| Considering existing research into risk factors for maternofetal transmission of HIV-1, and documentation of the efficacy of antiretroviral therapies in preventing such transmission, limited research has been conducted to evaluate whether antiretroviral resistance has an impact on HIV-1 transmission. Moreover, the exact mechanisms of transmission and of the prophylactic effect of antiretroviral therapies remain unknown.; Data from the Women and Infants Transmission Study (WITS), an ongoing multisite cohort study of HIV-infected pregnant women in the U.S. and Puerto Rico, were combined with measures of phenotypic and genotypic antiretroviral resistance derived from stored tissue culture supernatants in two quantitative analyses. The specific aims of these analyses were (1) To estimate the association between maternal virus zidovudine (ZDV) phenotypic resistance and vertical transmission in a sample of ZDV-exposed mothers with moderately advanced disease who enrolled in the WITS from 1989 through 1994, and to evaluate the relationship of resistance genotype and phenotype in this population, and; (2) To characterize rates and patterns of antiretroviral-resistance-associated mutations to the reverse transcriptase and protease segments of the HIV-1 maternal virus genome among transmitting and non-transmitting mothers who enrolled in the WITS from 1994 through 1999, and to analyze associations with vertical transmission among women in the multi-drug era.; In addition, a critical review of clinical, epidemiologic and basic science literature was focused around the question of the relative contribution of virus from varying maternal compartments to maternofetal transmission. Understanding the likelihood of transmission through various pathways has the potential to improve measures used in research and in the clinic in order to better inform both research design and transmission interventions. |
