been widely recognized as a potential way to prevent new infections among risk population. There is a paucity of abridged evidence on the level and barriers to PrEP service uptake in sub-Saharan Africa (SSA). Therefore, we conducted a systematic review to synthesize existing evidence on PrEP uptake in SSA. Relevant studies were searched from major databases (PubMed and PsychInfo) and direct Google Scholar. Data were extracted and recorded using a pilot-tested template. Methodological rigor, heterogeneity and publication bias of studies were assessed to minimize the inclusion of erroneous findings. A random effect model was used for the meta-analysis followed by narrative metasynthesis. The protocol of this systematic review has been by registered PROSPERO (ID: CRD42022308855). A total of 1830 studies were retrieved, and 30 studies met inclusion criteria of the systematic review. People who heard about PrEP ranged from 23% to 98%. The pooled prevalence of willingness to use PrEP was 64.2% (95% confidence interval: 55.5–72.0). Fear of side effect, stigma, nonreceptive attitude, cost of pills, low awareness about PrEP, perceived reason about the effectiveness of PrEP, and lack of friendly services were the common barriers to PrEP uptake in Africa. In conclusion, comprehensive knowledge and willingness to use PrEP were low in SSA. The barriers to low PrEP service uptake are avoidable through comprehensive awareness creation and availing essential services to key population in Africa. Expanding educational messages to key population using friendly approaches and more accessible platforms, engaging stakeholders, and integrating PrEP service with routine health care are important to foster HIV prevention and control in the future.

Introduction

Human immunodeficiency virus (HIV) attacks the host's immune system.¹ Globally, 38.4 million people live with HIV.^2
–4 The changing HIV pandemic, with a delinking prevalence of undiagnosed HIV, and the increasing importance of key populations, will bring new challenges to HIV prevention, treatment, and support, mainly in reaching key populations.⁵ About 25 million people were receiving antiretroviral therapies (ART) in Low- and Middle-income Countries (LMICs) in 2020, in which the number of people receiving ART grew by an average of 1.6 million between 2017 and 2020.⁶ The world aimed to achieve the 95-95-95 targets and above by 2030.^7

–11 The sub-Saharan Africa (SSA) remains the most affected by HIV infection with 1 in 25 adults living with the virus, accounting for 70% of people living with HIV worldwide.³

More than 2.5 million new HIV infections occur yearly in the absence of an effective vaccine worldwide. Pre-exposure prophylaxis (PrEP) has been recognized as a potential way to prevent HIV infections among high-risk population.⁹ The SSA attributes the highest burden of new HIV infections and deaths from AIDS, and PrEP offers an opportunity to curb HIV distribution.³ In 2015, the World Health Organization (WHO) recommended oral PrEP for people at substantial risk of HIV, and PrEP.¹⁰

PrEP is the use of ART medication by HIV-negative people to reduce the risk of acquisition of HIV infection,^11,12 which gives an additional option to prevent HIV infection substaintially.¹³ Truvada has been approved by the United States Food and Drug Administration (FDA) for use as PrEP, which is a combination of two anti-HIV drugs and emtricitabine as a single pill.¹² Likewise, injectable cabotegravir PrEP is recommended to reduce the risk of sexually acquired HIV for adolescents and adults whose weight is above 35 kg and is administered by a health care worker every 2 months. It is also approved for cisgender and transgender people with no limitation.¹⁴

In addition, tenofovir disoproxil fumarate (TDF) has been recommended by the WHO since 2015, as oral PrEP to be offered to people with a substantial risk of HIV infection, which is highly effective in preventing HIV. Then, dipivefrine has been used as an additional prevention choice for women at substantial risk of HIV in 2021.¹¹ Daily PrEP is recommended for people who are at substantial risk of acquiring HIV.¹³

The WHO has declared PrEP as an essential health service,¹⁰ and now a valuable additional option for people who are at high risk of acquiring HIV,¹⁵ such as the high HIV prevalence population who has had the risk factors in the past 6 months, and serodiscordant partners who are either not on ART or have not yet achieved viral suppression.¹³ PrEP is widely adopted, coincided with an increased uptake, which will contribute to ending HIV new infection by 2030.¹⁶ Oral PrEP use has been increasing worldwide, and over 600,000 people received PrEP in the year 2019, which is a 70% increase compared to 2018.¹⁰ Approximately 845,000 people received PrEP in 2020, which is a 43% increase compared to 2019.¹⁵ Consistent use of PrEP reduces the risk of getting HIV infection by more than 90%.^13,14,17

PrEP using oral TDF monotherapy or TDF with emtricitabine was significantly associated with decreasing the risk of HIV infection among high-risk people.^18,19 The availability of PrEP service and its uptake was as low as 28%. Three million people (8%) are targeted for PrEP in LMICs for 2020–2025.¹⁵ Men who have sex with men (MSM) and persons who injected drugs are at high risk of acquiring HIV infection and prioritized for PrEP.^18,20

