In an uncomfortable finding for advocates of treatment as
prevention, a study of heterosexual couples of differing HIV status in Uganda
has found no difference in the rate of HIV infections in the negative partner
when the positive partner was taking antiretroviral therapy (ART) and was
virally suppressed, when compared to couples where the positive partner was not on treatment. Findings were presented at the
19th International AIDS
Conference (AIDS 2012).
The finding came from an 'in the field' study of HIV patients
attending the TASO clinic in Jinja, Uganda, and their spouses or partners. While researchers cannot explain why its results are so different from
randomised controlled trials such as HPTN 052, which found that putting the HIV-positive partner on ART reduced the HIV trasnmission rate by 96%, it does serve
as a warning, as presenter Josephine Birungi said, that "It may be
difficult to extrapolate the results of randomised controlled trials to
real-life situations in low-income countries."
The survey was of 586 patients and their long-term partners, followed for a median of two years.
During the study, 238 (41%) of the HIV-positive partners stayed off ART because
they did not meet treatment criteria (which at the time of the study was a CD4
count under 250 cells/mm3 or an AIDS-defining illness), 99 (17%) started ART
and 249 (44%) were already on ART at enrolment. Ninety-three per cent of those
on ART had viral loads under 1000 copies/ml.
The only differences between the groups were average CD4
cell count (515 cells/mm3 in patients off ART, 248 in starters and 392 in those
already on ART), percentage of males (51% in those not on ART, 60% in those on
ART), and self-reported condom use at last sex. In the latter case, people
already on ART actually reported more condom use (67%) than people starting ART
(62%) or not on ART (51%). The average duration of relationship was ten years
when the positive partner was not taking ART and twelve if they were on ART or
had started it during the follow-up period.
During the study, there were 17 new HIV infections. There
were eight in people not taking ART, equivalent to an annual HIV incidence of
2.3%, and nine in patients on ART, meaning an HIV incidence of 2.1%. This
difference was not significant (relative risk 0.91). The transmitting partner
had to have been taking ARVs for at least three months to be categorised as
being 'on ART'. In transmissions from patients on ART, the average
time they had been taking ARVs was six months.
The viral load of 14 of the transmitting partners was tested
in the visit after the one where their partner tested HIV positive. In all of
the seven positive (transmitting) partners off ART, viral load was over 1000
copies/ml when they were tested, but only in three out of seven transmitting
partners on ART. Only three of the infected partners have so far had
phylogenetic testing to see if their virus is the same as their partner's. In
two cases it was, but in one it wasn't, meaning that the infection came from an
Four factors were significantly related to transmission. The
proportion of patients in the whole group with viral loads under 1000 copies/ml
was 65% (compared with 59% on treatment); in patients who transmitted HIV, 35%
had a viral load under 1000 copies/ml.
The other significant factors for new HIV infections in the
negative partner were:
- In women, age at sexual debut (15 in women who became
infected; 16 in those who didn't).
- A polygamous relationship (47% of those infected reported
one, compared to 24% of those who were not infected).
- The couple reporting that "men took the decision on
whether to have sex" (59% in those infected versus 35% in those not
Men in partnerships where infections occurred were also less
likely to be circumcised, and the length of relationship was shorter in these
couples (eight versus twelve years), but these differences were not
Josephine Birungi said
that it was difficult to understand the results of the study. Viral load
measurements were taken at least a month or two after infections occurred, and
viral load in the transmitting partner may not reflect the viral load at the
time of infection. Other co-factors like STIs could lead to more transmission of
virus at very low blood plasma viral loads. Or there could be significant
under-reporting of extramarital sex partners
– more phylogenetic testing needed
to be done to determine how many infections came from outside the primary relationship.
"Our results do not question ART working as a prevention
tool," she commented, "only that the effect can be undermined by
social, biological and cultural factors that can underlie transmission."
The survey had findings that were to some extent in conflict with a Ugandan study presented later in the week, which fund that expanding treatment produced lower community viral loads.