Browsing by Author "Eshleman, Susan"

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    Analysis of HIV Diversity Using a High-Resolution Melting Assay
    (AIDS research and human retroviruses, 2010) Towler, William I.; James, Maria M.; Ray, Stuart C.; Wang, Lei; Donnell, Deborah; Mwatha, Anthony; Guay, Laura; Nakabiito, Clemensia; Musoke, Philippa; Jackson, J. Brooks; Eshleman, Susan
    HIV viruses are usually genetically homogeneous shortly after infection, and become more heterogeneous over time. We developed a high-resolution melting (HRM) assay to analyze HIV diversity without sequencing. Plasma samples from the HIVNET 012 trial were obtained from nine Ugandan mother–infant pairs. DNA amplified from the HIV gag region was analyzed to determine the number of degrees over which the DNA melted (HRM score). HRM gag DNA was also cloned and sequenced (50 clones/mother; 20 clones/infant). The median HRM score for infants (4.3, range 4.2–5.3) was higher than that for control plasmids (3.4, range 3.2–3.8, p < 0.001) and lower than that for mothers (5.7, range 4.4–7.7, p = 0.005, exact Wilcoxon rank sum test). The intraclass correlation coefficient reflecting assay reproducibility was 94% (95% CI: 89–98%). HRM scores were also compared to sequenced-based measures of HIV diversity; higher HRM scores were associated with higher genetic diversity (p < 0.001), complexity (p = 0.009), and Shannon entropy (p = 0.022), but not with length variation (p = 0.111). The HRM assay provides a novel, rapid method for assessing HIV diversity without sequencing. This assay could be applied to any region of the HIV genome or to other genetic systems that exhibit DNA diversity.
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    Comparison of HIV-1 Mother-to-Child Transmission After Single-Dose Nevirapine Prophylaxis Among African Women With Subtypes A, C, and D
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2006) Eshleman, Susan; Church, Jessica; Guay, Laura A.; Mwatha, Anthony; Fiscus, Susan A.; Mmiro, Francis; Musoke, Philippa; Kumwenda, Newton; Jackson, J. Brooks; Taha, Taha E.; Hoover, Donald R.
    The HIVNET 012 trial in Uganda showed that mother-to-child transmission (MTCT) of HIV-1 can be prevented by providing pregnant women and their infants with a single dose (SD) of the antiretroviral drug, nevirapine (NVP).1,2 Safety and efficacy of 1- or 2-dose NVP prophylaxis for prevention of MTCT have been documented in other studies. We have shown that NVP resistance emerges in some women after SD NVP prophylaxis3 and that the portion of women with NVP resistance is influenced by HIV-1 subtype.4 At 6 to 8 weeks after SD NVP, NVP resistance was more common in women with subtype C (69.2%) than in women with subtype D (36.1%, P < 0.0001) or subtype A (19.4%, P < 0.0001).4 Selection of NVP-resistant HIV-1 variants in women after NVP dosing could theoretically lower the efficacy of NVP prophylaxis for prevention of HIV transmission by breast-feeding in the first few weeks after birth. In the HIVNET 012 trial, most women were infected with HIV-1 subtype A or D. Risk of MTCT was slightly (but not statistically) higher in women with subtype D.5 In this report, we combined data from the HIVNET 012 and NVAZ trials6 to compare the risk of MTCT in women with subtype C to the risk of MTCT in women with subtypes A and D in the setting of SD NVP prophylaxis.