Our study of 1927 HIV discordant couples in Zhumadian city, Henan province is the largest of its kind in China and found an incidence rate of 1.71 per 100 person-years. The only other study of discordant couples in China was conducted in Xinjiang province, but had a sample size of only 22.10
The incidence rate from our study is similar to the incidence rate of 2.3 per 100 person-years reported among a cohort of injecting drug users from a high prevalence region in southwestern China.16
This suggests that HIV-negative spouses living in discordant relationships in Zhumadian could be considered one of China’s high-risk groups.
The overall seroconversion rate also showed an increasing upward trend as the duration of follow-up lengthened. There are several possibilities for why this occurred. First, chronically-HIV infected patients may undergo immunologic failure, virologic failure, advance to later stages of disease, or acquire resistance, leading to higher rates of transmission over time.15, 17–19
Second, couples may engage in riskier behaviors such as increasing the frequency of sex or reducing the percentage of condom use, as knowledge and awareness of self-protection gradually declines.20, 21
Third, a desire to have children may be influencing the risk taking behaviors among these couples.7
Our findings highlight the importance of strengthening comprehensive HIV prevention interventions such as health education, condom promotion, STI treatment, and psycho-social care and support services.
Our study found no statistical difference between the male-to-female transmission and female-to-male transmission rates. These results are consistent with several other studies of discordant couples from Brazil, Haiti, Tanzania, Rwanda, Uganda, and India.4, 7–9, 22
It is unclear whether the higher rate of female-to-male transmission (1.75/100py) is a result of a chance or some other unmeasured biological or behavioral characteristic. Although the literature has been inconclusive, one large prospective study from Masaka region Uganda attributed the age-adjusted RR for infection for women of 2.2 (95% CI 0.9 – 5.4) to extra-marital sexual behavior among men and increased biological susceptibility in the female genital tract.5
However, in Henan province, the majority of those infected are non-migrant farmers with low rates of STIs, IDU, or extra-marital sex. In our cohort, only 7 out of 1,927 interviewed reported ever engaging in sex outside of marriage. Thus, in this cultural context, it is reasonable to assume that behavioral factors which influence higher HIV transmission in some parts of Africa are different than those of China.23
Male circumcision was not analyzed as a factor in this study because the prevalence of circumcision is extremely low among ethnic Han Chinese.
As with other studies, we found not always using condoms and a higher frequency of sexual activity to be associated with increased risk of HIV transmission.7, 24, 25
Having sex within the past 3 months and extra-marital sex were not statistically significant associations.
Our study also found that ART use in the HIV-positive spouse was associated with a decreased risk of seroconversion, but this result was not statistically significant (RR= 1.32; 95% CI, 0.78–2.22). A meta-analysis of serodiscordant couples studies found that ART reduced heterosexual transmission rates from 5.64 to 0.46 per 100 person-years.26
This suggests that our study may have been subject to misclassification as those who were labeled as on ART may have been non-adherent to treatment. One study of drug resistant HIV-1 variants in Henan found that 66% of patients had low adherence after 6 months of therapy.27
Another possibility is that patients were adherent to ART, but were on regimens that had become suboptimal or acquired drug resistance. This is supported from data from a recently published study which reported immunologic failure rates of 50% by year 5 among patients enrolled in China’s free national antiretroviral treatment program, most likely due to the lack of readily available second-line drugs.18
Furthermore, our data indicates that those who did not switch treatment regimens were more likely to transmit HIV (RR 2.66, 95% CI 1.15–6.15). Although this value became non-significant in multivariate analysis (most likely due to small sample size in those who had switched ART regimens), the data suggests that remaining on an originally prescribed ART regimen may have a detrimental effect on population-level heterosexual transmission dynamics in China because a large proportion of patients may be on ineffective treatment regimens.
As in other studies, we did not find CD4 cell levels to be associated with an increased rate of seroconversion.28, 29
Although viral load has been more directly correlated with rate of transmission, we were unable to obtain viral load data from these rural areas because of problems with physical infrastructure and human resource capacity.2, 30
The stage of disease has been associated with increased risk of transmission, but we did not find that an association between lower CD4 levels and with higher rates of seroconversion.31, 32
One explanation may be that the spouses with late-stage disease in this cohort may have had less frequent sex or used condoms more than those spouses in latency. Our data provides some support to the hypothesis that partners with late-stage disease may have less contribution to the HIV epidemic than early-stage partners or those who are acutely infected and do not know their status.32
One of the primary limitations of our study is that we were unable to obtain adherence data from those on ART because almost all patients received treatment from local community healthcare centers. Unfortunately, these centers did not reliably track adherence data. To address this limitation, future studies in this cohort will incorporate more detailed questions on drug adherence and attempt to better quantify drug resistance. While the lack of adherence or viral load data is problematic, it reflects real-world challenges associated with ART roll-out in resource-limited settings.33
Our findings suggest that ART treatment with first line drugs alone may not be sufficient to reduce HIV transmission among discordant couples in China. Another limitation of this study is that our data may be subject to recall bias because some subjects were surveyed at the end of the enrollment period and asked to recall behavior from the month(s) preceding their date of seroconversion. Self-reporting bias may also have resulted in the under-reporting of unprotected sex.34
On quality of life, we found that those who scored lower in the psychological, but not physical, social, or environmental domains was significantly associated with HIV seroconversion (RR=2.33; 95% CI,1.21–4.48). While the link between HIV transmission and indicators of psychological well-being is not well understood, the WHO quality of life assessment has been previously validated in patients with HIV.14
A study conducted in Moscow among Tajik migrant workers found that lack of social support and feeling unprotected by law may reduce self efficacy and self-protective behaviors.35
Thus, it is possible that initially HIV-negative spouses who had lower scores on the psychological domain may be engaging in more risky behaviors, such as having unprotected sex. Our results suggest that psychological assessments may serve as novel indicators of HIV transmission among serodiscordant couples and that interventions aimed at improving quality of life and reducing psychological distress may reduce this risk in China.36
However, more research on the type and effectiveness of these interventions as well as on the appropriateness of the survey instrument is needed for HIV discordant families in China.
Our study found a relatively low rate of HIV transmission among serodiscordant couples in Henan but the rate increased over time. We also found that not always using condoms, more frequent sex, not switching ART regimens, and a lower quality of life score on psychological domains were associated with increased risk of transmission. While adherence to treatment probably played an important factor, ART use and last recorded CD4 count were not found to be associated with HIV transmission. Our study suggests that the use of blanket ART programs alone may not necessarily reduce transmission among rural serodiscordant couples in China. To be most effective, treatment programs in these areas should be combined with HIV prevention interventions that emphasize always using condoms, less frequent sex, switching to more effective ART regimens, and care and support services for those affected by AIDS.