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The emergence of protease inhibitors (PIs) and multiple drug therapy for HIV infection has greatly decreased mortality in countries where these medications are available. Unfortunately, many patients eventually develop viral resistance to treatment because of HIV virus mutations. As clinicians await development of new drugs to combat resistant virus, innovative strategies with existing drugs may be particularly valuable. Patients having failed regimens containing nucleoside reverse transcriptase inhibitors (NRTIs) and PIs face limited options for future therapy. A regimen containing the two potent non-nucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine (NVP) and efavirenz (EFV), could provide an effective alternative, since both can be conveniently dosed once daily1, 2 and have demonstrated efficacy in patients with high viral loads.2–4
A retrospective chart review at an urban HIV hospital clinic identified 13 patients who had initiated an NVP + EFV based salvage regimen (table 1). Inclusion of these patient charts in this study was approved by a research ethics committee at Bellevue Hospital. All patients received NVP + EFV at standard doses. The lower limit of quantitation was determined at 50 HIV RNA copies/ml using Roche Amplicor HIV-1 Monitor (RNA) (Roche Diagnostics, Branchburg, NJ, USA). Median baseline values were: viral load 33 900 copies/ml (range 3100–750 000 copies/ml) and CD4+ count 190 cells ×106/l (range 2–440 cells). After a median follow up of 11 months (range 3–18 months), 85% (11/13) had viral loads <50 copies/ml. Considering previous treatment experience, 90% (9/10) of NNRTI naive patients had viral loads <50 copies/ml and 67% (2/3) of NNRTI experienced patients had viral loads <50 copies/ml. Effectiveness of the dual NNRTI combination in heavily pretreated patients is in contrast with a study using a single NNRTI plus two NRTIs in NRTI experienced patients in whom rapid virological failure was observed.5 These results suggest that the combination of two potent NNRTIs may be able to overcome development of NNRTI associated resistance, even when there are only one or two NRTIs in the combination. These data accord with those of Jordan and colleagues who demonstrated a sustained response to NVP + EFV in combination with only didanosine (ddI) in 19/21 patients after 12 months.6
The most common adverse event was elevated liver function test results (more than three times upper limit of normal) in three patients. One case of liver toxicity was attributed to Bactrim, and a second case resolved following interruption of EFV (EFV rechallenge in this patient was successful). No specific cause of liver toxicity could be identified in the third case, suggesting a possible association with antiretroviral treatment. Other adverse events included anaemia. The patient with EFV induced hepatotoxicity also had anaemia and EFV related central nervous system disturbances. None of the patients discontinued therapy because of adverse events. The relatively low incidence of adverse events and the absence of NNRTI associated metabolic disorders make this dual NNRTI based regimen additionally appealing.
This retrospective analysis demonstrated the effectiveness of the combination of two NNRTIs (NVP and EFV) in heavily pretreated PI experienced patients, with no apparent increase in NNRTI related side effects. Since few new antiretrovirals with novel resistance profiles are forthcoming in the near future, this regimen may provide a much needed alternative in heavily pretreated patients.