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The Body PRO Covers: The 10th Conference on Retroviruses and Opportunistic Infections

Antiretroviral Resistance Among Patients With Primary HIV Infection in the Southeastern U.S.

February 11, 2003

  • Antiretroviral Resistance Among Patients With Primary HIV Infection in the Southeastern U.S. -- Impact on Treatment Outcome (Poster 502)
    Authored by C. Hicks, J. Eron, J. Lennox, C. Pilcher, S. Fiscus, A. Weintrob, J. Giner, P. Menezes, E. Patrick, T. Alcorn
    View the original abstract


This study determined the rate of antiretroviral drug resistance in primary HIV infection (PHI) from a discrete geographic region (Southeastern United States: North Carolina and Georgia) during the years 1998-2002.

Genotypic and phenotypic resistance testing was performed on 31 (27 male, four female) patients with PHI at the time of diagnosis. Median time from PHI symptoms to testing was 26 days; HIV RNA values were predictably high (geometric mean 5.54 log). Phenotypic resistance based on the recommended Virco cutoffs was: NRTI: 7.4 percent, NNRTI: 11.1 percent, PI: 7.4 percent. Genotypic resistance was interpreted based on the Stanford database and was more modest: NRTI: 6.5 percent, NNRTI: 3.2 percent, PI: 0 percent.

Considering both genotypic and phenotypic results, a total of six patients had resistance to at least one of the drugs in the standard drug regimen administered: d4T (stavudine, Zerit) + ddI (didanosine, Videx) + nevirapine (NVP, Viramune) (with or without hydroxyurea). Of these, five had a complete response with HIV RNA <50 copies. Only one patient with resistance to d4T and ddI did not obtain an undetectable viral load and developed resistance to NVP.

Despite the fact that many large studies have been performed looking at resistance rates in newly infected patients, having up-to-date local data remains important for the practicing clinician. Rates from pooled national data or a study in San Francisco may not always mimic the rates in my practice in Georgia. I believe this is motivation for clinicians to support ongoing local cohorts.

The presence of HIV drug resistance in newly infected patients provides rationale for performing resistance testing in this population. Treatment need not be delayed if there is urgency and can be modified subsequently depending on results. If there is no urgency, the assay can be sent early and results received while we are still preparing our patient for the challenges of starting therapy. This of course depends on the clinical setting (such as PHI) and the time since infection. Only in situations where resources for resistance testing are very limited and testing need be strictly rationed, may one need to make decisions on the utility of such testing based on recent local rates.

This study provides additional insight into the difficulty of accurately defining baseline clinically relevant resistance. Reported rates of resistance vary between studies not only because of true geographic and temporal differences, but also due to the testing technology used (phenotype versus genotype) and how they are interpreted. This may be greatly influenced by the cutoffs used to interpret the phenotypic result and the mutational algorithm for the genotype.

In this study, rates for NNRTIs and PIs were a good deal higher for phenotypic than genotypic results. This would suggest some degree of reduced susceptibility was seen by the phenotypic assay without the presence of resistance mutations on genotyping. But does this degree of reduced susceptibility really effect therapy? Interestingly, in this study only one out of six patients did not respond, although larger studies are more appropriate to answer the question. Still it is clear we need clinically validated and more standardized definitions of resistance to help us make decisions on which drugs we can or cannot use in our newly infected patient.


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This article was provided by TheBodyPRO.com. It is a part of the publication The 10th Conference on Retroviruses and Opportunistic Infections.
 



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