The Use of Saquinavir/Ritonavir 1000/100 Mg Twice Daily in Patients with Tuberculosis Receiving Rifampin

Tuberculosis (TB) is a leading cause of death among people living with HIV/AIDS [1]. Yet despite the importance of HIV and TB co-infection, there is a shortage of data on antiretroviral (ARV) therapy in this population. The choice of ARV treatments for people with HIV/TB co-infection is limited, largely owing to twoway interactions between ARV and anti-TB therapies. For example, rifamycin-containing regimens are recommended for the treatment of active TB, but the rifamycins are potent inducers of cytochrome P450 isoenzymes, and can thus substantially reduce systemic exposure to protease inhibitors (PIs) and most nonnucleoside reverse transcriptase inhibitors [2]. While rifabutin would be preferred over rifampin because of its less potent induction of P450, its use has several limitations: current fixed-dose regimens do not include rifabutin, it is not available as a first-line anti-TB drug, and the high cost and limited availability precludes its use in resource-constrained settings [3]. Recently, Lopez-Cortes et al. reported that efavirenz Cmin and AUC decreased 25% and 22%, respectively, during concomitant treatment with rifampin [4]. The evidence supporting a role for nevirapine-containing regimens is much more controversial owing to conflicting reported results [5]. Veldkamp et al. have suggested that ritonavir’s potent inhibition of P450 compensates for the enzyme-inducing effect of rifampin [6], and the use of saquinavir/ritonavir 400/400 mg twice daily with concomitant rifampinbased anti-TB therapy continues to be suggested by the Centers for Disease Control and Prevention for treatment of HIV/TB co-infected patients [7,8]. Recently, saquinavir/ritonavir 400/400 mg twice daily has been superseded by the saquinavir/ritonavir 1000/100 mg twice-daily regimen, which demonstrates equivalent or superior efficacy but with much improved tolerability [9–11]. There is a need for data on the use of this boosted saquinavir regimen in patients co-infected with TB who are undergoing therapy with rifampin. We carried out a retrospective safety and efficacy analysis of two ARV regimens in HIV-infected patients receiving rifampin for TB by reviewing the clinical charts of patients undergoing concomitant treatment for TB and HIV at an ambulatory HIV clinic. Data from rifampin-treated patients receiving saquinavir/ ritonavir 1000/100 mg twice daily plus two nucleoside reverse transcriptase inhibitors (NRTIs) and rifampintreated patients receiving a triple-NRTI regimen were collected. The data included demographics, clinical status, hepatitis C or hepatitis B co-infection, TB localization, time from TB diagnosis to initiation of anti-TB treatment (baseline), virological and immunological data, and the incidence of adverse events over 24 weeks. Data were analysed using unpaired t-tests. A total of 89 patients with TB and HIV were identified. Of these, 41 received no concomitant ARV therapy, ten received two NRTIs, six received two NRTIs plus efavirenz, 14 received saquinavir/ritonavir plus two NRTIs (SQV/r group) and 18 received regimens with three NRTIs (3-NRTI group). Data from the 14 patients in the SQV/r group and the 18 patients in the 3-NRTI group were reviewed. All the patients were ARV naive and had no previous episodes of TB. Patients received the standard, body-weight adjusted doses of anti-TB treatment (a 2-month induction phase of isoniazid, rifampin, pyrazinamide and etambutol, followed by a 7-month consolidation phase of isoniazid and rifampin). No drug-level tests were performed at the time of this analysis. Baseline characteristics are described in Table 1. At 24 weeks, the mean plasma viral load was significantly lower in the SQV/r group than in the 3-NRTI group [1.6 and 3.38 log10 copies/ml, respectively (P=0.022)], with a median reduction from baseline in HIV-1RNAof3.46and1. 36log10 copies/ml, respectively