Nevirapine-based triple-drug combinations safe for use in pregnant African women

Christopher Gadd
Published: 10 July 2006

Triple-drug combinations containing nevirapine (Viramune) are safe and effective for most pregnant women in resource-limited settings, according to a review of medical notes from over 700 women in Africa. The study’s findings were published in the July edition of HIV Medicine.

Nevirapine is often used in resource-limited settings for the treatment of HIV infection and the prevention of mother-to-child transmission of the virus. However, there are concerns surrounding the risk of liver toxicity in pregnant women taking nevirapine, particularly in those with CD4 cell counts above 250 cells/mm3.

Previous studies have reached different conclusions about the safety of nevirapine in HIV-positive women, because they included small numbers of women. Therefore, investigators from Drug Resources Enhancement against AIDS and Malaria (DREAM), wished to assess the safety of nevirapine-based HIV treatment in a large sample of pregnant women from their programme in Mozambique and other sub-Saharan African countries.

The investigators analysed the notes of 703 women who took nevirapine-based drug combinations between May 2002 and July 2004. All of the women took treatment for at least 14 days, starting with normal liver enzyme levels.

The women began treatment in the 25th week of pregnancy, unless their CD4 cell count was below 200 cells/mm3 or their viral load was above 55,000 copies/ml: these women started in the 15th week of pregnancy. Treatment was continued after pregnancy, unless the women had a CD4 cell count above 200 cells/mm3 and no symptoms of HIV disease.

After two months of treatment, 79% of the women had viral loads below 1000 copies/ml, falling from a median of 11,200 to 50 copies/ml. CD4 cell counts increased from 490 to 630 cells/mm3 by two months, and to 694 cells/mm3 after four months.

Over a median of 118 days’ exposure, few of the women experienced severe side-effects (grades 3 or 4): 7% experienced liver toxicity, 2% skin rashes and 1% Stevens-Johnson syndrome, a severe reaction affecting the skin, with most cases of toxicity occurring within the first two months. Only ten of the 46 women with severe toxicity needed to change treatment, replacing nevirapine with either nelfinavir (Viracept) or indinavir (Crixivan).

The investigators could not detect a difference in the rate of liver toxicity caused by higher CD4 cell counts before treatment, but women with higher CD4 cell counts did experience liver toxicity earlier (p < 0.001).

Five women died during over the 27 months of the study. However, only one of these could be linked to antiretroviral treatment. This death rate (0.9%) was less than the registered average death rate of women in Mozambique (1%).

“The low frequency and mainly minor consequences of adverse reactions to a nevirapine-based regimen in poor women in this resource-limited environment suggest that such a regimen should be considered by policy makers and those involved in HIV programmes as the preferred treatment for HIV-positive pregnant women,” conclude the investigators.

At the end of the study, 554 of the women had reached the end of their pregnancies, and 96 were still pregnant, with the remainder dropping out of the study. Of the 331 children born before February 2004, the HIV infection rate was 3% and the mortality rate was 5%. The women were given formula milk free of charge to prevent HIV transmissions through breastfeeding.

Ninety per cent of the women took AZT (zidovudine, Retrovir and 3TC (lamivudine, Epivir) with nevirapine, although those with low haemoglobin levels took d4T (stavudine, Zerit) in place of AZT. The women with CD4 cell counts below 200 cells/mm3 also took co-trimoxazole (Septrin) to prevent opportunistic infections.

“When treating pregnant women, our goal should be to decrease the viral load as quickly and effectively as possible,” write the investigators. “It is clear from this and other studies that antiretroviral triple therapy represents the gold standard for accomplishing this goal. The limited drop-out rate in this large programme run in a public health setting in a limited-resource environment provides reassurance that this goal is possible even in developing countries.”

Reference

Marazzi MC et al. Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. HIV Med 7: 338-344, 2006.

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