The Body Covers: The 7th Annual Clinical Care Options for HIV Symposium
HIV-Infected Women: Transmission and Management Issues
Howard Minkoff, from SUNY Health Science Center, Brooklyn, discussed the management of the HIV-infected pregnant woman.
Rates of vertical transmission vary, depending on where the studies were conducted and presumably on the viral loads of the participants. Transmission rates as low as 14% have been reported from Europe and as high as 50% from Africa, with figures from the U.S. averaging around 20-30%. Risk factors for perinatal transmission included advanced HIV disease and high maternal viral load. Other potential risk factors have been studied. Richard Semba has found that in low vitamin A levels may increase the risk of perinatal transmission in Africa. However, since large doses of vitamin A can be teratogenic, it is too early to recommend that vitamin A supplements be given in such populations.
There is probably no viral load threshold below which transmission cannot occur. Interestingly, in ACTG 076, the landmark study which demonstrated the efficacy of AZT in preventing perinatal transmission, AZT was effective in all groups regardless of viral load. Clearly, the mechanism of AZT's effect cannot be simply one of viral load reduction, especially since we now know that AZT monotherapy has a relatively modest effect on HIV RNA.
The question of the timing of transmission was also addressed. The accumulated data suggest that at least 40%, and possibly as much as 80% of perinatal transmission occurs close to the time of birth. Some studies, in fact, have suggested that the risk of transmission is related to the duration of rupture of membranes, leading some to suggest a role for Caesarean section in reducing the risk of transmission. While a meta-analysis of a number of retrospective studies suggested a benefit associated with surgical delivery, the original studies and the subsequent analysis were flawed. It is premature to routinely recommend C-section in HIV-infected women in order to prevent vertical transmission. However, it is appropriate to recommend avoidance of artificial rupture of membranes. It is also appropriate to avoid invasive procedures (scalp electrodes, amniocentesis, etc.). Studies of vaginal lavage with microbicides have only shown efficacy in a subset of women with premature rupture of membranes.
ACTG 076 demonstrated a vertical transmission rate of only 8.3% in women taking AZT compared to 25.5% in those not taking AZT (p = .00006). A more recent study, ACTG 185, compared AZT plus IV immune globulin (IVIG) or AZT plus HIV immune globulin (HIVIG). The study was stopped early because it was clear that it would not be able to show a difference between the two groups. Interestingly, the transmission rates in that study were only 4.8% and 4.7% respectively, suggesting a possible benefit with some form of immune globulin. However, other studies have demonstrated rates in that range without immune globulin, so it is not possible to conclude that it adds efficacy to AZT. In that ACTG 185 women with prior AZT exposure did just as well as those who were naive to AZT, further suggesting that the benefit of AZT cannot be accounted for simply by a reduction in maternal viral load.
Nevertheless, there is clearly a relationship between maternal viral load and perinatal transmission, and that relationship, together with concern for the health of the HIV-infected mother, have driven clinicians to use more aggressive antiretroviral therapy in pregnant women. The new practice has been to treat the mother for her HIV infection, with the expectation that lowering her viral load will minimize the likelihood of transmission. There are some caveats, however. AZT should be probably used in any regimen because of the data from ACTG 076. That means that d4T is not a likely candidate, since it should not be combined with AZT. We also know that ddI and ddC do not cross the placenta well. Indinavir causes hyperbilirubinemia and nephrolithiasis, which may cause problems in newborns. And clearly, none of the antiretroviral agents have been demonstrated to be completely safe for use in pregnancy.
Dr. Minkoff concluded by pointing out that obstetrician/gynecologists are the physicians with the greatest opportunity to prevent HIV infection in women, to diagnose maternal HIV infection, and to prevent vertical transmission, but all too often they fail to discuss HIV with their patients or to consider testing. OB/GYNs need to become better educated about HIV infection and to learn how to discuss it with their patients so that this opportunity does not continue to be lost.
This article was provided by The Body PRO. Copyright © Body Health Resources Corporation. All rights reserved.