Preplanned Studies: Effectiveness of Frequent Viral Load Testing Plus Additional Interventions to Prevent HIV Transmission in Heterosexual, Serodiscordant Couples — Yunnan Province, China, 2019–2021

Approximately two-thirds of newly reported human immunodeficiency virus (HIV) infections in China originate from heterosexual contacts, with one-tenth stemming from a spouse or regular partner (1). It is thus crucial to manage transmission within serodiscordant couples to diminish the incidence of new infections. Although the World Health Organization (WHO) underlines the importance of regular viral load monitoring during the early stages of antiretroviral therapies (ART) (2), Chinese clinical guidelines currently advise conducting such tests only after six months of ART (3). In this study, we enrolled newly diagnosed HIV-1 serodiscordant couples from 15 health centers in Yunnan Province, assigning half to an enhanced prevention strategy. This strategy included a comprehensive reproductive plan, joint spouse testing and consultation, early treatment, frequent viral load monitoring, fertility advice, and ART. The remaining participants received ART alongside the standard care per Chinese guidelines. The enhanced strategy led to a significantly higher number of participants in the intervention group initiating ART within 7 and 14 days of diagnosis compared to the control group. Additionally, the intervention group showed significantly higher rates of viral suppression. None of the spouses in the intervention group were seroconverted (0/100 person-years), while three were in the control group (0.6/100 person-years). These findings support the notion that increased viral load testing frequency and comprehensive counseling can improve treatment outcomes and reduce HIV transmission among serodiscordant couples.

This randomized controlled trial (RCT) recruited HIV-1 serodiscordant couples, all participants being over 18 years of age, from 15 centers in Yunnan Province, China. Inclusion criteria were as follows: the HIV-positive partner was diagnosed during the study period (February 15, 2019 to March 31, 2021); their spouse was confirmed HIV-negative at baseline and maintained this status for three months subsequent to their partner’s diagnosis; both partners were aged between 18 and 59 years; the couples consented to participate in the study willingly and were able to provide informed consent; and the couple had engaged in sexual activity at least once in the preceding year. (Data and Sample Collection and HIV-1 Testing refer to the Supplementary Material)

Trained health professionals monitored newly reported positive cases. Couples who met the inclusion criteria were randomly assigned in a 1:1 ratio to either the intervention group or the standard-of-care group using sequential random grouping.

In the intervention group, health professionals assessed HIV-positive individuals at an outpatient facility, providing treatment consultations and pre-treatment physical examinations. These individuals began ART within one week and underwent viral load testing at 1, 2, 3, 9, 12, and 18 months post-diagnosis. Health professionals also encouraged the HIV-positive patients to disclose their status to their spouses within a week. Couples received counseling on condom usage, HIV care, treatment adherence, reproductive intentions, and safe pregnancy methods. Those planning to conceive were referred to maternal and child health services for expert fertility advice and strategies to prevent perinatal transmission. Viral load results were shared with both partners. The HIV-negative partners underwent testing for HIV seroconversion at 3, 12, 18, and 24 months after the initial HIV diagnosis of their spouses.

In the standard-of-care group, health professionals initiated contact with the treatment facility to commence ART for HIV-positive partners. These partners underwent viral load testing at 3 and 6 months post-diagnosis for comparative analysis with the intervention group. The HIV-negative spouses received testing for HIV seroconversion 3 months after their partners’ diagnosis and again at the study’s conclusion.

Cox regression was used to estimate relative risks, which were expressed as hazard ratios with 95% confidence intervals (CI). A P value of less than 0.05 was considered statistically significant. Kaplan-Meier estimates were employed to compare cumulative probabilities of seroconversion between participants in the intervention and control groups. All analyses were conducted using SPSS software (version 24.0, IBM, NewYork, USA).

A total of 2,213 HIV-positive individuals, who either were married or in a committed relationship and aged 18–59, were identified between February 15, 2019, and March 31, 2021, across 15 counties in Yunnan province, China (Figure 1). Of these, 1,470 couples were excluded due to not being serodiscordant or unreachable (n=1,469), or because one partner died within 3 months of diagnosis (n=1). By the close of enrollment on March 31, 2021, 743 couples remained, with 372 assigned to the intervention group and 371 to the control group (Figure 1). Within the intervention group, six couples withdrew due to divorce. In the control group, adverse outcomes included seroconversion in three couples and withdrawals due to divorce (three couples), death of the HIV-positive spouse (three couples), and one couple’s decision to cease participation. The duration of observation for those who withdrew did not significantly differ between the groups (P=0.808). (Eligibility flow diagram for HIV serodiscordant couples refer to Supplementary Figure S1)

Figure 1. 

Viral suppression iin intervention group and standard-of-care group. (A) VL <1000 copies/mL in intervention group; (B) VL <1000 copies/mL in standard-of-care group; (C) VL <200 copies/mL in intervention group; (D) VL <200 copies/mL in standard-of-care group; (E) VL <50 copies/mL in intervention group; (F) VL <50 copies/mL in standard-of-care group.

At enrollment, the majority of participants were male farmers with primary school education. The age of the HIV-positive spouse differed significantly between groups, although other demographic characteristics did not (Table 1). The median observation period was 15.3 (10.8–18.8) person-months for the intervention group and 15.8 (10.6–20.5) person-months per couple for the control group. Significantly more participants in the intervention group initiated ART within 7 and 14 days from diagnosis (P=0.011 and P<0.001, respectively). The median time from diagnosis to initiating ART was 5 days [inter-quartile range (IQR): 2–9] in the intervention group and 6 days (IQR: 2–18) in the control group (Table 2). Rates of achieving a viral load of <1,000 copies/L and <200 copies/L within 3 and 4 months of diagnosis were significantly higher in the intervention group (86.2% and 64.5%; 91.9%, and 75.3%, respectively) compared to the control group (56.3% and 43.1%; 82.8%, and 67.0%). Among those who underwent viral load testing, rates of obtaining viral loads of <1,000 copies/L, <200 copies/L, and <50 copies/L were significantly higher in the intervention group (97.8%, 94.4%, and 90.1%, respectively) compared to the control group (93.9%, 89.0%, and 81.8%) (P<0.05) (Figure 1).

Among HIV-negative spouses at baseline, the seroconversion rates were 0.6 per 100 person-years (3/371) in the control group and 0 per 100 person-years in the intervention group (P=0.081). (Assessment of Linkage of Seroconversions and Analysis of seroconversion case sequences refer to Supplementary Figures S2–S3)

Characteristics of the seroconverted spouses are summarized. (Characteristics of the three seroconverted couples refer to the Supplementary Table S1) The time intervals from the diagnosis of HIV-positive status to spouse seroconversion were 117, 121, and 182 days, respectively. Phylogenetic analysis confirmed that all seroconversion cases were linked to their HIV-positive partners (refer to Supplementary Figure S2).