Studies: transmission between men and women

One randomised controlled trial, HPTN 052, and six prospective studies have been published or presented that include couples where the HIV-positive individuals were on treatment. In five studies just some of them were treated, allowing for a within-study comparison of transmission rates by treated and untreated people. For HPTN 052 see the end of this section.

Castilla and colleagues¹ followed 393 heterosexual couples in Spain between 1991 and 2003 and found that in the 60 couples where the HIV-positive partner was on antiretroviral therapy with a viral load below 50 copies/ml no HIV transmission was observed, compared to a rate of transmission of 8.6% among partners of untreated patients.

Melo and colleagues² followed 93 heterosexual couples in Brazil over six years, and found that there was no transmission in the 41 couples where the HIV-positive partner was on antiretroviral therapy with an undetectable viral load, compared with six transmissions in the couples where the HIV-positive partner was not on therapy.

A 2008 study from Tororo in Uganda³ enrolled 928 HIV-positive individuals, all of whom began antiretrovirals. Among 62 serodiscordant couples, one husband of a female participant became HIV-positive within the first year of the study. (No viral load test was done on this participant around the time of transmission, though it was emphasised by the researchers that she had been slow to respond to ARVs. It was estimated that HIV treatment had cut the risk of HIV transmission by 91% over a three-year period. Interestingly, this estimate was 99% at the end of two years, but increases in risky behaviour amongst some participants between years two and three caused the researchers to revise their estimates of the likelihood of infection.

A study from Rakai, Uganda,⁴ enrolled 205 heterosexual couples who were followed for a median of just 1.5 years. Even though only 15 of the 20 HIV-positive partners on treatment had achieved a viral load below 400 copies/ml after six months of treatment, no transmissions were observed in all 20 couples over 1.1 years of follow-up, compared with 34 transmissions where the positive partner was not on treatment.

A much larger study on the effects of treatment on transmission took place in Zambia and Rwanda.⁵ Here, a total of 2993 serodiscordant heterosexual couples were followed-up for a median of 512 days between 2002 and late 2008. However, no viral load testing was done. Of 175 transmissions confirmed (by phylogenetic analysis) to have taken place within the relationship, six transmissions occurred in couples where the HIV-positive partner was on treatment, although two of these took place in the first three months following treatment initiation. Excluding the two transmissions early in treatment, the HIV-incidence rate on antiretrovirals was calculated to be 0.7 per 100 couple-years, compared to an incidence of 3.4 per 100 couple-years when HIV treatment was not being taken – a fivefold risk reduction.

In a meta-analysis of these studies, Attia and colleagues⁵ calculated that in the two studies where viral load was known to be undetectable (Castilla, Melo) there were zero transmissions over a total of 291 person-years of follow-up, so the transmission rate was zero. Because of the limits of statistical uncertainty, this does not mean the actual rate in the real world is zero and transmission from people with undetectable viral loads never occurs. The authors state that the data are “compatible with one transmission per 79 person-years", based on their upper 95% confidence limit of 1.27 per 100 person-years. Moreover, if the studies that did not measure viral load were included, this involves five transmissions from people on treatment in five studies, meaning a transmission rate of 0.46% or one transmission per 217 people on treatment per year.