PrEP service uptake is highly limited to MSM, who were more likely to accept it.¹⁸ Lack of willingness for PrEP utilization is a known challenge that is entrenched with an individual's awareness level of the person injected drugs, and MSM.^20,21 Decentralization of the PrEP service, peer mentors, effective linkage to local health care facilities, sexual partners, disclosure of PrEP use by beneficiaries, active stakeholder involvement, and/or engagement were good facilitators.²²

However, being young and mobile individuals,²³ stigmas, drug side effects, limited resources for routine screening and medication monitoring,^18,22,24 frequent relocation of beneficiaries, and limited number of qualified health care workers for PrEP distribution and administration,²² low-risk perception, low decision-making power, an unacceptable regimen,²⁴ and self-perceived low efficacy¹⁸ were the barriers to PrEP service implementation (initiation and persistence). Very little is done on abridged evidence on PrEP. Therefore, the main aim of this systematic review and meta-analysis was to produce synthesized knowledge using available primary studies on PrEP uptake and its barriers in SSA.

Systematic review question(s)

▪ What is the level of PrEP uptake among key population in SSA?

▪ What are the factors associated with PrEP use in SSA?

▪ What are the recommended interventions to improve the uptake of PrEP service in SSA?

Methods

This systematic review and meta-analysis work have been registered in the International Prospective Register of Systematic Reviews (ID: PROSPERO 2022:CRD42022308855).²⁵ The methods are written following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements guidelines,^26

–30 and the checklist for PRISMA is filled (Supplementary Table S1).

Data source and search strategies

The Medical Subject Headings (MeSHs) keywords were constructed based on the systematic review question. In addition, synonyms of each key term were used for searching in different databases according to its interface. Studies were searched using constructed search strings in main electronic databases, such as PubMed and PsychInfo, and direct from Google Scholar. Studies published until August 2022 were searched and recorded. In addition, efforts were made to retrieve studies using email messages to authors to request publications. Further studies were searched using citations (forward and backward search strategy), comprehensively. Searching strings were constructed using a combination of MeSH terms “such as antiretroviral PrEP for HIV infection, service utilization, service uptake determinants, barriers, associated factors, risks, correlates, influencing factors, key population to HIV prevention and control program and/or care and support service” (Supplementary Table S2). The search results were compiled using Mendeley Desktop citation management software.³¹

Eligibility criteria for systematic review

▪ Community- and/or facility-based observational (cross-sectional, case–control, follow-up studies, survey, and surveillance)

▪ Studies conducted among key population who have a higher risk of HIV infection according to the WHO African Region include youth, female sex workers (FSWs), MSM, persons who injected drugs, prisoners, and other sexual minorities³²

▪ Studies conducted in SSA,

▪ Both published or unpublished studies that were written in English language before August 31, 2022, were retrieved for the systematic review.

Selection of studies into the systematic review

The search for research materials was conducted until August 31, 2022. Studies were selected systematically based on pre-determined eligibility criteria. Initially, studies were screened by “title.” Studies that clearly mentioned PrEP to people who have high-risk of HIV new infection in SSA countries were considered for the subsequent evaluation. Then the two authors (A.S. and K.F.) had independently screened the studies' abstracts to proceed to the next step of systematic selection. In the abstract section, studies that had reported the PrEP service uptake and its associated factors were included in the final evaluation. The full text of selected studies was re-assessed independently by two authors (A.S. and K.F.).

The body of studies' (aim, methods mainly design, participants, sampling procedure and measurement procedures/tools, analysis, results, conclusion, and recommendation) sections was assessed. Eventually, studies that have reported PrEP service uptake and its associated factors were selected for systematic review and meta-analysis. In addition, those studies that report the prevalence of PrEP and its associated factors were considered for further appraisal. The study selection process flow diagram is adapted from PRISMA statements (Fig. 1) and other relevant literature.^33
–35

FIG. 1.

Diagrammatic presentation of the selection process of articles for systematic review.

Measuring outcome and exposure

PrEP service uptake is the main outcome variable for this systematic review and meta-analysis, and it was measured using primary studies' reports considering PrEP use, willingness to use, and knowledge. Quantitative surveys directly reported frequency as an event. Factors associated with the PrEP were assessed using synonymous terms such as determinants, predictors, barriers, associated factors, risk factors, correlates, and influencing factors. Pooled quantitative analysis and narrative synthesis for qualitative data were carried out for both the outcome and exposure variables accordingly.

