Abstract
HIV self-testing (HIVST) allows individuals to interpret and report their own test results, thus decentralizing testing. Yet, this decentralization can make it difficult to verify self-testing results, which is important for linkage to care and surveillance. The aim of this systematic review is to summarize methods for verifying HIVST use and results. We followed guidance from the Cochrane Handbook 5.1 on systematic reviews. We searched four journal databases (PubMed, Embase, Scopus, and Cochrane Library), one clinical trials database (
Introduction
HIV self-testing (HIVST) is recommended by the World Health Organization (WHO) as a complementary HIV testing strategy. 1 It is a process by which individuals collect their own blood or oral fluid sample, conduct the diagnostic test, and then interpret their results. 1 With 9.4 million people living with HIV (PLWH) unaware of their status, 2 HIVST is an important approach toward the first of The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets, that is, 90% of PLWH will know their status by 2020. 3 HIVST may reach individuals at high-risk for HIV acquisition who require frequent testing and key populations who may avoid standard HIV testing services due to stigma and discrimination. 1,4 Moreover, it has several advantages compared to provider-delivered HIV testing services, such as enhanced confidentiality for testers 5 and potential cost savings for health systems. 6 This form of testing also provides greater convenience for testers by mitigating barriers related to accessing care, particularly traveling far distances to clinics 7,8 and long waiting times. 9 –11 HIVST has the ability not only to expand uptake of HIV testing but also to increase the autonomy a person has over their care.
Despite the potential of HIVST in increasing testing access, there are challenges associated with verifying the results for individuals who self-test. Verification of testing and results involves methods that can link the test result to the individual performing the self-test. The shift of HIV testing away from health care facilities makes it difficult to verify self-testing results, which are keys for confirming HIV status, linkage to care, and routine surveillance. Many HIV projects have relied on self-reported outcomes of self-testing, 12 –14 which has important limitations. Individuals may inaccurately report their HIVST use or HIV status, 15 possibly due to social desirability bias, fear of stigma, or loss to follow-up. This can impact programming for HIV services and make it difficult to measure HIV prevalence in a population, to determine the proportion of persons who are aware of their HIV status, and to conduct epidemic surveillance.
We conducted a systematic review to consolidate global literature on reported methods that are used to verify HIVST, describe the different methods, and explore the appropriateness of each method based on testing conditions.
Methods
Search strategy
Our search strategy followed best practices as defined in the Cochrane Handbook version 5.1.
16
We developed a comprehensive search, in collaboration with a health sciences research librarian, to identify studies that used HIVST verification methods published from January 1, 2008 to October 15, 2018. We searched four journal databases (PubMed, Embase, Scopus, and the Cochrane Library), one clinical trials database (
Study selection
We included original quantitative studies that had a focus on HIVST, described a method to verify HIVST results, were written in English, and were published between 2008 and 2018. We excluded HIVST studies before 2008 for three reasons: (1) the accuracy of HIVST kits before 2008 was not well-established and the technology has evolved in the past decade; (2) the policy environment actively discouraged self-testing compared to official WHO and national policies supporting self-testing now; and (3) the greater requirements for informed consent before HIV testing created obstacles for HIVST research before 2008.
We identified studies through database search and imported them into EndNote (X7.8), where we deleted duplicate articles. Two researchers (K.M.T. and J.J.O.) independently screened the titles of the remaining unique articles and selected studies for abstract review. We uploaded the EndNote file consisting of the selected studies to Covidence, an online screening and data extraction tool. 17 We then screened the abstracts and full texts to determine which articles were eligible for study inclusion. The two researchers resolved any discrepancies during a meeting to discuss study selection.
Data extraction and analysis
We developed a data extraction form that was independently used by two researchers (K.M.T. and J.J.O.). We extracted the following general study information: author name, year of study, geographic location, study design, sample size, and sample demographics (sex, age, population), and type of HIVST. We also extracted the following HIVST verification details: clinic- or community-based testing, type of verification method, who performed the HIVST results verification, percent of results verified, and primary or secondary kit distribution. We collected data regarding primary or secondary kit distribution to evaluate the performance of verification procedures when kits are distributed directly to the study participant or to their partners or members of their social network. A third researcher (N.E.R.) was available to resolve any discrepancies regarding study inclusion or data extraction.
