https://orcid.org/0000-0002-7143-8400
Figures
Abstract
Introduction
HIV infection is still a global public health problem. More than 75% of HIV-infected people are in Africa, and up to 54% are unaware of their HIV status, limiting access to antiretroviral treatment.
Context and purpose of the study
This review aimed to determine whether HIV self-testing (HIVST) increases the uptake of testing, the yield of new HIV-positive diagnoses, and the linkage to antiretroviral treatment, and social harms among adults in Africa.
Methods
PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Pan African Clinical Trials Registry, The Cochrane Database of Systematic Reviews (CDSR), Databases of Abstracts of Reviews of Effectiveness (DARE), Social Sciences Citation Index, Web of Science and African Index Medicus databases were searched from 1998 to 2019 (updated in December 2019). Eligible trials employed randomized controlled trials (RCTs), before/after studies, and interrupted time series design comparing HIVST to standard HIV testing services or comparing different approaches to HIVST among adults living in Africa were systematically sought.
Results
After searching 2,617 citations eleven trials were identified including 59,119 participants from four (4) African countries. Meta-analysis of seven trials showed a significant increase in the uptake of HIVST compared to standard HIV testing services: Both fixed-effects (Rate Ratio (RR) = 2.64, 95% CI: 2.51 to 2.79), and random-effects (RR) = 3.10, 95% CI: 1.80 to 5.37, and a significant increase in the uptake of couples’ HIVST (RR = 2.50, 95% CI: 2.29 to 2.73 in fixed-effects models; and RR = 2.64, 95% CI: 2.01 to 3.49 in random-effects model). A decrease in linkage to care and ART was observed in HIVST compared to standard HIV testing services (RR = 0.88, 95% CI: 0.88 to 0.95 in fixed-effects models; and RR = 0.78, 95% CI: 0. 56 to 1.08 in random-effects models). Six RCTs measured social harms, with a total of ten reported cases related to HIVST. One RCT comparing two approaches to HIVST showed that offering home-based HIVST with optional home-initiation of antiretroviral treatment increased the reporting of a positive HIV test result (RR: 1.86; 95% CI: 1.16 to 2.98), and linkage to antiretroviral treatment (RR: 2.94; 95% CI: 2.10 to 4.12), compared with facility-based linkage to antiretroviral treatment.
Conclusions
HIVST has the potential to increase the uptake of HIV testing compared to standard HIV testing services. Offering HIVST with optional home initiation of HIV care compared to HIVST with facility-based HIV care increases HIV positivity and linkage to antiretroviral treatment. Reported incidences of intimate partner violence related to HIVST were rare. Future research should focus on the potential of HIVST to reach first-time testers, the effect of using different approaches to HIVST, and strategies for linkage to HIV services.
Systematic review registration
This systematic review was prospectively registered on the Prospero International Prospective Register of Systematic Review (CRD42015023935).
Citation: Njau B, Damian DJ, Abdullahi L, Boulle A, Mathews C (2021) The effects of HIV self-testing on the uptake of HIV testing, linkage to antiretroviral treatment and social harms among adults in Africa: A systematic review and meta-analysis. PLoS ONE 16(1): e0245498. https://doi.org/10.1371/journal.pone.0245498
Editor: Joseph K.B. Matovu, Makerere University School of Public Health, UGANDA
Received: June 17, 2020; Accepted: December 31, 2020; Published: January 27, 2021
Copyright: © 2021 Njau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The authors received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Globally, an estimated 35.0 million people are living with HIV, with more than 2.1 million [1.9 million–2.4 million] new HIV infections and 1.5 million deaths in 2013 [1]. Africa remains the most affected region, contributing more than two-thirds of the global burden of HIV [2]. The UNAIDS/WHO has set a “95-95-95” global target to be reached by 2030. The global target stipulates that 95% of adults will know their HIV status, 95% of HIV positive will receive sustained antiretroviral treatment (ART), and 95% of those who are on ART will achieve viral load suppression by 2030 [3].
In Africa, HIV testing coverage remains low with up to 54% of adults are unaware of their HIV status, despite substantial efforts to increase HIV testing [4]. The low coverage observed undermines the ability to reach the first "90" target and is a critical barrier to scaling up HIV prevention, care and treatment programmes. Also, late presentation for ART and delay harms treatment outcomes among HIV–positive people in Africa, leading to high mortality, and high transmission of the virus [5, 6].
Existing literature shows that HIV self -testing (HIVST) has the potential to provide an opportunity for individuals who have never tested for HIV to know their HIV status [7]. According to WHO and UNAIDS, HIVST broadly refers to “a process whereby an individual, who is willing to know his/her HIV status collects a specimen, performs the test and interprets the test results in private” [8].
A distinction is made from the mail-in self-testing models of home specimen collection where primarily a person collects a specimen in private and sends it by post to a laboratory for testing and waits for the results [9]. Further, HIVST testing should be regarded as a screening tool only, since they do not provide a definitive diagnosis. A follow-up to a health facility or seeing a health care provider for further confirmatory testing is mandatory after receiving a positive HIVST result [8].
