A study from the Henan province of China published recently shows that antiretroviral therapy (ART) may not be as effective at suppressing HIV and preventing onward transmission in ‘real world’ settings as it is in the best clinical practice.
The study found that ART given to the partner with HIV within monogamous heterosexual couples with different HIV status only reduced the number of HIV infections passed on between them by about 50% over the course of a study period – though its effectiveness of ART did increase over time and by the end of the study stood at 67%.
Background
The study examined a cohort of people with HIV, in which research had already yielded two contradictory estimates of the effectiveness of ART in preventing transmission. Many of the original HIV-positive partners were infected through selling blood in non-sterile conditions between the early 1990s and 1998. In 1998, the practice was outlawed, but not before it had created a local HIV epidemic.
There appear to be low rates of extramarital sex and sexually transmitted infections (STIs) in this group, so HIV infections are usually directly transmitted between partners, allowing estimates of infectiousness to be made.
In 2010, a study (Wang) reported on Aidsmap caused concern by finding no association between the HIV-positive partner being on ART and transmission to the HIV-negative partner. In fact, 5% of partners who were on ART transmitted HIV to their spouses during the study period but only 3% not on ART, though this difference was not statistically significant. When adjusted for baseline characteristics, 32% fewer infections came from partners on ART than from partners not on ART; this was still not statistically significant.
At the time the researchers were puzzled themselves, saying that ART status could have been misreported, though also pointing out that a previous Chinese study (Li) had found that only a third of patients in the same cohort were adherent to their therapy after six months. A clue was provided by the fact that people who had not changed their ART regimens were over 2.5 times more likely to transmit HIV, suggesting that a combination of poor drug tolerance, low adherence and resistance could be the reason.
Less well publicised was a follow-on study in 2013 (Wang 2013) by the same researchers that completely contradicted their first result. With three more years of data, the annual incidence of HIV within serodiscordant couples had halved over the whole time period of the study from 1.7% to 0.8%. It had fallen by two-thirds within three years from 2.14% at the end of 2008 to 0.9% by the end of 2010. And, most strikingly, the chance of a partner with HIV transmitting the virus to their spouse was 95% lower if they were on ART at the time of their most recent clinic visit. This result was in line with randomised controlled studies like HPTN 052 but the stark contrast with the previous findings was a puzzle.
The study and findings
The present study (Smith 2015) suggests some explanations. In this study, all available data from initially treatment-naive serodiscordant couples in Henan Province between 2006 and 2012 were analysed: a total of 4916 couples who contributed an average of 5.4 years’ follow-up. This is a larger group than in the previous studies.
Their average age was 44, and 54% of the HIV-positive partners were women. Forty-seven per cent of the positive partners had originally been infected through blood plasma donation. Nearly all (90%) were farmers, with low education levels. Condom use was reported as quite high – 63% said they ‘always’ used condoms. Only 0.7% (32 individuals) reported any extramarital sex and only 0.4% of the HIV-negative partners (13 people) had had an STI diagnosed in the previous year.
The important difference between this and previous studies is that it only looked at HIV-positive partners who were treatment-naive at the start of the study: unlike the previous studies, it excluded people who were already on ART at the start of the period studied. The reason for this is to eliminate two opposite sources of bias caused by the fact that there are fewer data on what happened to people on ART in the pre-study period.