HIV-uninfected Children Research Articles

Features associated with underlying HIV infection in severe acute childhood malnutrition: a cross sectional study

Up to half of all children presenting to Nutrition Rehabilitation Units (NRUs) in Malawi with severe acute malnutrition (SAM) are infected with HIV. There are many similarities in the clinical presentation of SAM and HIV. It is important to identify HIV infected children, in order to improve case management. This study aims to identify features suggestive of HIV in children with SAM. All 1024 children admitted to the Blantyre NRU between July 2006 and March 2007 had demographic, anthropometric and clinical characteristics documented on admission. HIV status was known for 904 children, with 445 (43%) seropositive and 459 (45%) seronegative. Features associated with HIV were determined. Associations were found for the following signs: chronic ear discharge (OR 14.6, 95%CI 5.8-36.7), lymphadenopathy (6.4, 3.5-11.7), clubbing (4.9, 2.6-9.4), marasmus (4.9, 3.5-6.8), hepato-splenomegally (3.2, 1.8-5.6), and oral candida (2.4, 1.8-3.27). Any one of these signs was present in 74% of the HIV seropositive, and 38% of HIV uninfected children. A history of recurrent respiratory infection (OR 9.6, 4.8-18.6), persistent fever, recent outpatient attendance, or hospital admission were also associated with HIV. Persistent diarrhoea was no more frequent in HIV (OR 1.1). Orphaning (OR 2.1, 1.4-3.3) or a household contact with TB (OR 1.7, 1.1-2.6), were more common in HIV. Each of these features were present in >10% of seropositive children. HIV infected children were more stunted, wasted, and anaemic than uninfected children. Features commonly associated with HIV were often present in uninfected children with SAM, and HIV could neither be diagnosed, nor excluded using these. We recommend HIV testing be offered to all children with SAM where HIV is prevalent.

The safety of highly active antiretroviral therapy for the HIV-positive pregnant mother and her baby: is 'the more the merrier'?

Highly active antiretroviral therapy (HAART) is frequently indicated for pregnant women both for maternal health and for prevention of mother-to-child HIV transmission, which can be reduced to <1%. Prospective data and large cohort studies have not found any evidence that antiretroviral therapy significantly increases the risk of congenital malformation. Nucleoside analogue reverse transcriptase inhibitors (NRTIs) are, to varying degrees, toxic to mitochondria, and molecular and clinical evidence of mitochondrial toxicity has been reported, albeit rarely, in NRTI-exposed but HIV-uninfected children. However, with NRTI-based fully suppressive antiretroviral therapy this effect was not seen. Although conflicting observational data have been reported, an increased risk of pre-term delivery with HAART compared with zidovudine monotherapy remains a concern.

Limited duration of vaccine poliovirus and other enterovirus excretion among human immunodeficiency virus infected children in Kenya

BackgroundImmunodeficient persons with persistent vaccine-related poliovirus infection may serve as a potential reservoir for reintroduction of polioviruses after wild poliovirus eradication, posing a risk of their further circulation in inadequately immunized populations.MethodsTo estimate the potential for vaccine-related poliovirus persistence among HIV-infected persons, we studied poliovirus excretion following vaccination among children at an orphanage in Kenya. For 12 months after national immunization days, we collected serial stool specimens from orphanage residents aged <5 years at enrollment and recorded their HIV status and demographic, clinical, immunological, and immunization data. To detect and characterize isolated polioviruses and non-polio enteroviruses (NPEV), we used viral culture, typing and intratypic differentiation of isolates by PCR, ELISA, and nucleic acid sequencing. Long-term persistence was defined as shedding for ≥ 6 months.ResultsTwenty-four children (15 HIV-infected, 9 HIV-uninfected) were enrolled, and 255 specimens (170 from HIV-infected, 85 from HIV-uninfected) were collected. All HIV-infected children had mildly or moderately symptomatic HIV-disease and moderate-to-severe immunosuppression. Fifteen participants shed vaccine-related polioviruses, and 22 shed NPEV at some point during the study period. Of 46 poliovirus-positive specimens, 31 were from HIV-infected, and 15 from HIV-uninfected children. No participant shed polioviruses for ≥ 6 months. Genomic sequencing of poliovirus isolates did not reveal any genetic evidence of long-term shedding. There was no long-term shedding of NPEV.ConclusionThe results indicate that mildly to moderately symptomatic HIV-infected children retain the ability to clear enteroviruses, including vaccine-related poliovirus. Larger studies are needed to confirm and generalize these findings.

