Sixteen per cent of treatment-naïve patients enrolling in Glaxo SmithKline-sponsored clinical trials in the United States in 2005 already had resistance to at least one antiretroviral drug, according to data presented by company researchers at the Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco on Thursday.
Furthermore, the frequency of drug resistance has almost tripled since 2000, and almost two-thirds of those with resistance in 2005 showed resistance to a non-nucleoside reverse transcriptase inhibitor. This class of drugs forms the linchpin of first-line treatment for the majority of people beginning treatment in the United States. The findings reinforce the recent US Department of Health and Human Services recommendation that all people with HIV should receive a resistance test before starting treatment.
The study analysed data from 2035 treatment-naïve individuals who enrolled in GSK-sponsored studies in the US between 2000 and 2005. The recruited population was predominantly male (84%), 48% were white and 36% black, with a median CD4 cell count of 252 cells/mm3. There was a slight disparity in recruitment by year (less than 250 people were recruited to studies in 2000 and in 2005, but over 400 people entered studies in each of the other years).
Exposure category data were available on 1529 patients: 67% were gay men, 35% heterosexual, 5% had acquired HIV through injecting drug use and 2% through blood transfusion.
The researchers used two different classification systems for resistance to analyse the prevalence of resistance: the International AIDS Society definitions and the Stanford University definitions.
NNRTI resistance prevalence grew from 2% in 2000 to 10-11% in 2005, while nucleoside analogue resistance prevalence grew from 4-5% in 2000 to 7-8% in 2005 depending on which classification system was used. However, the two systems were in close agreement for all years and all drug categories regarding resistance prevalence.
Protease inhibitor resistance showed less of a trend towards increase, and remained below 5% throughout the period.
In the multivariate analysis the likelihood of participants having any resistance mutations significantly increased over time between 2000-2005, (p=0.0151 IAS or p=0.0219 Stanford respectively). Similarly the likelihood of having either NRTI or NNRTI mutations significantly increased over time by either IAS (p=0.0419, p=0.0109 respectively) or Stanford definitions (p=0.0116, p=0.0074 respectively).
Multivariate analysis also showed:
- No significant difference between gay men and heterosexuals in the risk of resistance (although using the Stanford University resistance definitions, heterosexuals appeared to have a lower risk of acquiring protease inhibitor resistance).
- A significantly lower risk of drug resistance overall among black men and women compared to whites (around 40% reduced risk), and a lower risk of nucleoside analogue resistance too (53% lower risk). The Stanford and IAS databases did not agree on whether a reduced risk of resistance for NNRTIs and PIs also applied to blacks.
- A greater risk of resistance in later years among people with lower viral load (HIV RNA
- There was greater resistance in the West of the United States in 2005 (around 25%) but this did not appear to be a trend, except for NRTI resistance.
Ross L et al. Factors associated with HIV-1 mutations linked to drug resistance in antiretroviral therapy naïve HIV-infected individuals in the United States from 2000-2005 (PREPARE study). 46th ICAAC, San Francisco, abstract H-0993, 2006.