Antiretroviral Regimens to Prevent Intrapartum HIV Infection
Antiretroviral Regimens to Prevent Intrapartum HIV Infection
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Dean, Western Michigan University School of Medicine, Kalamazoo, Michigan, is Associate Editor for Infectious Disease Alert.
Dr. Jenson reports no financial relationship in this field of study.
Synopsis: For infants whose mothers did not receive antiretroviral therapy during pregnancy, postpartum prophylaxis with a two- or three-drug antiretroviral regimen is superior to zidovudine alone for prevention of intrapartum HIV transmission. The three-drug regimen was associated with a significantly increased rate of neutropenia.
Source: Nielsen-Saines K, et al. Three postpartum antiretrovirals regimens to prevent intrapartum HIV infection. N Engl J Med 2012;366:2368-70.
A total of 1745 infants from 17 sites in Brazil (70.1%), South Africa (27.4%), Argentina (1.6%) and the United States (0.8%) born to women with a peripartum diagnosis of HIV type I infection were randomized within 48 hours of birth to receive one of three six-week postpartum antiretroviral regimens. The mothers had not received antiretroviral therapy during pregnancy, and all infants were formula fed.
Ten infants did not receive study drugs, and 51 mothers were HIV-negative on than 40 confirmatory tests. There were a total of 1684 infants enrolled, including 566 infants receiving zidovudine alone for six weeks, 562 infants receiving zidovudine for six weeks plus three doses of nevirapine during the first eight days of life (first dose within 48 hours of birth, second dose 48 hours after the first dose, and third dose 96 hours after the second dose), and 556 infants receiving zidovudine for six weeks plus nelfinavir and lamivudine for two weeks. Fixed dosing was used based on weight categories (birth weight <=2.0 kg, or >2.0 kg).
The overall transmission rate at three months of life was 8.3% (140 infants), with an increased transmission rate in the zidovudine-alone group (P=0.03) compared to the other two groups. The overall rate of in utero transmission of HIV was 5.7%, ranging from 5.1% to 6.8% across the three groups. The rate in the zidovudine-alone group did not differ significantly from the other two groups (P=0.24 for both comparisons). Intrapartum transmission occurred in 24 infants in the zidovudine alone group (4.8%; 95% CI, 3.2-7.1%), compared to 11 infants in the two-drug group (2.2%; 95% CI, 1.2-3.9%) and 12 infants in the three-drug group (2.4%; 95% CI, 1.4-4.3%). Multivariate analysis showed that zidovudine monotherapy, higher maternal viral load, and maternal use of illegal substances were significantly associated with HIV transmission.
Complete blood count and hepatic aminotransferase levels were measured at birth, 4-7 days, 10-14 days, 4-6 weeks, and 3 months of age. The rate of neutropenia was significantly increased in the three-drug group (P<0.001). Elevated aminotransferase levels were uncommon and occurred in only 2.5% of all infants, which did not differ significantly among the groups.
Mutations conferring resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) were present in 12 infants: three in the zidovudine-alone group, six in the two-drug group, and three in the three-drug group (P=0.15 for multiple comparisons). Mutations conferring resistance to nucleoside analogue reverse-transcriptase inhibitors (NRTIs) were found in two infants in the three-drug group and one infant in the two-drug group, and mutations conferring resistance to protease inhibitors were present in two infants in the three-drug group. No significant differences in the distribution of resistance mutations were found among the groups.
COMMENTARY
The standard antiretroviral regimen for infants whose mothers had not received antenatal therapy has been a six-week course of zidovudine alone, based on the Pediatrics AIDS Clinical Trials Group Protocol 076 study that was published in 1994. In this study, the intrapartum HIV transmission rate in the zidovudine-alone group was similar to other studies, and transmission rates were reduced by half in the two- and three-drug groups compared to zidovudine alone.
This study demonstrates that the administration of additional antiretroviral drugs to zidovudine significantly reduces the risk of intrapartum transmission of HIV. The availability, ease of administration, and low cost of the zidovudine-nevirapine regimen, and the significantly higher rate of neutropenia with the three-drug regimen, all favor the zidovudine-nevirapine regimen. Combination zidovudine-nevirapine therapy rather than zidovudine alone should be used for HIV prophylaxis of infants of mothers who have not received antenatal antiretroviral therapy.
A total of 1745 infants from 17 sites in Brazil (70.1%), South Africa (27.4%), Argentina (1.6%) and the United States (0.8%) born to women with a peripartum diagnosis of HIV type I infection were randomized within 48 hours of birth to receive one of three six-week postpartum antiretroviral regimens.Subscribe Now for Access
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