Browsing by Author "Fauci, Anthony S."

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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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    A Randomized, Controlled, Trial of Short Cycle Intermittent Compared to Continuous Antiretroviral Therapy for the Treatment of HIV Infection in Uganda
    (PLoS One, 2010) Reynolds, Steven J.; Kityo, Cissy; Kabuye, Geoffrey; Atwiine, Diana; Mbamanya, Frank; Ssali, Francis; Davey, Richard T.; Mugyenyi, Peter; Fauci, Anthony S.; Dybul, Mark R.
    Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs. A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count $125 cells/mm3 and HIV RNA plasma levels ,50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection. Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39). Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy