'Real-world' evidence shows that antiretroviral therapy reduces risk of HIV transmission in heterosexual couples

Michael Carter
Published: 04 December 2012

A study conducted in China has provided 'real-world' evidence of the impact of antiretroviral therapy on the risk of transmission in heterosexual couples. Published in The Lancet, the retrospective research showed that the risk of HIV transmission was reduced by 26% in serodiscordant couples where the HIV-infected partner was taking antiretroviral therapy when compared to serodiscordant couples where the HIV-positive partner remained treatment naive.

“Our results strongly support the population-wide, real-world feasibility of treating HIV-positive individuals in serodiscordant couples to prevent HIV transmission in a developing country setting,” comment the authors.

Thanks to antiretroviral therapy, many HIV-positive people now have a near-normal prognosis. This treatment also has another major benefit, of preventing onward transmission; in the large HPTN 052 trial effective therapy was shown to reduce the risk of HIV transmission in serodiscordant heterosexual couples by 96%.

On the basis of these results and similar outcomes in observational studies, the World Health Organization (WHO) now advocates a policy of antiretroviral therapy regardless of CD4 cell count for all HIV-positive individuals in a heterosexual relationship with an HIV-negative partner.

However, the impact of the use of HIV treatment as prevention in resource-limited settings outside the context of clinical trials is far from clear.

Investigators from China therefore performed a retrospective analysis comparing rates of HIV transmission in serodiscordant couples according to the use of antiretroviral therapy.

A total of 38,862 serodiscordant couples were included in the study. These couples contributed a total of 101,295 person-years of follow-up.

Treatment guidelines in China recommend that HIV-positive people should start therapy if they are ill because of HIV or if they have a CD4 cell count below 350 cells/mm3.

There were 24,057 couples where the HIV-positive partner was taking antiretroviral therapy. The HIV transmission rate among these couples was 1.3 per 100 person-years.

This was significantly lower than the rate of 2.6 per 100 person-years observed in the couples where the HIV-positive partner remained treatment naive.

The investigators calculated that antiretroviral therapy reduced the risk of transmission by a highly significant 26% (AHR = 0.74; 95% CI, 0.65-0.84; p < 0.0001).

“The evidence of a preventive effect is sound,” writes Dr Sten H Vermund in an editorial accompanying the study.

However, the impact of treatment on the transmission rates was significantly lower than that seen in the HPTN 052 study. The authors think that this because of “treatment non-adherence, resistance and the potential for…non-linked HIV transmission”. The study reported treatment data gathered since 2003, when much less well-tolerated treatment regimens were in use in China.

The authors also note that second-line treatment is still not widely available in all Chinese provinces, and previous analysis of China's HIV treatment programme showed that half of all patients on treatment for five years were classified as immunological treatment failures, that is, they had experienced a decline in CD4 cell count of at least 30% after an initial increase, implying the failure of treatment in the absence of viral load monitoring.

Another study of treatment responses in China cited by the authors found that at least one-third of people treated for at least two years had experienced virologic treatment failure, implying an increased risk of transmission despite treatment.

Taken together, these examples suggest the widespread existence of sub-optimal standards of antiretroviral treatment in China. Whilst the partner transmission data reported in this study reflects a real-world experience, the results may not be generalisable to settings where much higher standards have been achieved, both in well-resourced settings and in low- and middle-income countries.

Treatment reduced the risk of transmission in the first year of therapy (AHR = 0.64; 95% CI, 0.54-0.76), but not the second (AHR = 0.75; 95% CI, 0.56-1.01) or subsequent years of therapy. In all groups beyond one year of treatment, the sample size was substantially smaller than the cohort treated for one year, limiting the robustness of the findings.

The protective effect of treatment also differed according to HIV risk group.

It was significant when the HIV-positive partner had been infected by blood products or plasma transfusion (AHR = 0.76; 95% CI, 0.59-0.99) or heterosexual intercourse (AHR = 0.69; 95% CI, 0.56-0.84).

However, antiretroviral therapy did not reduce the risk of transmissions when the HIV-infected partner had been infected via injecting drug use (AHR = 0.98; 95% CI, 0.71-1.36). The sample size was inadequate to yield robust evidence regarding the efficacy of  treatment as prevention when the HIV-positive male partner was infected via sex with another man.

“That our results show a significant 26% reduction in HIV transmission under real-world conditions in a developing country suggests that such a public health prevention strategy is feasible on a national scale an helps to validate the WHO recommendation in support of the treatment-as-prevention approach,” comment the authors. “How durable the protection is over time and whether or not these results are generalisable to other risk groups, such as injecting drug users, are not clear from our anaylsis and need to be further studied to establish how widely such a treatment-as-prevention public health approach can be implemented.”

Reference

Jia Z et al. Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study. The Lancet, online edition. Dx.doi.org/10.1016/s1040-6736(12)1898-4, 2012.

Vermund SH Treatment as prevention in China. The Lancet, online edition. Dx.doi.org/10.1016/s1040-6736(12)62005-4, 2012.

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