Effect Of Antiviral Therapy On Sexual Transmission Between Husband And Wife In Zhumadian And Its Influencing Factors

BackgroundWith the widespread recognition of antiretroviral therapy’s role on the prevention of HIV transmission, it is imperative to further understand its preventive effect over the long term. Under the scale-up of treatment on HIV infections, researches should be carried out among HIV infected population receiving antiretroviral therapy and their close contacts to evaluate the effect of treatment on the prevention of HIV transmission to uninfected partners and on clinical events in infected persons, which will provide a useful reference for HIV control and prevention in the future.Objectives1. To analyze HIV seroconversion rate of initially HIV-negative partners and relevant risk factors among HIV serodiscordant couples in Zhumadian city, Henan province; and evaluate the effect of antiretroviral therapy on the prevention of HIV transmission in negative partners and on the clinical event of index partners; and build the association of HIV transmission to negative partners with clinical effect of index partners among HIV serodiscordant couples.2. To further analyze relevant risk factors of HIV transmission among HIV serodiscordant couples with index partners receiving ART, and on the basis of age-period-cohort description of HCV prevalence in HIV negative partners, explore the additive interaction effect of HCV infection among initially HIV-negative partners and unprotected sex among couples on the transmission of HIV among serodiscordant couples. 3. To understand the long-term clinical effect of ART among couples with index partners receiving ART and the similar risk factors comparing with HIV seroconversion of their negative partners.MethodsThis research was based on a prospective and open cohort study among HIV serodiscordant couples in Zhumadian city, Henan province. The study subjects were followed up annually through 2008-2014. Information on demographic and sexual behavioral characteristics of each partner was collected by using face-to-face interviews. Index partners were tested for CD4+T cell counts and viral load, while negative partners were tested for HIV and HCV antibodies in serum. The primary end point was HIV seroconversion among initially HIV negative partners. The secondary end point was all-cause death of index partners during the period of follow-up. Cox proportional hazard model was used for univariate and multivariate analyses on factors contributing to mortality among index partners and HIV seroconversion rate among initially negative partners. Age-period-cohort analysis was conducted to describe the temporal trends of HCV prevalence among HIV negative partners. A Cox proportional hazard model was also built to assess the additive interaction effect of HCV infection among initially negative partners and unprotected sex among couples on the transmission of HIV among HIV serodiscordant couples whose index partners have initiated antiretroviral therapy.ResultsA total of 4689 HIV serodiscordant couples were enrolled from 2008 to 2014 in Zhumadian city. On average, HIV seroconversion rate of negative partners was 0.50 per 100 person-years. Factors influencing HIV seroconversion of negative partners were:index partners no less than 50 years old (HR=1.76,95% CI: 1.08-2.89), baseline CD4+T cell counts no greater than 350/mm3 (HR=1.66,95% CI:1.04-2.63), having received ART during follow up (HR=0.46,95% CI: 0.25-0.83), and using condom consistently among couples in recent year (HR=0.03,95% CI:0.02-0.05). ART use can reduce 54% of HIV transmission among couples. Risk of HIV transmission among couples whose index partners have got treated longer than 11 years was 0.30 times than that of couples with index partners treated for 11 years or less. For each subgroup, the risk of HIV transmission to the uninfected and death of the infected among couples with index partners treated were basically higher comparing with those untreated.Among 4196 HIV serodiscordant couples with index partners having received ART, the average HIV seroconversion rate of negative partners was 0.44 per 100 person-years (95% CI:0.43-0.45). In multivariate analysis, factors influencing HIV seroconversion of negative partners included:index partners over 50 years old (HR=1.79,95% CI:1.08-2.95), baseline viral load more than 400 copies/ml (HR=2.57,95% CI:1.58-4.18), being asymptomatic at baseline (HR=1.79,95% CI:1.06-3.05), initiating treatment after baseline (HR=2.26,95% CI:1.14-4.49), having HCV infection of negative partners (HR=1.94,95% CI: 1.17-3.20), and unprotected sex among couples (HR=4.85,95% CI:2.95-7.99).According to age-period-cohort analysis, HCV prevalence of initially HIV negative partners among these couples decreased (χ=7.50, P=0.01), with the peak of birth cohort occurring between 1950 and 1954 among negative partners. To examine the interactive effect of HCV infection and unprotected sex on HIV transmission, we used negative partners of couples with HCV negative and not having unprotected sex as a reference group (HIV seroconversion rate:0.23 per 100 person-years). On hazard ratio scale, the independent effect of having unprotected sex on HIV transmission (HR=3.48,95% CI:1.37-8.85) was higher than that of having HCV infection (HR=1.46,95% CI:0.77-2.78) in negative partners. The joint effect of these two factors (HR=7.59,95% CI:3.87-14.88) was larger than the sum of their independent effects. After adjusting for potential confounders, there was statistically significance for all three indices:RERI=3.65 (95% CI:0.61-6.70), API=0.48 (95% CI:0.18-0.79), SI=2.24 (95% CI: 1.01-5.02).Among the above couples with index partners having received ART, the average mortality rate of index partners was 1.88 per 100 person-years (95% CI: 1.86-1.90). Couples having higher mortality of index partners also were likely to get higher risk of HIV transmission. Factors affecting mortality of index partners among these couples included index partners no less than 50 years old (HR=3.48, 95% CI:2.67-4.55), baseline viral load over 400 copies/ml (HR=1.71,95% CI: 1.32-2.22), and initiating treatment after baseline (HR=1.53,95% CI:0.95-2.46), which were the same as those influencing HIV seroconversion of negative partners, as well as lower education level (HR=1.33,95% CI:1.00-1.79), and baseline CD4+T cell counts no greater than 350/mm3 (HR=1.82,95% CI: 1.39-2.39).ConclusionsHIV seroconversion rate of negative partners during 2008 to 2014 was relatively low among HIV serodiscordant couples in Zhumadian. The effects of ART reduced prevention of HIV transmission to negative partners and clinical events to index partners. The preventive effect of ART was in parallel with the duration of treatment, indicating the personal and public health benefits from therapy.HCV infection can affect HIV transmissions, which underpins and justifies the need to monitor HCV status among HIV related population, highlighting the importance of HCV screening. Age-period-cohort analysis helps the screening among HCV high risk population and detection of HCV cases, improving efficiency of practical work.Higher risk of HIV transmission to negative partners was found among couples whose index partners also had higher mortality.