The Diagnostic and Prognostic Accuracy of Five Markers of Serious Bacterial Infection in Malawian Children with Signs of Severe Infection

BackgroundEarly recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children.Methodology and Principal FindingsChildren presenting with a signs of meningitis (n = 282) or pneumonia (n = 95), were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74%) had SBI and 83 (22%) died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01). In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively). In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and CD163 was higher in non-survivors (p = 0.05). The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs) were 0.81 (95% CI 0.73–0.89) and 0.86 (95% CI 0.79–0.92) respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50–0.71).ConclusionsAdmission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting.

Predictors and consequences of anaemia among antiretroviral-naïve HIV-infected and HIV-uninfected children in Tanzania

Predictors and consequences of childhood anaemia in settings with high HIV prevalence are not well known. The aims of the present study were to identify maternal and child predictors of anaemia among children born to HIV-infected women and to study the association between childhood anaemia and mortality. Prospective cohort study. Maternal characteristics during pregnancy and Hb measurements at 3-month intervals from birth were available for children. Information was also collected on malaria and HIV infection in the children, who were followed up for survival status until 24 months after birth. Dar es Salaam, Tanzania. The study sample consisted of 829 children born to HIV-positive women. Advanced maternal clinical HIV disease (relative risk (RR) for stage > or =2 v. stage 1: 1.31, 95 % CI 1.14, 1.51) and low CD4 cell counts during pregnancy (RR for <350 cells/mm3 v. > or =350 cells/mm3: 1.58, 95 % CI 1.05, 2.37) were associated with increased risk of anaemia among children. Birth weight <2500 g, preterm birth (<34 weeks), malaria parasitaemia and HIV infection in the children also increased the risk of anaemia. Fe-deficiency anaemia in children was an independent predictor of mortality in the first two years of life (hazard ratio 1.99, 95 % CI 1.06, 3.72). Comprehensive care including highly active antiretroviral therapy to eligible HIV-infected women during pregnancy could reduce the burden of anaemia in children. Programmes for the prevention of mother-to-child transmission of HIV and antimalarial treatment to children could improve child survival in settings with high HIV prevalence.

Detection of tuberculosis in HIV-infected children using an enzyme-linked immunospot assay

To evaluate an enzyme-linked immunospot assay (ELISPOT) for the diagnosis of tuberculosis (TB) in HIV-infected children with suspected TB and to compare the performance of ELISPOT with the tuberculin skin test (TST). Interferon-gamma responses to Mycobacterium tuberculosis-specific antigens were measured by ELISPOT in HIV-infected children with suspected TB. HIV-infected and HIV-uninfected children without TB were taken for comparison. Results were available for 188 children, of whom 139 (74%) were HIV-infected. Of these, 22 were classified as having definite TB: 24 probable TB, 14 possible TB and 128 not having TB. The median (range) age of patients was 20 (10-54.1) months. Median interferon-gamma responses to early-secreted antigenic target-6 and culture filtrate protein-10 were higher in children with definite or probable TB compared with children without TB (P < 0.002). In HIV-infected children with an interpretable ELISPOT result, the ELISPOT was positive in 14/21 (66%) with definite TB. A significantly higher proportion of HIV-infected children with definite or probable TB had a positive ELISPOT compared with a positive TST [25/39 (64%) vs. 10/34 (29%), P = 0.005]. In contrast to TST, results from ELISPOT were not affected by young age or severe immunosuppression. In HIV-infected children without active TB disease, 27% had a positive ELISPOT, suggesting latent TB infection. ELISPOT is more sensitive than TST for the detection of active TB in HIV-infected children. However, the sensitivity of current ELISPOT assays is not sufficiently high to be used as a rule out test for TB.