Methodological quality assurance measures

Comprehensive searching techniques were applied to capture studies in SSA using direct electronic search from major databases, and forward and backward search of citations of retrieved studies. Both published and unpublished studies on PrEP uptake by high-risk population were included in the systematic review to minimize publication bias. Eligibility criteria, selection method, studies' quality appraisal, key finding extraction template, and regular meeting for discussion schedule were pre-designed by authors to assure the quality of the systematic review. The methodological quality assessment tools were adapted from relevant literature.^33,36

–39 The methodological quality of studies was appraised using the Joanna Briggs Institute (JBI) checklist for prevalence studies³⁹ (Supplementary Table S3). Selection of studies, quality appraisal, and data abstractions were employed independently by two authors (A.S. and K.F.). Authors regularly met for discussion, rigorous evaluation of the systematic review process, and compilation of extracted data. Any difference was resolved through consensus.

Data abstraction

The data extraction template was prepared and piloted in Microsoft Word and Excel (2016) spreadsheet. Two authors (A.S. and K.F.) extracted the data from selected studies and presented on a pre-designed and piloted data extraction template. Qualitative information such as author, study area or country, aim, design, sample size, sampling procedure, response rate, main findings, and author's key conclusions were summarized and recorded in the pre-constructed table. Also, the raw data for the event (number of PrEP users) and total sample size were recorded on the Microsoft Excel (2016) template to export to Stata 18 software for pooled analysis (Supplementary Table S4).

Data synthesis and analysis

The abstracted raw data were managed through pooled analysis and metasynthesis. Quantitative statistical analysis was computed using Stata 18.⁴⁰ Meta-analysis of observational studies was carried out based on the recommendation of meta-analysis of observational studies in epidemiology.⁴¹ Heterogeneity between studies was assessed using the I ² statistics, and substantial heterogeneity assumed if I ² > 75%.^42,43 Potential publication bias was assessed using funnel plot for visual illustration,^44,45 and quantifying methods,⁴⁶ such as carrying out Begg's⁴⁷ and Egger's test.⁴⁸

The pooled prevalence of PrEP was computed to determine PrEP uptake by key population. The random-effects DerSimonian-Laird model and weighting method were applied for effect size measure.⁴⁹ The publication bias was examined using a funnel plot (Fig. 2), with Egger's test being 0.045 and Begg's test of 0.849. As a result, only 18 studies were included in the meta-analysis to compute the pooled prevalence of willingness to use PrEP in SSA. Meta-synthesis was carried out to narrate key findings of included studies due to existing high variations.

FIG. 2.

Funnel plot to illustrate publication bias (n = 18). 95% CI, 95% confidence interval.

Results

Characteristics of the included studies

A total of 1830 studies on PrEP in SSA were retrieved from major databases (mainly PubMed and PsychInfo) and direct Google Scholar search. Of these retrieved studies, 1673 duplicates were removed. The remaining studies had passed through screening by title, abstract, and full text to filter the most appropriate studies to answer the review questions. The details of the screening and selection process and reason for exclusion are presented using the PRISMA flow diagram (Fig. 1). Key findings from the included studies' abstracted data underwent narrative synthesis using four themes. Of these, 18 studies were included in the meta-analysis, but others were used for the narrative synthesis using a theme, including PrEP service acceptability, willingness, uptake, barriers to uptake of service, strategies to improve PrEP service uptake, and evidence recommendation for future improvement.

A total of 30 studies^{22,50

–78} were included in the systematic review and meta-analysis. Of these, 18 were included in the meta-analysis. Of key populations, six studies were among men who have sex with men (MSM),^{50,55,67,68,73,78} eight studies on FSWs,^{50,52,57,61,70,73,75,77} five studies on transgender people,^{56,59,65
–67} nine studies on young people (15–24 years old),^{22,53,54,58,60,64,69,74,76} two studies in discordant,^51,63 long-distance truck drivers,⁶² and persons who inject drugs (PWID),⁷⁰ and other high-risk population, including fisher men.⁷² The study's description is presented in detail as an additional file (Supplementary Table S4).

Knowledge and source of information about PrEP

In eight studies from six SSA, a significant number of high-risk populations (MSM and FSWs) to HIV infection knew PrEP service.^{50,52,53,55,57,58,68,71,73} The prevalence of high-risk people who had ever heard about PrEP ranged as 23.2% in Uganda,⁵⁸ 50.7% in Benin,⁵⁵ 72.6% in Cote D'ivore,⁶⁸ and two studies in Nigeria, 46.4%⁵⁰ and 95.2%.⁷³ In one study, only 3.9% of high-risk population reported that they had heard about injectable PrEP.⁵⁸

Even though the majority of the high-risk population had heard about PrEP, very few of them had awareness. Of these, approximately half (46%) of MSM had no prior awareness of PrEP in Nigeria.⁵⁰ Likewise, in one study, almost one in five (18.9%) high-risk people had awareness of PrEP in Nigeria.⁵³ One study in Rwanda has reported that almost half (48%) of the high-risk population had good awareness about PrEP.⁵⁷ Nevertheless, a couple of studies in Ghana reported that comprehensive knowledge of PrEP was very low.^51,52,71 Further, in one study in Nigeria, community dialogs were the main source of information about PrEP.⁷³ One study in Uganda reported that 4% of high-risk people had heard about injectable PrEP.⁵⁸

