Infants who are infected with HIV by their mother at birth are significantly more likely to be alive at age three if they commence anti-HIV treatment within the first two months of life, according to a US study published in the May 11th edition of the Journal of the American Medical Association. The investigators believe that this finding emphasises the importance of the early detection of HIV-positive pregnant women and the prompt treatment of their infants.
The impact of treatment on the progression of HIV disease in infants infected at birth by their mothers is poorly understood. However, two distinct patterns in infants' HIV progression have been observed:
- Early disease progression with the median progression to AIDS within four months.
- Late disease progression with the median progression to AIDS at age six.
In the pre-HAART era it was estimated that approximately a third of all infants born with HIV would experience early disease progression. Accordingly, the early initiation of HAART and PCP prophylaxis is recommended in infants.
Nevertheless, there are concerns about the safety and durability of this approach and there are limited data on the optimum timing for the initiation of HAART in infants.
Using data collected in the US state of North Carolina between 1988 – 1992, investigators from Stanford University had previously demonstrated that providing infants with PCP prophylaxis and antiretroviral monotherapy delayed progression to AIDS.
The investigators extended their study to include infants born with HIV in North Carolina between 1988 and the end of 2003. They wished to determine early progression of HIV and survival by age three in different eras according to the availability of mono, dual, and triple antiretroviral therapy.
A total of 205 infants were included in the investigators analysis. A total of 43 children died in the first three years of life, 41 of these infants dying of causes related to HIV and therefore eligible for inclusion in the investigators’ analysis.
Antiretroviral therapy, PCP prophylaxis, or both were provided to 134 (64%) of the children by age three. Of these, 37 (28%) progressed to AIDS, compared to 44 of the 71 (62%) children who received no treatment (p
Overall survival was 80% (164/2-205) and treatment was significantly associated with improved survival (p = 0.02).
Of the 134 infants who received treatment, 99 (74%) received both antiretroviral therapy and PCP prohpylaxis, 20 (15%) only received PCP prophylaxis, and 15 (11%) only received antiretroviral. Of the children who received antiretroviral therapy, 52% received monotherapy, 28% were treated with dual therapy, and 20% took HAART. None of the 23 infants who were treated with HAART before the age of three progressed to AIDS.
The median age for the diagnosis of the first AIDS-defining illness was four months for infants who received no treatment, eight months for children who received PCP prophylaxis only, and 16 months for infants treated with mono or dual antiretroviral therapy (p
To determine whether very early treatment with antiretrovirals (with or without PCP prophylaxis) delayed progression to AIDS, the investigators compared infants who received treatment in the first two months of life with those who started treatment aged three or four months. The investigators established that treatment in the first two months of life was significantly associated with delayed and reduced progression to AIDS (p = 0.02). Of the ten children who received mono or dual therapy by the age of two months, only one progressed to AIDS within the first twelve months of life, and a total of three progressed to AIDS by the age of three. In contrast, of the 16 children who started treatment with mono or dual therapy aged three or four months, eight progressed to AIDS within a year and eleven within three years.
Of the 33 infants infected with HIV at birth in the HAART era, all survived. Seven (21%) of these infants did however progress to AIDS, but six of these infants had received no anti-HIV treatment.
“Our novel finding of improved outcomes even with mono/dual antiretroviral therapy begun by age two months versus age three or four months…suggests the importance of very early diagnosis and treatment,” write the investigators. “Initiating antiretroviral therapy within the first two months of life offers the potential to begin therapy at or near the time of primary infection.”
The investigators note that their study has limitations, including the small sample size and observational nature of the study design, but observe that their findings are consistent with those of clinical trials, which found immunological and virological responses to early antiretroviral therapy in HIV-positive infants.
As only one of the 26 children who received antiretroviral therapy in the HAART era progressed to AIDS, the investigators conclude: “This finding emphasises that aggressive testing of pregnant women and early detection of HIV in infected infants must continue in order to maximise the benefits of early HAART and PCP prophylaxis.”
Berk DR et al. Temporal trends in early clinical manifestations of perinatal HIV infection in a population-based cohort. JAMA 293 (18): 2221 – 2231, 2005.