Combination ART reduces intrapartum infection

Intrapartum HIV transmission rates remain as high as 12 to 26%, but a new study suggests combination ART reduces maternal-fetal transmission.

Preventing maternal-fetal transmission of HIV remains an important goal in overall HIV prevention. The risk for HIV transmission is highest for infants born to HIV positive women who did not receive antiretroviral therapy (ART) during pregnancy. Based on previous clinical studies, the current standard regimen for infants born to HIV-1 infected mothers who had not been on ART has been a 6 week course of zidovudine. after birth Despite this regimen, observational studies show that intrapartum HIV transmission rates remain as high as 12 to 26%. As such, there has been growing interest to determine if using a combination of 2 or more antiretroviral drugs can further reduce this risk. A recent study, published in the June issue of the New England Journal of Medicine, has looked further into this issue.

The study compared the efficacy of three different antiretroviral drug regimens for prevention of intrapartum HIV-1 transmission in infants whose mothers did not receive ART during pregnancy. The study, which only included infants who were formula-fed, randomly assigned newborn infants (<48 hours old) to one of three ART regimens which were as follows: 1) zidovudine alone for 6 weeks 2) zidovudine regimen plus three doses of nevirapine 3) zidovudine regimen plus nelfinavir and lamivudine for 2 weeks.. Infants were tested for HIV at birth and then subsequently at 10 to 14 days, 4-6 weeks, 3 months, and lastly at 6 months of age. If the infants were confirmed to be HIV positive at any of these points (including birth), the prophylaxis ART regimen was discontinued and they were initiated on treatment ART. It should be noted that infants found to be HIV positive at birth were excluded from statistical analysis. The primary study end point was intrapartum HIV-1 transmission at 3 months of age.

2- and 3-drug ART reduces intrapartum HIV infection

The results of the study showed that 2 and 3 drug ART regimens were far more effective in preventing intrapartum HIV infection. Statistical analysis showed that the Zidovudine only group had a transmission of 4.8 percent . The transmission rate was 2.2 percent in the two-drug group and 2.4 percent in the three-drug group. While both the multi-drug regimens were about equally effective, there was an increased risk of adverse effects (particularly neutropenia) in the three-drug group when compared to the 2-drug regimen. 

While early identification of positive HIV status in the prenatal period and timely initiation of ART for the mother remains the most effective strategy to prevent intrapartum HIV infection, this study offers support for a second window of opportunity. Even in situations where mothers are identified as being HIV positive in the brief intrapartum period, the use of a two or three-drug ART regimen offers more protection to the infant from HIV transmission than the current standard single drug regimen. Given these findings, combination ART regimens are likely to become standard of care for post exposure prophylaxis in this population of infants.

References

Nielsen-Saines, Karin etal. Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV infection. New England Journal of Medicine June 2012; 366:2368-2379.

Other resources:

Stem cell therapy approaches to HIV. An update on basic-science HIV research.

HIV superinfection rates comparable to primary infection rates. A study raises concerns about the effectiveness of HIV infection.

 

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