Willingness to use PrEP

Willingness of high-risk people (MSM and FSWs) to use PrEP ranged as 35.3% in Cote D'ivore,⁶⁸ 45% of FSWs and MSM in Cameroon,⁶⁷ 49.0% in South Africa,⁷⁴ 53.5% of FSWs, of whom 79.7% of FSWs younger than 25 years in Ghana,⁵² 79% in Tanzania,⁶¹ 80.1% in Nigeria,⁵⁰ 82.4% in Senegal,⁵⁶ 83% in Rwanda,⁵⁷ 84.6% in Nigeria MSM and FSW,⁷³ and 90% of MSM in Benin,⁵⁵ 92.2% in Uganda,⁶³ and 98% in Zimbabwe.⁷⁵ In addition, one study from four west African countries, 74.4% and 25.6% of high-risk to HIV people chose event-driven and daily PrEP, respectively.⁶⁹ In Cote D'ivore, 61.3% of high-risk people would prefer the daily regimen and 38.7% would opt for the on-demand regimen.⁶⁵

In Zambia, the number of people willing to start PrEP increased by over sixfold, and significant number of people opt for client-initiated PrEP in Zambia.⁵⁴ The meta-analysis of 18 studies in SSA has shown that the pooled prevalence of willingness to use PrEP was 64.2% (95% confidence interval: 55.5–72.0; Fig. 3).

FIG. 3.

Pooled prevalence of key population willingness to use PrEP in SSA (N = 18). PrEP, pre-exposure prophylaxis; SSA, sub-Saharan Africa.

PrEP service uptake and preferred site

A study in Ghana shows that only 6.4% of high-risk people for HIV had ever used PrEP.⁵² Similarly, in one study in Nigeria, 29.7% had previously used PrEP.⁵⁰ Further, one study from Senegal reported that 79.9% and 73.4% were retained in PrEP care at 6 and 12 months, respectively.⁵⁶ Participants' most preferred PrEP distribution channels were public clinics (51.2%) and hospitals (23.8%). More men than women preferred distribution through schools and NGOs.⁷⁴ In one study, the majority (95.2%) of the key population (MSM and FSWs) had heard about PrEP. Of these, nearly three-fourths (71.3%) of them heard about PrEP from community dialog. Fewer than half of the respondents were aware of the clinical care required for PrEP.⁷³

Barriers to willingness and use of PrEP

Sociodemographic factors

Gender was a significant barrier to willingness to use PrEP in SSA. In one study from South Africa, men dislike taking PrEP pills compared with women,⁷⁴ and in Uganda, women at young age were willing to use PrEP.⁶³ Similarly, more female and young people (15–29 years), and serodiscordant partners had initiated PrEP.^60,64 There is a concern that taking PrEP is perceived as a marker of adopting HIV risky behaviors.⁵⁵ Of these, young women who have ever had transactional sex and multiple partnerships were significantly associated with more consultation to start PrEP.⁶⁴

In one study, people who had ever tested for HIV, ever used condoms, nude exchanges, and knowledge of their partner's HIV status were significant determinants of awareness of PrEP.⁵³ In addition, in one study, people who have location-based “apps” for seeking sexual partners, health insurance, a history of suicidal thoughts, and a history of PrEP use were significantly associated with good uptake of PrEP service.⁵⁰

Stigma and discrimination

Two forms of stigma emerged as potential barriers to PrEP use: misidentification as living with HIV and disclosure of membership in a priority population. The acceptability of PrEP was dampened for this sample of potential PrEP users due to anticipated stigmatization.⁷⁶ In four studies, stigma was reported as a major barrier to PrEP uptake.^22,70,73,78 Similarly, the nonreceptive attitude of the community and health care providers was a barrier to PrEP uptake.⁷⁸ In one study, it was discouragement from others and worry and disbelief about participants' health,⁷² stigma, social impacts, and rumors.⁶⁶ Stigma and attitude toward PrEP use was a major barrier among MSM.⁷⁰ Mitigating stigma should be a key component of effective PrEP delivery.⁷⁶

Fear of side effects

Fear of PrEP pill's side effects has impacted the service uptake and willingness to use pill. In four studies, having concern or fear of side effects of PrEP pills was reported as a determinant of PrEP uptake.^{22,66,71,72,74,77,78} Similarly, perceived lack of effectiveness was the reason provided to not utilize PrEP,⁷¹ and possible drug-drug interactions.⁷³