Different from the conventional HIV rapid diagnostics tests (RDTs), which are restricted to health care providers, HIVST consists of approaches for testing products specifically designed and marketed for use by laypersons [10–12]. In response to HIVST recommendations, several African countries have incorporated the HIVST approach in their national HTS policy [11, 13, 14]. Other countries are at different stages in considering including HIVST in policy and practices [11]. Also, results from a five-year (2015–2020), Unitaid-funded HIV Self-testing Africa (STAR) initiative, which supports HIV self-testing in five sub-Saharan countries informed WHO HIVST guidelines [15].
Systematic reviews have been conducted in high- and low and middle -income countries on the acceptability of HIVST [16], performance accuracy among laypersons [17], and the uptake of HIVST [18]. Since the last reviews in 2014, several new studies on HIVST in Africa have been published.
By 2010, new evidence showed that people living with HIV (PLHIV) would benefit more if ART were initiated much earlier. The ART eligibility criteria were revised from a CD4 cell count of 200 to 350 based on the evidence [4]. The changes increased the number of PLHIV enrolled in ART by 1.5 times by the end of 2010 compared to 2008 indicating an increase in expectation and demand for ART [4]. In 2013, new evidence emerged which showed more benefits associated with much earlier initiation of ART and the WHO recommended that the cut–off point for initiation of ART for PLHIV should be a CD4 cell count of 500 [4]. The current guideline suggests that PLHIV should initiate ART irrespective of the CD4 cell count [3]. Linkage to HIV prevention, care and treatment is the ultimate goal for making people in the general population, aware of their HIV status. However, existing evidence suggested that only about 18% of ineligible ART patients at diagnosis remain continuously in care until ART eligibility. Several main reasons for poor retention at pre–ART care documented includes perceived lack of therapeutic benefits compared to cost of attending clinic, risk of losing employment due to frequent clinic visits, cost of transport or fear of visibility as clients of an HIV clinic among asymptomatic patients, and death among those with very low CD 4 counts [19].
According to the WHO definition, social harms, or adverse events refers to any undesirable experience or intended or unintended harm related to HIV testing, including self-testing [8]. Existing evidence so far does not support incidences of social harm directly related to HIVST, however, the WHO guideline underscores the importance of assessing social harm related to HIVST [8].
This systematic review aims to synthesize the evidence on the effects of HIVST among adults in Africa on the uptake of testing, the yield of new HIV–positive diagnoses, linkage to ARV treatment, and the incidence of social harms.
Methods
This systematic review followed guidance from the Cochrane Collaboration [20] and is reported based on the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA) statement. A review protocol was developed and registered in the PROSPERO International Prospective Register of systematic reviews: (http://www.crd.york.ac.uk/PROSPERO/ PROSPERO registration number: CRD42015023935) [21].
Eligibility criteria
Study designs.
Experimental studies including randomized controlled trials (RCTs), before/after studies, and interrupted time-series studies were eligible for inclusion in this review.
Intervention and comparisons.
HIV self–testing refers to a process whereby an individual, who is willing to know his/her HIV status collects his/her specimen, performs the HIV test and interprets the results in private at home or in other settings. HIVST can be delivered with direct assistance, for example, an in-person demonstration on how to use self-test, or unassisted using manufacturer instructions alone. In this review, we compared the effects of HIV self-testing, either alone, or in addition to the standard HIV testing services (HTS). Standard HIV testing services (HTS) was defined as: routine HTS services provided by trained health care providers at health facilities or HIV testing points, and might involve: (1) provider-administered testing, (2) door-to-door testing, (3) mobile testing, (4) index testing, (5) workplace testing, and (6) client-initiated testing, or some combination of these approaches. We also compared different approaches to HIVST.
Outcomes.
The primary outcomes were: uptake of HIV testing and the yield of new HIV-positive diagnoses among adults in African countries. The primary outcomes were defined as:
- Uptake: the proportion of participants offered HIV testing who underwent HIV testing [22].
- The yield of new HIV–positive diagnoses: the proportion of participants offered HIV testing who were newly diagnosed as HIV-positive [23, 24].
The secondary outcomes were defined as:
- HIV positivity: the proportion of participants offered HIV testing who was diagnosed with HIV positive [25].
- Linkage to ARV treatment: the proportion of diagnosed HIV-positive participants who were enrolled in ARV treatment at any time after testing.
- CD4 count: the proportion of diagnosed HIV-positive participants who had their CD4 count measured [26].
- Social harm: the number of participants for whom any episode of harm was observed or reported, during or after HIV testing (e.g. intimate partner violence, coercive testing by a partner, or suicide, etc.) [27].
Inclusion and exclusion criteria.
All experimental studies which included RCTs, before/after studies and interrupted time-series studies, and compared HIVST with the standard of HTS and/or which compared different approaches to HIVST were eligible for inclusion. Editorials, reviews, perspectives, and studies not evaluating self–testing strategies (e.g. home-based but non-self–test) were excluded. Studies, which did not clearly define the type of HIV testing strategies, were also excluded. Abstracts were included if full-texts were not available. Any disagreements in study inclusion/exclusion were resolved by consensus during a meeting between reviewers.
