Impact of HIV-1 Subtype on Women Receiving Single Dose Nevirapine Prophylaxis to Prevent HIV-1 Vertical Transmission

Little is known about the relationship between HIV-1 subtype (clade) and HIV-1 transmission or pathogenesis. Subtypes A and D account for most HIV-1 infections in Uganda. The HIV Network for Prevention Trials (HIVNET) 012 study in Uganda recently demonstrated that single-dose Nevirapine (NVP) prophylaxis is effective for preventing mother-to-child transmission (MTCT) of HIV-1. In the HIVNET 012 study, pregnant Ugandan women received a single dose of NVP at the onset of labor, and infants received a single dose of NVP within 72 hours of birth. Because clinical outcome of women in HIVNET 012 was monitored for only 6-8 weeks, it was not possible to evaluate the relationship of HIV-1 subtype with clinical outcome.

Recent reports compared the rate of disease progression in persons infected with subtype A versus subtype D. One study of women in Senegal with non-A subtypes (C, D, or G) found that the women were more likely to develop AIDS within 5 years of infection than were women with subtype A. Two other studies, including one from Uganda, found no significant difference in disease progression in persons with subtype A or D.

This exploratory study examines the relationship between HIV-1 subtype, MTCT, and the development of NVP resistance in women enrolled in HIVNET 012. In this study, virus loads and CD4 cell counts before NVP administration were similar among women with subtypes A and D. Women had not received prior antiretroviral therapy and did not receive antiretroviral therapy after the single dose of NVP, which is consistent with the standard of care in Uganda. Of the 102 women analyzed in this study, 50 (49 percent) had subtype A, 35 (34 percent) had subtype D, 4 (4 percent) had subtype C, and 12 (12 percent) had recombinant HIV-1, which is similar to the distribution of subtypes found in Uganda in recent epidemiological studies. Because only the subtypes of the HIV-1 pol region were analyzed, it is possible that the subtypes of other HIV-1 genes may differ, reflecting the high rate of HIV-1 intersubtype recombination in Uganda.

Researchers found no difference in the rate of MTCT in women with HIV-1 subtype A or D, which is consistent with a recent study from Kenya, which found no significant difference in the frequency or mode of MTCT in women with HIV-1 subtypes A or D. More extensive studies are needed to define further the role of HIV-1 subtype on MTCT in different clinical settings. However, researchers observed a higher rate of NVP resistance in women with subtype D than those with subtype A after single-dose NVP prophylaxis. Confirmation in larger studies is needed to evaluate further the influence of subtype A after single-dose NVP prophylaxis. A higher rate of NVP resistance in women with subtype D HIV-1 could reflect a high replication rate of subtype D HIV-1. HIV-1 subtypes also differ in the frequency of amino acid polymorphisms at positions associated with antiretroviral drug resistance. Such differences may influence the fitness of HIV-1 with antiretroviral drug resistance mutations, such as K103N. The authors concluded that the potential selection of NVP resistance in women receiving the HIVNET 012 regimen "must be balanced against the simplicity, efficacy, and cost-effectiveness of the regimen. Implementation of this regimen could prevent HIV-1 infection in millions of HIV-1 exposed infants over the next decade."

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