Short course of ART during primary HIV infection has immunological and virological benefits after treatment is stopped

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.

“Short-course 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 progression.”

Early responses to HIV infection are associated with subsequent disease progression. For instance, a 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 September 2013.

To be included in the analysis, the studies were required to have both treatment and control arms.

The primary 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 of treatment.

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 stopped.

Pooled results 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.

“Theoretically, 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.

The investigators 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.”

Restricting 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.

Increasing the 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.