In 2020, United Nations Member States committed to implementing 17 Sustainable Development Goals (SDGs), in which one of the motivations/goals is to end the AIDS epidemic by 2030 via using the Fast-Track approach with the 95-95-95 targets: by 2030, 95% of people living with HIV (PLWH) should know their HIV status, 95% of people who know their status should be on antiretroviral treatment (ART), and 95% of those on treatment should be virally suppressed (1–3). Acute and primary HIV infection, also known as early HIV infection (EHI), is the early stage of HIV infection. Acute HIV infection occurs 2 to 4 weeks after infection with both HIV RNA and p24 antigen present, and primary HIV infection occurs 6 months after infection. The high concentration of the virus during EHI leads to increased infectiousness, possibly as much as 26 times greater than during chronic infection (4). Improving the identification of EHI cases is important for HIV infection management to achieve the goal by 2030. However, in China, only 68% of people living with HIV were aware of their serology status by the end of 2015 (5). Only 15% of the identified cases are EHI in some high HIV prevalence provinces, which means most of the cases were diagnosed late (5). Thus, effective ways for early identification of EHIs are needed.

In the past years, several laboratory-based assays have been tested to identify early HIV infection according to the natural serological responses after infection (6). However, they were based on population data. When applied to individuals, false-positive results that classify long-term infection as a recent infection could occur. Thus, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommend using recent infection testing algorithms (RITAs) to improve the accuracy of identifying recent HIV infections, which integrate HIV recency tests with multiple routinely used clinical assays (7). In the other words, a RITA is a combination of laboratory tests used to classify an HIV infection as recent (recent infections were acquired generally within 4 to 12 months) (8) or long-term (9). The limiting antigen avidity enzyme immunoassay (LAg-EIA) is one of the widely used serological assays to identify EHI (10–12). CD4+ T-cell count and viral load (VL) test are the other two clinical assays used for the majority of RITAs to reclassify recent infections (7). In comparison to the sole use of serological assays for the classification of recent HIV infection, RITAs, which combine various clinical information with the HIV recency assay, have been proven to accurately classify recent infection cases and effectively reduce false recent rate (FRR) (7).

Voluntary counselling and testing (VCT) and provider-initiated testing and counselling (PITC) are the majority of HIV tests conducted within health facilities and still represent the most common testing approach in most countries (3, 13). However, facility-based HIV testing (HIVFBT) is not accessible to the most at-risk population on time and tends to identify the case late. Thus, we will need a decentralized tool to reach the most at-risk participants.

The WHO encourages HIV rapid tests for screening high-risk populations (3, 14). In July 2019, 77 countries adopted policies or guidelines for the implementation and support of HIV self-testing (HIVST) (15). In China, the demand for and acceptability of HIVST among men who have sex with men (MSM) had been high, and many local community-based organizations were working with health bureaus in piloting HIVST among MSM (16, 17). A recent study has demonstrated that a model of social media-based HIVST with a secondary distribution is feasible and acceptable among MSM in China (18). HIVST can be used to identify first-time testers, promote HIV case identification, and link to care (18).

The aim of this study was to evaluate whether HIVST can identify PLWH earlier than the facility-based method.

In total, 124 (99.2%) of the 125 eligible men agreed to participate. Of them, 60 (48.0%) were from the HIVST group, while the other 64 (51.2%) were from the HIVFBT group.

To our knowledge, this is the first study to compare the effectiveness of early detection of HIV infection between HIVST and HIVFBT among MSM in China and the first to compare the HIV genotype differences between HIVST and HIVFBT. This study provided strong evidence of the importance and effectiveness of assessing the early detection of HIV by self-testing. Along with other findings from the same project, the results demonstrated that HIVST expanded the coverage of HIV testing and improved the possibility of identifying new HIV cases in the Chinese MSM sample (18, 21).

