Background We evaluated the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) and mortality in Kenyan HIV-1 infected women and their infants. Methods Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1 infected women. Hazard ratios, adjusted for baseline maternal CD4 count (aHRCD4) were calculated for associations between IGRA positivity and risk of active TB and mortality over 2-year postpartum follow-up in women and their infants. Results Of 333 women tested, 52 (15.6%) had indeterminate IGRAs. Of the remaining 281 women, 120 (42.7%) had positive IGRAs, which were associated with a 4.5-fold increased risk of active TB [aHRCD4: 4.5; 95% confidence interval (CI): 1.1–18.0; p=0.03]. Among immunosuppresed women (CD4<250 cell/mm3), positive IGRAs were associated with increased risk of maternal mortality (aHRCD4: 3.5; 95% CI: 1.02–12.1; p=0.045), maternal active TB or mortality (aHRCD4: 5.2; 95% CI: 1.7–15.6; p=0.004) and infant active TB or mortality, overall (aHRCD4: 3.0; 95% CI: 1.0–8.9; p= 0.05) and in HIV-1 exposed uninfected infants (aHRCD4: 7.3; 95% CI: 1.6–33.5; p =0.01). Conclusions Positive IGRAs in HIV-1 infected pregnant women were associated with postpartum active TB and mortality in mothers and their infants.

Background Breast-feeding by infants exposed to human immunodeficiency virus type 1 (HIV-1) provides an opportunity to assess the role played by repeated HIV-1 exposure in eliciting HIV-1–specific immunity and in defining whether immune responses correlate with protection from infection. Methods Breast-feeding infants born to HIV-1–seropositive women were assessed for HLA-selected HIV-1 peptide–specific cytotoxic T lymphocyte interferon (IFN)–γ responses by means of enzyme-linked immunospot (ELISpot) assays at 1, 3, 6, 9, and 12 months of age. Responses were deemed to be positive when they reached ⩾50 HIV-1–specific sfu/1 × 106 peripheral blood mononuclear cells (PBMCs) and were at least twice those of negative controls. Results A total of 807 ELISpot assays were performed for 217 infants who remained uninfected with HIV-1 at ∼12 months of age; 101 infants (47%) had at least 1 positive ELISpot result (median, 78–170 sfu/1 × 106 PBMCs). The prevalence and magnitude of responses increased with age (P = .01 and P = .007, respectively); the median log10 value for HIV-1–specific IFN-γ responses increased by 1.0 sfu/1 × 106 PBMCs/month (P < .001) between 1 and 12 months of age. Of 141 HIV-1–uninfected infants with 1-month ELISpot results, 10 (7%) acquired HIV-1 infection (0/16 with positive vs. 10/125 [8%] with negative ELISpot results; P = .6). Higher values for log10 HIV-1–specific spot-forming units at 1 month of age were associated with a decreased risk of HIV-1 infection, adjusted for maternal HIV-1 RNA level (adjusted hazard ratio, 0.09 [95% confidence interval, 0.01–0.72]). Conclusions Breast-feeding HIV-1–exposed uninfected infants frequently had HIV-1–specific IFN-γ responses. Greater early HIV-1–specific IFN-γ responses were associated with decreased HIV-1 acquisition.

Background There is limited information regarding the pattern and correlates of viral replication in vertically HIV-1–infected children and its role on their outcomes in resource-limited settings. Methods HIV-1–infected infants were followed from birth to 24 months. Serial HIV-1 RNA levels were compared in infants infected in utero (<48 hours), peripartum (48 hours–1 month), and late postnatal (after 1 month). Cofactors for viral peak [highest viral load (VL) within 6 months of infection] and set point and mortality were determined. Results Among 85 HIV-1–infected infants, 24 were infected in utero, 41 peripartum, 13 late postnatal; 7 had no 48-hour assay. HIV-1 VL set point was significantly lower in infants infected >1 month vs. ≤1 month (5.59 vs. 6.24 log10 copies per milliliter, P = 0.01). Maternal VL correlated with peak infant VL (P < 0.001). Univariately, infant peak and set point VL and 6-month CD4% <15% predicted mortality; and 6-month CD4% <15% remained independently predictive in multivariate analyses (hazard ratio = 4.85, 95% confidence interval: 1.90 to 12.36). Conclusions Infants infected after the age of 1 month contained virus better than infants infected before 1 month of age. Maternal VL predicted infant VL, which, in turn was associated with early mortality.