Combo treatment cuts HIV in newborns
Ease of use, reduced toxicity, availability, and low cost suggest that zidovudine plus nevirapine is an attractive option for prophylaxis in infants at high risk for perinatal HIV-1 infection.
Babies whose HIV-positive mothers had not received anti-retroviral therapy during pregnancy were more effectively protected from intrapartum transmission of the virus with a two- or three-drug regimen than with zidovudine (Retrovir) alone, an international clinical trial found.
The rate of intrapartum HIV transmission at 3 months was 4.8% (95% CI 3.2 to 7.1) in neonates given zidovudine monotherapy compared with 2.2% (95% CI 1.2 to 3.9, P=0.046) in those treated with zidovudine plus nevirapine (Viramune), according to Karin Nielsen-Saines, MD, of the University of California Los Angeles, and colleagues.
Similarly, the transmission rate in infants receiving zidovudine plus nelfinavir (Viracept) and lamivudine was 2.4% (95% CI 1.4 to 4.3, P=0.046), the researchers reported in the June 21 issue of the New England Journal of Medicine.
Previous studies have found that HIV transmission rates were lower when infants whose mothers had untreated infection began prophylaxis with zidovudine within the first 2 days of life. However, because rates remained high with monotherapy, combination therapy has increasingly been used, despite a lack of clear evidence for this practice.
Therefore, Nielsen-Saines and colleagues enrolled 1,684 infants from South America, Africa, and the United States between 2004 and 2010, randomizing them to one of the three anti-retroviral regimens.
None of the mothers had received antenatal anti-retroviral therapy, but had positive results on HIV rapid tests administered during labor or delivery, or during the first 2 days following the birth.
The infants were fed formula exclusively.
All of the neonates were given zidovudine for 6 weeks. The two-drug group also had three doses of nevirapine within 8 days after birth, and the triple-drug group were given 2 weeks of treatment with nelfinavir and lamivudine.
At baseline, median maternal age was 26, and more than three-quarters were mixed race or black.
Syphilis coinfection was present in 9.3%, and illicit substances had been used during pregnancy by 8.8%.
Almost two-thirds of the mothers had received some prenatal care and nearly half had been seen at least three times yet had not had their HIV infection diagnosed.
"These findings indicate that there were numerous missed opportunities to diagnose maternal HIV-1 infection and provide prophylaxis against mother-to-child transmission," the investigators observed.
The overall rate of HIV infection in the offspring was 8.3%, including those infected in utero and those becoming positive by 6 weeks and by 3 months.
In addition, the overall transmission rate was 11% in the zidovudine group compared with 7.1% and 7.4% in the two-drug and three-drug groups, respectively (P=0.03 for both).
A total of 2.6% of the neonates died, with no differences being seen according to treatment group and no deaths being attributed to the study treatments.
When the investigators considered risk factors that were associated with an increased risk for HIV transmission, they determined that zidovudine monotherapy was one such independent risk factor.
This was shown by the finding that, compared with monotherapy, the adjusted odds ratios for HIV transmission in the two-drug and three-drug groups were 0.39 (95% CI 0.19 to 0.82, P=0.01) and 0.50 (95% CI 0.24 to 1.01, P=0.05), respectively.
Other risk factors included maternal viral load, with an adjusted odds ratio of 2.28 (95% CI 1.56 to 3.35, P<0.001), and illicit maternal substance use during pregnancy (OR 2.51, 95% CI 1.08 to 5.86, P=0.03).
Grade 2 neutropenia developed in 16.4% of patients on zidovudine alone, in 14.9% of patients on the two-drug regimen, but in 27.5% of patients receiving three drugs (P<0.001).
Serious adverse events considered to be probably related to drug treatment, most often neutropenia and anemia, were seen in 4.9% of the three-drug group and in 3.7% and 1.8% of the monotherapy and two-drug groups, respectively.
The investigators observed that both multidrug regimens cut the transmission rates in half, but noted that the nevirapine combination was more easily administered because a liquid formulation is available and is better absorbed in infants than is nelfinavir.
"Our findings show that large-scale rapid HIV-1 testing during labor or the immediate postpartum period, followed by prompt initiation of [anti-retroviral therapy] in infants, is feasible, acceptable, and effective," stated Nielsen-Saines and colleagues.
While the standard prophylaxis for infants whose mothers are HIV-positive has been 6 weeks of treatment with zidovudine alone, this study supported the use of combination therapy, according to the investigators.
"Ease of use, reduced toxicity, availability, and low cost suggest that zidovudine plus nevirapine is an attractive option for prophylaxis in infants at high risk for perinatal HIV-1 infection," they concluded.
Three of the study drugs were donated by the manufacturers.
A number of the investigators have received funding from the National Institutes of Health. Some also have received funding from organizations such as the CREATE consortium, the Oswaldo Cruz Foundation, IMPAACT, and the HIV Prevention Trials Network.
By Nancy Walsh
Primary source: New England Journal of Medicine Source reference: Nielsen-Saines K, et al "Three postpartum antiretroviral regimens to prevent intrapartum HIV infection" N Engl J Med 2012; 366:2368-2379.
Source: MedPage Today