We conducted a cross-study synthesis of HIVST verification methods, which included a quantitative count and descriptive review of the current reported methods. We also conducted random effects meta-analyses to obtain weighted average percentages with 95% confidence intervals (CIs) for studies that reported the proportion of participants who sent results for verification and participants who were linked to care. We measured the variation in study results due to heterogeneity using the I2 statistic and performed an Egger's test for small-study effects. Meta-analyses were performed in Stata version 15. 18
Quality assessment
We assessed the quality of included studies using The Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. 19 The checklist contains nine criteria pertaining to study design, conduct, and data analysis. Each criterion was categorized as a “yes,” “no,” “unclear,” or “not applicable.” Studies that received a total score of five or less were considered low quality. We include the quality assessment in the Supplementary Table S2.
Registration
We registered the study protocol in PROSPERO (CRD42019124421), the International Prospective Register of Systematic Reviews.
Results
We identified 5421 citations, of which 1568 citations were duplicates. Among the 3853 unique citations that were screened by title, 248 records were identified for abstract review. Subsequently, 187 articles were selected for full-text review, during which 147 studies were excluded for one of the following reasons: no verification method was described (n = 119), study was a systematic or scoping review (n = 18), not written in English (n = 1), or the study was not focused on HIVST (n = 9). Ultimately, 40 studies were included in our analysis (Fig. 1).

Study flow diagram. HIVST, HIV self-testing.
Characteristics of included studies
Of the 40 studies included (Tables 1–3), 13 were conducted in high-income countries, 16 in middle-income countries, and 11 in low-income countries. 20 Fifteen studies were randomized controlled trials, 14 were cross sectional, 7 were prospective cohort, and 1 each for surveillance, pilot screening service, facility-based integration of HIV testing, and implementation research.
Characteristics of Included Studies That Verified HIV Self-Testing Results Reporting Through Supervision
Study year indicates the year the study was conducted.
HIVST, HIV self-testing; MSM, men who have sex with men; RCT, randomized controlled trial; TGW, transgender women.
Characteristics of Included Studies That Verified HIV Self-Testing Results Reporting Through Returning of Used Kits
Study year indicates the year the study was conducted.
Characteristics of Included Studies That Verified HIV Self-Testing Results Reporting Through Electronic Transmission Photographic Verification or Internet-of-Things
Study year indicates the year the study was conducted.
The mean and median sample size of participants who opted or were assigned to HIVST in the studies were 2454 and 330, respectively. Twenty-two studies involved community-based HIVST, 17 involved HIVST at a clinic or study site, and 1 study provided the option for participants to self-test in the clinic or in the community. Two studies used secondary kit distribution to reach partners or peers of the participants.
Two studies focused on youth. Seventeen studies focused on key populations, including 14 for men who have sex with men (MSM) and 1 each for female sex workers, transgender people, and MSM and transgender women together. One study in Kenya focused on truck drivers, as they are considered to be a key population in Africa due to their high risk for HIV. The remaining 21 studies focused on heterosexuals, mixed populations, and pregnant women. No studies were targeted for prisoners or people who inject drugs. The number of published studies or protocols on HIVST increased over the years: 5 studies in 2010–2012, 21 –25 7 studies in 2013–2015, 26 –32 and 28 studies in 2016–2018. 33 –60
Verification methods
We identified three methods that verified HIVST results and one method that verified opening a self-test kit, each with their own strengths and limitations (Table 4). Twenty-three studies had a clinician or study team member supervise participants as they took an HIVST (Table 1). 21 –27,33–48 Ten studies requested used HIVST kits to be returned to the clinic or study site (Table 2). 28 –31,49–54 Six studies requested participants to take a photo and upload their test results to an online or mobile portal (Table 3). 32,55 –59 One study equipped HIVST kits with Bluetooth sensors to detect the opening of kits and notify the study team (Table 3). 60 Below, we describe each of these verification methods in greater detail.
