Study design and participants. This randomized implementation trial was conducted between August and November, 2018 in Kisangani, DRC. Trained research assistants (physicians or nurses) enrolled participants at four facilities (University hospital of Kisangani, General Hospital of Kabondo, and the health centers of Neema and Saint Joseph). Participants were eligible for the study if they were between 18 and 49 years, at high risk for acquiring HIV infection, unknowing their HIV status, lived or worked in Kisangani for at least 6 months prior to enrolment, and available and accessible by phone. High risk for HIV infection acquisition was defined as sexually active participants with: a history of unprotected intercourse with one or more partners of unknown HIV sero-status within the past 6 months, new sex partners in the past 6 months, symptoms of sexually transmitted infections (STIs) in the same period, commercial sex activity, or being in a known HIV discordant partnership .
Randomization procedures. Participants were randomized to a ratio of 1:1 through block randomization (block size 4, 6, 8). Eligible participants were randomly assigned to one of two self-testing groups (Fig. 1): DAH or UH by using a sealed randomization envelope sequentially. Because of the nature of intervention, study participants and study staff could not be blinded. However, study staff and participant were unaware of the assignment until the envelope is opened.
Study procedures and data collection. The blood-based HIVST was done using the Exacto® Test HIV (Biosynex, Strasbourg, France) self-test kit which included A3 format color printed pictorial simplified instructions for use in French, Lingala, and Swahili, as previously reported . After obtaining written informed consent and before randomization, participants were administered a baseline questionnaire that measured their demographic characteristics, sexual behaviour, and HIV testing history using self-administrated questionnaire, then they received adequate pre-test HIV counselling.
In the DAH arm, a brief, 10-min face-to-face demonstration of how to use the self-test familiarized participants with the contents of the self-test kit. After this, participant were asked to perform the HIV self-test in a confidential room supervised by trained research assistants (supervisors). Once the test was completed and the participant had recorded the practicability report on a standardized sheet. The supervisor-interpreted results and the appeals for oral assistance were recorded by supervisor on a standardized sheet. Not that, the supervisors had received rigorous training, including how to talk to participants asking for any support concerning the HIVST.
In the UH arm, participants were asked to perform the HIV self-test at home or in a convenient private location, and read the results guided by the instructions for use without 10-min demonstration and supervision. Participant received training to self-record within 10 minutes after performing the self-test the practicability report on a standardised sheet. Furthermore, participant was invited to return with test cassette and the standardised sheet (putted in a sealed envelope) to the facility within 12–72 h for rereading of test results and additional evaluation. Telephone assistance was offered to the participant if needed. The need for assistance from a trusted person was self-declared by the participant, and recorded by investigators.
In each study arm, confirmatory HIV test using national algorithm rapid tests [21, 22] was performed after HIVST if the test was reactive. If seropositivity was confirmed, participants were referred to the care services. Post-test counselling were provided to participant if needed. The standardised sheet included the information on the confirmation of blood presence in the square well of the test, appearance of a control strip on the self-test, and the overall interpreted self-test result. The overall results were recorded as one of three outcomes: (i) may have HIV (preliminary positive); (ii) don’t have HIV (preliminary negative); and (iii) test not working (invalid). There was a 24-hour helpline for participants in which the anonymity was assured by recommending participants to introduce themselves using their three-character randomization code. The investigator recorded all information about the telephone assistance on a follow-up sheet.
An exit questionnaire was self-administered after all testing process. It concerned the satisfaction questionnaire, the willing to by HIV self-test kit and the unit purchase price of the test in United State dollar (USD).
Study Outcomes. The primary outcomes was the difference in practicability of the Exacto® Test HIV (Biosynex) self-test kit, comparing the UH versus DAH. Practicability was defined as the successful performance of HIV self-test and the correct interpretation of the HIV self-test result. The successful performance of the HIV self-test was conditioned by the presence of the control strip. Secondary outcomes included the proportions of participants who requested for assistance, the retention rate, the linkage to care, and willing to buy HIV self-test kit if locally available. Retention rate was defined as the number of included participant who completed all evaluation process through the follow-up period. We determined the above secondary outcomes as our measures of implementation effectiveness of HIVST comparing UH to DAH in field conditions of the DRC.
Sample size. A one-sided design to test non-inferiority between groups was used, specifically to test the hypothesis that the practicability of UH is objectively non-inferior to that of DAH. The sample size was estimated using the following formula:
with πN and πR the percent of practicability’s success of UH and DAH, respectively; with α = 0.05 for a 95% confidence interval; and b = 0.2 for a power of 80%; with the non-inferiority limit (ΔL) corresponding to the greatest loss of effectiveness that is possible to consent . The non-inferiority limit was conventionally set at −10 %, guided by previous studies [8, 13, 22]. We assumed that πN=98% and πR=88%. The sample size (n=456) was increased by 10% of lost to follow up, giving a final sample size of 530.
Statistical analysis. Primary analysis involved descriptive statistics using mean (standard deviation) or median (interquartile range) for normally distributed or skewed distribution, respectively, then a comparison of outcome measures in study arms was computed by using Pearson's chi-squared test for categorical data or Student t test for means. For the analysis of the primary study outcome, we compared the successful performance of HIV self-test and the correct interpretation of HIV self-test results within individuals between the two arms. For the analysis of the secondary study outcome, we compared the requested for assistance, retention rate, linkage to care, and willing to buy HIV self-test kit if locally available between the two arms. A one sided Wald asymptotic test was used to assess for non-inferiority. The confidence interval for the difference was based on the Wald asymptotic method, at an alpha level of 0.05 corresponding to 95 % confidence limits. Non-inferiority was defined as a lower limit > –10 of the 95% CI around the difference in outcomes. Percent agreement and Cohen's κ coefficient were used to estimate agreement between the participant-interpreted results and investigator-interpreted results.
The satisfactions were assessed using arbitrary quantitative Likert scale based on four different scale ranging from 1 (most difficult), 2 (difficult), 3 (easy) to 4 (very easy). The mean and standard deviation for Likert scale data were calculated and compared between the two arms, using Student t test.
In order to determine the effects of interventions (UH versus DAH) on primary and secondary outcomes, risk ratios from regression of Poisson were evaluated, using two-sided statistical tests with significance level set at P < 0.05. Note that, participants who were not successfully followed up were not included in the analyses as it was not possible to determine the primary and secondary outcomes for them. All analyses were done with SPSS 20.0 (SPSS Inc, Chicago, IL).
Ethical statement. This study received ethical approval from the ethics committee of the Health Public School of Kinshasa’s University. All participants provided written informed consent. No compensation were provided for participating in this study. The study was conducted by the Research, Teaching, and Care Unit of the Faculty of Medicine and Pharmacy of Kisangani’s University. This trial was retrospectively registered by the Pan African Clinical Trial Registry (www.pactr.org) database, ID number PACTR201904546865585.