During the pre-antiretroviral therapy era, the mortality rate in HIV-infected Zambian children was 7- and 25-fold higher than in HIV-uninfected Zambian children, respectively, according to the results of a prospective study published in the September 15th edition of Clinical Infectious Diseases.
About one-third of HIV-infected children in sub-Saharan Africa are not on antiretroviral therapy and show high mortality rates. Poor access to health care, poor nutrition, and exposure to other infections are important factors that have been associated with high mortality rates in these children.
Reports from a small number of studies show that approximately one-half of HIV-infected children do not reach their second birthdays. However, there is a paucity of longitudinal studies on the survival and risk factors of mortality of HIV-infected children in sub-Saharan Africa before the antiretroviral therapy era.
In order to address this issue, a team of US, British, and Zambian investigators assessed survival rates from the age of nine months, risk factors for death, and circumstances at the time of death according to HIV-infection or HIV-exposure status in Zambian children before antiretroviral treatment was available.
The study site was a public clinic in Luzaka, Zambia. The study population were children two to eight months old who were HIV-1 seropositive children and a sample of HIV-1 seronegative children; both groups attended the clinic for childhood immunisation.
The study was part of a bigger observational study of a measles vaccine for which children were recruited for vaccination at nine months of age. At study entry, they underwent a medical examination and completed a standard questionnaire for demographic characteristics and medical history.
Children were randomised for follow-up at one or three months after vaccination. Mothers were asked to return all children at 15 and 27 months after vaccination and to seek medical care from the study team whenever the child was ill. Home visits were performed every three months until three years of age. Verbal autopsies were performed to assign specific causes for deaths.
HIV testing was carried out using an immunoassay; HIV infection in HIV-seropositive children was established by detection of HIV RNA by RT-PCR. At each scheduled visit, haemoglobin levels and CD4 T lymphocyte percentage were measured.
Of the eligible 492 children vaccinated against measles at nine months of age, 127 (26%) were HIV seronegative, 292 (59%) were HIV seropositive but uninfected, and 73 (15%) were HIV infected at study entry. Thirty-two (11%) of the children who were HIV seropositive but uninfected at study entry became HIV infected during follow-up. Thus, 105 children (21% of all study children) were HIV infected for part of the follow-up period.
Maternal mortality prior to study entry was low in all three groups of children. By contrast, paternal mortality was higher among HIV-seropositive but uninfected and HIV-infected children.
Among the 492 study children, there were 56 deaths during follow-up to three years of age. Thirty-nine percent of the 105 children with HIV infection died during the study period, compared with 5% of the 260 HIV-seropositive but uninfected children and 1.6% of the 127 HIV-seronegative children.
The estimated survival probabilities, from nine to 36 months of age, were 52% among HIV-infected children, 95% among initially HIV-1 seropositive but uninfected children, and 98% among HIV-seronegative children.
The most common illnesses which contributed to deaths were diarrhoea (in 61% of deaths), acute respiratory tract infection (in 49%), and malnutrition (in 39%). Tuberculosis, malaria and meningitis contributed to mortality but to a lesser magnitude.
Two statistical models identified the risk factors that were significantly associated with mortality among the HIV-infected children. These included a history of a clinic visit within four weeks prior to study entry, haemoglobin level
This longitudinal study confirmed the high mortality rates reported by previous studies in HIV-infected children in resource-poor settings. Only approximately one-half of HIV-infected Zambian children who were alive at nine months of age survived to their third birthdays.
Sutcliffe CG et al. Survival from 9 months of age among HIV-infected and uninfected Zambian children prior to the availability of antiretroviral therapy. Clinical Infectious Diseases 47:837–844, 2008.