Although the occurrence of transmission of drug-resistant HIV is well recognized, the impact of this transmission on natural history of HIV infection is not known.

To assess the question of the impact on natural history and on response to first line therapy in HIV patients, 300 HIV positive, treatment-naive individuals were enrolled between 1987 and 1993. The results of resistance tests administered within 18 months of infection were assessed.

The investigators estimated the impact of transmitted drug resistance (TDR) on subsequent CD4 cell count decline in the absence of treatment. They also assessed the response to antiretroviral therapy based on the number of active drugs utilized (according to genotypic resistance results).

Results

• Infection with any form of drug-resistant HIV-1 was associated with a steeper decline of CD4 cell count over the first year of infection.
• Estimated rates of decline in the first year were 5.0 and 1.7 CD4 cells per year for TDR and no TDR, respectively (P = 0.005).
• For an individual at a CD4 cell count of 500 cells/microliter at seroconversion, these rates correspond to a CD4 cell loss of 199 and 73 cells/microliter, respectively, in the first year.
• Thereafter no evidence of a difference in the rate of CD4 cell decline was found (P = 0.32).
• Initiation of HAART after calendar year 2000, but not number of active drugs, was associated with improved responses.

Based on these findings, the authors conclude, “The impact of transmitted HIV-1 drug resistance on CD4 cell decline is time dependent, with greater rates of decline in the first year following infection.”

“We found no evidence of a longer term effect of TDR on natural history of HIV-1 infection.”

CASCADE Virology Collaboration

01/27/06

Reference
CASCADE Virology Collaboration. The impact of transmitted drug resistance on the natural history of HIV infection and response to first-line therapy. AIDS 20(1): 21-28, January 2, 2006.

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