Perinatal HIV down as treatment increases
Perinatal HIV down as treatment increases
Treatment with nevirapine enters Phase III trial
Voluntary HIV testing of pregnant women is working, and more infected pregnant women are accepting zidovudine treatment as trials testing the safety and efficacy of other drugs are under way, say leading researchers in pediatric AIDS.
In a large study of infected mothers presented recently at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy in Toronto, researchers at the Centers for Disease Control and Prevention report that as many as 80% of mothers whose HIV-positive children were identified through HIV/AIDS surveillance knew their HIV status before giving birth. At the same time, the proportion of children receiving some component of the recommended perinatal HIV prophylaxis treatment rose from 36% in 1994 to 77% in 1996. From September 1994 to December 1995, 12% of treated children were infected with the virus, compared to a 30% infection rate among children born to mothers who did not receive treatment.
"We are seeing decreases and that is good news," says Mary Lou Lindegren, MD, medical epidemiologist in the CDC’s HIV/AIDS surveillance branch. "There are still some women who haven’t been tested, but we are picking up more and more as testing gets better."
The study is an analysis of surveillance data reported through 1996 from 29 states that monitor perinatally HIV-exposed children. More than 1,000 children were followed throughout the study period, Lindegren says.
The CDC is helping states use the data to determine how well they are meeting new Ryan White CARE Act guidelines, which require that states significantly increase the number of pregnant women tested for HIV and reduce the rate of perinatal infections. The criteria include having 95% of all pregnant women know their HIV status, and decreasing perinatal infections by 50%. If the requirements aren’t met before the deadline imposed by Congress, states would have to institute mandatory HIV reporting for pregnant women.
New drugs being tested
With the approval of new antiretrovirals, researchers have been interested in whether these new drugs alone or in combination with AZT can further decrease the transmission rate. Other approaches also are being studied. Earlier this year, for instance, ACTG 185 was stopped because the rate of transmission was so low less than 5% that the study lost its predictive power. Women in that study were treated with AZT combined with hyper-immune globulin and/or HIV antibodies. The low rate of transmission was surprising, considering that many of the women in the study had low CD4 counts and long-term AZT use prior to pregnancy, says Lynn Moffison, MD, associate chief for clinical research in the pediatric, adolescent and maternal AIDS branch of the National Institute of Child Health and Human Development.
"We saw a transmission rate of 4.8%, so based on that I think we can say the effect seen in ACTG 076 [the original perinatal AZT trial] can be extended to all populations of women, not just healthy women, but women who are sicker and have used AZT before," she tells AIDS Alert.
A number of Phase I trials are under way to assess the pharmacokinetic and safety profiles of new antiretrovirals. They include combinations of AZT and 3TC, plus one of each of the four approved protease inhibitors. Another Phase I trial assessing d4T and 3TC together is complete, and data will be presented early next year, Moffison says, adding that preliminary data indicate that the pharmacokinetics of d4T may be modified during pregnancy.
The study farthest along is a Phase III study of nevirapine (Viramune), a non-nucleoside reverse transcriptase inhibitor. The study, ACTG 316, recently began enrolling women at 18 centers in the United States. Combined with study sites in Europe, the trials could enroll enough women an estimated 1,500 to 2,000 patients to ensure statistical significance, Moffison says.
Patients in the double-blind placebo-controlled study will be given nevirapine or a placebo along with the standard ACTG 076 regimen. Women must have no previous experience with a non-nucleoside reverse transcriptase inhibitor, but can continue taking protease inhibitors and nucleoside analogues for their own treatment. Viramune will be given to the enrollees during labor. Newborns will also receive the drug between 48 hours and 72 hours after birth.
The study will test the hypothesis that most HIV transmission occurs during labor, and that an antiretroviral agent given during that time should further reduce transmission. "It is a very directed question as opposed to using several different drugs throughout pregnancy," Moffison says, adding that preliminary data should be available in less than a year.
Nevirapine was chosen for the study because researchers had already gathered pharmacokinetic and safety data on it from a Phase I trial, ACTG 250. Currently, nevirapine is indicated for HIV-positive adults who have failed on other drugs.
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