Primary HIV-1 Infection in African Children Infected Through Breastfeeding

Little is known about primary HIV infection (PHI) in children. In industrialized countries, infants are infected in utero or perinatally, making it difficult to assess the clinical picture of an acute illness associated with HIV seroconversion. However, in sub-Saharan Africa, where more than 90 percent of infected children are living, about one-third of all transmissions are postnatal (PT), resulting from breastfeeding.

The current study compares clinical features in children infected postnatally by breastfeeding and in uninfected children born to HIV seropositive mothers participating in the ANRS 049 DITRAME project on the prevention of mother-to-child transmission (MTCT) performed in 1995-1998 in Cote d'Ivoire. The authors' goals were to estimate the frequency of acute retroviral syndrome (ARS) associated with pediatric HIV-1 infection, and to describe its symptomatology and associated viral parameters.

Researchers used a matched case-control study retrospectively within the ANRS 049 DITRAME project. Cases were children infected postnatally through breastfeeding, all of whom were negative by at least 45 days of age, but positive on a subsequent DNA PCR sample. Clinical signs and symptoms occurring between the last negative HIV-1 DNA PCR test and the first positive test were compared to signs and symptoms observed and recorded for uninfected children during the same time period of life. For example, a case infected between three and six months was compared with two controls from three to six months of age.

Of the 22 children infected postnatally, 21 exhibited at least one clinical sign associated with PHI. Among the uninfected children, 27 of 44 exhibited a sign/symptom. The authors identified three independent clinical signs associated with pediatric PHI: mononucleosis-like illness (MLI), dermatitis, and generalized lymphadenopathy. The signs are non-specific and do not allow for an easily targeted PHI screening, but in combination they seem to reach better predictive values. MLI was the most sensitive symptom for PHI diagnosis. Generalized lymphadenopathy was the most specific symptom for PHI. A combination of MLI and generalized lymphadenopathy was observed in six infected cases versus one control. There was no significant association between PHI and less common symptoms such as diarrhea, plain fever, otitis, and conjunctivitis, nor was oral candidiasis associated with PHI. Among infected cases, initial median plasma HIV-1 viral load was 5.92 log10 copies/ml; this declined to 4.96 log10 twelve months after the first positive viral load.

The authors stated that, to their knowledge, their study is the first one to examine the occurrence of ARS in African children infected through breastfeeding. They mentioned limitations to the study: the lack of information on both the duration of the clinical signs associated with PHI and the rate of progression to AIDS according to the occurrence of ARS; the fact that concomitant CD4 cell count measurements are missing; the fact that the HIV-1 RNA decrease over time may reflect a selection bias considering the declining number of samples tested during follow-up.

"However," the researchers concluded, "our retrospective survey provides meaningful information on clinical and virological features associated with PHI in African children infected by breastfeeding. This emphasizes the urgent need to implement alternatives to predominant breastfeeding in order to prevent the high risk of HIV-1 PT observed in African cohorts."

Furthermore, the authors suggested the findings could also be useful to identify early cases of PT and encourage adequate HIV screening in corresponding mothers and families. They pointed out that combination antiretroviral therapy during PHI reduces progression to AIDS, and "given the current content of increasing access of antiretroviral drugs in Africa, our study may also be useful to propose effective antiretroviral treatment to control the early viral replication observed in this frequent form of pediatric HIV infection."

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