Management of community-acquired pneumonia in HIV-infected children

Pneumonia is a major cause of childhood mortality and morbidity worldwide, particularly in low-income countries. Often, these are also the countries most affected by the HIV epidemic. Pneumonia is the leading cause of death in HIV-infected children and a major cause of hospitalization and healthcare utilization. A broader spectrum of organisms, such as Pneumocystis jiroveci and Gram-negative bacteria, cause pneumonia in HIV-infected children compared with uninfected children. Etiologic organisms have higher rates of antimicrobial resistance in HIV-infected children. Polymicrobial disease is more common in HIV-infected children and associated with an exponential increase in mortality rate. HIV-infected children develop more severe pneumonia and have a worse outcome than HIV-uninfected children. HIV-exposed but HIV-negative children are also at higher risk of severe pneumonia and death compared with HIV-unexposed children. Although case-management guidelines for childhood pneumonia have led to an overall decrease in global childhood morbidity and mortality, HIV-infected children continue to have unacceptably high treatment failure and case fatality rates despite adherence to these guidelines. Standard guidelines require adaptation for use in high HIV-prevalence areas. Specific preventive interventions, including chemoprophylaxis for P. jiroveci pneumonia or for TB and early initiation of highly active antiretroviral therapy, may significantly reduce the burden of pneumonia in HIV-infected children.

Prevention of Invasive Pneumococcal Disease in HIV‐Infected Children: Expanding the Toolbox

Invasive pneumococcal disease (IPD) remains a threat to HIV-infected children adolescents and adults in both developed and emerging nations. In the pre-highly active antiretroviral therapy (HAART) era Mao et al. identified a cumulative incidence of 6.1 cases per 100 patient-years through age 7 years among HIV-infected children in Massachusetts a rate 100-300-fold that seen in HIV-uninfected immunocompetent children in the United States. Similarly Westwood et al. reported an IPD rate of 13 cases per 100 patient-years in Capetown South Africa a large proportion of which were lower respiratory tract infections. With widespread use of HAART in the United States the rate of pneumococcal bacteremia declined by 80% to 1.9 cases per 100 patient-years; this residual rate still remained at least 10-fold greater than that among HIV-uninfected children and children who suffered an episode of pneumococcal bacteremia were more likely to die during follow-up than were HIV-infected children without an episode. These data identify the need to protect HIV-infected children from infection with Streptococcus pneumoniae even in populations treated with HAART. (excerpt)

Quantitative and Qualitative Anamnestic Immune Responses to Pneumococcal Conjugate Vaccine in HIV‐Infected and HIV‐Uninfected Children 5 Years after Vaccination

Administration of pneumococcal conjugate vaccine (PCV) to HIV-infected children during infancy confers limited long-term protection in the absence of antiretroviral therapy. The objective of the present study was to determine the immune responses to PCV at 5 years of age in HIV-infected and HIV-uninfected children who had been primed with vaccine during infancy (i.e., previous vaccinees) and in those receiving their first dose of vaccine (i.e., control subjects). Serotype-specific antibodies were quantified by enzyme immunoassay, and antibody functionality to serotypes 6B, 9V, and 19F were evaluated using an opsonophagocytic killing assay 1 month after vaccination. Of the HIV-infected children, 19.7% were receiving antiretroviral therapy, and 40.5% had a CD4(+) cell percentage <15%. Geometric mean concentrations of antibody and the proportion with a concentration 0.35 microg/mL after vaccination were greater among HIV-uninfected children than among HIV-infected children for both previous vaccinees and control subjects. Antibody concentrations after vaccination were lower for 3 of 7 serotypes among HIV-infected previous vaccinees than among control subjects. Detectable opsonophagocytic activity to all studied serotypes was lower among HIV-infected than among HIV-uninfected previous vaccinees and control subjects. Postvaccination antibody-mediated killing activity as determined by the opsonophagocytic killing assay was enhanced in control subjects compared with previous vaccinees among HIV-uninfected children. HIV-infected vaccinees experience a partial loss of anamnestic responses to PCV. The optimal timing and frequency of booster vaccination as well as the responses to them among HIV-infected children need to be determined.

Dynamics of T cell activation accompanying CD4 recovery in antiretroviral treated HIV-infected Ugandan children

Africans have elevated T cell activation compared to residents of Europe or the USA. Levels of T cell activation also correlate with disease progression in HIV-infected individuals. We sought to determine if treatment with antiretroviral therapy (ART) would reduce levels of T cell activation (CD38 and HLADR co-expression) in HIV-infected Ugandan children. The median CD8+ T cell activation level among 199 ART-treated children (30%) was lower than in 57 ART-naïve children (45%, p<0.001), but remained higher than in 30 HIV-uninfected children (18%, p<0.001). Among ART-treated children, CD4% was inversely correlated with both CD8- (rho=-0.61, p<0.001) and CD8+ (rho=-0.38, p<0.001) T cell activation. Prospectively, CD4 recovery correlated with post-treatment CD8+ T cell activation level (p=0.008). Our data suggest that significant decreases in T cell activation accompany CD4 recovery in ART-treated HIV-infected African children, to levels that approach but do not reach those of uninfected children.

