Safety and efficacy after switch to a saquinavir-containing antiretroviral regimen in protease inhibitor pretreated HIV-positive patients

Abstract

ObjectiveThe RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naïve patients.MethodsMulticenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48.ResultsA total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels < 50 copies/mL at week 48 was 60.3% (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm3 from baseline (p < 0.01) and 60.3% of patients achieved HIV-1 RNA < 50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride < 200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR 1024; 0) for baseline triglyceride > 750 mg/dL (p < 0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC < 200 mg/dL (p < 0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC > 300 mg/dL (p < 0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects.ConclusionsThese data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naïve patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.

HIV Protease Inhibitors in Pulmonary Hypertension: Rationale and Design of a Pilot Trial in Idiopathic Pulmonary Arterial Hypertension

“…SQV was the first HIV‐PI approved by the US Food and Drug Administration (FDA) and has been shown to be safe even when chronically administered to humans. SQV is typically administered with RIT, which increases the bioavailability of SQV 38 , 39 . The FDA‐approved dosage of SQV+RIT for HIV infection is SQV 1,000 mg twice daily (5 × 200‐mg capsules or 2 × 500‐mg tablets), in combination with RIT 100 mg twice daily.…”

“…Patients will receive SQV plus ritonavir (RIT; SQV+RIT) treatment. RIT is also a first‐generation HIV‐PI but is used primarily to increase the bioavailability of SQV 38 , 39 . A 28‐day, open‐label, single‐blind, pre‐post study will investigate whether SQV+RIT will reduce biomarkers of inflammation and improve pulmonary hemodynamics in IPAH patients.…”

“…SQV is typically administered with RIT, which increases the bioavailability of SQV. 38,39 The FDA-approved dosage of SQV+RIT for HIV infection is SQV 1,000 mg twice daily (5 × 200-mg capsules or 2 × 500-mg tablets), in combination with RIT 100 mg twice daily. RIT is to be taken at the same time as SQV and within 2 hours after a meal.…”

“…An abundance of clinical studies have demonstrated that this regimen is well tolerated and safe in HIV-infected subjects. [38][39][40][41][42] A pilot study was conducted in steroid-dependent and steroidresistant nephrotic syndrome patients treated with SQV (30 mg/kg/ day) for at least 6 months; clinical benefit was observed, and no adverse drug reaction was reported, apart from transitory mild diarrhea. 35 To ensure the safety of SQV+RIT in IPAH patients, besides contraindicated drugs, we will define potential interaction medications and formulate management of each drug ( Table 2).…”

“…RIT is also a first-generation HIV-PI but is used primarily to increase the bioavailability of SQV. 38,39 A 28-day, open-label, single-blind, pre-post study will investigate whether SQV+RIT will reduce biomarkers of inflammation and improve pulmonary hemodynamics in IPAH patients. If results of this study yield positive results, we would propose further investigation of this drug combination to treat refractory IPAH.…”