Starting antiretroviral therapy (ART) within the first six months of life sustained viral suppression better than starting ART later in two cohorts of South Africa infants. Starting ART within six months rather than later did not consistently affect chances of initial viral suppression in another three cohorts.
Early ART reduces morbidity and mortality in infants, and these findings support the current recommendation to start ART immediately in HIV-infected infants and children regardless of CD4 count and clinical status. The report of the "Mississippi baby", who started ART within 30 hours of birth and maintained viral suppression for 27 months without ART, further stoked interest in the potential merits of fast ART. To explore these issues in greater detail, researchers assessed the impact of ART within six months of birth versus later ART in five cohorts of South African infants.
The investigators examined associations between age when ART began and initial virologic response in three non-overlapping cohorts including 1260 infants and young children starting ART (cohort A, B and C1). They assessed the impact of age when ART began on sustained virologic control in two cohorts (C2 and D) including 488 infants and children who had achieved control. Both analyses compared infants who began ART within six months of birth (early ART) with children who began between six and 24 months of age (late ART).
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Average age when ART began ranged from 8.7 to 10.5 months across the five cohorts. Proportions of infants starting ART in the first six months of life were 47.5% in cohort A, 35.1% in cohort B, 31.6% in cohort C1, 27.7% in cohort C2 and 46.4% in cohort D.
In the three cohorts in the first analysis (A, B and C1), a higher proportion starting ART early than late had a viral load at or above 750,000 copies/mL. Only children in cohort A were more likely to reach a viral load below 50 copies/mL within six months if they started ART early. Results did not change after adjustment for pretreatment viral load, sex, CD4 percentage or weight-for-age Z score. Analysis of these three cohorts combined did not show that early ART improved chances of viral suppression, even after statistical adjustment. In cohort A, there was a trend toward lower mortality in the group that started ART early (11.1% versus 20.2%, P = .076).
In the second main analysis, starting ART early in both cohorts C2 and D improved chances of sustained virologic control across scheduled study visits. In cohort C2, a generalized estimating equation (GEE) model accounting for repeat visits determined that odds of having a viral load between 50 and 1000 copies/mL versus <50 copies/mL was 66% lower at scheduled visits in the early ART group (odds ratio [OR] 0.34, 95% confidence interval 0.19 to 0.61). In cohort D a GEE model accounting for randomization group determined that starting ART early lowered chances of a viral load between 50 and 1000 copies/mL versus <50 copies/mL by 54% across study visits (OR 0.46, 95% CI 0.24 to 0.87).
"Although the better virologic response in children initiating ART early observed in Cohort A is encouraging," the researchers observe, "the lack of confirmation in the other two cohorts leads us to suspect that other factors [beyond early ART] may be involved" in initial viral control. They add that only 31%, 40.1% and 26.5% of early-treated infants in cohorts A, B and C1 reached a viral load below 50 copies/mL with six months of starting ART.
Findings of sustained virologic control with early ART in cohorts C2 and D "suggest that there are virological benefits of early treatment" in infants in addition to the previously reported benefits of lower morbidity and mortality, better growth and improved neurologic outcomes. The new findings, the authors propose, "provide additional impetus for early initiation of ART in HIV-infected infants."