Information sources
Electronic databases.
A comprehensive search strategy was developed to identify both published and unpublished articles with no language restrictions from January 1998 to December 2019. The start-time period search restriction was used because since 1998 there has been an emergence of the advanced development of rapid HIV diagnostic tests including self–testing [28]. The review searched for related studies in PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Pan African Clinical Trials Registry, The Cochrane Database of Systematic Reviews (CDSR), Databases of Abstracts of Reviews of Effectiveness (DARE), Social Sciences Citation Index, Web of Science and African Index Medicus. Also, we searched websites and databases for grey materials (generally refers to no publicly published literature) such as greynet.org, World Health Organization Library Information System (WHOLIS), WHO Global Index Medicus, The Joint United Nations Programme on HIV/AIDS (UNAIDS resource library), Alliance of Health Policy & Systems Research, The World Bank. We also searched for conference abstracts of the following conference databases: International AIDS Conference 1st International symposium on self-testing for HIV, International AIDS Society Conference (IAS), and Conference on Retroviruses and Opportunistic Infections (CROI). Terms for self-testing only were used to search for HIV-related conference abstracts published between 2001–2019 to overcome the limitations of search functions. We also searched the HIV Self-Testing Research and Policy Hub (HIVST.org) for ongoing updates of ongoing studies. The search strategies for electronic databases incorporated medical subject headings (MeSH), free–text terms and comprehensive African search filter that was adapted to suit each database using an applicable controlled vocabulary [29, 30]. We also checked reference lists of included studies for other eligible reports. We also checked reference lists of the included studies and other relevant systematic reviews for further eligible reports using Google Scholar, and Web of Science. Before the publication of this review, we conducted an updated search for HIVST studies in Africa that were published from 1st January 1998 to 31st December 2019.
Search strategy.
This systematic review used a search strategy described in a previously published protocol and summarized in Additional file 1 [21].
The search was restricted to human subjects. The full search string for PubMed is included as supplementary material S1 File. We sought expert views on the search strategy to assess the search terms proposed for this review.
Study records
Data management.
All search results were merged into reference management software EndNote and were all imported into Convidence (https://www.Convidence.org/), and BN and DD performed an automatic check to exclude duplicate entries.
Selection process.
Two reviewers (BN and DD) independently screened the titles to exclude all irrelevant studies and select potentially eligible studies. In this process of abstract screening, the two reviewers included, excluded or classified abstracts as ‘maybe’. The reviewers met to discuss the disagreements, with a consensus to include or exclude. BN then obtained the full text of potentially eligible studies and later BN and DD independently conducted the final study selection for inclusion in the review. The two reviewers provided the reasons for excluding studies at this stage. The final included studies for data collection and the screening process created by Convidence are presented as part of the PRISMA study flow chart shown in Fig 1.
Data collection process.
Two reviewers, independently extracted data using a pre-designed data extraction form. A third reviewer (LA) was consulted to resolve any differences of opinion between the two reviewers that arose. We conducted a pilot trial of the data extraction form to check its adequacy and made necessary changes.
Data items.
Extracted data included: study design, setting of the study (e.g. city/ country/or rural/urban or facility-based /community–based), year of study, year of publication–1998 to date, type of HIV self–testing (e.g. supervised or unsupervised), type of comparator (e.g. standard HIV testing services), study population (e.g. general population or key populations), and study outcomes of interest.
Assessment of risk of bias in included studies.
Two authors (BN and DD) independently assessed the risk of bias (low risk of bias, high risk of bias, or unclear risk of bias) using the Cochrane risk of bias instrument, including an evaluation of random sequence generation and allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and unclear risk of bias (either due to lack of information or uncertainty over the potential bias). We resolved disagreements by consensus. Trials reporting > 20% of missing data were judged at a high risk of attrition bias. In HIV testing studies, it is difficult to bind participants, and/or researchers to the interventions resulting in a high risk of performance bias been made. However this should not infer that the methodological quality of the trials was poor, but the reviewer's acknowledging the inevitable bias related to lack of blinding [31]. The assessments of risk of bias are summarized in Tables 1, 3 and 4 and Fig 6.
Investigation of heterogeneity.
The I2 statistics were used to evaluate the heterogeneity of results for each outcome, across trials. We interpreted values of 25, 50, and 75% as low, medium, and high heterogeneity respectively. The observed I2 statistics relies on the magnitude and direction of effects, and the strength of evidence for heterogeneity. Although not a measure of absolute heterogeneity, the I2 statistics describe the percentage of variability in the point estimates that is due to heterogeneity rather than sampling error [32].
Assessment of reporting biases.
