Immediate initiation of antiretroviral treatment produced
the biggest boost in CD4 cell count for people infected with HIV less than six
months previously, an analysis of the START study of prompt HIV treatment has
found. Writing in the July issue of AIDS, the study investigators say that the benefit of early
treatment for people with recent HIV infection may have been understated in START.

The START trial’s overall finding was that starting treatment at a CD4 count above 500 cells/mm3
was associated with a 72% reduction in the risk of AIDS-defining events when
compared to deferring treatment until a CD4 count of 350 cells/mm3
was reached or HIV-related symptoms developed.

A greater CD4 count increase in people with recent infection
might protect against HIV-related illness. Although the START study was not
designed to look at differences in clinical outcomes according to duration of infection (it would have needed many more participants to
carry out these comparisons), investigators were able to look at changes in CD4 cell
count as a surrogate marker.

The START study randomised 4684 adults living with HIV with
CD4 cell counts above 500 cells/mm3 to start treatment immediately
or defer treatment until a CD4 count of 350 cells/mm3 was reached or HIV-related symptoms.

In START, 373 people were classified as recently infected
(Group 1). They either self-reported acquiring HIV within the six months prior
to joining the study or had been diagnosed with HIV in the previous six
months and had antibody markers that indicated recent HIV infection. Of those
with a known infection date, the median time between exposure to HIV and
randomisation in the study was 4.8 months.

People with early HIV infection are especially vulnerable to HIV disease progression without immediate treatment. 

The majority of study participants had been living with HIV
for between 6 and 24 months (2634 persons, Group 2). A further 1605
participants had been living with HIV for at least two years (Group 3).
Seventy-two participants were excluded from the analysis owing to missing
samples.

At baseline the recently-infected group had slightly higher
CD4 cell counts than the other groups (660 cells/mm3 compared to 654 in Group 2
and 644 in Group 3 (p=0.007). They also had lower CD8+ cell counts, indicating
greater abnormality in immune function in this group.

The recently-infected group were significantly more likely
to have a viral load above 50,000 copies/ml and significantly less likely to
have a viral load below 3,000 copies/ml (both p0.001) than the other
groups.

After starting treatment, the mean CD4 cell gain was 194
cells/mm3 higher in the immediate treatment group after an average
follow-up of three years, but this difference was greater in the
recently-infected group (+231 cells) compared to groups 2 and 3 (+202 and
+171 cells/mm3 respectively, p 0.001). The recently-infected
group also experienced greater increase in CD4:CD8 ratio, indicating greater
normalisation of immune function.

In those who deferred treatment, the rate of CD4 cell
decline to 350 cells/mm3 or development of AIDS was greater in the recently-infected group.
People infected for less than six months were 52% more likely to reach one of
these endpoints than people infected for at least two years (HR 1.52, 95% CI
1.14-2.05), showing that people with early HIV infection are especially
vulnerable to HIV disease progression without immediate treatment. The
incidence of disease progression was 15.6 per 100 person-years of follow-up in
the recently-infected group compared to 10.5 per 100 person-years in those
infected for two years or more.

The findings from the START study reinforce the findings of
the SPARTAC study of immediate versus deferred treatment in early HIV
infection, which showed that people randomised to immediate treatment less than
12 weeks after seroconversion were less likely to experience a CD4 cell
decline below 350 or need to start treatment for other reasons.

Starting treatment soon after HIV infection may be
especially protective. The study findings emphasise the importance of
clinical services which can offer same-day treatment initiation.

START investigators will continue to follow participants to
2021 to look at the long-term implications of the study findings, including the
greater immunological recovery in recently-infected participants.