The identification of novel cross-resistance patterns among approved NNRTIs illustrates the need for a systematic approach for testing novel NNRTIs against clinical virus isolates with major NNRTI-resistance mutations and for testing older NNRTIs against virus isolates with mutations identified during the evaluation of a novel NNRTI.

Although coinfection with tuberculosis and human immunodeficiency virus (HIV) is emerging as a major problem in many developing countries, nutritional status has not been well characterized in adults with tuberculosis and HIV infection. We compared nutritional status between 261 HIV-positive and 278 HIV-negative adults with pulmonary tuberculosis in Kampala, Uganda, using anthropometry and bioelectrical impedance analysis. Among 163 HIV-positive and 199 HIV-negative men, intracellular water-to-extracellular water (ICW:ECW) ratio was 1.48 +/- 0.26 and 1.59 +/- 0.48 (P = 0.006) and phase angle was 5.42 +/- 1.05 and 5.76 +/- 1.30 (P = 0.009), respectively. Among 98 HIV-positive and 79 HIV-negative women, ICW:ECW was 1.19 +/- 0.16 and 1.23 +/- 0.15 (P = 0.11) and phase angle was 5.35 +/- 1.27 and 5.43 +/- 0.93 (P = 0.61), respectively. There were no significant differences in BMI, body cell mass, fat mass or fat-free mass between HIV-positive and HIV-negative adults. Among HIV-positive subjects, BMI, ICW:ECW, body cell mass, fat mass and phase angle were significantly lower among those with CD4(+) lymphocytes < or = 200 cells/microL compared with those who had > 200 cells/microL. In sub-Saharan Africa, coinfection with pulmonary tuberculosis and HIV is associated with smaller body cell mass and intracellular water, but not fat-free mass, and by large differences in ICW:ECW and phase angle alpha.

Vitamin A is essential for immunity and growth. A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia, low birth weight, growth failure, HIV transmission, and mortality. Women received daily doses of iron and folate, either alone or combined with vitamin A (3 mg retinol equivalent), from 18-28 weeks' gestation until delivery. In the vitamin A and control groups, respectively, the mean (+/-SE) birth weights were 2895+/-31 g and 2805+/-32 g (P=.05), the proportions of low-birth-weight infants were 14.0% and 21.1% (P=.03), the proportions of anemic infants at 6 weeks postpartum were 23.4% and 40.6% (P<.001), and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6% and 27.8% (P=.76) and 27.7% and 32.8% (P=.21). Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia, but it did not affect perinatal HIV transmission.

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H uman immunodeficiency virus type 1 (HIV-1) protease is a highly mutable protein. More than one-half of the enzyme's 99 amino acids are subject to variation under protease inhibitor (PI) selection pressure (1, 2). In addition, viruses from patients treated unsuccessfully with multiple-PI-containing antiretroviral (ARV) treatment regimens often develop complex patterns of PI resistance amino acid substitutions (3, 4). The many genetic manifestations of PI resistance present challenges to researchers who require representative PI-resistant viruses for in vitro mechanistic studies and for testing of new inhibitors active against the most clinically relevant multi-PI-resistant variants.To address these challenges, we created a panel of recombinant infectious molecular virus clones containing clinically derived protease genes with amino acid substitution patterns similar to those in the most common multiple-PI-resistant viruses. The panel was drawn from a repository of cryopreserved plasma samples from patients who received multiple PIs and harbored viruses with multiple PI resistance amino acid substitutions. To assess the validity of this panel, we performed an independent correlation network analysis of PI resistance amino acid substitutions in publicly available sequences from more than 10,000 patients. MATERIALS AND METHODS PI resistance amino acid substitutions and phenotypic cutoffs.Amino acid substitutions were defined as differences from the consensus B protease sequence (http://hivdb.stanford.edu/DR/asi/releaseNotes/index .html#consensusbsequences). PI resistance amino acid substitutions were defined as (i) protease substitutions that give rise to HIV-1 variants with reduced susceptibility to one or more PIs in cell culture assays (5); (ii) nonpolymorphic substitutions, defined here as those occurring in Յ0.5% of pooled group M viruses from PI-naive persons; and (iii) substitutions occurring in Ն0.5% of virus isolates from PI-experienced patients. Fortyone substitutions at 23 positions met two or more of these criteria: L10F, V11I, L24I, D30N, V32I, L33F, K43T, M46IL, I47AV, G48MV, I50LV, F53L, I54ALMSTV, Q58E, G73ACST, T74P, L76V, V82ACFLST, N83D, I84V, N88DS, L89V, and L90M (see Table S1 in the supplemental material). Each amino acid substitution had a prevalence of Յ0.5% in pooled group M viruses from PI-naive individuals, and with the exception of the V82C substitution, each has been shown to significantly contribute to decreased in vitro PI susceptibility (5). In addition, each amino acid substitution except for I47A (0.3%), I50L (0.4%), and V82L (0.3%) had a prevalence of Ն0.5% in pooled group M viruses from PI-experienced patients.High-level resistance was defined according to the Monogram Biosciences (South San Francisco, CA) clinical cutoffs for the PhenoSense assay (6): atazanavir-ritonavir (ATV/r) at Ͼ6-fold, darunavir-ritonavir (DRV/r) at Ͼ90-fold, fosamprenavir-ritonavir (FPV/r) at Ͼ11-fold, indinavir-ritonavir (IDV/r) at Ͼ10-fold, lopinavir-ritonavir (LPV/r) at Ͼ56-fold, nelfinavir (NFV) at Ͼ...