HIV-1 infection in Zambian children impairs the development and avidity maturation of measles virus-specific immunoglobulin G after vaccination and infection.

BACKGROUND: Endemic transmission of measles continues in many countries that have a high human immunodeficiency virus (HIV) burden. The effects that HIV infection has on immune responses to measles and to measles vaccine can impact measles elimination efforts. Assays to measure antibody include the enzyme immunoassay (EIA), which measures immunoglobulin G (IgG) to all measles virus (MV) proteins, and the plaque reduction neutralization (PRN) assay, which measures antibody to the hemagglutinin and correlates with protection. Antibody avidity may affect neutralizing capacity. METHODS: HIV-infected and HIV-uninfected Zambian children were studied after measles vaccination (n=44) or MV infection (n=57). Laboratory or wild-type MV strains were used to infect Vero or Vero/signaling lymphocyte-activation molecule (SLAM) cells in PRN assays. IgG to MV was measured by EIA, and avidity was determined by ammonium thiocyanate dissociation. RESULTS: HIV infection impaired EIA IgG responses after vaccination and measles but not PRN responses measured using laboratory-adapted MV. Avidity was lower among HIV-infected children 3 months after vaccination and 1 and 3 months after measles. Neutralization of wild-type MV infection of Vero/SLAM cells correlated with IgG avidity. CONCLUSION: Lower antibody quality and quantity in HIV-infected children after measles vaccination raise challenges for assuring the long-term protection of these children. Antibody quality in children receiving antiretroviral therapy requires assessment.

Survival from 9 months of age among HIV-infected and uninfected Zambian children prior to the availability of antiretroviral therapy.

BACKGROUND: Few prospective studies have measured survival rates among human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa prior to the availability of antiretroviral therapy. METHODS: In the context of an observational study of the immunogenicity of measles vaccine in Zambia, we prospectively followed up children from approximately 9 months of age and assessed survival rates, risk factors for mortality, and circumstances at the time of death according to HIV-infection or HIV-exposure status. RESULTS: There were 56 deaths among 492 study children during follow-up to 3 years of age. Thirty-nine percent of the 105 children with HIV infection died during the study period, compared with 5.0% of the 260 HIV-seropositive but uninfected children and 1.6% of the 127 HIV-seronegative children. Estimated survival probabilities from 9 through 36 months of age were 52% among HIV-infected children, 95% among initially HIV-seropositive but uninfected children, and 98% among HIV-seronegative children. In multivariable analyses, history of a clinic visit within the 4 weeks prior to study entry (adjusted hazard ratio, 4.6; 95% confidence interval, 1.5-13.5), hemoglobin level <8 g/dL at study entry (adjusted hazard ratio, 4.4; 95% confidence interval, 1.5-12.6), and CD4(+) T lymphocyte percentage <15% at study entry (adjusted hazard ratio, 3.2; 95% confidence interval, 1.1-9.5) were associated with mortality among HIV-infected children. CONCLUSIONS: Only approximately one-half of HIV-infected Zambian children who were alive at 9 months of age survived to 3 years of age, supporting the urgent need for the prevention of mother-to-child transmission of HIV and the early diagnosis and treatment of HIV infection in children in sub-Saharan Africa.

The influence of HIV-1 exposure and infection on levels of passively acquired antibodies to measles virus in Zambian infants.

BACKGROUND: The age at which passively acquired antibodies are lost is critical to determining the optimal age for measles vaccination. Little is known about the influence of human immunodeficiency virus type 1 (HIV-1) infection on levels of prevaccination antibodies to measles virus. METHODS: Antibodies to measles virus were measured by plaque reduction neutralization assay in HIV-1-infected, HIV-seropositive but uninfected, and HIV-seronegative Zambian infants aged 6 weeks to 9 months. Regression models were used to estimate age-specific antibody concentrations. RESULTS: Neutralizing antibodies to measles virus were measured in 652 plasma samples collected from 448 infants, of whom 61 (13.6%) were HIV-1 infected, 239 (53.4%) were HIV seropositive but uninfected, and 148 (33%) were HIV seronegative. The best fitting model suggests that HIV-1-infected infants have lower levels of passively acquired antibodies to measles virus at birth than do HIV-seronegative infants, but their antibody levels decrease more slowly. By 6 months of age, 91% (95% confidence interval, 83%-99%) of HIV-1-infected infants, 83% (95% confidence interval, 77%-89%) of HIV-seropositive but uninfected infants, and 58% (95% confidence interval, 51%-64%) of HIV-seronegative infants were estimated to have antibody levels that were unlikely to affect immune responses to measles vaccine (cutoff value for immune response, <50 mIU/mL). By 9 months of age, 99% of all infants had antibody levels <50 mIU/mL. CONCLUSIONS: Infants born to HIV-1-infected women are less likely to have passively acquired antibodies that would neutralize measles vaccine virus and, thus, have an increased risk of measles prior to the age of routine vaccination. Protection could be achieved by administration of the first dose of measles vaccine prior to 9 months of age.

Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: an observational study.

BACKGROUND: Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination. METHODS: We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka, Zambia. RESULTS: From May 2000 to November 2002, 696 children aged 2-8 months were enrolled. Within 6 months of vaccination, 88% of 50 HIV-1-infected children developed antibody levels of >or=120 mIU/mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P=.3). By 27 months after vaccination, however, only half of the 18 HIV-1-infected children who survived and returned for follow-up maintained measles antibody levels >or=120 mIU/mL, compared with 89% of 71 uninfected children (P=.001) and in contrast with 92% of 12 HIV-1-infected children revaccinated during a supplemental measles immunization activity. CONCLUSIONS: Although HIV-1-infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence.