Safe babies, threatened mothers?

The most basic way of preventing mother-to-child transmission of HIV appears to cause resistance to one of the key anti-HIV drugs in women more than six months after they give birth. Previous studies had suggested that this would not happen.

This new research finding means that tens of thousands of women may be taking antiretroviral therapy that is less effective than expected if they received the basic prophylaxis to protect their children from HIV, namely a single dose of nevirapine (SD-NVP) during childbirth.

The findings have caused researchers to call for an emergency response from government to adjust the “hopelessly out of date” guidelines on adult antiretroviral therapy (ART).

The new research involves an Octane (optimal combination therapy after nevirapine exposure) trial, part of which has been halted since it was discovered that 24% of women on ART that contained nevirapine either died or failed to contain the virus, compared to just 7% of women on the alternative treatment. The other part of the trial, which involves women who had not received SD-NVP, will continue until the expected end date next year.

“The implications are huge, we must change policy,” said Francesca Conradie of the clinical HIV research unit at Wits University and the site leader for the South African arm of the Octane trial. “It’s a pivotal study and cannot be ignored because it will allow us save the lives of hundreds of thousands of women.”

However, Conradie cautioned that the results should not be interpreted to mean that the use of SD-NVP to protect babies against HIV should not have been implemented in South Africa. “This strategy reduced mother-to-child-transmission significantly and has protected thousands of babies from HIV. When it was implemented that was the best method that we knew that could be used in a South African context. Now that we have new research, to continue using SD-NVP would be like driving a car from 1980 in 2008 and expecting it to compare.”

One of the designers of the Octane trial was Professor James McIntyre, of the perinatal HIV research unit (PHRU) at Wits, who said the results could have major implications for the antiretroviral treatment programme.

One implication is that women who have already had SD-NVP and who need chronic antiretroviral therapy for themselves should be started on a drug combination that does not include nevirapine or another drug in the same class.

The alternative would be to give them a protease inhibitor, such as Kaletra. This is currently used for second-line treatment in South Africa and such a change would drive up treatment costs, since Kaletra alone costs the same as the three drugs currently used in the first-line regimen.

McIntyre said that while the results so far indicate that SD-NVP had a greater impact on drug resistance than expected, some of the differences between the two treatment regimens being compared could arise from the alternative drug combination simply being more effective.

South Africa has belatedly updated its guidelines for prevention of mother-to-child transmission therapy so that women are given two antiretroviral drugs during late pregnancy and childbirth. But the guidelines fail to require the strategy of “covering the tail” by giving two anti-HIV drugs to the mother for a week after the child’s birth. These additional drugs prevent the development of drug resistance as the levels of nevirapine within the woman’s body slowly falls.

McIntyre said researchers had been arguing for such “tail cover” since 2004. François Venter, head of the Southern Africa HIV Clinicians Society, welcomed the research, saying: “It is good to see a focus on women’s health in HIV, rather than simply trying to ensure HIV-negative orphans.”

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