Lack of awareness

PrEP willingness was positively associated with having PrEP knowledge, but distinct differences were observed in media and occupation factors.⁷⁴ Knowledge/awareness is a main factor for PrEP use in SSA.⁷⁴ In Benin, not all MSM know about PrEP.⁵⁵ On the contrary, FSW and MSM with no comprehensive knowledge of HIV were more willing to take PrEP.⁵² In one study, no acceptability of PrEP was attributed to limited knowledge as the reason provided to not utilize PrEP.⁷¹ Limited awareness level is a significant determinant of PrEP uptake.^50,51,57,58 Knowledge of PrEP (i.e., as an effective, short-term ART to use before HIV exposure for people at high risk) was also a barrier to PrEP uptake.⁶²

Perceptions

Being pre-occupied by the fact that PrEP could be inefficient⁷⁸ and other misconceptions about PrEP were common.⁷³ Fear of disease infection,⁷² lack of full protection conferred by PrEP, that is, level of protection,⁷⁸ and perceived lack of effectiveness were the reasons provided to not utilize PrEP.⁷¹ Frequency of HIV counseling was low.⁷³ In addition, attitudes toward PrEP use, lack of confidence to change behavior compounded with misconceptions and doubts deterred FSWs from uptake.⁷⁷ In addition, clinical barriers like depressive symptoms were associated with a lower willingness to use PrEP.⁵⁰

Cost

The cost of health care service,^70,73 lack of resource for routine screening and medication monitoring, and skilled health care provider for PrEP distribution²² were the determinants of PrEP service uptake in SSA that affected the provision of free PrEP delivery.⁷⁸ One key factor associated with PrEP acceptability is not having to pay for PrEP.⁵⁵ Concerning the pill supply system, 74.7% of MSM agreed that it is very important to avoid stockouts to encourage PrEP acceptability.⁷⁸

Lack of access to service

Lessons learnt from risk-based criteria for PrEP ensures access to those most in need of HIV prevention. Health care worker training in PrEP service delivery and the health needs of key and priority populations are crucial.⁵⁴ Healthcare providers and women overwhelmingly showed interest in PrEP, and women living with HIV and providers have concerns about PrEP use. With the correct support, PrEP could be a useful option for sero-discordant couples in SSA contexts.⁵¹ In addition, PrEP is not yet currently widely available to MSM in Rwanda.⁵⁷ Population-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls before PrEP availability. HIV infections were significantly lower among women who started PrEP.⁶⁰ Ongoing training will be needed to optimize PrEP delivery services and expand delivery to levels needed for population-level impact.⁶²

Negative implication of PrEP

If PrEP effectiveness were 90% or more, nearly 88% of the high-risk population thought they would decrease condom use. Coverage of sex acts with PrEP⁶⁸ decreased during follow-up⁷⁰ and number of sex acts with casual male partners.⁶⁸ Concerns included possible condom mitigation, increased risk for STIs and pregnancy for FSWs, and poor adherence to medication and hospital schedules.⁷³ Condom use has protection against other STIs and sexual partner factors.⁷¹

Lack of effective system

Monitoring,²² complex procedures for PrEP initiation and implementation,⁷⁸ length of time for visits,⁷² low referrals stemming from lack of screening (39% of clients with negative HIV test results), and lack of eligibility among clients who were screened (only 6% of those screened qualified as candidates for PrEP per the national screening tool) were the challenges for PrEP uptake in SSA.⁷⁵ Acceptability of PrEP was conditioned on it having minimal side effects, being affordable and efficient in preventing HIV infection.⁷¹

PrEP continuation rate was 37% at 3 months, 28% at 6 months, and 19% at 12 months,⁶⁷ and approximately half had not attended school (41.2%).⁵⁶ Poor sensitization with providers to mitigate and integration of PrEP into existing services, and lack of innovative strategies to improve use of PrEP were health system barriers to PrEP uptake.⁷⁰ Healthcare workers noted challenges in PrEP delivery in terms of inadequate clinic preparedness, infrastructure, staff capacity, and poor attitudes toward key populations by untrained health workers. They felt further training was needed to ensure a smooth scale-up of services without stigmatization.⁶²

Risk-taking behavior

Alcohol dependency of the key population was a significant determinant of PrEP service uptake, and those with multiple sexual partners, but was lower among those who reported consistent condom use with recent sexual partners. Insertive anal sex acts in the last 30 days^50,59 and inconsistent condom use increased substantially among both FSW and MSM. This may be because oral PrEP was provided as part of a combination prevention strategy that included counseling and condoms, but could also be due to the low retention rates among those who initiated.⁵⁹ High attention should be given to integrating PrEP into existing services. While over three-fourths of providers indicated they would personally provide PrEP to HIV-negative partners of HIV-positive clients (87%), people who have multiple sex partners (83%), and FSWs (78%), a smaller percentage indicated they would provide PrEP to MSM (66%) and PWID (58%).⁷⁰

Facilitator for PrEP use

In one study, PrEP use was associated with being of young age (<35 years), and being FSW at young age^{25

–34}; partners who had STIs were more likely to take PrEP.⁵² On the other hand, older age among FSWs was found to be the only significant predictor of lower discontinuation, or older age was the only significant predictor of higher PrEP retention.⁵⁶