Strengths and Limitations of Each Verification Method
There were 23 studies (Table 1) involving supervised HIVST. Supervision of HIVST involved a health professional, study staff, or community outreach worker watching participants self-test for HIV. Sixteen studies supervised participants in clinics or study sites, four of which focused on key populations. Seven studies utilized supervision outside of the clinic, of which four involved online counseling with HIVST. 33,43,46,47 In five of the seven studies where supervision was conducted outside of the clinic, the study participants consisted of key populations. Out of the 23 studies that utilized supervision as a verification method, 20 were conducted in middle- or high-income countries. All 23 studies involved primary kit distribution.
Ten studies requested participants to return their used HIVST kits (Table 2) in person, 28,31,50,51 through mail, 30,49 or at a designated drop box. 28,30,52,54 Seven of these studies distributed oral HIVST kits to participants. One study focused on key populations, particularly MSM. Eight of these studies were conducted in Malawi, Uganda, and Zimbabwe. The only two studies in the review to focus on secondary kit distribution both utilized returned used kits as a verification procedure. Eight studies reported the percentage of participants who returned used kits. The weighted average percentage of used kits return was 75% (95% CI: 60–87%, I2 = 99.9%). The p value of small-study effects was 0.44, suggesting that the test for small-study effects did not provide evidence of publication bias. Two studies sent participants reminders, one through short message service (SMS) and one through phone calls, to return their used samples. 49,50 In the study that used SMS, the overall return percentage was 54.2% (95% CI: 53.2–55.2%). 49 This study found that SMS reminders that included behavioral insights—messages that prompted participants to set aside time to self-test, encouraged self-efficacy, reminded participants to return their used kits, and included a deadline for self-testing—increased the kit return percentage.
Photographic verification of self-test results, which was utilized in six studies (Table 3), involved participants taking a photo of their HIVST results and submitting the picture to the study team. Three studies allowed participants to submit their photos through an online database 55,56,59 and one study provided the option to submit through a website portal or e-mail. 32 Two studies allowed participants to submit their photos through WeChat, an instant messaging service popular in China. 57,58 Of the six studies that used electronic transmission of photographic verification, five were conducted in China and one was conducted in the United States. All six studies focused exclusively on MSM and involved primary kit distribution. Four studies reported the percentage of participants who submitted photographs of their results. The weighted average percentage for electronic transmission of photographs was 78% (95% CI: 38–100%, I2 = 99.7%). The p value of small-study effects was 0.40, suggesting that the test for small-study effects did not provide evidence of publication bias.
One study equipped HIVST kits with Bluetooth sensors and installed mobile applications on participant's smartphones to detect when kits were opened (Table 3). The Bluetooth sensors connected to the smartphones, which then sent a notification to the study team that a kit had been opened. This allowed investigators to reach out to participants (within 24 h in this study protocol) to provide counseling and referrals. The test kit sensors detected that 73.4% of the study kits had been opened over the course of entire study period; 100% of detected opened kits resulted in post-test counseling. Researchers believe that failure to detect kit opening could have been due to participants deleting the study mobile app from their phone or switching to a different phone altogether. This study involved MSM in the United States. 60
Secondary outcomes
Fifteen studies that verified HIVST results also reported the proportion of identified HIV-positive participants linked to care after self-testing. 26,29,31 –33,37,40 –43,48,52,54,55,59 Eight of those used supervision to verify HIVST results, 26,33,37,40 –43,48 of which three were community-based. 33,43,48 Four studies verified results through returning kits 29,31,52,54 and three studies used electronic transmission of photographs. 32,55,59 None of the studies reported referral to HIV prevention services for participants who tested negative for HIV. All 15 studies involved primary kit distribution. The weighted average percentage for linkage to care was 85% (95% CI: 53–100%, I2 = 99.5%). The p value of small-study effects was 0.02, possibly indicating evidence of publication bias. The percentage for linkage to care may not have been solely influenced by the verification method utilized. Other factors, such as stigma, fear of disclosure of HIV status, or denial of HIVST results could have affected linkage to care.
