Preventive Effect Of High - Efficiency Antiretroviral Therapy On HIV Transmission In Single - Maternal Spouse

Background Based on clinical and epidemiological studies over the past 20 years, the theory that Highly Active Antiretroviral Therapy (HAART) can eliminate HIV transmission risk is proposed ("treatment as prevention" strategy). But the effectiveness of treatment as a prevention strategy in the real world is still under investigation, and much less is known about its long-term effectivness. A better understanding of the effectiveness of HAART use for prevention of sexual HIV transmission in a population of HIV serodiscordant couples can provide deeply insight into prevention programming and counseling in similar settings.Objectives The study aimed to 1) understand the HIV seroconversion rate of non-index partner and the risk factors of seroconversion in Zhumadian city, Henan province; 2) evaluate the effectiveness and long-term effective changes of HAART in preventing HIV sexual transmission between HIV-serodiscordant couples.Methods Open cohort study design and new-user design were used to conducted a follow-up study in Zhumadian City, Henan Province. HIV-serodiscordant couples who met the inclusion criteria were followed up once a year in the context of informed consent. Poisson distribution was applied to estimate the 95% confidence interval of HIV seroconversion rate. Cox and time-dependent Cox regression model was used to identify risk factors of HIV seroconversion. In the meanwhile, we evaluate the effectiveness of HAART in preventing HIV sexual transmission and the trend of this effectiveness over time by Cox regression model and marginal structural Cox model respectively. In addition, gene phylogenetic analysis was used to understand whether the non-index partner’s HIV seroconversion were attributed to the sexual transmission in the family.Results From the end of 2008 to the end of 2013, a total of 4241 HIV serodiscordant couples who met the inclusion criteria were enrolled in our open cohort study with a total follow-up time of 16543.71 person-years, and the mean duration of follow-up was 3.90 years. Eighty-two non-index partners seroconverted during the entire follow-up process and the cumulative HIV seroconversion rate was 0.49/100 person-years (95% CI: 0.39-0.61). In multivariate time-dependent Cox regession analysis, the harzard ratio of HIV seroconversion between consistent condom use and non-consistent condom use was 0.04; the harzard ratio of HIV seroconversion between index-partners’ last CD4 count equal or more than 350 and less than 350 was 0.44; the harzard ratio of HIV seroconversion between index-partners’last viral load equal or more than 400 and less than 400 was 2.83;while index-partners were on HAART was proctective against HIV seroconversion (HR=0.25). The harzard ratio of HIV seroconversion between index-patners who were on HAART over 9 years and under 9 years was 0.30.The new user design cohort study included 1093 HIV serodiscordant families with a total of 4216.42 person-years of follow-up with an average follow-up of 3.86 person-years. During the years of follow-up, we observed 24 seroconversions and the cumulative seroconversion rate was 0.57/100 person-years (95%CI:0.37-0.83). In multivariate time-dependent Cox regession analysis, the harzard ratio of HIV seroconversion between consistent condom use and non-consistent condom use was 0.04; the harzard ratio of HIV seroconversion between index-partners’ last CD4 count equal or more than 350 and less than 350 was 0.06; while index-partners were on HAART was proctective against HIV seroconversion (HR=0.23). After adjusted the time-dependent confounding bias, the harzard ratio between index-partner on HAART and not on HAART for HIV transmission was 0.14 (95%CI:0.02-0.80).In the 18 couples of blood samples we collected from HIV sero-accordant spouses, 12 couples of viral RNA were extracted successfully. The gene phylogenetic analysis showed that 11 couples were sexual transmission and 1 couple may not household transmission.Conclusions The HIV seroconversion rate was pretty low among serodiscordant couples in Zhumadian City, Henan Province during the year 2008 to 2013. Consistent condom use, index-partner on HAART, high CD4 cell count were protective against HIV seroconversion, while high viral load of index-partner was risk factor of seroconversion. HAART can prevent the sexual transmission of HIV in serodiscordant couples, and we did not observed the prevention effectivness vanished over time during the follow-up of this open cohort.