AEGiS-13IAC: Treatment of tuberculosis in HIV-infected patients: Safety and antiretroviral efficacy of the concomitant use of Ritonavir and Rifampin.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Treatment of tuberculosis in HIV-infected patients: Safety and antiretroviral efficacy of the concomitant use of Ritonavir and Rifampin.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB543)

Moreno S, Podzamczer D, Blazquez R, Iribarren JA, Ferrer E, Reparaz J, Pena JM, Cabrero E, Usan L
S. Moreno, Hospital Ramon y Cajal, Servicio de Enf. Infecciosas, Ctra. Colmenar, Km 9,100, 28034 Madrid, Spain, Tel.: +34 91 336 87 10, Fax: +34 91 336 87 92, E-mail: smoreno@hrc.insalud.es

BACKGROUND: Rifampin (RF) is contraindicated in HIV-infected patients (pts) with tuberculosis (TB) who receive HAART, due to in vitro pharmacokinetic interactions with PIs and NNRTIs. However, the interaction between ritonavir (RTV) and RF is only mild.

OBJECTIVES: To evaluate the safety and the antiretroviral efficacy of RTV administered together with RF in HIV-infected pts with TB.

METHODS: Pts with culture-proved TB, naive for PIs, received antiTB therapy including isoniazid (300 mg/d), rifampin (600 mg/d) for 9 months, and pyrazinamide (1250 mg/d) during the first 2 months. Two months after initiation of antiTB treatment, 2 NRTIs plus ritonavir (600 mg bid) were administered. Clinical evaluation, liver function tests, CD4 counts, HIV viral load (VL), and drug plasma levels were measured at week 4, 8, 12, 20, and 28 of therapy, and 3 months after completion of therapy.

RESULTS: 15 pts were included. Early discontinuation (less than 4 weeks) occurred in 7 patients (3 intolerance to the liquid formulation of RTV, 2 consent withdrawal, 1 opportunistic infection, 1 loss). Baseline characteristics: median age 37.5, intravenous drug users 56%, median CD4 count 85/mm³ (6-312), median VL 6.01 log₁₀ (5.2-6.3). At the end of antiTB therapy (28 weeks of therapy with RTV), median CD4 count was 432/mm³ (median increase 347/mm³) and median VL was >2.3 log₁₀ (median decrease 3.72 log₁₀). Four of the eight patients had undetectable viral load (>200 copies/ml). All patients showed clinical and microbiological cure of the TB at the end of therapy. No patient developed grade 3-4 liver toxicity. At week 8, trough plasma levels of RTV ranged from 0.35 to 5.63 ?g/ml, and were above the IC95 (0.65 ?g/ml) in all but one patient.

CONCLUSIONS: Ritonavir and rifampin can be concomitantly administered in HIV-infected pts with TB, with good clinical, immunological and virological response. The combination was not associated with increased liver toxicity.

Keywords: AEGIS, Ritonavir, HIV Infections, CD4 Lymphocyte Count, Tuberculosis, Viral Load, Rifampin, Antiretroviral Therapy, Highly Active, Drug Therapy, Combination, HIV Seropositivity, In Vitro, Human, therapy, utilization, drug therapy
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