WHO Updates Treatment Guidelines for Pregnant Women and Infants Using Single-dose Nevirapine

	SUMMARY: The World Health Organization (WHO) this week updated its antiretroviral therapy (ART) guidelines for women and infants who received single-dose nevirapine (Viramune) to prevent mother-to-child HIV transmission during delivery. The revision is based on 2 studies, published in the October 14, 2010 New England Journal of Medicine, showing that even a single dose of nevirapine was associated with drug resistance and subsequent treatment failure. Therefore, WHO recommends, women exposed to single-dose nevirapine within the past year should be treated with a combination regimen containing drugs other than NNRTIs, and babies should receive lopinavir/ritonavir (Kaletra).

By Liz Highleyman

Single-dose nevirapine is commonly used for prevention of mother-to-child transmission in resource-limited settings, especially for women who do not receive care until the time of delivery. But prior studies have shown that women and infants exposed to a single dose often develop drug resistance, which can compromise the effective not only of nevirapine itself, but also other non-nucleoside reverse transcriptase inhibitors (NNRTIs).

The first study, known as OCTANE A5208, looked at 745 women in 7 African countries who required ART for their own health; 241 of them had previously received single-dose prophylactic nevirapine during delivery.

Women treated with a nevirapine-based ART combination regimen were significantly more likely to experience virological failure or death than those using a lopinavir/ritonavir-based regimen, both also containing tenofovir/emtricitabine (Truvada) (26% vs 8%, respectively; P = 0.001).

Nevirapine resistance was detected in 14% of previously exposed women. Looking just at this subgroup, 73% of those who subsequently received the nevirapine combination regimen experienced virological failure or death, compared with 6% of those using the lopinavir/ritonavir regimen.

In an analysis of 500 women who had never received prophylactic single-dose nevirapine, rates of treatment failure or death were the same in the nevirapine and lopinavir/ritonavir combination therapy arms (both 14%).

Nevirapine resistance, and the associated risk of treatment failure, diminishes over time, however, and the guidelines advise that women can safely use the drug again if at least 12 months have passed since they received the single prophylactic dose.

In the second study, Paul Palumbo and colleagues with the P1060 study team looked at treatment outcomes among 164 infants (age 6-36 months) in 6 African countries who were exposed to single-dose nevirapine during delivery or immediately after birth.

Researchers found that babies subsequently treated with a nevirapine-based combination regimen were significantly more likely than those receiving lopinavir/ritonavir (both in combination with zidovudine/lamivudine, or Combivir) to experience virological failure or discontinue treatment at 24 weeks (40% vs 22%, respectively; P = 0.02).

Baseline nevirapine resistance was detected in 12% of the infants, and it predicted treatment failure. Among babies with resistance mutations, 83% of those taking the nevirapine-based regimen experienced virological failure or stopped therapy, compared with 18% of those on the lopinavir/ritonavir-based regimen.

"Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required," the study authors concluded.

But this presents a challenge, Marc Lallemant and Gonzague Jourdain from Harvard School of Public Health acknowledged in an accompanying editorial, because nevirapine is among the cheapest and most widely available antiretroviral drugs in low-income countries.

"The results of the OCTANE and P1060 trials are highly relevant despite the paradigm shift away from interventions incorporating single-dose nevirapine to interventions comprising highly active antiretroviral drugs for the prevention of mother-to-child transmission," they wrote. "In resource-limited settings, where many women still present late for antenatal care and too few are screened for CD4+ cell count, single-dose nevirapine will most likely remain an important component of the toolkit for the prevention of mother-to-child transmission."

The WHO treatment guidelines are available online:

	Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach -- 2010 revision: http://www.who.int/hiv/pub/arv/adult2010/en/index.html.
	Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach -- 2010 revision: http://www.who.int/hiv/pub/paediatric/infants2010/en/index.html.

10/19/10

References

P Palumbo, JC Lindsey, MD Hugher, A Violari, and others. Antiretroviral treatment for children with peripartum nevirapine exposure. New England Journal of Medicine 363(16): 1510-1520 (Abstract). October 14, 2010.

S Lockman, MD Hughes, J McIntyre, JS Currier, and others. Antiretroviral therapies in women after single-dose nevirapine exposure. New England Journal of Medicine 363(16): 1499-1509 (Abstract). October 14, 2010.

M Lallemant and G Jourdain Preventing mother-to-child transmission of HIV -- protecting this generation and the next (Editorial). New England Journal of Medicine 363(16): 1570-1572. October 14, 2010.

Other Source

National Institute of Allergy and Infectious Diseases. NIH Studies Influence Revision of WHO Guidelines for Treating HIV-Infected Women, Infants. NIH News press release. October 13, 2010.