January 16, 2007

Nevirapine Works After Use in Pregnancy
(AIDSmeds.com)

HIV-positive pregnant women who use single-dose Viramune® (nevirapine) during labor to prevent transmission of the virus to their babies may still benefit from using the drug in a complete treatment regimen to protect her own health, provided that at least six months have passed since the time of delivery. This important finding, from a study published in the January 11 issue of the New England Journal of Medicine, is encouraging news for HIV-positive women in developing nations where treatment options are limited and the use of single-dose Viramune is a very popular strategy to reduce the risk of mother-to-child HIV transmission (MTCT).

A single dose of Viramune, or its generic equivalent (nevirapine), used at the time of labor – with or without a short course of Retrovir® (zidovudine) during the last weeks or months of pregnancy – is a common regimen given to prevent MTCT in resource-poor countries where the standard, more expensive, multi-drug treatment regimens are not widely available. Previous studies have indicated, however, that the single-dose Viramune may cause high-level HIV resistance to the drug. In turn, she may be less likely to respond favorably to Viramune if she needs it later, as part of a complete drug regimen, to safeguard her own health.

To determine if single-dose Viramune use during labor really does limit the effectiveness of the drug at a later time point, Shahin Lockman, MD, of Boston’s Brigham and William’s Hospital and her colleagues followed 218 women in Botswana taking a Viramune-based drug combination to protect their own health. All of the women had participated in an earlier clinical trial, while pregnant, evaluating Viramune combined with zidovudine to prevent transmission of their HIV infection to their babies.

The previous study enrolled 1,200 HIV-positive women between March 2001 and October 2003. All women received a course of zidovudine from the 34th week of pregnancy to delivery. They were also randomized to receive either a placebo or a single dose of Viramune given at the beginning of labor. Additionally, infants received either a placebo or a single dose of Viramune between 48 to 72 hours after birth.

The 218 volunteers in the more recent study included women who eventually needed combination therapy for their own health after they had given birth. Of these women, 112 had originally been randomized to receive single-dose Viramune and another 106 women had originally been randomized to receive Viramune placebo.

Sixty of the women required combination therapy within six months of receiving either single-dose nevirapine or placebo during labor. Among those who received single-dose nevirapine during labor, 41.7% still had detectable viral loads after receiving six months of treatment, indicating that the drug regimen used was not effective. Among those who took Viramune placebo during delivery, all had undetectable viral loads after six months of treatment.

The rates of detectable viral loads did not differ significantly among the other 158 women who were able to hold off on starting their Viramune-based regimens for at least six months after receiving single dose nevirapine or placebo. Of these, 12% of those in the Viramune group and 7.8% of those in the placebo group still had detectable HIV levels after receiving six months of treatment, indicating equal effectiveness in both groups.

Dr. Lockman and her colleagues wrote that their findings are consisting with earlier study results, indicating that while Viramune-resistant strains of HIV could be present after using single-dose Viramune, these strains begin to fade with time and eventually make up a minor proportion of HIV strains in a patient's body.

In conclusion, Dr. Lockman’s group stressed that Viramune-based antiretroviral therapy should be considered a worthwhile option for women who received a single-dose Viramune preventive regimen more than six months ago. While the authors point out that there will likely be many women requiring antiretroviral therapy – for their own health – before six months have passed, they recommend that these women be started on a regimen that does not include Viramune.

"Every effort should be made," Dr. Lockman’s team writes, to provide combination antiretroviral treatment during pregnancy to women who need it for their own health, as these women are at highest risk for AIDS-related complications or death, for passing HIV on to their infants, and for developing Viramune resistance after a single dose of the drug.

Source:

Lockman S, Shapiro RL, Smeaton LM, et al. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 356:135-47, 2007.