A short course of
antiretroviral therapy during primary HIV infection (PHI) has immunological and
virological benefits after treatment is stopped, a meta-analysis published in
the online journal PLoS One shows. The benefits of treatment were greatest
for people with lower baseline CD4 cell counts and higher baseline viral
loads, but did not last in the long term.
treatment during PHI was associated with better immunological and virological
outcomes after treatment interruption,” write the authors. “This change is a
clinically significant change, which may have a profound effect on HIV disease
Early responses to
HIV infection are associated with subsequent disease progression. For instance,
recent study showed that severity of PHI is associated with longer-term
outcomes. However, the benefits of short-course antiretroviral therapy
during PHI are unclear. A team of investigators from China therefore performed
a meta-analysis of studies examining this question that were published before
To be included in
the analysis, the studies were required to have both treatment and control
outcome was the effect of short-course therapy on CD4 count and viral load
after the cessation of treatment. Other analyses examined the efficacy of
therapy according to factors such as baseline characteristics and the duration
A total of eight
studies met the investigators’ inclusion criteria. These were published between
2004 and 2012 and had sample sizes ranging from 11 to 822 patients. The
duration of short-course therapy was between 12 and 86 weeks, and participants
were followed for between nine months and six years after treatment was
showed that short-course therapy during PHI had significant immunological and
virological benefits. Twelve months after stopping, early treatment increased CD4
count by 86 cells/mm3 and reduced viral load by 0.30 log10
copies/ml, compared to untreated controls.
the prevention of severe loss of CD4 T cells in peripheral blood and lymphoid
tissues occurring during PHI, the preservation of HIV-specific cellular and
humoral immune responses, the restriction of viral diversification, and the
reduced size of the HIV reservoirs exerted by treatment during PHI may be the
reasons explaining these benefits,” the investigators suggest.
believe that short-course treatment during PHI had even greater benefits than those
revealed in their headline finding.
They noted that,
compared to untreated participants, individuals who received therapy had lower
baseline CD4 counts (weighted mean difference = -77 cells/mm3) and higher viral loads
(WMD = 0.22 log10 copies/ml). “After baseline correction,” write
the authors, “the net changes of CD4 count and viral load derived from early
treatment were much greater than those without baseline correction.”
analysis to randomised-controlled trials (RCTs) showed that participants who
received short-course treatment had a CD4 count benefit of 162 cells/mm3
and a virological benefit of -0.42 log10 copies/ml, compared to
participants who did not receive therapy during PHI. Benefits of early treatment
were less pronounced in non-RCTs (CD4 = 72 cells/mm3; viral load =
-0.25 log10 copies/ml).
But the benefits
of early treatment did not last. The CD4 difference 12 to 24 months after
the completion of treatment between treated and non-treated patients had fallen
to 35 cells/mm3 and the viral load benefit at this time was 0.18 log10
copies/ml. These differences were not significant.
duration of early therapy did not confer any additional benefits.
“Compared to the
untreated arm, treatment during PHI not only increased CD4 count but also lowered
viral load after treatment interruption,” conclude the authors. “As CD4 count
and viral load are strong predictors of HIV disease progression, early
treatment possibly delays HIV disease progression for at least a period of
time.” They call for more research examining the risk and benefits of
short-course therapy during PHI and the acceptability of this strategy to
people with HIV.