Browsing by Author "Martens, Craig"

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    Previously Transmitted HIV-1 Strains Are Preferentially Selected During Subsequent Sexual Transmissions
    (The Journal of infectious diseases, 2012) Redd, Andrew D.; Collinson-Streng, Aleisha N.; Chatziandreou, Nikolaos; Mullis, Caroline E.; Laeyendecker, Oliver; Martens, Craig; Ricklefs, Stacy; Kiwanuka, Noah; Hninn Nyein, Phyu; Grabowski, Mary K.; Kong, Xiangrong; Manucci, Jordyn; Sewankambo, Nelson; Wawer, Maria J.; Gray, Ronald H.; Porcella, Stephen F.; Fauci, Anthony S.; Sagar, Manish; Serwadda, David; Quinn, Thomas C.
    A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear. Methods. Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9). Results. Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1–discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner’s HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03). Conclusions. These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains.
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    The rates of HIV-1 superinfection and primary HIV-1 infection are similar in female sex workers in Uganda
    (Theoretical Medicine and Bioethics, 2008) Redd, Andrew D.; Ssemwanga, Deogratius; Vandepitte, Judith; Wendel, Sarah K.; Ndembi, Nicaise; Bukenya, Justine; Nakubulwa, Susan; Grosskurth, Heiner; Parry, Chris M.; Martens, Craig; Bruno, Daniel; Porcella, Stephen F.; Quinn, Thomas C.; Kaleebu, Pontiano
    To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers in Kampala, Uganda. Design—A retrospective analysis of individuals who participated in a clinical cohort study among high-risk female sex workers in Kampala, Uganda. Methods—Plasma samples from HIV-infected female sex workers (FSW) in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSW from the same cohort, and incidence rate ratios were compared. Results—The rate of superinfection in these women (7/85; 3.4/100py) was not significantly different from the rate of primary infection in the same population (3.7/100py; IRR=0.91, p=0.42). Seven women also entered the study dual infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (p=0.05), and trended to be older and more likely to be widowed (p=0.07). Conclusions—In this cohort of female sex workers, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar-workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.