Availability of support groups for skilled counseling service

Participants felt that trained peer educators and HIV test counselors could provide information and refer clients to clinics that provide PrEP. PrEP can be provided through peer-led facilities for MSM and FSWs, although its access should be expanded to all persons who are at substantial risk for HIV to prevent negative labeling of PrEP.⁷³ Accessibility within MSM networks,⁵⁵ the use of the safe space model, decentralization of PrEP support and delivery, peer mentors, effective linkage to local health care facilities, the sensitization of parents and male sexual partners, disclosure of PrEP use by beneficiaries, active stakeholder involvement, and community engagement were among some facilitators to PrEP uptake.²² Having personal support regarding PrEP would facilitate its acceptability.⁷⁸

Intentionally linking clients with negative results to PrEP immediately following HIV testing was found to be acceptable from both provider and client perspectives, yet screening procedures need closer examination and reinforcement for the program to realize a larger impact.⁷⁵ Pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of nonadherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants were the supportive actions to enhance PrEP uptake.⁷² Clients were happy to learn about PrEP following HIV testing, and the additional support of accompanied referrals and fast-tracking encouraged them to access PrEP and made them feel valued.⁷⁵

Positive perception

The primary reason for acceptability was that PrEP provided an extra level of protection against HIV,⁷¹ attention should be paid to this to ensure PrEP reaches its full prevention potential.⁶⁸ Public awareness about the use of antiretrovirals for HIV prevention is needed to prevent labeling of PrEP users as being HIV positive.⁷³ One-quarter (26.4%) of the participants had a neutral point of view on whether or not engagement in multiple sexual partnerships may be a plausible reason for PrEP uptake.⁷⁸ Perceived parental sex education and exposure to community campaigns for HIV prevention were both associated with increased awareness of HIV prevention measures and openness to PrEP.⁶⁹ Relationship difficulties due to being perceived as HIV positive were prevalent and adherence was challenged by complexities of daily life,⁶⁶ and attitudes toward PrEP use, and misconceptions, their lack of confidence.⁷⁷

Risk-taking behavior

PrEP is challenged by complexities of daily life, alcohol use around the time of sex, mobile populations, and transactional sex work.⁶⁶ Openness toward PrEP was significantly higher among those reporting versus not reporting past-year sexual activity and binge drinking.⁶⁹ Many advantages of PrEP were mentioned: protection in case of a condom break, protection in case of high-risk sexual behavior, self-reliance, decreasing HIV fear, and ease of use. Barriers to the use of PrEP included the following: it does not protect against other STIs, taking a pill regularly is necessary, the size of the pill, the possibility of side effects, the cost, and accessibility. Six participants (19.3%) admitted that they would use condoms less if they took PrEP.⁶⁵ PrEP availability helped prevent HIV infection, and 74% of MSM agreed it did not lead to an increase in risky sexual behaviors or other STIs.⁶⁸

Evidence recommendations to improve PrEP service uptake

PrEP service uptake was relatively good, but retention of the PrEP service has affected HIV prevention and control programs in SSA. Therefore, comprehensive stakeholder engagement intervention, awareness creation about the importance of PrEP, improvement PrEP delivery strategies, and continuous advocacy to align the HIV prevention activity for key population are critical issues to improve PrEP uptake.

Stakeholder engagement

A task force of key stakeholders can rapidly develop and implement health policy, which may serve as a model for countries seeking to implement PrEP.⁵⁴ Likewise, creating demand and providing more intensive support for adherence and continuation may support the scale-up of PrEP service in Cameroon for equitable and prolonged impact on HIV prevention.⁶⁷ Addressing structural barriers, like gender inequities, is very important to break the barriers to and facilitate access to PrEP service.⁷³ Health authorities should consider PrEP for all high-risk groups to avoid worsening stigmatization by targeting MSM only.⁶⁵ Understanding participants' experiences with participation in PrEP efficacy trials will inform strategies to increase adherence and retention in future implementation of PrEP programs.⁷² In Ghana, it is important that key stakeholders preemptively address potential barriers to PrEP acceptability, uptake, and adherence, especially among MSM, once PrEP becomes available in Ghana.⁷¹

Awareness creation

Increasing awareness about the importance of PrEP in HIV new infection prevention is one of the recommended interventions.^74,77 Using multi-farious media strategy⁷⁴ and creating awareness is crucial to reduce high-risk sexual behavior, decrease HIV fear, ease of use, improving self-reliance, and condom use for protection.^65,77 Similarly, improving awareness is critical to increase PrEP uptake for higher-risk populations such as alcohol dependents and those with multiple sexual partners,⁵⁸ and address young people's low levels of PrEP awareness. It also shows relatively increased willingness, gendered PrEP awareness, and distribution preferences.⁷⁴ Educational messages are necessary to ensure appropriate PrEP scale-up, especially tailored toward MSM.⁵⁰ PrEP implementation among MSM networks should be accompanied by awareness-raising campaigns explaining its utility.⁷⁸

