antiretroviral therapy significantly reduced the risk of AIDS and HIV-related illness in a large study in low and middle-income countries,
according to the final results of the HPTN 052 study published in Lancet Infectious Diseases. Participants in this large multi-site study were randomised to take immediate or
delayed HIV therapy. Overall, participants in the early treatment arm had a lower
risk of AIDS, tuberculosis, symptomatic HIV disease and also some
had previously shown that early antiretroviral treatment reduced the risk of
HIV transmission by 96%.
benefits with a striking effect on transmission risk gives additional strength
to the argument for early initiation of antiretroviral treatment,” write the
antiretroviral therapy, many people living with HIV now have a normal life
However, there is
uncertainty about the best time to start HIV treatment.
the HPTN 052 study hoped their data could clarify this important question.
controlled trial was conducted at 13 sites in nine countries. HIV serodiscordant
couples (in which one person has HIV and the other does not) were eligible for enrolment if the HIV-positive partner had a CD4
count between 350 and 550 cells/mm3.
participants were randomised on a 1:1 basis to start immediate HIV therapy or
to delay treatment until their CD4 count fell to 250 cells/mm3 or the development
of symptomatic HIV-related disease.
A total of 1763
HIV-positive participants were randomised. Median CD4 cell count at baseline was
436 cells/mm3. The median duration
of follow-up was 2.1 years.
were death, progression to AIDS, tuberculosis, severe bacterial infections,
cardiovascular disease, serious liver and kidney disease, non-AIDS cancers and
included symptomatic HIV disease (WHO stage 2 and stage 3), malaria, renal and
hepatic dysfunction, hypertension, lipodystrophy, dyslipidaemia, peripheral
neuropathy and some blood disorders.
In total, 57 participants (6%) in the early treatment group and 77 participants (9%) in the delayed
therapy arm experienced a primary outcome. The cumulative two-year probability of a
primary outcome was 4.8% for participants receiving early treatment compared to
7.9% for those who delayed therapy. Early treatment reduced the risk of a
primary event by a non-significant 27% (p = 0.074).
An AIDS event was
diagnosed in 5% of participants in the early treatment arm compared to 7% of people in the delayed therapy arm. The cumulative two-year probability of AIDS
was 3.3% for those who received early treatment and 6% for individuals delaying
treatment. Early treatment reduced the risk of developing an AIDS-defining illness by
36% (0.64; 95% CI 0.43-0.96, p = 0.031).
diagnosed in 2% of participants in the early treatment arm and 4% of participants
randomised to delay therapy. Early treatment was associated with a 1.2%
two-year probability of TB, whereas the probability was 3.7% for people who delayed
treatment. The authors calculated that early treatment reduced the risk of TB
by 51% (p = 0.018).
secondary outcomes, serious non-HIV-related events were rare, occurring in
twelve participants who started early treatment compared to nine individuals in the
delayed treatment arm.
incidence of primary events for people taking early treatment was 3.5 per 100
person-years, compared to an incidence of 4.5 per 100 person-years for people
in the delayed therapy arm. This difference was not significant. However, there
was a significantly lower incidence of tuberculosis in the delayed treatment
arm (0.8 vs 1.8 events per 100 person years, p = 0.009).
The frequency of
secondary outcomes was similar between the early and delayed treatment arms
(36 vs 34%, respectively).
and secondary outcomes showed that these occurred in 37% of people taking
early treatment and in 40% of people in the delayed therapy arm. Combined
incidence rates were significantly lower among people in the early versus the
delayed treatment arm (24.9 vs 26.5 per 100 person-years, p = 0.025).
secondary events were not concentrated in people with low CD4 counts; in fact
most occurred in people with CD4 counts above 350 cells/mm3. The
median CD4 count at which primary events occurred was 353 cells/mm3
for people in the delayed treatment arm and 502 cells/mm3 for people taking immediate treatment.
antiretroviral treatment…can be expected to delay the time to AIDS-defining
events, tuberculosis, and WHO stage 2 and 3 events and significantly reduce the
incidence of these events,” comment the authors.
the differences in outcomes between the study arms were small, but believe
“they offer the potential for reduced morbidity among millions of people with