The review employed strategies to search and include relevant unpublished studies to reduce publication bias. The strategies included searching the gray literature, including conference proceedings (e.g., International AIDS Conference), and prospective trial registration database to over-come lime-lag bias. To investigate publication bias, if there were ≥ 10 trials included in an analysis, we planned to use a funnel plot to explore the possibility of small study effects-a tendency for smaller studies to report larger beneficial effects. However, this review did not use a funnel plot test because of fewer trials (< 10 trials) were included in an analysis, as the power of tests is too low to distinguish chance from publication bias [33].
Data analysis.
Where data from ≥ 2 trials were available, pooled intervention effect estimates are expressed as risk ratios with corresponding 95% confidence intervals (CI) for each outcome included in the study. The review used the fixed effects models and random-effects models for analysis in the Cochrane Review Manager. Pooled estimates were calculated using random-effects models were high heterogeneity was found among studies. The random-effects model approximates the extent of the heterogeneity and allocates a greater variability to the estimate of overall effect to account for the heterogeneity. In the result section we present forest plots of random-effects models, and forest plots of fixed effects models as Supporting file S2 Fig [33].
Sensitivity analysis.
Sensitivity analyses were performed on outcomes where an effect of excluding outlier studies and those with high overall bias risk might affect the overall estimate. Visual inspection of forest plots was used to identify trials, which were outliers, and the I2 was re-evaluated without the outliers. We also investigated the influence of a single study on the overall estimate by excluding 1 study in each turn [32].
Results
Description of included studies
Search results.
A total of 2,617 citations were identified through electronic search and other sources, which after screening resulted in eleven trials met the review eligibility criteria (Fig 1). There are ongoing trials conducted by The Self-Testing (STAR) Initiative in Malawi (NCT02718274), Zambia (NCT02793804), and Kenya (NCT03135067).
Eleven trials [25, 34–44] conducted between 2011 and 2019, and including 59,119 participants met the eligibility criteria for inclusion in the review (Fig 1 Study flow diagram).
Eight of the trials were reported in full-text articles [25, 34–36, 38, 40, 42, 43, 45], and three were reported in conference abstracts [37, 41, 44]. Of the 11 trials, three were from Kenya [34, 35, 38, 43], two from Zambia, [36, 41], two from Uganda, [39, 40] and four from Malawi [25, 37, 42, 44]. Four trials were conducted in facility-based [34, 37, 40, 42], two were community-based [41, 44], and five were both facility-based and community-based [25, 35, 38, 41, 43, 44]. Five trials used direct assisted HIVST [25, 35, 37, 40, 44], two used unassisted HIVST [34, 39], and one trial used both [43]. Four trials aimed to increase the uptake of HIV testing among male partners of pregnant women attending antenatal clinics or women attending postnatal clinics after the birth of a child, [34, 35, 40, 42], two trials among female sex workers [36, 39], two trials among adult patients attending health facilities [37, 44], one trial among male truck drivers[38, 43], and three trials were conducted among adults aged 16 years and older from the general population [25, 41, 44]. Across all 11 trials, none reported on the yield of new HIV-positive diagnoses, (one of our primary outcomes), and instead reported HIV positivity (n = 7).
Ten of the trials compared HIVST to standard HTS [34–37, 40–45], and one trial compared the optional home-based confirmatory testing and initiation of antiretroviral therapy (ART) to HIVST accompanied with referral to facility-based HIV care services [25]. All 11 trials used free oral fluid-based HIVST, followed by confirmatory HIV rapid diagnostic tests, and none used finger stick/ or whole blood-based RDTs or both oral and blood specimens.
HIVST compared with standard HIV testing services
Uptake of HIV testing.
Three trials in Kenya, Malawi, and Uganda [35, 40, 42], recruited women (n = 5450), with no risk of intimate partner violence, and with their male partners of unknown HIV status or known HIV-negative status, at antenatal and postnatal care and invited them to either distribute HIV self-tests to their male partners (intervention arm) or an invitation card and referral vouchers for free HIV testing, here assumed to be standard HIV testing services (comparison arm). Two trials conducted in Zambia and Uganda [36, 39] recruited adult female sex workers (n = 1,925), who reported the exchange of any vaginal, anal, or oral sex for money, goods, or other items of value and invited them to either direct delivery of HIV self-tests, or coupons for free collection of HIV self-tests (intervention arms) or referral for standard HIV testing services (comparison arm). One trial in Kenya [43] recruited male truck drivers (n = 305) and offered a self-administered HIVST under the supervision/ or un-supervised self-administered HIVST at home (intervention arms) or routine PITC HIV testing, here assumed to be standard HIV testing services (comparison arm). One trial in Malawi [37] recruited adult patients attending the out-patient department (n = 3918) and offered self-administered HIVST (intervention arms), or routine PITC HIV testing, here assumed to be standard HIV testing services (comparison arm). A meta-analysis showed an increase in the uptake of HIV testing in the HIVST arm compared with the standard HTS arm (RR = 3.10, 95% CI: 1.80 to 5.37; Tau2 = 0.52; Chi2 = 808.64; df = 6 (p < 0.00001; I2 = 99% in random-effects models)). The I2 of 99% is the proportion of the variation in observed effects due to variation of the true effects (Fig 2).
