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Resistance Test Before ART Erases Risk of Poor Viral Response
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XVII International AIDS Conference
August 3-8, 2008
Mexico City
Mark Mascolini
Basing first-line antiretroviral therapy (ART) on pretreatment genotypic resistance testing ensured that German patients starting ART with resistant HIV responded as well as people without resistant virus through 96 weeks of follow-up [1]. In univariate and multivariate analyses, pre-ART resistance mutations had no impact on virologic response.
German clinicians studied untreated people with chronic HIV infection in the prospective RESINA cohort. Among 677 people infected from 2001 through 2006, 78% were men. Their age averaged 39.6 years (standard deviation [SD] 10.3 years), pretreatment CD4 count averaged 197 (SD 167), and pretreatment viral load averaged 200,000 copies. One third of cohort members had AIDS before they started ART.
Counting resistance mutations specified on a list of resistance mutations for surveillance studies [2], the RESINA team figured that 9.7% of the cohort had at least one resistance mutation before beginning therapy. That rate matches prevalence across Europe [3]. Clinicians used the geno2pheno tool to pick active first-line regimens for people with resistant virus.
After 48 weeks of ART an intent-to-treat analysis determined that 66.7% with pretreatment resistance mutations had a viral load below 50 copies, compared with 72.3% of people without resistance mutations before treatment, a nonsignificant difference (P = 0.39). After 96 weeks of treatment sub-50-copy response rates were 60.9% in the pretreatment resistant group and 64.0% in the nonresistant group, also a nonsignificant difference (P = 0.75).
On-treatment analyses figured sub-50-copy response rates of 80.8% versus 86.6% for the resistant group versus the nonresistant groups after 48 weeks of treatment, and 85.5% versus 87.7% for those groups after 96 weeks. Both of these small differences between groups also lacked statistical significance (P = 0.23 and P = 1.0).
Only two variables analyzed affected risk of pretreatment resistant virus, male gender and infection with HIV-1 subtype B virus. Resistance rates measured 10.9% in men versus 6.6% in women (P = 0.04). Gay men had pretreatment mutations more often than other transmission risk groups (11.0% versus 8.8%), but that difference fell short of statistical significance (P = 0.17). Among people with subtype B virus, 11.5% had one or more pretreatment resistance mutations, compared with 6.1% infected with non-B viruses (P = 0.002). That difference, common throughout Europe, reflects heavier exposure to ART by white, European, subtype B-infected people than by Africans and other immigrants with non-B viruses.
Because of these results the RESINA investigators urged that "genotypic resistance testing should be strongly taken into account for tailoring the first-line HAART."
1. Reuter S, Oette M, Kaiser R, et al. First-line HAART guided by genotypic resistance testing - long-term follow-up data from the RESINA-study. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract MOPDA201.
2. Shafer RW, Rhee SY, Pillay D, et al. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance. AIDS. 2007;21:215-223.
3. Wensing AM, van de Vijver DA, Angarano G, et al. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management. J Infect Dis. 2005;192:958-966.
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