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Short Antiretroviral Therapy Beneficial during Primary HIV Infection

A short course of combination antiretroviral therapy (ART) started during primary HIV infection is associated with CD4 T-cell gains and viral load reductions after treatment is stopped, according to a meta-analysis published in the December 6 edition of PLoS ONE.

Over the course of the AIDS epidemic researchers have explored whether starting antiretroviral drugs very soon after infection can offer long-term immunological and virological benefits, perhaps even a "functional cure." A small number of patients -- including the French VISCONTI cohort -- appear to benefit from prompt ART followed by treatment interruption, but the overall effects are not clear.

Jingjing Chen and colleagues from the First Hospital of China Medical University performed a systematic review and meta-analysis to evaluate the immunological and virological effects of short-course ART during primary HIV infection, as well as the influence of treatment initiation time, ART duration, and follow-up time after treatment interruption.

The authors searched the PubMed database and Cochrane Library (through September 2013) and relevant conference abstracts (Conferences on Retroviruses and Opportunistic Infections through 2013 and International AIDS Society Conferences through 2012) for controlled studies describing the effects of short-course combination ART during primary infection on CD4 count and HIV viral load in adults and adolescents.

Out of 3168 studies initially reviewed, 152 were identified as relevant for further evaluation and 19 were deemed eligible for inclusion. Of these, 2 were duplicates and 9 did not have patient-level data available, leaving 8 studies in the final meta-analysis (6 for CD4 count and 7 for viral load). ART was started within 3 to 6 months after initial infection and lasted for a maximum of about 3 years.

Results

• Overall, ART during primary HIV infection was associated with a CD4 count increase of 86 cells/mm³ compared to untreated arms within 1 year after treatment interruption.
• Early ART also was associated with a viral load reduction of 0.30 log copies/mL within 1 year after interruption.
• The benefits of early ART declined gradually after stopping treatment, however, and were no longer significant by 12-24 months after ART interruption.
• CD4 gains declined from 86 cells/mm³ within 12 months after interruption to 35 cells at 12-24 months and 38 cells/mm³ at 24-36 months post-treatment, while the viral load reduction decreased from 0.30 to 0.18 log copies/mL at 12-24 months.
• Extending early treatment duration beyond 12 months did not increase immunological or virological benefits.

"Short-course treatment during primary HIV infection was associated with immunological and virological benefits which last for at least 1 year after treatment interruption," the researchers summarized.

"However, the benefits derived from early treatment mentioned above may be underestimated, as most of the enrolled studies are observational ones that are susceptible to recruitment bias and loss of follow-up," they elaborated in their discussion. Looking only at the 3 included randomized controlled trials, the CD4 gain was 162 cells/mm³ and viral load decline was 0.52 log copies/mL within 1 year after treatment interruption.

"Our analysis demonstrated that the early treated patients had higher baseline viral load and lower baseline CD4 cell counts," they wrote. "After baseline correction, net benefits derived from early treatment were greater."

"Findings from this meta-analysis are of great significance for the clinical management of primary HIV infection," the authors concluded. "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. Although extended follow-up studies are needed to ascertain the long-term benefits of early treatment, this adds to the evidence that supports early treatment."

They noted that the participants enrolled in these studies were adults and adolescents, so the conclusions are applicable only to this population. A recent case of a Mississippi child who appears HIV-free off treatment after starting ART at about 30 hours after birth offers hope that this strategy may be particularly beneficial for infants.

1/10/14

Reference

J Chen, X Han, M An, et al. Immunological and Virological Benefits Resulted from Short-Course Treatment during Primary HIV Infection: A Meta-Analysis. PLoS ONE 8(12):e82461. December 6, 2013.