Combination antiretroviral therapy without a nucleoside reverse transcriptase inhibitor: experience from 334 patients in three cohorts.

BACKGROUND: Toxicity and resistance may limit the use of HIV nucleoside reverse transcriptase inhibitors (NRTIs). We assessed the safety and activity of regimens that did not include an NRTI. METHOD AND PATIENTS: We analysed NRTI-sparing regimens using pooled data from three cohorts in Australia and France where HIV RNA viral load, CD4 lymphocyte count and metabolic parameters are assessed prospectively. The inclusion criterion was the commencement of any antiretroviral combination excluding NRTIs.
RESULTS: A total of 334 (3.9%) of 8477 patients were included in the present study for a median follow-up time of 105 weeks. Therapeutic combinations were one nonnucleoside reverse transcriptase inhibitor (NNRTI) plus one protease inhibitor (PI) (58%), two PIs (26%), one PI (16%), and one NNRTI plus two PIs (8%). At baseline, the median CD4 lymphocyte count was 264 cells/muL (interquartile range 164-446 cells/muL) and 25% of patients had plasma HIV RNA below 500 HIV-1 RNA copies/mL. In intent-to-treat analysis, 64% of patients had HIV RNA <500 copies/mL at 6 months and 68% at 24 months. The mean CD4 lymphocyte count increase was 60 cells/microL (95% confidence interval 41-76 cells/microL) at 6 months and 111 cells/microL (95% confidence interval 82-140 cells/microL) at 24 months. Prognostic factors for having HIV RNA <500 copies/mL at 6 months included independently having undetectable HIV RNA at baseline and being naïve for NNRTIs. The proportion of patients with triglycerides >2.3 mmol/L increased from 32% to 63% at 6 months and to 62% at 24 months (P-trend=0.002), and those with total cholesterol >6.2 mmol/L increased from 18% to 38% at 6 months and to 44% at 24 months (P-trend <0.001), with an increased risk for patients treated with NNRTI+PIs. Forty-one per cent of patients discontinued their NRTI-sparing regimen.
CONCLUSION: In these antiretroviral-experienced patients, NRTI-sparing therapy appeared to have satisfactory virological and immunological efficacy. However, hyperlipidaemia was frequent and requires monitoring of cardiovascular risk factors.