The RR and horizontal lines represent the 95% CI in random-effect model.
A meta-analysis including three trials [34, 35, 40], among pregnant women (n = 8,397), showed an increase in the uptake of couples HIV testing in the HIVST arm compared to standard HTS (RR = 2.50, 95% CI: 2.17 to 2.89; Tau2 = 0.01; Chi2 = 5.08; df = 1 (P = 0.08; I2 = 61% in random-effects models)). Couples HIV testing referred to the participant and her male partner testing for HIV together at the same time. The I2 of 61% is the proportion of the variation in observed effects due to the variation of the true effects (Fig 3).
The RR and horizontal lines represent the 95% CI in random-effect model.
HIV positivity.
Seven trials [35–37, 40–42, 45], assessed HIV positivity among male partners of pregnant women (n = 3), female sex workers following HIV testing (n = 2), adult patients attending health facilities (n = 1), and adults in the general population (n = 1). HIV positivity rate was determined as the proportion of participants diagnosed HIV-positive over those who accepted HIV testing. A meta-analysis showed no statistically significant difference in reporting HIV positivity among male partners of pregnant women, and female sex workers from HIVST compared to standard HTS (RR = 1.00, 95% CI: 0.87 to 1.15; Tau2 = 0.00; Chi2 = 5.95; df = 6 (p < 0.43; I2 = 0% in random-effects models)). The I2 of 0% is the proportion of the variation in observed effects due to variation of the true effects (Fig 4).
The RR and horizontal lines represent the 95% CI in random-effect model.
Linkage to care and antiretroviral treatment.
Six trials, [35, 36, 40–42, 45], reported on linkage to care and ART among participants who were diagnosed HIV positive (n =). A meta-analysis showed that participants from HIVST are less likely to seek HIV–related care and initiating ART compared to participants from HTS (RR = 0.78, 95% CI: 0.56 to 1.08; Tau2 = 0.10; Chi2 = 24.54; df = 5 (p < 0.0002; I2 = 80% in random-effects models)). The I2 of 80% is the proportion of the variation in observed effects due to variation of the true effects (Fig 5).
The RR and horizontal lines represent the 95% CI in random-effect model.
Social harms.
Six trials assessed social harms, following HIVST or standard HTS among adult participants. The trial in Kenya [35] reported a single incidence of harm in each group between two HIV-negative participants in the HIVST group, and the control group. In both groups, the reported harm was verbal and/ or physical intimate partner violence. The trial in Zambia [36] reported four incidences of harm, with three participants in the direct delivery of HIVST intervention arm, and one participant in the coupon intervention arm, reporting physical violence following primary partner learning of their HIVST use. None incidence of harm was reported in the standard of care arm. The trial in Uganda [39], reported four incidences of harm, with one participant in the direct delivery of HIVST intervention arm, and one participant in the coupon intervention arm, reporting verbal abuse following primary partner learning of their HIVST use/or mental distress following a positive HIV self-test result. Two participants in the standard of care arm reported verbal abuse after the disclosure of their HIV status. Two trials among male partners of pregnant women and patients attending health facilities in Malawi reported no social harms after HIVST [37, 42]. Another trial in Malawi among the the general population of rural communities reported three incidences of social harm [44].
Sensitivity analysis.
Exclusion of 5 studies from a meta-analysis reporting uptake of HIV testing in HIVST arm compared with the standard of HTS arm altered the overall estimate and heterogeneity (RR = 1.20, 95% CI: 1.12–1.27; P = 0.99, I2 = 0%). Exclusion of studies from meta-analyses reporting uptake of couples HIV testing, HIV positivity, and linkage to care and ART did not alter the existing heterogeneity.
HIVST with optional home-initiation of HIV care compared to HIVST with facility-based HIV care
One RCT in Malawi (n = 16,660) compared different approaches to HIVST [25].
HIV positivity.
The trial reported HIV positivity among participants following HIV testing. HIV positivity rate was determined as the proportion of participants diagnosed HIV-positive over those who accepted HIV testing. There was a significant difference in reporting a positive test result between the home and facility groups (RR: 1.86; 95% CI: 1.16 to 2.98; P = .010) to HIVST accompanied with referral to facility-based HIV care services.
Tested for CD4 counts.
The study compared the receipt of CD4 count test results among newly diagnosed HIV-positive individuals. In the arm with the offer of optional home-based confirmatory testing and initiation of ART group, 72. 5% (n = 79/109) of newly diagnosed HIV positive individuals received CD4 count results compared to 51% (n = 23/63) in the facility group (RR = 0.70, 95% CI: 0.54 to 0.91; P = .007).
Linkage to care and antiretroviral treatment.
The trial reported ART initiation and retention in care. In the arm with the offer of optional home-based confirmatory testing and initiation of ART group, initiation of ART was 2.2% (n = 181/8,194) compared to 0.7% (n = 63/8,466) in the control arm (RR, 2.94; 95% CI: 2.10 to 4.12; P < .0001). After adjusting for reported household mortality at baseline, the effect of availability of home ART care was (ARR, 2.44; 95% CI: 1.61 to 3.68; P < .001).
