The Body Covers: The XIII International AIDS Conference
New Developments in Reducing Mother-to-Child HIV Transmission
July 13, 2000
Nevirapine (NVP) is an antiretroviral drug that has been used in the United States and other developed nations for several years for treatment of HIV infection. It is a member of the class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs have potent anti-HIV effects, but it is also relatively easy for HIV to develop resistance to NNRTIs. Resistance happens most often if NNRTIs are used alone or in combinations that do not fully suppress the replication (growth) of HIV. NVP lasts for a long time in the body, which is a good characteristic when you want a simple treatment, but is potentially a bad feature if it is given (as a sole treatment) to people whose virus is replicating (since the virus may develop resistance to NVP).
Two presentations addressed how often NVP resistance occurs in women receiving NVP for prevention of mother-to-child transmission of HIV.
The first study tested a subgroup of women participating in a study done in Uganda called the HIVNET 012 study. The details of the main study (Owor et al., LBOr1) are summarized by another conference attendee. The main outcome was that NVP was more effective than a short course of zidovudine (AZT) in preventing mother-to-child transmission of HIV. With both treatments, some babies still got HIV. Women whose babies got HIV despite their mothers getting NVP were tested six weeks after delivery for the presence of NVP resistance. Nearly one quarter (7 of 31) of these women had HIV resistant to NVP (Jackson et al., LBOr13). This resistance had developed since delivery. The babies were also tested. HIV from three of the babies was resistant to NVP, but the pattern of genetic changes was different than in their mothers, suggesting that the resistance came from the baby's dose of NVP, not from their mother. Months after delivery, resistance virus was no longer detectable in the mother's blood. There was no apparent effect of the NVP resistance on the clinical course of the women or babies. It is unknown if NVP would still be effective for preventing HIV transmission in future pregnancies for these women (if they occurred), but there are reasons to think that it might still be useful.
The results of this study are not surprising, given what we know about viral resistance with NVP and other NNRTIs. However, this less-than-favorable information needs to be weighed against the data about NVP as an inexpensive, easy regimen for the prevention of perinatal transmission in the developing world. The main downside of NVP resistance is that NVP (and probably other NNRTIs) would not be effective HIV treatment (if available) for any women who had had resistant virus.
Data about resistance to NVP from a study of perinatal transmission in the United States was also presented in the same session (Sullivan et al, LBOr14). This study compared NVP (one dose to mother and baby) to a placebo (inactive medicine). Unlike the African study described above, the women in this study also received other antiretrovirals. The good news about this study is that it was stopped because the rate of HIV transmission to the babies was so low (2-3%). However, NVP resistance also occurred. Thirty-two women who had a HIV viral load above 3,000 copies/mL at delivery and who got NVP were tested for NVP resistance. Four or 13% developed NVP resistance.
This information is especially important for women with HIV who might become pregnant to know about if they live in countries where NVP is available for treatment of HIV. Since NVP and NNRTIs are a useful HIV therapy, it is preferable to avoid developing resistance to them. This data emphasizes the importance of early prenatal care for HIV-infected women. Early prenatal care allows time to consider the various options for prevention of mother-to-child transmission of HIV that do not carry as high a risk for the development of NVP resistance.
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