Innovative delivery strategy

Improving PrEP delivery strategy is highly demanded; developing PrEP delivery models and assessing PrEP initiation and adherence in FBW appear warranted.⁶¹ User-friendly delivery strategies are highly needed to counteract these barriers and facilitate PrEP uptake.⁷⁷ Further, free access to evidence-based HIV preventive strategies using PrEP may benefit public health.⁶⁹ The free availability of the drug and its accessibility in the MSM networks are important facilitators. The possibility of a decrease in condom use should not be a barrier to the prescription of PrEP if made available.⁵⁵ In addition, culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.^65,66

Outreach and linkage to places where MSM can access respectful, nondiscriminatory care, including nursing models of care to extend PrEP use once available.⁵⁷ PrEP should be part of a global prevention program, which includes counseling, STI screening, and promotion of safe sex practices.⁶⁵ The community rollout of PrEP will lead to successful PrEP implementation, increased PrEP initiation, and enhanced uptake among adolescent girls and young women.²² PrEP expansion into primary health care clinics and community education is required to reach its full potential.⁵⁴

Advocacy

Advocacy intervention programs are required to improve the uptake of PrEP.⁵² To ensure no one is left behind in the goal of elimination of new HIV infections, intervention to expand access to these preventive strategies is needed in the study settings.⁵³ PrEP uptake was high, but retention was very low, especially among those at the highest risk of HIV: fisher folk, sex workers, truck drivers, and adolescent girls. Research on reasons for PrEP discontinuation could help optimize retention.⁶³

Discussion

This systematic review and meta-analysis determined the level of willingness to use and actual PrEP uptake in SSA. The awareness level of PrEP was relatively good, but comprehensive knowledge concerning PrEP was very low. Willingness to use PrEP is relatively good; however, the use of PrEP was still unacceptably low. PrEP uptake is overwhelmingly affected by fear of side effects, stigma, nonreceptive attitude, cost of pills, low awareness about the availability of PrEP service, perceived reason about the effectiveness of PrEP pills, and lack of friendly counseling service to minimize stigma and nonreceptive attitudes. Key stakeholder engagement, awareness creation, improved delivery strategy, and advocacy for integrated PrEP service in SSA are recommended actions.

This systematic review has rigorously reviewed primary studies, identified common limitations of primary studies in SSA, recruited high-quality primary studies, synthesized basic recommendations, and identified common barriers to PrEP service uptake to inform policymaking, guideline development and program design to improve PrEP service uptake. This finding is consistent with limited evidence from both the general and key population in SSA to examine the level, facilitators, and barriers to PrEP service. Some of the very limited numbers of systematic reviews undertaken on specific antiretroviral drug effectiveness in SSA setting, for example, tenofovir effectiveness focus on women.⁷⁹ Most others focused on high-income countries.²⁰ Others cover just immediately after initiation of PrEP program,²⁴ in addition to other reviews on PrEP uptake by MSM.^80,81

This finding is also consistent with available evidence, which has reported that improving awareness of PrEP through increasing access to PrEP-related health education and enhancing risk perceptions of HIV infection could have positive effects on the willingness to use PrEP among MSM.⁸² The delivery mechanism of PrEP service has an imperative role in its service uptake. PrEP service is highly demanded through integration with other reproductive health, to build awareness of PrEP and foster awareness of its availability. Integrating demand creation efforts, national policies and guidelines to support PrEP-FP integration, and building on broader efforts to promote SRH integration across population is necessary.^83,84

In this systematic review and meta-analysis, there is a growing willingness to use PrEP by a high number of key populations in HIV program. This in line with the existing literature on urgent need for rational use of PrEP in the prevention of HIV/AIDS in SSA.³ Likewise, scale-up of existing PrEP services is highly demanded to increase access to PrEP for population(s) at high risk for HIV infection.^85,86

Optimal distribution of prevention resources, and choices of whether to implement PrEP in subnational regions should depend on the scope for impact of other possible interventions, local incidence in population groups, and total resources available.⁸⁷ In this systematic review, individual-level barriers to PrEP uptake and persistence use have been characterized, such as low awareness, low willingness to use PrEP, and the gap between self-perceived and actual HIV risk.⁸³ In addition, fear of side effects of PrEP is one of the major barriers to service use. There is also perceived safety concern for pregnant and breastfeeding women in SSA. PrEP may be considered part of a broader combination of HIV prevention strategy,⁸⁸ and should address stigma and nonrespectful attitudes of some providers.⁸⁹