Assessment of risk of bias in included studies.
The risk of bias in the included studies was assessed as described above. The assessments of risk of bias in included studies are presented in the risk of bias graph below (Fig 6), while additional details are included in Tables 1, 3 and 4.
Assessment of overall quality of the evidence.
We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence and generate absolute estimates of effect for the outcomes as described in the GRADE profiler (GRADEpro) software [31, 83]. The GRADE methodology defines the quality of evidence for each outcome as ‘ the extent to which one can be confident that an estimate of effect or association is close to the quantity of specific interest” [20]. The quality rating across studies has four levels: high, moderate, low or very low. RCTs are initially categorized as providing high-quality evidence with the option of downgrading the quality. Quality of evidence can be downgraded based on limitations in design, indirectness of evidence, unexplained heterogeneity or inconsistency of results, imprecision of results or high probability of publication bias [20]. We did not downgrade based on lack of blinding alone due to difficulties of blinding participants, and or research personnel in HIV testing intervention trials. Downgrading was done based on the risk of bias when a lack of blinding was accompanied by additional high risks of bias (e.g., selection bias and incomplete outcome reporting). We summarized the quality of evidence for the studies separately for each outcome in the GRADE Summary of Findings Tables [31].
The overall quality of evidence.
The overall quality of evidence for the 10 trials [34–37, 39–44] was moderate. The quality of evidence was downgraded because of the risk of bias, imprecision, and inconsistency (Table 3).
The overall quality of the evidence for the cluster RCT [25] was moderate. The quality of evidence was downgraded because of the risk of bias (Table 4).
Discussion
Summary of main results
The objective of this systematic review was to synthesize the evidence on the effects of HIVST among adults in Africa on the uptake of testing, the yield of new HIV–positive diagnoses, linkage to ARV treatment, and the incidence of social harms. This review included eleven trials conducted in Malawi, Kenya, Zambia, and Uganda.
Two models of HIV testing were assessed in the included studies of this review. The first model included ten trials comparing HIVST versus standard HTS, and the second model included one trial comparing different approaches to HIVST. In the first model, 10 RCTs in Kenya, Zambia, and Uganda found a positive effect on the uptake of HIVST compared to standard HTS. Similarly, in three trials in Kenya and Uganda reported a positive effect on the uptake of couples' HIVST compared to standard HTS.
Seven trials reported no statistically significant difference in reporting HIV positivity among participants from HIVST compared to standard HTS. Also, six trials reported no statistically significant difference in linkage to care and ART among HIV positive participants from standard HTS compared with those from HIVST. Finally, ten incidences of any kind of social harm were reported following HIVST and standard HTS from 6 RCTs in Kenya, Zambia, and Uganda.
In the second model, one trial in Malawi reported a statistically significant difference, showing participants who received HIVST and an optional home-based confirmatory testing and initiation of ART were more likely to report HIV positive test results than those in the control group. Further, the trial showed an increased proportion of newly diagnosed HIV positive participants in the homegroup received CD 4 count tests than those in the control group. Finally, the trial reported a statistically significant difference showing that participants who reported HIV-positive test results from home-based HIVST with optional home-based confirmatory testing and initiation of ART were more likely to initiate ART care compared with their counterparts from the home-based HIVST with facility-based HIV care.
Summary of evidence: HIVST versus standard of HIV testing services
Uptake of HIVST.
Seven trials were included in the meta-analysis, and showed a moderate quality of evidence, for the uptake of HIV testing compared to standard HTS. Furthermore, two RCTs were included in the meta-analysis also showed the moderate quality of evidence for uptake of couple HIV testing. Although the results of the meta-analysis report that HIVST can double the uptake of HIV testing compared to standard HTS, there is some uncertainty because of heterogeneity in effect size between the studies. Besides, the evidence was limited to male partners of pregnant and post-partum women and adult female sex workers.
HIV positivity.
Seven trials included in this review with moderate evidence showed no difference between HIVST compared to standard HTS in reporting HIV- positivity. The quality of evidence was downgraded for the risk of bias, detection bias, selection bias, and imprecision. None of the trials reported the yield of new HIV positive diagnoses. Yield and HIV positivity are important for designing appropriate and sustainable HIV testing interventions because it determines the number of tests needed to diagnose a new case of HIV, and has cost and resource implications [84]. However, all trials included in this review, none reported on the yield of new HIV positive diagnoses, underscoring the need to assess this important indicator in future studies, particularly in high HIV prevalence settings.
Linkage to HIV care.
Six trials included in this review with moderate evidence showed poor linkage to HIV care following confirmatory testing between HIV positive participants in the HIVST group compared to those in the standard HTS group.
Social harms.
