2- or 3-Drug Regimen Lessens Intrapartum HIV Transmission

Brian Hoyle

March 11, 2011

March 11, 2011 (Boston, Massachusetts) — A phase 3 randomized trial of infants born to women who were diagnosed with HIV at or just before delivery, and whose antiretroviral therapy was initiated just before labor, has shown that neonatal therapy with a 2- or 3-drug regimen incorporating zidovudine is superior to zidovudine alone in preventing intrapartum transmission of HIV, according to a study reported here at the 18th Conference on Retroviruses and Opportunistic Infections.

"Ideally, the time of delivery is not when you want to diagnose a mother with HIV. Diagnosis should be done during or before pregnancy. Nonetheless, there is a significant number of women who are only diagnosed when they show up for delivery or when seeking early postpartum care," Karin Nielsen-Saines, MD, from the University of California–Los Angeles David Geffen School of Medicine, told Medscape Medical News

"The study was designed to evaluate the best treatment that can be given as prophylaxis to infants born to women who are only diagnosed with HIV at delivery, and so who have not received any antiretroviral therapy during pregnancy."

The intent of the international NICHD HPTN 040/PACTG 1043 study was to optimize the treatment regimen of neonates born to women whose HIV-positive status was not established until shortly before labor, with the goal of preventing mother-to-child transmission.

"We compared a 6-week regimen of zidovudine with 2 other regimens that were all started within the first 48 hours of life," Dr. Nielsen-Saines told Medscape Medical News.

Of the 1745 infants screened, 1739 were enrolled; 1684 were evaluable after the exclusion of 55 infants because of false-positive results on the HIV assay. The infants, from South America (Brazil and Argentina), South Africa, and the United States, were randomly assigned in the same numbers to 3 zidovudine-based treatment groups: zidovudine alone for 6 weeks; zidovudine for 6 weeks plus 3 doses of nevirapine during the first week of life (2-drug group); and both zidovudine and nevirapine for 6 weeks and lamivudine for 2 weeks (3-drug group). Infants born to mothers who received zidovudine antiretroviral therapy during labor were eligible. HIV status was determined by DNA polymerase chain reaction at birth, at 10 to 14 days of age, at 4 to 6 weeks of age, and at 3 to 6 months of age.

The treatments were delivered in infant formula.

"Feeding using formula is common in Brazil [where 70% of the enrolled infants were from], so the prophylaxis was delivered in a way that is in line with standard feeding practice," Dr. Nielsen-Saines told Medscape Medical News.

Maternal and neonatal physiological characteristics were similar in all the study groups.

The primary outcome was the detection of HIV infection at 3 months of age in infants who were not infected at birth (excluding in utero infection).

Total in utero transmission was 5.7% (n = 93) and occurred similarly in the 3 groups. The total intrapartum transmission rate was 3.2% (n = 47). The intrapartum transmission rate for the zidovudine group was 4.9% (n = 24; 95% confidence interval [CI], 3.3% to 7.2%); for the 2-drug group was 2.2% (n = 11; 95% CI, 1.2% to 4.0%); and for the 3-drug group was 2.5% (n = 12; 95% CI, 1.4% - 4.3%). Compared with the zidovudine group, the differences were significant in the 2- and 3-drug groups (= .045 for both). Overall, the rate of mother-to-child transmission was 8.5% (n = 140); this rate was significantly higher in the zidovudine group (= .034).

Multivariate analyses determined that treatment group and viral load were associated with HIV transmission, whereas maternal age, race, CD4 count, prenatal care, antiretroviral therapy during labor, the presence of maternal syphilis, geographic region, type of delivery (vaginal vs caesarean), and gestational age were not associated with transmission.

Forty-three deaths (2.6%) occurred. There was no difference in the frequency of deaths in any treatment group. The deaths mainly involved infants from Brazil and Argentina, and the HIV status at death was unknown in almost half of the infants.

An adverse effect was noted: neutropenia was significantly higher in the 3-drug group (P < .001).

"Because of its lower toxicity and greater ease of use, the 2-drug regimen . . . may be preferable to the 3-drug regimen. But a caveat right now is the lack of data on drug resistance," Dr. Nielsen-Saines told Medscape Medical News. Antiretroviral resistance testing is ongoing, and results are not yet available.

"Also, the 3-drug group had a much higher incidence of neutropenia, which clinicians need to bear in mind when considering treatment. Our recommendation is to change current practice in favor of the 2-drug regimen [P < .001]," she added.

"These are important results that are starting to complete the puzzle of how best to prevent neonatal transmission of HIV," Elaine Abrams, MD, from the Mailman School of Public Health, Columbia University, New York City, told Medscape Medical News.

The authors have disclosed no relevant financial relationships.

18th Conference on Retroviruses and Opportunistic Infections (CROI): Abstract 124LB. Presented March 2, 2011.


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