Scottsdale, Arizona: The selection of nevirapine resistance mutations following exposure to a single dose of the drug given at the onset of labour for the prevention of mother-to-child HIV transmission, appears more likely in women infected with HIV subtype D than other subtypes. This new information has been derived from participants in the Ugandan HIVNET 012 study, and was presented at the Fifth International Resistance Workshop in Arizona yesterday.
In HIVNET 012, 311 women receiving nevirapine prophylaxis gave birth to 320 live children. Nearly all breastfed. Forty-nine of the 320 children were HIV-infected despite exposure to nevirapine; 37 by age 6-8 weeks. Blood samples taken from the mothers 6-8 weeks after nevirapine had been administered were genotyped. This analysis included 33 of 36 women whose children were infected by 6-8 weeks. In addition, samples from 72 women whose children were not infected were also analysed for resistance.
102 of 105 samples were successfully genotyped. HIV subtype was also assigned for 29/32 women with infected children, and 60/70 women whose children were not infected. Of these 89 women, 50 were infected with subtype A, 35 with subtype D, and 4 with subtype C. The remaining 13 carried an A/D inter-subtype recombinant virus.
The resistance analysis demonstrated that a higher proportion of women with subtype D (10/35; 29%) developed mutations associated with nevirapine resistance than women with subtype A (6/50; 12%). There was no difference in the rate of HIV transmission between different subtypes.
Baseline viral loads in women with subtype D and subtype A were similar, and so differences in disease stage do not appear to explain the higher rate of mutations in women with subtype D. The authors suggest that differences in replicative capacity between the two subtypes could have allowed for differences in the rate of emergence or disappearance of mutations (Eshleman). There is no evidence at present to support this hypothesis, though other research groups are looking into viral fitness of other HIV subtypes. Data from the Israel AIDS Study Group, also presented at the Resistance Workshop yesterday, found greater fitness amongst a panel of subtype C viruses compared to a subtype B reference strain (Schapiro).
Eshleman SH et al. Impact of HIV-1 subtype on women receiving single dose nevirapine prophylaxis to prevent HIV-1 mother-to-child transmission in HIVNET 012. Antiviral Therapy 2001; 6(Supplement 1):124.
Schapiro JM et al. A preliminary report on associations among clade-C genotype, phenotypic drug susceptibility, and replication capacity. Antiviral Therapy 2001; 6(Supplement 1):115.