ZDV/3TC for Pregnant Woman With Low HIV Viral Load?
ZDV/3TC for Pregnant Woman With Low HIV Viral Load?
How inappropriate is the use of zidovudine/lamivudine alone in an HIV-infected, treatment-naive pregnant woman with a baseline viral load of 400 copies/mL and a CD4+ cell count of 443 cells/mm? Is it really necessary to use a third agent? Once on zidovudine/lamivudine her viral load decreased to < 50 copies/mL and her CD4+ cell count increased to 489 cells/mm.
Guidelines for the prevention of perinatal HIV transmission with prophylactic antiretroviral therapy are not very specific, in that multiple options are given. This is because multiple scenarios present to providers and there are many possible treatment regimens available in the United States and other developed countries. In addition, guidelines for treating adults with HIV, which recommend 3- or 4-drug highly active antiretroviral therapy (HAART) regimens as first-line therapy, also need to be taken into consideration.
Your patient is lucky in that she has had low-level viral replication and a relatively high CD4+ cell count in the absence of any therapy. If your patient were not pregnant you would most likely not have initiated antiretroviral therapy. However, her pregnancy means that you need to treat to minimize the risk of mother-to-child HIV transmission; although that risk is quite low in the setting of low plasma viral load, it is not zero. Transmission of HIV can occur at any stage of pregnancy or during the birthing process (as well as during the postnatal period through breastfeeding), although studies suggest that most infants who acquire HIV perinatally (70% to 80%) are infected during delivery, by exposure to infected maternal blood or other fluids. Moreover, we have recently demonstrated that although there is a strong association between the plasma HIV-1 RNA level and the genital tract HIV-1 RNA level, women with plasma viral load < 500 copies/mL may nevertheless have detectable virus in the genital tract.
When initiating antiretroviral therapy in a pregnant woman at our center, we always use triple combination therapy, most often with 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus nevirapine or, in some cases, nelfinavir. Our aim is to choose a regimen that not only is effective at reducing perinatal transmission, but also is best for the woman herself (and for the infant should it be infected). A 3-drug regimen decreases the likelihood of viral rebound and the possibility of the development of resistant virus, which would reduce the woman's future treatment options, and could also be transmitted to the infant with similar consequences. In choosing a potent regimen, we expect that with good compliance the women's viral load will be suppressed rapidly and maintained at an undetectable level for the duration of the pregnancy and through labor and delivery.
Conversely, a regimen of zidovudine/lamivudine has been shown to reduce the risk of mother-to-child transmission by 37% to 50% in breastfeeding populations. Similarly, this regimen was associated with a 5-fold reduction in transmission, to 1.2%, in a French study. However, the risk of ongoing low-level viral replication or viral rebound is greater than with a HAART regimen. High-level resistance to lamivudine only requires a single mutation (M184V) and develops rapidly in the presence of viral replication. In the French study of pregnant women treated with zidovudine/lamivudine, 39% were found to have the M184V mutation postpartum, compared with only 2% at the time therapy was initiated. For this reason, this 2-drug regimen would not be my personal choice for therapy during pregnancy, or in fact at any time, if other agents are available to you.
How inappropriate is the use of zidovudine/lamivudine alone in an HIV-infected, treatment-naive pregnant woman with a baseline viral load of 400 copies/mL and a CD4+ cell count of 443 cells/mm? Is it really necessary to use a third agent? Once on zidovudine/lamivudine her viral load decreased to < 50 copies/mL and her CD4+ cell count increased to 489 cells/mm.
Guidelines for the prevention of perinatal HIV transmission with prophylactic antiretroviral therapy are not very specific, in that multiple options are given. This is because multiple scenarios present to providers and there are many possible treatment regimens available in the United States and other developed countries. In addition, guidelines for treating adults with HIV, which recommend 3- or 4-drug highly active antiretroviral therapy (HAART) regimens as first-line therapy, also need to be taken into consideration.
Your patient is lucky in that she has had low-level viral replication and a relatively high CD4+ cell count in the absence of any therapy. If your patient were not pregnant you would most likely not have initiated antiretroviral therapy. However, her pregnancy means that you need to treat to minimize the risk of mother-to-child HIV transmission; although that risk is quite low in the setting of low plasma viral load, it is not zero. Transmission of HIV can occur at any stage of pregnancy or during the birthing process (as well as during the postnatal period through breastfeeding), although studies suggest that most infants who acquire HIV perinatally (70% to 80%) are infected during delivery, by exposure to infected maternal blood or other fluids. Moreover, we have recently demonstrated that although there is a strong association between the plasma HIV-1 RNA level and the genital tract HIV-1 RNA level, women with plasma viral load < 500 copies/mL may nevertheless have detectable virus in the genital tract.
When initiating antiretroviral therapy in a pregnant woman at our center, we always use triple combination therapy, most often with 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus nevirapine or, in some cases, nelfinavir. Our aim is to choose a regimen that not only is effective at reducing perinatal transmission, but also is best for the woman herself (and for the infant should it be infected). A 3-drug regimen decreases the likelihood of viral rebound and the possibility of the development of resistant virus, which would reduce the woman's future treatment options, and could also be transmitted to the infant with similar consequences. In choosing a potent regimen, we expect that with good compliance the women's viral load will be suppressed rapidly and maintained at an undetectable level for the duration of the pregnancy and through labor and delivery.
Conversely, a regimen of zidovudine/lamivudine has been shown to reduce the risk of mother-to-child transmission by 37% to 50% in breastfeeding populations. Similarly, this regimen was associated with a 5-fold reduction in transmission, to 1.2%, in a French study. However, the risk of ongoing low-level viral replication or viral rebound is greater than with a HAART regimen. High-level resistance to lamivudine only requires a single mutation (M184V) and develops rapidly in the presence of viral replication. In the French study of pregnant women treated with zidovudine/lamivudine, 39% were found to have the M184V mutation postpartum, compared with only 2% at the time therapy was initiated. For this reason, this 2-drug regimen would not be my personal choice for therapy during pregnancy, or in fact at any time, if other agents are available to you.