Quality of life in patients treated with first-line antiretroviral therapy containing nevirapine and/or efavirenz.

OBJECTIVE: To assess whether differences in safety profiles between nevirapine (NVP) and efavirenz (EFV), as observed in the 2NN study, translated into differences in 'health related quality of life' (HRQoL). DESIGN: A sub-study of the 2NN study, with antiretroviral-naive patients randomly allocated to NVP (once or twice daily), EFV or NVP+EFV, in addition to stavudine and lamivudine. METHODS: Comparing differences in changes of HRQoL over 48 weeks as measured with the Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire, using analysis of variance. RESULTS: The 2NN study enrolled 1216 patients. No validated questionnaires were available for 244 patients, and 55 patients had no HRQoL data at all, leaving 917 patients eligible for this sub-study. A total of 471 (51%) had HRQoL measurements both at baseline and week 48. The majority (69%) of patients without HRQoL measurements did, however, complete the study. The change in the physical health score (PHS) was 3.9 for NVP, 3.4 for EFV and 2.4 for NVP+EFV (P=0.712). For the mental health score (MHS) these values were 6.1, 7.0 and 3.9, respectively (P=0.098). A baseline plasma HIV-1 RNA concentration (pVL) > or = 100,000 copies/ml and a decline in pVL (per log10) were independently associated with an increase of PHS. An increase of MHS was only associated with pVL decline. Patients experiencing an adverse event during follow-up had a comparable change in PHS but a significantly smaller change in MHS, compared with those without an adverse event. CONCLUSIONS: First-line ART containing NVP and/or EFV leads to an improvement in HRQoL. The gain in HRQoL was similar for NVP and EFV, but slightly lower for the combination of these drugs.

Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes.

OBJECTIVE: We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor, empagliflozin, added to multiple daily injections of insulin (MDI insulin) in obese patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Patients inadequately controlled on MDI insulin ± metformin (mean HbA1c 8.3% [67 mmol/mol]; BMI 34.8 kg/m(2); insulin dose 92 international units/day) were randomized and treated with once-daily empagliflozin 10 mg (n = 186), empagliflozin 25 mg (n = 189), or placebo (n = 188) for 52 weeks. Insulin dose was to remain stable in weeks 1-18, adjusted to meet glucose targets in weeks 19-40, then stable in weeks 41-52. The primary end point was change from baseline in HbA1c at week 18. Secondary end points were changes from baseline in insulin dose, weight, and HbA1c at week 52. RESULTS: Adjusted mean ± SE changes from baseline in HbA1c were -0.50 ± 0.05% (-5.5 ± 0.5 mmol/mol) for placebo versus -0.94 ± 0.05% (-10.3 ± 0.5 mmol/mol) and -1.02 ± 0.05% (-11.1 ± 0.5 mmol/mol) for empagliflozin 10 mg and empagliflozin 25 mg, respectively, at week 18 (both P < 0.001). At week 52, further reductions with insulin titration resulted in changes from baseline in HbA1c of -0.81 ± 0.08% (-8.9 ± 0.9 mmol/mol), -1.18 ± 0.08% (-12.9 ± 0.9 mmol/mol), and -1.27 ± 0.08% (-13.9 ± 0.9 mmol/mol) with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively, and final HbA1c of 7.5% (58 mmol/mol), 7.2% (55 mmol/mol), and 7.1% (54 mmol/mol), respectively. More patients attained HbA1c <7% (<53 mmol/mol) with empagliflozin (31-42%) versus placebo (21%; both P < 0.01). Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses (-9 to -11 international units/day) and weight (-2.4 to -2.5 kg) versus placebo (all P < 0.01) at week 52. CONCLUSIONS: In obese, difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses, empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements.

Efficacy and safety of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents: 5 years of experience.

BACKGROUND: To evaluate the long-term (up to week 292) safety, efficacy and tolerability of ritonavir-boosted tipranavir in HIV-1-infected pediatric patients. Long-term follow up of patients enrolled in the randomized, open-label pediatric trial (1182.14/PACTG1051). METHODS: HIV-1-infected pediatric patients (2-18 years) who participated in the PACTG 1051 trial were followed for ritonavir-boosted tipranavir-based regimen efficacy, safety and tolerability through week 292. RESULTS: In patients <12 years of age, 51/62 (82%) were receiving drug at week 48 and 13/62 (21%) at week 288. Among adolescents (12-18 years of age), 35/53 (66%) were receiving drug at week 48 and 2/53 (4%) at week 288. Among patients 2 to <6 years of age, 18/25 (72%) had viral loads <400 copies/mL at week 48. By week 292, 9/25 (36%) of patients had viral loads <400 copies/mL. Among older patients, week 48 responder rates were 35% (13/37 of patients 6 to <12 years of age) and 32% (17/53 of patients 12 to 18 years of age). By week 292, 6/37 (16%) of those 6 to <12 years of age and 2/53 (4%) of those 12 to 18 years of age had viral loads <400 copies/mL. Overall safety and tolerability profiles were best for children who initiated treatment between 2 and <6 years of age. Drug-related adverse events (investigator defined) were similar across all age groups (55-65%). CONCLUSIONS: Pediatric patients who begin treatment at the earlier ages, and who are stable on a ritonavir-boosted tipranavir-based regimen at week 48, generally continue to demonstrate good safety, tolerability and virologic efficacy profiles up to 292 weeks of treatment.

Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients. DESIGN: Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen. METHODS: HIV-1-infected patients (2-18 years) with plasma viral load 1500 copies/ml or more were randomized to TPV/r 290/115 or 375/150 mg/m twice-daily oral solution and optimized background regimen. Week 48 efficacy, safety and tolerability results were evaluated. RESULTS: Children (n = 115; 97% treatment experienced) were randomized to low or high dose therapy. Eighty-eight remained on-treatment through 48 weeks. Baseline characteristics were similar between dose groups. At study entry, half of the HIV-1 isolates were resistant to all protease inhibitors. At 48 weeks, 39.7% low-dose and 45.6% high-dose TPV/r recipients had viral load less than 400 copies/ml and 34.5 and 35.1%, respectively, achieved viral load less than 50 copies/ml. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase elevations were observed in 6.3% of patients. No grade 4 alanine aminotransferase or grade 3/4 aspartate aminotransferase elevations were reported. CONCLUSIONS: TPV/r achieved a sustained virologic response, showed a good safety profile and was well tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response.