Addressing factors driving low use of PrEP and poor adherence to HIV interventions in this high-risk population is urgently needed.⁷⁹ PrEP has the potential to substantially reduce new HIV infections in HIV-endemic countries in SSA. It is necessary for PrEP to be made widely available beyond those at highest individual risk and continued integration into a range of national services and at the community level to significantly bring down the costs and improve cost-effectiveness.⁹⁰

PrEP was cost-effective in 71% of all settings. Cost effective and contexualized risk-informed PrEP community education played a key role in making PrEP easily accessible for all adults in SSA. In the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with a prevalence of HIV viral load greater than 1000 copies per milliliter among all adults higher than 2%.⁸⁶ Further, PrEP uptake has been slow and several client- and provider-related barriers are limiting uptake. Maximizing the public health impact of PrEP will require rollout to be combined with interventions to promote uptake, support adherence, and prevent increases in risky behavior.^91,92

There was little opposition in general to oral PrEP; however, there were significant nuances in its broader acceptability, applicability, and usability. These relate to balancing complexities of personal empowerment and stigma; navigating complex risk environments; influences of relationships and partners; efficacy and side effects; and practicalities of use.⁸⁹ Overcoming these barriers will require further efforts to understand and address them first. Scaling up PrEP is crucial.⁸³

Although TDF/emtricitabine (FTC) was recommended by WHO in 2015 and has relatively lower prices than tenofovir alafenamide/emtricitabine (TAF), which implies in decreasing the price of PrEP, there is controversy that the safety differences between TAF and TDF/FTC-formulated PrEP appear to have little clinical significance for most PrEP users. As a result, current messaging through physicians and other sources has emphasized the superior safety of TAF, implying that TDF/FTC may not be safe in the long term. Efforts to shift users onto TAF may undermine public perception of TDF-formulated PrEP.^93,94 Further, PrEP service is not effectively implemented in SSA countries due to many circumstances that are associated with the lack of awareness about when PrEP is necessary, and risk perceptions. In addition, there is need of evidence to better inform PrEP guidelines and the decisions adolescent girls and young women make on how to use PrEP based on their risk context.^94

–97

In conclusion, information heard about PrEP among high-risk people for HIV infection seems universal. However, comprehensive knowledge about PrEP is very low. Although PrEP service uptake among high-risk population is low, willingness to use PrEP is relatively good. However, willingness to use PrEP was affected by fear of side effects, stigma, nonreceptive attitude, cost of pills, low awareness about the availability of PrEP service, perceived reason about the effectiveness of PrEP pills, and lack of friendly counseling service to minimize stigma and nonreceptive attitudes.

Key stakeholder engagement, awareness creation, and demand generation improved delivery strategy, including differentiated service delivery of PrEP in communities and advocacy for integrated PrEP service in SSA, are suggested as the way forward. Most of the barriers are preventable through awareness creation and making the service available at different points of care to improve HIV prevention and gear toward HIV epidemic control in Africa. Therefore, expanding educational messages to key population using friendly, more accessible platforms, engaging stakeholders and integrating PrEP service with routine reproductive health care are important to foster HIV prevention and control in the future.

Limitations

This systematic review has some limitations. A relatively high level of variation was observed among studies, and it was a major reason for overwhelmingly relying on narrative synthesis instead of meta-analysis. Relatively limited studies are conducted on PrEP in LMICs, including SSA. Most of the studies are difficult to use for systematic reviews of strict methodological rigor and huge heterogeneity, and have huge variations and publications, as illustrated using funnel plot complemented with Egger's test and Begg's test.

Since PrEP service adoption varies across SSA countries, it is in the infancy stage with low coverage, and most of the studies focused on willingness to use, and awareness-related assessments. Directly measuring PrEP was very challenging. Most of the studies reported the barriers to PrEP service using qualitative findings. For instance, 12 out of 30 studies were qualitative studies and were not included in the meta-analysis. The meta-analysis relied on studies that reported willingness to use PrEP quantitively. Heterogeneity between studies was huge, which is why we used narrative synthesis to produce abridged evidence to inform policy and program.

Footnotes

Acknowledgments

We would like to thank USAID/JSI Strengthening the Care Continuum Project for the financial support and Population Council, Ghana, for facilitating the systematic review and meta-analysis work.

Authors' Contributions

K.F., H.N., H.T., E.A., A.S., and A.A. conceived and designed the study. A.S. drafted the article and he is the guarantor of the review. A.S., K.F., and A.A. developed the search strings. All authors have extensively reviewed the article and incorporated intellectual input in the protocol development. All authors read, provided feedback, and approved the final version of the article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This work is financially supported by USAID, which is tenable through the USAID Strengthening the Care Continuum Project, Cooperative Agreement Number AID-641-A-16-00007, implemented by John Snow Inc., and Population Council, Ghana. The funder has no role in the study selection, data extraction, analysis/synthesis, and interpretation of the findings.

Supplementary Material

Supplementary Table S1

Supplementary Table S2

Supplementary Table S3

Supplementary Table S4

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