Discussion
This systematic review identified three methods to verify HIVST results: self-testing supervised by a study team member, returning of used kits, and electronic transmission of photographs. The review also found one method that used Bluetooth sensors to verify the opening of an HIVST kit. These methods have been implemented in various settings and are associated with a broad range of return rates. This study extends the literature on HIVST by focusing on verifying self-testing results beyond self-reporting and evaluating linkage to care after HIVST. Each verification method identified in this review has strengths and limitations.
Supervised HIVST may be more likely to ensure that test results are correctly linked to testers. Supervision by health care professionals or lay health workers may enhance linkage to care. However, supervision removes important benefits of HIVST, including convenience and confidentiality of testing and results. Sixteen of the 23 studies that verified HIVST through supervision had verification done at a clinical site, which maintains barriers typically associated with facility-based testing. There are many groups that may fear seeking facility-based HIV testing services, including undocumented migrants, people living in remote areas, and some sexual minorities. 61 This fear of facility-based services could also make supervised HIVST verification not feasible.
Returning used self-test kits was used in eight studies in three low-income countries (Malawi, Uganda, and Zimbabwe). Returning self-test kits could be done at a community site, clinic, or through mail. Returning the used test kit at a community site could alleviate some of the transportation barriers that are known to discourage HIV care seeking. 62 Moreover, self-testers returning their used HIVST kits to a community location may decongest health facilities because of fewer individuals who do HIV test. Given limited technological access, returning used kits may be an appropriate and useful verification method for low-resource settings and populations. However, this verification approach does not guarantee that the individual returning the used kit is the same individual who self-tested for HIV.
Photographic verification of HIVST was also used in one upper middle-income country (China) and one high-income country (United States). Photographic verification has a tester take a photograph of the completed test kit and send it through a private, secure transmission to a test organizer. All photo-verification studies were among MSM. Data from the United States 63 and China 58 suggest that men are comfortable taking a photograph of HIVST test results and sending it through a mobile platform. Further implementation science on photographic verification of HIVST among other key populations is needed. In addition, one study used Bluetooth sensors to detect opening of kits and notify study counselors. This verification method is an example of internet-of-things technology, in which devices communicate with one another through the internet to share and receive data. Internet-of-things technology is a method that can link self-test results to surveillance programs, and allow for real-time monitoring of self-testing procedures and timely reporting of information. Further research is needed on internet-of-things technology to better understand their role in public health surveillance, preventative care, and treatment. However, internet-of-things technology is not currently linked to completion of the test itself. Integration of internet-of-things to test completion could be a major advance for HIV surveillance, follow-up services, and linkage.
None of the HIVST verification methods identified guaranteed results notification. Testers may fail to verify results due to possible fear of disclosure if HIV positive or the stigma of being outed as being at-risk for HIV infection. Testers may also forget or delay verification procedures, contributing to subsequent delays in linkage to services. Verification procedures should emphasize to testers the advantages of verified HIVST results, particularly enhanced linkage to clinical services.
Given the broad scale-up of HIVST in a variety of settings, these results are timely and have public health and programmatic implications. Current HIVST verification methods are limited, but implementation of HIVST services should incorporate verification procedures to improve HIV test result capture. Ideally, these verification technologies would be performed in real time and connect patients to appropriate post-HIVST services, while retaining some of the important benefits of HIVST such as autonomy and confidentiality. Moreover, these procedures would be pertinent to the settings and populations, in which verification is performed to ensure uptake, feasibility, scale-up, and sustainability. Verification methods that not only verify results but also encourage patients to be engaged in their own care can better facilitate linkage to HIV care and related HIV services.
Footnotes
Author Disclosure Statement
No competing financial interests exist.
Funding Information
This work was supported by NICHD UG3HD096929 and NIAID K24AI143471.
Supplementary Material
Supplementary Table S1
Supplementary Table S2
References
Supplementary Material
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