From the current study, it has been found that more new HIV infection cases were found via self-testing than HIVFBT. Another study in China using the same RITAs has similar results that HIVST could identify more cases in EHI among MSM than other methods (22, 23). This may be because HIVST enables individuals to perform HIV antibody tests privately (24). Therefore, HIVST overcomes HIV-related stigma and discrimination and has the potential to increase the uptake of testing by reducing the structural barriers associated with clinic attendance (25, 26). Furthermore, normally, self-testing is designed as a rapid and easy-to-operate method like finger stick HIV self-tests. In this way, the time and effort spent traveling and attending a clinic or hospital and the waiting period can be reduced greatly. Although this method may also provide less sensitivity than laboratory-based testing, the period from detectable seroconversion to the first positive screening using self-tests may be shortened, as self-tests could increase testing frequency (27, 28). This is further proved by another study from the same project that HIV self-test kits, which showed an increase not only in case identification among MSM but also in the coverage of HIV testing as HIVST, are an easier way for secondary distribution from target participants (18). Notably, the target participants as sexual health influencers were associated with encouraging more alters with less testing access to self-tests for HIV (29). These results and evidence have demonstrated that HIVST could be a promising approach for increasing the rate of HIV testing in the period of EHI.

Identified cases in EHI in this study mainly occur in younger and better-educated MSM between the HIVST and HIVFBT groups. The same trend was reported in HIV annual reports in China and worldwide (30, 31). In China, young MSM aged 18 to 29 have a higher risk of spreading HIV than heterosexuals of a similar age, and the trend keeps increasing (32–39). In the United States, young MSM aged 20 to 29 were more likely to have “any” sexually transmitted infection, because they were more likely to have HIV-discordant condomless receptive intercourse and avoid disclosing same-sex behavior to healthcare providers or delay HIV/STI diagnosis and treatment (40, 41). These results and evidence have demonstrated that HIVST could be a promising approach to reach more at-risk populations on time.

The current study also assayed the genotypes of EHI cases. The results have discovered similar proportions in the genotypes of the EHI case compared to those in other cities in the same province. For example, the first dominant HIV-1 subtype circulating among MSM in Guangzhou was CRF07_BC (41.6%), followed by CRF01_AE (30.0%), and the same was found in Shenzhen, with CRF07_BC (39.1%) and CRF01_AE (35.1%) being the most predominant (42, 43). HIV-1 subtypes are associated with the pathogenesis and progression of AIDS-defining illness in the infected host (44). A systematic review of the trend of disease progression among HIV-1 different subtypes indicated that HIV-1 genetic diversity did seem to affect the rate of disease progression in ART-naive patient populations (45). Therefore, the similar proportion of subtypes among different cities keeps the comparability on EHI and inspires the possibility of the implementation of future community- and societal-level interventions.

Several limitations have been noticed in this study. Firstly, the results of LAg-EIA are largely affected by ART (World Health Organization, 2018) (9), and although information on receiving ART was not able to be collected in this study, the participants were firstly diagnosed as HIV positive in Zhuhai, and they were less likely to receive ART. Secondly, CD4+ T-cell count or VL testing information was missing for some participants in the HIVFBT group mainly due to a lack of specimens, and thus some cases could not be reclassified. However, the missing data should not greatly influence the chance of a significant difference between the two groups, as the EHI cases were also evaluated by the RITA 4 approach. Thirdly, the limited number of patients included in this study might result in lower statistical power. Finally, this study was a cross-sectional study. Only the associations or differences between the subgroups in a certain period can be reported due to the nature of the study design. Hence, it is hard to provide any direct evidence regarding the causes of EHI.

This study showed that HIVST improved HIV early detection among MSM. Young and better-educated MSM seem more vulnerable to HIV infection than others, but this may be because of more likelihood of using HIVST methods. Compared with HIVFBT, HIVST is more accessible to the most at-risk population on time and tends to identify the case early. Thus, HIVST will be an important promising tool to reach the most at-risk population. Further implementation studies are needed to fill the knowledge gap on this medical service model among MSM and other target populations.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving human participants were reviewed and approved by Human Research Ethics Committee of Zhuhai Center for Disease Control and Prevention. The patients/participants provided their written informed consent to participate in this study.

YZ designed the study and wrote the manuscript in collaboration with SLH, MC, and ZG. HT, YF, YW, ZG and MC, YN, YL, FJ, SZH, and JL performed laboratory work and/or data analysis. All authors discussed the results and commented on the manuscript. All authors contributed to the article and approved the submitted version.

This study received support from Medical Research Funding of Guangdong Province funds (A2021011).

We appreciate the contributions from all study participants, CBO volunteers, and staff from Zhuhai Center for Disease Control and Prevention, Zhuhai Xutong Voluntary Services Center, and SESH Group.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The editor declared a shared affiliation with the authors, YN and YL, at the time of review.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.