It was 2011 that finally saw publication of conclusive
evidence of the efficacy of HIV treatment as prevention, from a randomised
controlled trial that specifically aimed to measure its effect.
The HPTN 052 trial was originally designed to report its
findings in 2015 but was stopped in 2011 when it became obvious that the
reduction in transmissions seen was so great that it would be unethical to
continue recruiting study participants to the less protected arm.
The HPTN 052 study found that the efficacy of treatment as
prevention was 96%
– in other words HIV-positive people taking ARVs were more
than 20 times less likely to infect their partners than untreated people.
The study, conducted in 18 sites in eight countries in three
continents across the world, began enrolling participants in 2005, recruiting
1736 serodiscordant couples. Most were heterosexual but there were 38 male/male
To enrol, the HIV-positive partner had to have a CD4 count
between 350 and 550 cells/mm3 at baseline. The trial then randomised
them so that 50% started taking ARV drugs immediately and 50% waited until
their CD4 count had fallen below 250 cells/mm3, unless they
developed an AIDS-defining illness first. (At the time the trial protocol was
designed, WHO’s recommended CD4 threshold was 200 cells/mm3. This was revised to 350 cells/mm3
When recruited, the average age of participants was 33, just
over half (52%) of the HIV-positive participants were male, and their average
baseline CD4 count was 438 cells/mm3.
The investigators stopped the trial in May 2011, four years
before its planned ending date, when the trial’s Data and Safety Monitoring
Board found that out of 28 HIV infections observed in the HIV-negative partners
where the positive partner was clearly the source, only one occurred in a
couple where the HIV-positive partner was taking ARVs. This equates to a 96%
(over twentyfold) risk reduction.
There was also a health advantage to starting treatment early for the
HIV-positive partner: there were only three cases of TB in the people who
started ARVs immediately and 17 in those who delayed treatment: an 82%
reduction in TB cases.
There was one case of transmission from an HIV-positive
partner who had been taking ARVs. At the time of writing, we do not have viral
load data for this individual, as detailed data from the study have not yet
There were also eleven transmissions where phylogenetic
analysis showed that the virus could not have come from the primary partner who
was taking ARVs. This proportion of transmission from ‘extramarital’ partners
(28%) was almost exactly the same as the proportion of extramarital
transmissions seen in the Partners in Prevention study.
The conclusive nature of the HPTN 052 result is leading to
demands for a more rational, evidence-based approach to HIV prevention and
treatment provision worldwide, with a greater emphasis on the provision of
antiretrovirals (see later in this section).
To summarise: none of these studies have documented a proven
case of heterosexual transmission where the HIV-positive partner had an
undetectable viral load, though statistical uncertainty means that the
possibility cannot be ruled out. They do document that providing ARV treatment
to the positive partner in a heterosexual couple reduces the chances of HIV
infection by 90% or more.