Long-Term Effects of Short-Term Perinatal Exposure to Antiretroviral Drugs

Evaluation of: Benhammou V, Warszawski J, Bellec S et al.: Incidence of cancer in children perinatally exposed to nucleoside reverse transcriptase inhibitors. AIDS 22, 2165–2177 (2008). The prevention of mother-to-child transmission of HIV hinges on administration of perinatal antiretroviral drugs, reducing transmission rates from 40 to less than 2%. The safety of short-term exposure to antiretroviral drugs in HIV-uninfected children is paramount to justify widespread implementation. Besides mitochondrial toxicity, lower birth weight and mild hematotoxicity, no major long-term adverse effects, such as teratogenicity, have been documented. Nucleoside inhibitors can potentially be embedded in the genetic material of fetuses. This genotoxicity may predispose HIV-uninfected children to cancers later in life. However, except for didanosine, no increase was measured in childhood cancer up to 5 years after exposure in a large French prospective cohort study, lending further support to the relative safety of short-term use of pre- and perinatal antiretroviral drugs. Nevertheless, the increased likelihood of rare cancers in the CNS after didanosine exposure warrants longer-term follow-up studies.

BCG vaccination in South African HIV-exposed infants--risks and benefits.

Until 2007, the World Health Organization (WHO) recommended that bacille Calmette-Guerin (BCG) vaccination should be contraindicated in infants with symptomatic HIV disease in countries with a high burden of tuberculosis. This recommendation was based on the perceived low risk of serious adverse events in HIV-infected infants. The WHO revised its recommendations regarding BCG vaccination in HIV-infected infants in 2007, making HIV infection a full contraindication to BCG vaccination.1 BCG induces protective efficacy against tuberculous meningitis of 73% (67 – 79%) and against miliary disease of 77% (58 – 87%) in HIV-uninfected children.2 The efficacy against childhood pulmonary disease is variable;3 there is no evidence that BCG induces a protective effect against tuberculosis in HIV-infected infants and children.4 BCG is a safe vaccine in immunocompetent infants, and severe vaccine adverse events in HIV-uninfected infants occur only with rare primary immune deficiencies in approximately 1 per million vaccinees.5

CD4 Counts Decline Despite Nutritional Recovery in HIV-Infected Zambian Children With Severe Malnutrition

The objective of this study was to establish the contribution that severe malnutrition makes to CD4 lymphopenia in HIV-infected and uninfected children and to determine the changes in CD4 count during nutritional rehabilitation. Fifty-six children with severe malnutrition and with and without HIV infection were recruited from a pediatric ward in Lusaka for measurement of CD4 counts on admission, on discharge, and at final nutritional recovery. HIV-uninfected children with severe malnutrition had normal CD4 counts. In contrast, CD4 counts in HIV-infected children with severe malnutrition were reduced, more so in those without edema compared with those with edema. Mean CD4 count of HIV-infected SM children fell despite nutritional recovery so that at the time of full nutritional recovery, >85% of HIV-infected children required antiretroviral therapy. Severe malnutrition did not reduce the CD4 counts of children without HIV. HIV-infected children with severe malnutrition may respond well to nutritional rehabilitation, despite low CD4 counts, but nearly all require early antiretroviral therapy to prevent disease progression.

Intensified Case Finding for Tuberculosis in Prevention of Mother-to-Child Transmission Programs: A Simple and Potentially Vital Addition for Maternal and Child Health

The intersection of HIV and tuberculosis (TB) poses a serious threat to HIV-infected women and their children. The majority of patients with TB in sub-Saharan Africa are infected with HIV and together the overlapping epidemics synergistically accelerate illness and death. Escalating case rates increased mortality and the recent emergence of extensively drug-resistant TB highlights how catastrophic a once preventable and curable disease has become among people with HIV/AIDS. The HIV epidemic requires new strategies to control TB in high-burden areas especially as women of reproductive age are disproportionately affected by the epidemic. Intensified case finding for TB has the potential to reduce morbidity and mortality for people living with HIV especially pregnant women their families and infants. (excerpt)

Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa

BackgroundThe efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of HIV-exposed children. Potential modifying factors such as stunting need addressing.ObjectiveTo determine whether adding zinc, or zinc plus multiple micronutrients, to vitamin A reduces diarrhoea incidence, and whether this differs between strata of stunted or HIV-infected children.MethodsWe analyzed data from a randomized, controlled double-blinded trial (ClinicalTrials.gov NCT00156832) of prophylactic micronutrient supplementation to children aged 6–24 months. Three cohorts of children: 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers, received vitamin A, vitamin A plus zinc, or multiple micronutrients that included vitamin A and zinc. The main outcome was incidence of diarrhoea. Poisson regression was used in intent-to-treat analyses. Stratified analyses followed testing for statistical interaction between intervention and stunting.ResultsWe observed no significant differences in overall diarrhoea incidence among treatment arms. Stunting modified this effect with stunted HIV-uninfected children having significantly lower diarrhoea incidence if supplemented with zinc or multiple micronutrients compared to vitamin A alone (2.04 and 2.23 vs 3.92 episodes/year respectively, P=0.024). No meaningful sub-group analyses could be done in the cohort of HIV-infected children.ConclusionCompared with vitamin A alone, supplementation with zinc, and with zinc and multiple micronutrients, reduced diarrhoea morbidity in stunted rural South African children. Efficacy of zinc supplementation in HIV-infected children needs confirmation in studies that represent the spectrum of disease severity and age groups.

Patterns and Predictors of CD4 T-cell Counts Among Children Born to HIV-infected Women in Tanzania

We assessed age-specific CD4 T-cell counts and their determinants among Tanzanian children born to HIV-infected mothers to address a major research gap. A total of 474 HIV-uninfected and 69 HIV-infected children were followed until age of 12 months. Maternal predictors were measured during pregnancy and child predictors at birth and throughout the follow up. Child CD4 T-cell counts were evaluated at the age of 3 months and subsequent 3-month intervals; they decreased linearly among HIV-infected (beta = -8 cells per week; 95% CI -12 to -4; P = 0.0003) and increased linearly among HIV-uninfected children (beta = 4 cells/week; 95% CI 2-7; P = 0.0008). Decreased child counts were predicted by low child anthropometry, maternal HIV stage > or =2, and maternal mid-upper arm circumference <27 cm among HIV-infected children; and by weight-for-height <-2 z-score, maternal HIV stage > or =2, maternal erythrocyte sedimentation rate <81 mm/h and maternal haemoglobin <8.5 g/dl among HIV-uninfected children. The maternal and child predictors described may serve as intervention targets among HIV-exposed children.

Immunologic Analysis of HIV-Uninfected Taiwanese Children with BCG-Induced Disease

The aim of this study was to evaluate immunity in HIV-uninfected children with bacille Calmette-Guerin-induced disease (BCG-ID) over an 8-year period, with particular emphasis on underlying diseases. Patient afflicted with BCG-ID proven by clinical courses, dermatologic features, pathology, specific polymerase chain reaction, and/or spoligotyping were enrolled between 2000 and 2007. Lymphocyte proliferation, polymorphonuclear function, interleukin (IL)-12/23-interferons (IFN)-gamma circuit, and Toll-like receptor 2-associated signaling were investigated. Of the 271,618 total live births who received the BCG vaccine, eight patients (seven males) with BCG-ID were enrolled during an 8-year period and presented as three disseminated, two distant, and three regional BCG-ID. Their age at onset ranged from 1 to 28 months. All had a vaccine-injection scar except for one with lower CD3 and natural killer cells, compatible with severe combined immunodeficiency (SCID) identified by IL-2 receptor common gamma chain (IL2RG) mutation (Arg226Lys). The other SCID patient with de novo IL2RG mutation (Trp74Gly) had more recurrent infections. The third patient with primary autoimmune neutropenia had disseminated BCG-ID extending to abdominal wall. The fourth patient with chronic mucocutaneous candidiasis had regional BCG-ID and impaired lymphocyte proliferation to Candida and BCG antigens. No defective evidence of polymorphonuclear functions, IL-12/23-IFN-gamma circuit, and Toll-like receptor 2-associated signaling was detected in the remaining four patients. Immunologic analysis in HIV-uninfected patients with BCG-ID reveals primary immunodeficiency diseases, especially in those with deficiencies in T-cell and neutrophil functions observed in our cohort, including primary autoimmune neutropenia and chronic mucocutaneous candidiasis.

