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.
On the one hand, ART in China before 2006 may have been far less tolerable and subject
to interruption than it has become more recently. At this point, as the
researchers point out, quite toxic drugs like didanosine (ddI, Videx) were still being used.
On the other hand, with regimens where toxicity is less of an issue, people who have been on ART
for a long time are often more settled on it, have better adherence, and are
less likely to switch and a lot less likely to experience treatment failure, than people in
their first year on therapy. By including people who had been on ART since
before the start of the study, researchers could have been biasing their study
group in the direction of stability and underestimating the potential for
transmission during the HIV-positive partner’s first year on ART when they are
more likely to have detectable viral load and to experience treatment failure or switch their therapy.
In
the event, over 80% of the initially HIV-positive partners had started ART by
2012. Establishing the start date of therapy also enabled the researchers to
see whether ART became more or less efficient at restricting HIV transmissions
over time in a more sensitive way than the 2013 study.
There
were 157 HIV infections noted in over 26,000 couple-years of follow up, an
incidence of 0.59% a year. Incidence in couples before the HIV-positive partner started ART was considerably
higher: 5.87% a year. However, because the cohort spent the majority of time
with the initially HIV-positive partner on ART, a higher number of actual infections
(84 versus 73) came from a positive partner on ART. This mean that, crudely, the
actual reduction in risk conferred by the HIV-positive partner taking ART
was only 29%.
However,
people are more likely to start treatment if they are sicker, which also means
they are more infectious but have less sex. After adjusting for this, the reduction
in risk conferred by putting the HIV-positive partner on ART was 48%.
More
sex or lower self-reported condom use was also associated with higher HIV
transmission rates. The direction of transmission in terms of gender – male-to-female
or female-to-male – did not influence transmission rates.
The
efficacy of ART in reducing transmission increased as time went on. Between
2006 and 2008 it only had a modest 32% efficacy in reducing the likelihood of HIV
infection, in agreement with the 2010 study; but between 2009 and 2012 its efficacy was 67%. This efficacy is in
accordance with some other cohorts, though nothing like that seen in randomised
controlled trials or prospective cohorts like PARTNER.
One
other striking finding was that the efficacy of ART in reducing transmission
did not apply at all when the initially HIV-positive partner had a CD4 count
below 250 cells/mm3. Below this, there was no difference in
transmission rate; above it, the efficacy of ART in reducing risk was 59%.