14th International HIV Drug Resistance Workshop 7-11 June 2005, Québec City, Canada

RESISTANCE AFTER SINGLE DOSE NEVIRAPINE PROPHYLAXIS VARIES BY VIRAL SUBTYPE IN INFANTS FROM SUB-SAHARAN AFRICA

Antivir Ther. 10, Suppl 1:S12 (abstract no. 10)

SH Eshleman¹, DR Hoover², SE Hudelson¹, S Chen¹, LA Guay¹, A Mwatha³, SA Fiscus⁴, F Mmiro⁵, P Musoke⁵, JB Jackson¹, NI Kumwenda¹, and T Taha^1
1Johns Hopkins University, Baltimore, MD, USA; ²Rutgers University, Piscataway, NJ, USA; ³Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA; ⁴University of North Carolina, Chapel Hill, NC, USA; ⁵Makerere University, Uganda

BACKGROUND: The Ugandan HIVNET 012 trial found that administration of single dose nevirapine to women in labour and to infants after birth can prevent HIV-1 mother-to-child transmission. The NVAZ study in Malawi included women and infants who received the same single dose nevirapine regimen. A previous comparison of maternal nevirapine resistance in HIVNET 012 and NVAZ revealed that resistance was more frequent in women with subtype C HIV-1 (45/65=69%) than in women with subtype A (28/144=19%, P<0.0001) or D (35/97=36%, P<0.0001). The higher frequency of nevirapine resistance among subtype C strains was independent of baseline viral load, maternal age, parity or the time between nevirapine dosing and resistance testing. It is not known whether subtype influences emergence of nevirapine in infants who become HIV-1 infected despite nevirapine prophylaxis.

METHODS: We analysed nevirapine resistance in HIVNET 012 and NVAZ infants who became HIV-1 infected despite nevirapine prophylaxis. All of the mothers and infants in this analysis received the HIVNET 012 regimen without other antiretroviral prophylaxis. Nevirapine resistance was analysed with the ViroSeq HIV Genotyping System using 0.1 ml infant plasma samples collected 6–8 weeks after single dose nevirapine administration (6–8 weeks after birth).

RESULTS: Genotypes were obtained for HIV-1 from 24 infants in HIVNET 012 (nine with subtype A, one with subtype C, nine with subtype D, and five with intersubtype recombinant HIV-1) and 23 infants in NVAZ (all with subtype C). Nevirapine resistance mutations were detected in HIV-1 from 11/24 (46%) infants in HIVNET 012, compared to 20/23 (87%) infants in NVAZ (P=0.005, exact test).

CONCLUSION: Nevirapine resistance was more frequent in Malawian infants with subtype C than in Ugandan infants (mostly with other subtypes) 6–8 weeks after single dose nevirapine. This is consistent with the higher frequency of nevirapine resistance observed in these trials among mothers with subtype C than with A or D. Further studies are needed to evaluate whether the higher frequency of nevirapine resistance observed in Malawian infants after single dose nevirapine reflects effects of HIV subtype, or other factors.

PRESENTING AUTHOR: SH Eshleman

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2005-06-07
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