NRTIs May Show Continued Anti-HIV Activity Despite Long Durations of Partially Suppressive Therapy and the Presence of Resistant HIV  
 
Antiretroviral (ARV) treatment decisions are difficult for HIV-1-infected patients on complex treatment regimens who have partial suppression of HIV-1 replication and limited treatment options. Information on the ARV activity of the components of a complex regimen would be useful.

Sixteen subjects who had received prolonged therapy with zidovudine/ ZDV (Retrovir) and lamivudine/ 3TC (Epivir), with a median duration of 32.5 months, were discontinuing this dual-nucleoside regimen and volunteered to have plasma HIV-1 RNA levels monitored over the 2 weeks after discontinuation.

Results

All subjects experienced an increase in HIV-1 RNA after discontinuation, with a median increase of 0.54 log10 copies/mL over 2 weeks (range: 0.31-1.71; P < 0.001).

An inverse correlation existed between the decline in HIV-1 RNA levels over 2 to 3 years on nucleoside analogue therapy and the increase over the 10 to 14 days off therapy (P = 0.036).

Over the 2-week period, a subset of individuals who had genotype testing at multiple reverse transcriptase codons associated with ZDV and 3TC resistance had no changes in genotype off therapy.

The authors conclude, “Nucleoside analogue reverse transcriptase inhibitors (NNRTIs) may have continued ARV activity despite long durations of partially suppressive therapy and the presence of resistant HIV-1.”

Discussion

These results suggest that combination nucleoside analogue therapy that includes ZDV and 3TC can have a persistent ARV effect even after 2 to 3 years of therapy. The patients studied were a nonrandom subset of a larger cohort of patients treated during two trials of dual-nucleoside therapy who remained on dual-nucleoside therapy for several years. Therefore, these results should be interpreted cautiously.

Overall, these results support the hypothesis that the NRTI component of a multi-class combination ARV regimen retains at least some antiviral activity despite the presence of NRTI resistance in HIV-1-infected patients with partial viral suppression.

Whether the ARV and immunologic benefits observed in such patients with limited treatment options can be sustained over long periods with nucleoside analogue therapy alone to decrease toxicity, resistance emergence, pill burden, and cost should be studied in carefully controlled clinical trials.

12/10/04

Reference
J J Eron Jr and others. Persistent Antiretroviral Activity of Nucleoside Analogues After Prolonged Zidovudine and Lamivudine Therapy as Demonstrated by Rapid Loss of Activity After Discontinuation. Journal of Acquired Immune Deficiency Syndromes. 37(5): 1581-1583, December 15, 2004.

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