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Resistance Already Emerging in First Months of Treatment Despite Viral Load Decline

The emergence of drug resistance is already detectable in the first months of HIV treatment even if viral load is falling, and is especially pronounced// in people who experience slower viral load declines, a small, intensive German study has found.

As selection of drug-resistant virus correlated significantly with the length of time until viral load became undetectable, the researchers recommend therapy intensification during the early treatment phase be considered as a strategy to control replication.

In this study, published in the March 30th edition of AIDS, 15 mainly chronically infected patients were followed just prior to and during the early months of antiretroviral therapy.

Plasma sampling was performed before and during treatment, as was HIV-1 quantification and genotypic analysis. Three key resistance mutations were tracked, the L90M (protease) and K103N and M184V (reverse transcriptase), using a PCR assay designed to detect the three specific mutations.The specificity of the assay allowed the detection of mutant virus populations if they comprised no more than 0.01-0.2% of the total virus population, compared to a normal resistance assay threshold of around 10-15%.

The drug regimens varied, but all contained 3TC combined with another nucleoside reverse transcriptase inhibitor (NRTI) plus either a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI).

Fourteen of the patients were chronically infected and eleven were first diagnosed with HIV showing AIDS-defining symptoms. Two of the patients were women, the mean age was 39 (median 32), CD4 cells ranged from 6 to 912 cells/mm3, and viral loads ranged from 7500 to 360,000 HIV-1 RNA copies/mL.

Four patients had one or two drug-resistant mutations at baseline and selection of drug-resistant variants occurred following treatment. Two other patients did not have detectable drug-resistant mutations at baseline,
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