Implications for prognosis

It is unclear whether unfit virus with little capacity to replicate will mean slower progression. Three studies in recently infected individuals found no evidence of a slower rate of disease progression in terms of CD4 cell loss.1 2 3

However, researchers in San Francisco have produced contradictory conclusions, finding that those with genotypic evidence of drug resistance or virus with reduced replication capacity had significantly higher CD4 cell counts after controlling for duration of infection.4

At the Seventh International Congress on Drug Therapy in HIV Infection in 2004, Dr Mark Wainberg of McGill University AIDS Centre in Montreal, Canada, argued that the clinical consequences of infection with multidrug-resistant virus were unpredictable, varying from repeated treatment failure to long-term non-progression. Low replicative capacity of multidrug-resistant virus may correlate with low viral load and delayed progress, but this theory is yet to be proven.

Of course, acquiring drug-resistant HIV is assumed to reduce treatment options. Resistance testing can be used to select active regimens for many people in this situation, and there is evidence that baseline resistance may not affect the short-term efficacy of first-line treatment when selected to account for resistance.5 6 However, experts suspect that second- and third-line therapy may be compromised. NRTI and NNRTI resistance has been linked a greater risk of death in a large Canadian cohort followed between 1996 and 2003.7

Effects of acquiring drug-resistant virus appear to differ by drug class. Compared to recent seroconverters with wild-type virus, those with PI- and NRTI-associated resistance have shown consistently lower viral loads over time, and those with NNRTI-associated resistance had significantly higher viral loads over time.8

References

  1. Pillay D et al. The impact of transmitted resistance on time to CD4< 350 cells/ml. Antivir Ther 7: S147, 2002
  2. de Mendoza C et al. Impact of drug-resistant HIV viruses on viral load, CD4 counts and CD4 decline in recent seroconverters. Twelfth International HIV Drug Resistance Workshop, Los Cabos, abstract 81, 2003
  3. Bhaskaran K et al. Do patients who are affected with drug-resistant HIV have a different CD4 cell decline after seroconversion? An exploratory analysis in the UK Register of HIV Seroconverters. AIDS 18: 1471-1473, 2004
  4. Grant RM et al. Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA 188: 181-188, 2002
  5. Pillay D et al. The effect of transmitted drug resistance on virological response to HAART regimens adjusted for genotypic resistance at baseline. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 685, 2004
  6. Oette M et al. Primary drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing. J Acquir Immune Defic Syndr 41(5): 573-581, 2006
  7. Hogg RS et al. Drug resistance is associated with an increased risk of death in patients first starting HAART. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 712, 2005
  8. Little S Transmission of HIV drug resistance and treatment response. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 60, 2007
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