HIV-infected infants who start HIV treatment within three months of birth have a significantly reduced risk of developing AIDS or dying, European investigators report in the March 13th edition of AIDS. “Deferring treatment in infected infants is no longer an option,” write the investigators.
Without HIV treatment, approximately 20% of HIV-infected infants born in richer countries like the UK will develop AIDS or die in the first year of life. The introduction of combination HIV treatment in the mid 1990s lead to suggestions that starting HIV treatment soon after birth could reduce the risk of disease progression in infected children. There were, however, concerns about the pharmacokinetics of antiretroviral drugs in children, the lack of paediatric formulations and the risk of both short- and long-term side-effects.
Nevertheless, a number of non-randomised studies in richer countries demonstrated that HIV treatment before six months of age reduced the risk of disease progression, lowered viral load and strengthened the immune system.
Furthermore, a randomised study in South Africa involving 375 HIV-positive infants demonstrated clear advantages to starting HIV treatment within three months of birth, the risk of death being reduced by 76%.
European researchers therefore looked at medical records obtained from 13 cohorts in eleven European countries to determine the benefit of HIV-infected, symptom-free infants starting antiretroviral treatment before three months of age.
The children were born between 1996 and 2004. A total of 124 infants started treatment before three months of age (the early treatment group) and 86 did not (the deferred treatment group).
Of the infants who started HIV treatment early, four developed AIDS (three cases of encephalitis and one of wasting disease) and two died. HIV treatment was started within a year by 58 of the infants whose treatment was deferred. This included six children who did so because of the development of an AIDS-defining illness (three cases of encephalitis, one of PCP pneumonia, one of CMV and one serious recurrent bacterial infection). Of the 52 children who started treatment without having developed serious HIV-related illness, six subsequently developed AIDS (another three cases of encephalitis, two CMV, and one serious recurrent bacterial infection).
A total of 28 children had not received HIV treatment by their first birthday, and six AIDS-defining illnesses were reported amongst these infants.
Infants who started HIV treatment within three months of birth had a 2% risk of developing AIDS in their first year of life compared to a 12% risk for children who deferred treatment. Furthermore, infants taking early HIV treatment had a lower risk of developing AIDS within their first five years (5%) than children who deferred treatment (22%). These differences in risk were highly significant (p < 0.001).
Deferred treatment was associated with a hazard ratio (HR) of death of 5.0 (95% confidence interval [CI], 2.0 to 12.6, p = 0.001). This remained the case when the investigators took into account possible confounding factors such as year of birth, use of HIV treatment during pregnancy and delivery, mode of delivery, length of pregnancy, birth weight, CD4 cell percentage, use of PCP prophylaxis, and number of drugs in first antiretroviral combination.
There were significant differences in the characteristics of children in the cohorts included in the analysis. Taking these into account slightly reduced the hazard ratio of death for infants whose treatment was deferred (HR = 3.0, 95% CI, 1.2 to 7.9, p =0.021). However, restricting the analysis to infants who took triple HIV treatment consisting of either three nucleoside reverse transcriptase inhibitors (NRTIs) or two NRTIs plus the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (Viramune) strengthened the association between deferred treatment and poorer outcome (HR = 7.9, 95% CI, 2.3 to 27.6, p < 0.001).
“The benefit of systematic antiretroviral therapy before 3 months of age to avoid…rapid progression has been recently demonstrated in the South African controlled randomized trial. Our analysis confirmed that this is also the case in routine clinical practice in industrialized countries,” write the investigators.
They conclude, “antiretroviral therapy initiated before the age of 3 months has a dramatic effect on reducing progression to AIDS and death in high income countries.”