Using a resistance test prior to starting anti-HIV therapy for the first time may mean that HIV-positive patients with primary drug resistance have just as good a response to antiretroviral therapy as patients with wild-type HIV, a German study published in the April 15th edition of the Journal of Acquired Immune Deficiency Syndromes has found. The study was conducted between 2001 and 2003, and involved 296 individuals starting anti-HIV therapy in the German state of North Rhine-Westphalia.
The results of the study mean that all patients commencing HIV therapy in the state now have a resistance test to check for primary drug resistance before starting antiretroviral treatment. Treatment guidelines of the British HIV Association recommend that all HIV-positive individuals in the United Kingdom should have a resistance test prior to commencing anti-HIV treatment.
An increasing proportion of individuals are becoming infected with a strain of HIV that is resistant to anti-HIV drugs. This can mean that these individuals are less likely to achieve suppression of HIV to undetectable levels when they start anti-HIV treatment. Resistant HIV can persist for years after it is acquired, and resistance testing may therefore help to select a combination of anti-HIV drugs with the greatest chance of achieving virological suppression in patients with primary resistance.
German doctors therefore conducted genotypic resistance tests on all patients starting anti-HIV treatment for the first time at 42 treatment centres in the state of North Rhine-Westphalia, where over 20% of all HIV-positive patients in Germany live. They compared virological response to treatment in patients with primary resistance, who had their treatment regimen selected on the basis of the results of their resistance tests, to treatment outcomes in patients with fully drug-sensitive HIV.
The 296 patients included in the investigators’ analysis had a median age of 39 years, 75% were male, 77% were white, 40% had been diagnosed with AIDS, the median CD4 cell count was 177 cells/mm3 and median viral load was 171,000 copies/ml.
Genotypic tests showed that 30 patients (11%) had primary drug resistance, with 9% having resistance to drugs in the nucleoside reverse transcriptase inhibitor (NRTI) class, 4% in the non- nucleoside reverse transcriptase inhibitor (NNRTI) class, and 2% to protease inhibitors.
A wide variety of antiretroviral regimens were selected on the basis of these resistance tests. Virological failure – a viral load above 50 copies/ml after a year of treatment – was observed in 13% of patients with primary resistance and 13% of patients with wild-type HIV. The investigators then examined at virological response at six months and one year using intent-to-treat and on-treatment analysis. They found that there was no difference in treatment response between patients with wild-type HIV and individuals with primary resistance who had their antiretrovirals selected on the basis of genotypic resistance testing.
Similar increases in CD4 cell count were seen in both groups of patients at six months (wild-type, 310 cells/mm3 versus primary resistance, 376 cells/mm3, difference not significant) and twelve months (wild type 361 cells/mm3 versus primary resistance 410 cells/mm3, difference not significant). Multivariate analysis was then to see if factors such as gender, ethnicity, CD4 cell count and viral load at baseline affected treatment outcome. No significant relationships were found.
“Our study demonstrates similar virologic and immunologic efficacy of first-line HAART guided by genotypic resistance testing in patients harbouring primary resistance as compared to patients with wild-type virus”, write the investigators.
Oette M et al. Primary HIV drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing. J Acquir Immune Defic Syndr 41: 573 – 581, 2006.