Survival by infant HIV exposure/infection status according to feeding practices in the first 6 months.

<div><p>a. All infants. 2b. Infants infected perinatally or timing unknown. 2c. Infants infected postnatally.</p> <p>2d. HIV-exposed uninfected infants. 2e. HIV unexposed infants.</p></div

Exclusive Breastfeeding, Diarrhoeal Morbidity and All-Cause Mortality in Infants of HIV-Infected and HIV Uninfected Mothers: An Intervention Cohort Study in KwaZulu Natal, South Africa

<div><p>Introduction</p><p>Antiretroviral drug interventions significantly reduce the risk of HIV transmission to infants through breastfeeding. We report diarrhoea prevalence and all-cause mortality at 12 months of age according to infant feeding practices, among infants born to HIV-infected and uninfected mothers in South Africa.</p> <p>Methods</p><p>A non-randomised intervention cohort study that followed both HIV-infected and HIV-uninfected mothers and their infants until 18 months of age. Mothers were supported in their infant feeding choice. Detailed morbidity and vital status data were collected over the first year. At the time, only single dose nevirapine was available to prevent mother-to-child transmission of HIV. </p> <p>Results</p><p>Among 2,589 infants, detailed feeding data and vital status were available for 1,082 HIV-exposed infants and 1,155 HIV non-exposed infants. Among exclusively breastfed (EBF) infants there were 9.4 diarrhoeal days per 1,000 child days (95%CI. 9.12-9.82) while among infants who were never breastfed there were 15.6 diarrhoeal days per 1,000 child days (95%CI. 14.62-16.59). Exclusive breastfeeding was associated with fewer acute, persistent and total diarrhoeal events than mixed or no breastfeeding in both HIV-exposed infants and also infants of HIV uninfected mothers. In an adjusted cox regression analysis, the risk of death among all infants by 12 months of age was significantly greater in those who were never breastfed (aHR 3.5, p<0.001) or mixed fed (aHR 2.65, p<0.001) compared with those who were EBF. In separate multivariable analyses, infants who were EBF for shorter durations had an increased risk of death compared to those EBF for 5-6 months [aHR 2.18 (95% CI, 1.56-3.01); p<0.001].</p> <p>Discussion</p><p>In the context of antiretroviral drugs being scaled-up to eliminate new HIV infections among children, there is strong justification for financial and human resource investment to promote and support exclusive breastfeeding to improve HIV-free survival of HIV-exposed and non-exposed infants.</p> </div

Most frequently recognized clade C CD4+ T cell epitopes.

<p>Most frequently recognized clade C CD4+ T cell epitopes.</p

Cross clade recognition of the p24 Gag peptide YVDRFFKTLRAEQATQDV.

<p>In a subset of 28 subjects, we found that the C and B clade versions of peptide YVDRFFKTLRAEQATQDV induced the same magnitude of IFN-γ response in 7 patients, as detected by the ELISPOT assay.</p

The total HIV-1–specific CD4+ T cell response is dominated by Gag.

<p>Using IFN-γ ELISPOT assay to identify HIV-1 specific CD4+ T cell epitopes in 32 subjects, we found that irrespective of the viral load, the Gag protein is the most commonly targeted and therefore makes the greatest contribution to the overall CD4+ T cell response. Subjects 1–16 had viral loads below the median, while subjects 18–32 had viremia greater than the median (36 550 copies/ml plasma). Acc (accessory) denotes the Vpr, Vpu and Vif proteins pooled together. Subjects 24 and 25 both targeted a single Vpr protein.</p

Estimated 18-month unadjusted mortality for HIV-infected children since acquisition of HIV infection (n = 2,509).

<p>Estimated 18-month unadjusted mortality for HIV-infected children since acquisition of HIV infection (n = 2,509).</p

The majority of the HIV-1 C clade CD4+ epitopes cluster in the Gag region.

<p>ELISPOT screening was conducted on 32 randomly selected subjects. (A) 33 CD4+ restricted epitopes were identified, with 27 epitopes located in the Gag region, 3 in the Polymerase region, 1 in the Vpr region and 2 in the Nef region. There were no CD4+ epitopes present in the Vif, Vpu, Rev, Tat, or Envelope proteins. (B) The peptides identified by the ELISPOT assay utilizing CD8+ depleted PBMCs were confirmed by flow cytometry using whole PBMCs to be CD4+ restricted. The dot plot above represents data from the negative control on the left and a CD4+ IFN-γ response to the p24 Gag peptide YVDRFFKTLRAEQATADV.</p

Characteristics of the mother-infant pairs included in the pooled analysis (first generation studies, before year 2000).

<p>Characteristics of the mother-infant pairs included in the pooled analysis (first generation studies, before year 2000).</p

Characteristics of the mother-infant pairs included in the pooled analysis (second generation studies, after year 2000).

<p>Characteristics of the mother-infant pairs included in the pooled analysis (second generation studies, after year 2000).</p