640 Continued Reverse Transcriptase Inhibitor Therapy is Sufficient to Maintain Short-Term Partial Suppression of Multi-drug Resistant Viremia S G Deeks*1, J N Martin1, R Hoh1, T Wrin2, C Petropoulos2, R M Grant1,3 1Univ of California, San Francisco, SF CA; 2ViroLogic, South San Francisco, CA; and 3Gladstone Institute of Virology and Immunology, SF CA
Background: We hypothesized that among treated patients with multi-drug resistant HIV, interruption of all drugs from a single therapeutic class ("partial treatment interruptions", PTI) could (1) maintain partial viral suppression and its associated immunologic benefit, (2) prevent overgrowth of wild-type HIV, (3) delay viral evolution, and (4) reduce drug-toxicity and drug costs.
Methods: This is a prospective non-randomized pilot study of patients interrupting either the protease inhibitor (PI) or reverse transcriptase inhibitor (NRTI) component of a combination regimen. Eligible subjects had persistent viremia (>400 copies/mL) and > 90% adherence to a regimen containing both NRTIs and PIs. The decision to interrupt either PI or NRTI therapy was based on subject-specific toxicity.
Results: Twenty subjects were studied. The median baseline viral load was 3.9 log copies/ml (IQR 3.6 - 4.5) and the median CD4 Tcell count was 336 cells/mm; these pre-PTI values represented a median 1.2 log copies/mL decrease in viral load relative to pre-treatment levels. Interruption of all PIs (and continuation of all NRTIs) in 15 subjects was associated with stable viremia and CD4+ T cell counts. The mean change in viremia was 0.005 log copies/week (95% CI -0.01 to +0.02; p=0.49). Significant decreases in fasting triglyceride (-90 mg/dL; p=0.02) and non-HDL cholesterol (-30 mg/dL, p=0.03) were observed at week 12. Genotypic and phenotypic resistance remained stable in all patients interrupting PI therapy (through week 16-24); however, PI mutations waned and replicative capacity and viremia increased in two patients after week 24. In contrast, all 5 subjects that interrupted NRTI therapy (and continued PI therapy) exhibited immediate and sustained increases in viremia (+0.03 log copies/week, P < 0.001). Three of 5 subjects interrupting NRTI therapy exhibited a delayed loss of M184V, which was temporally associated with a rise in viremia.
Conclusions: Interrupting PI therapy in patients with multi-drug resistant HIV is associated with stable viremia, reduced toxicity, and halted accumulation of drug resistance (which may preserve future PI options). In contrast, interruption of NRTI therapy was associated with rapid rises in viremia, indicating that NRTIs may have continued antiviral effects against drug resistant HIV. Partial treatment interruptions may be appropriate for maintaining partial virologic responses in persons with limited treatment options.
