Around one in seven of a large sample of treatment-naïve HIV-positive Americans from 40 cities showed evidence of resistance to at least one antiretroviral drug, and 23% had reduced susceptibility to at least one drug, according to findings from a study presented on Saturday at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington DC.
The study, conducted by GlaxoSmithKline and the University of Miami, evaluated samples from 317 HIV-positive individuals collected in 2003 for reduced drug susceptibility and antiretroviral drug resistance mutations.
Participants in the cohort had a mean CD4 cell count of 277 cells/mm3, mean viral load of 52,500 copies/ml and 29% had viral load above 100,000 copies/ml (5.0 log10 copies/ml). Unlike a recent study in the United Kingdom, the population in this cohort were not exclusively recent seroconverters, and so may be more representative of the population of patients ready to start antiretroviral treatment under current United States guidelines.
Reduced susceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was most frequently observed: 18% of patients had reduced susceptibility to at least one NNRTI. However, only 6% had a specific mutation associated with NNRTI resistance, suggesting that the finding of reduced susceptibility may reflect population variation in drug susceptibility that may not prove clinically meaningful. Indeed, when drug susceptibility was broken down by drug, it became evident that whilst 16% of patients had reduced susceptibility to delavirdine (Rescriptor, a drug not used in first-line treatment), only 6% had reduced susceptibility to efavirenz (Sustiva) and 9% had reduced susceptibility to nevirapine (Viramune). The degree of reduction in susceptibility was not stated, creating a further difficulty in assessing the clinical relevance of the finding of reduced susceptibility.
In contrast, reduced susceptibility to nucleoside analogues (NRTIs) was very low: only 0.9% had evidence of reduced susceptibility to one or more NRTIs, even though 8% of patients had at least one resistance mutation associated with NRTI resistance (most frequently V118I [4%]). No other NRTI mutation was present in more than 1% of the study population.
Resistance mutations associated with protease inhibitor resistance were similarly rare. Although 6% of patients had reduced susceptibility to at least one protease inhibitor, only 2% had specific resistance mutations.
Ethnic differences in drug resistance were most pronounced between Hispanic and Asian patients and other groups (white, African-American). Hispanic and Asian patients (12% of sample) had a significantly lower prevalence of reduced susceptibility (6%) than white (55% of sample) or African-American (33% of sample; 27 and 23% prevalence respectively; p = 0.022). However, Hispanic patients showed a trend towards a higher prevalence of drug resistance mutations (17 vs. 13 [white] and 14% [African-American]), particularly NRTI mutations (14 vs. 7% for other groups).
Ross L et al. Prevalence of antiretroviral drug resistance and resistance mutations in antiretroviral therapy (ART)-naïve HIV-infected individuals from 40 US cities during 2003. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract H-173, 2004.