One trial from Kenya compared the distribution of HIVST kits by pregnant women to their male partners with standard HTS, and 2 trials from Zambia and Uganda, compared the delivery of HIVST kits with standard HTS among adult female sex workers and assessed IPV resulting from HIVST. The trial reported a total of 10 incidences of any form of social harm related to HIV self-testing reported by different adult populations, such as pregnant women, and female sex workers. It is possible that self-testing does alter IPV experiences, but is currently not accurately measured by the extant literature. This finding of reported rare cases of IPV related to HIVST is consistent with several studies assessing harm across all forms of HIV testing services [27, 85, 86]. However, it is important to introduce HIVST with caution among vulnerable populations (e.g. female sex workers (FSW)) [8, 54].
Summary of evidence: Comparison of different approaches to HIVST
HIV positivity.
One trial from Malawi with moderate-quality evidence, assessed different approaches to HIVST and, observed that participants from home-based HIVST with optional home-based confirmatory testing and initiation of ART were significantly more likely to report a positive result than participants from home-based HIVST with facility-based HIV care [25].
Tested for CD 4 count.
The same trial showed a high proportion of newly diagnosed HIV-positive participants, from the intervention arm compared to participants form the control arm tested for CD4 counts [25]. The finding supports the evidence that a high proportion of CD4 counts could be achieved outside the health facilities when offered together with HIV test results, and may facilitate immediate treatment for improved health and to decrease the probability of further HIV transmissions [18, 27].
Started ART.
Additionally, the same trial in Malawi reported an increased proportion of participants who reported HIV-positive results from the intervention arm compared to the control arm. However, this RCT reported the loss to follow-up 6 months after the home-initiation of ART compared with the facility-initiation of ART. ART initiators in the homegroup had higher rates of loss from ART compared with their counterparts in the facility group.
Overall completeness of the evidence and applicability of evidence.
The observed results on increased uptake concur with results from other systematic reviews [16–18, 87, 88] and observational studies from Kenya [56], Lesotho [89], Malawi [27, 46], and Zimbabwe [90], which reported similar increases in the uptake of HIV testing through HIVST. For instance, the systematic reviews reported an uptake of HIVST ranging from 50% to 96% in other parts of the world [16–18] and 20% to 74% in the key populations [18, 88]. Also, a two-year prospective study in Malawi reported s consistently high uptake of community-based HIVST among adolescents aged 16–19 years of age; young people aged 16–29 years of age, women, and men [27].
Although HIVST primarily focuses on an individual, two trials in this review were conducted in Kenya where women distributed HIVST kits to their male partners. The trials also reported an increased uptake of the couple’s testing from HIVST compared with the approach of giving male partners invitation letters or vouchers for free HTS. These results suggest that men may be more likely to prefer HIVST than standard HTS [91]. This observation underscores the importance of getting men to utilize HTS because it is well documented that men compared with women are known to underutilize HTS and present late for care ending up with worse outcomes on treatment [5, 6].
Observational studies among key populations, including men who have sex with men (MSM) [88], people who inject drugs (PWIDs) [92], and female sex workers [93], revealed high uptakes of HIV testing following the offer of HIVST. It is well documented that to achieve universal knowledge of HIV status, it is imperative to have innovative interventions such as HIVST to increase access to HIV testing. This review confirms that HIVST is an important strategy to improve awareness of HIV status among adults in SSA, and provides additional HIV testing options to other approaches such as VCT, PITC, school-based, and work-place testing [8, 92].
Earlier HIV diagnosis supports timely access to ART, with several beneficial consequences, such as improved life expectancy, reduced HIV transmission, decreased stigma related to HIV testing, and the provision of HIV prevention interventions [87]. These results are consistent with results from observational studies among the general populations in SSA, which reported HIV-positivity ranging from 3 to 14% [27, 53, 54, 90], and from 1 to 30% among key populations [54, 93]. As coverage of HIV testing increases, the proportion of HIV-positive tests and new HIV diagnoses will be likely to decrease, and hence calls for more focused HIV testing methods to continue to achieve the same or higher levels of HIV-positivity [8, 92].
This review identified gaps in the evidence on linkage to care and ART. Linkages to further HIV testing and HIV prevention, treatment, and care services are a critical component in the HIV testing cascade. This is more important in HIVST because it requires linkage to confirmatory testing, particularly among those who report a positive HIV test result [87]. The most probable explanation to the observed low level of linkage could be due to a few diagnosed HIV-positives, under-reporting and the possibility that some men were aware of their HIV-positive status and already in care. These findings suggest that innovative follow-up strategies post HIVST such as the use of mobile phones or short message services, or facilitated HIV care assessments and ART initiation interventions could be put into place to encourage linkage [8, 27, 87, 92].
HIV testing experts recognize the importance and complexity of monitoring, reporting, evaluating and mitigating social harms related to HIV testing. The rare cases of social harm related to HIVST reported in this review, help to alleviate a major concern of HTS experts, regarding IPV related to HIVST. The findings may suggest that HIVST does not directly influence the risk of IPV, but the risks are largely context-specific, including the settings (e.g. urban/rural) and the relationship dynamics of couples and partners. To emphasize this critical concern, the WHO recommends that HIV testing programmes consider context-specific strategies to implement HIV testing approaches, including HIVST [8, 91]. Furthermore, fear of status disclosure or stigma, the possibility of false-positive diagnoses, lack of confirmatory HIV testing, and insufficient quality control procedures highlight the need to address legal and human rights issues related to HIVST [8, 85, 87].