Role of breastfeeding cessation in mediating the relationship between maternal HIV disease stage and increased child mortality among HIV-exposed uninfected children

Maternal CD4 count predicts child mortality in HIV-uninfected children born to HIV-infected women. To explore the mediating role of breastfeeding cessation in this relationship, we compared marginal structural models of maternal CD4 count on child death with and without adjustment for breastfeeding. In crude analyses, children of mothers with CD4<200 during pregnancy were 3.2 times more likely to die by 18 months (CI 1.3-8.1) as children whose mothers had CD4>500. Earlier breastfeeding cessation was also associated with low CD4 (HR 1.8; CI 1.2-2.7). After adjusting for breastfeeding and low birth weight using a marginal structural model, the low CD4 count-child mortality association through 18 months was reduced 17%. The change was overestimated using a traditional Cox proportional hazards model (35% reduction in HR from 3.4 to 2.5). Our analysis suggests that only a small part of the effect of low vs high CD4 count on child mortality through 18 months is mediated through breastfeeding cessation. Our results must be taken into account when deciding whether or not to recommend breastfeeding for infants of HIV-infected mothers.

Evaluation of the Immune Response to a 2‐Dose Measles Vaccination Schedule Administered at 6 and 9 Months of Age to HIV‐Infected and HIV‐Uninfected Children in Malawi

The World Health Organization recommends that infants at high risk for developing measles before 9 months of age, including human immunodeficiency virus (HIV)-infected infants, receive measles vaccination (MV) at 6 and 9 months of age. Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to receive MV at 6 and 9 months, MV at 9 months, or routine MV without follow-up. Blood samples were obtained before and 3 months after each MV. Data were collected on adverse events for 21 days after each MV, at all clinic visits, on any hospitalization, and for subjects who died. HIV-infection status was determined by antibody assays and polymerase chain reaction; the presence of measles IgG was determined by EIA. Twenty-two hundred mother-infant pairs were enrolled. After the first and second doses of measles vaccine, respectively, the percentages of children who were measles seropositive were 59% (36 of 61) and 64% (29 of 45) among HIV-infected children, 68% (152 of 223) and 94% (189 of 202) among HIV-exposed but uninfected children, and 62% (288 of 467) and 92% (385 of 417) among HIV-unexposed children. Of 521 HIV-unexposed children vaccinated only at 9 months, 398 (76%) were measles seropositive at 12 months. No serious vaccine-related adverse events were identified. An early, 2-dose MV schedule was immunogenic, but a higher proportion of HIV-infected children remained susceptible to measles, compared with HIV-uninfected children (whether HIV exposed or HIV unexposed).

Infant feeding, HIV transmission and mortality at 18 months: the need for appropriate choices by mothers and prioritization within programmes.

To determine the late HIV transmission and survival risks associated with early infant feeding practices. A nonrandomized intervention cohort. HIV-infected pregnant women were supported in their infant feeding choices. Infant feeding data were obtained weekly; blood samples from infants were taken monthly to diagnose HIV infection. Eighteen-month mortality and HIV transmission risk were assessed according to infant feeding practices at 6 months. One thousand one hundred and ninety-three live-born infants were included. Overall 18-month probabilities of death (95% confidence interval) were 0.04 (0.03-0.06) and 0.53 (0.46-0.60) for HIV-uninfected and HIV-infected children, respectively. The eighteen-month probability of survival was not statistically significantly different for HIV-uninfected infants breastfed or replacement fed from birth. In univariate analysis of infant feeding practices, the probability of HIV-free survival beyond the first 6 months of life in children alive at 6 months was 0.98 (0.89-1.00) amongst infants replacement fed from birth, 0.96 (0.90-0.98; P = 0.25) and 0.91 (0.87-0.94; P = 0.03) in those breastfed for less or more than 6 months, respectively. In multivariable analyses, maternal unemployment and low antenatal CD4 cell count were independently associated with more than three-fold increased risk of infant HIV infection or death. Breastfeeding and replacement feeding of HIV-uninfected infants were associated with similar mortality rates at 18 months. However, these findings were amongst mothers and infants who received excellent support to first make, and then practice, appropriate infant feeding choices. For programmes to achieve similar results, the quality of counselling and identification of mothers with low CD4 cell count need to be the targets of improvement strategies.