Quality of the evidence.
According to the GRADE system, well-conducted RCTs provide high-quality evidence, while observational studies provide low-quality evidence. This review included only trial data, and we found the quality of evidence reported from trials for the HIVST versus standard HTS was generally moderate. The model for comparison of different approaches for HIVST, including one high-quality trial provided moderate quality of evidence.
Potential biases in the review process.
We used a broad search strategy to capture as many studies as possible. We limited our search to those studies conducted in Africa from 1998 to date to improve comparability. A random-effects model was used to pool data. Despite using a broad search strategy, we were able to capture eleven trials (8 full test studies, and 3 abstracts) conducted across four countries in SSA. Further, there are limited studies from other parts of Africa, which may limit the generalizability of the review findings.
We, therefore, cannot exclude the possibility that of the dispersion presented, what proportion is due to variance in true effects rather than sampling error [32]. Publication bias was not formally assessed because of the limited number of trials for each outcome, since analytical methods such as funnel plots and funnel plots asymmetry tests, were not appropriate [20].
Agreements and disagreements with other studies or reviews.
To the authors’ knowledge, this is the first systematic review evaluating the effects of HIVST on the uptake of HIV testing, linkage to care and ART, and social harms among adults in Africa. Previous reviews focused on HIVST strategies, the acceptability of HIVST, and different community-based HIV testing approaches globally. The findings of this review provide important information on the potential of HIVST as an option for HTS among adults in Africa. A key finding of our review is that the uptake of HIVST is promising among different adult populations in both rural and urban settings in Africa, particularly in SSA. Importantly, it is the observation of high participation by male partners in couples' HIV testing through HIVST. However, more data are needed on the yield of new HIV positive diagnoses, particularly from countries with high HIV prevalence in SSA in terms of the diverse range of context and settings.
Further research among key populations such as MSM, PWIDs, and vulnerable populations such as adolescents, and factors associated with their participation in HIVST, is important to inform policy and practice. In addition, further key areas for research includes: the effectiveness of HIVST in detecting previously undiagnosed HIV infection, or number of repeat non-testers, linkage to care following a reactive self HIV test result or a confirmatory positive test, retention of care among those identified HIV-positive, linkage to prevention services among participants with negative results (e.g. male circumcision), and social harms from HIVST, which are important to help guide policy on HIVST in Africa. Interventions to facilitate a timely linkage to care are ongoing in Zimbabwe (PACTR20160700171788), and Malawi (ISRCTN18421340), with preliminary findings reporting significant benefits on linkage to VMMC and ART using financial and non-financial incentives.
Implication for research.
This review has reported moderate-quality evidence for the uptake of HIVST, suggesting that self-testing has the potential to provide an innovative strategy to increase uptake of HIV testing and increase awareness of HIV status among undiagnosed adults in Africa, particularly in SSA. However, we also reported no statistically significant difference in reporting HIV positivity between participants from HIVST and HTS, indicating a need for further research particularly in high HIV prevalence settings in SSA. This review recommends that high-quality evidence from trials would provide valuable insight into whether HIVST as an additional HIV testing option could facilitate early detection, early linkage to HIV care, treatment, and prevention. Additional trial findings will provide data on HIVST as an invaluable tool for the health authorities of African governments to increase access to HIV care, treatment, and prevention to achieve the "95-95-95" global target by the year 2030.
Supporting information
S1 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: Uptake of HIV testing.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s003
(DOCX)
S2 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: Uptake of couple’s HIV testing.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s004
(DOCX)
S3 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: HIV positivity.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s005
(DOCX)
S4 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: Linkage to HIV care and ART.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s006
(DOCX)
S5 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: Uptake of HIV testing.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s007
(DOCX)
S6 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: Uptake of couple’s HIV testing.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s008
(DOCX)
S7 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: HIV positivity.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s009
(DOCX)
S8 Fig. Forest plot: Comparison of HIVST versus standard of HIV testing services; outcome: Linkage to HIV care and ART.
The RR and horizontal lines represent the 95% CI in fixed-effect model.
https://doi.org/10.1371/journal.pone.0245498.s010
(DOCX)
Acknowledgments
The authors acknowledge Ms. Dilshaad Brey the UCT Libraries, Health Sciences, and Information Services Librarian, and Elizabeth Pienaar Senior Scientist: Cochrane Centre South African Medical Research Council, for their technical support in the planning of the search strategy. Dr. Mark Engel and Dr. Mahmoud Werfalli of Evidence-Based Medicine Research Support Unit, Faculty of Health Sciences at the University of Cape Town, Darshini Govindasamy of South African Medical Research Council and Claire Gudex of Department of Clinical Research, University of Southern Denmark, for technical support.
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