COMBINE Study: report at week 36 of 48 week studu of nelfinavir+Combivir vs nevirapine+Combivir

COMBINE Study: Nevirapine+Combivir vs Nelfinavir+Combivir

Abstract 694:  Combine Study (NVP vs. NFV).  142 antiretroviral naÔve patients were randomized to, either NFV 1250 bid or NVP 200 bid, as well as Combivir bid.  Entry viral loads were a mean of 5.21 (164,000 copies/ml), a median of 4.81 log copies (65,000 copies/ml) in the NFV arm, and a mean of 5.07 (119,000 copies/ml), and median of 4.77 (60,000 copies/ml) log copies in the NVP arm.  The results reported were 36 weeks.  Using an intent to treat analysis, with the <200 copy assay, 70.8% of the NVP arm and 55.7% of the NFV arm were undetectable.  Using the <20 copy assay 66.7% of the NVP arm and 38% of the NFV arm were undetectable.  Regarding an entry VL >100,000 copies/ml, using an on treatment analysis, NVP showed a statistically significant difference over NFV in achieving <20 copies/ml but not <200 copies/ml.  Regarding T-cell there was no statistical difference between the arms.  Commentary: NFV performed less well than it usually does so this raises questions about the results. It could be that there was more non-adherence in the NFV arm and there didnít appear to be a method in this study for collecting that information.     Mike Norton, PA

COMBINE STUDY: 36-Week Results from 48 week study comparing nelfinavir to nevirapine (both with 2 NRTIs) in treatment-naÔve patients in Spain & Argentina

Written by Jules Levin

This is a randomized, open-label, multi-center study in 12 hospitals in Spain (8) and Argentina (3). 142 HIV-infected treatment-naÔve patients with HIV viral load >1500 copies/ml and without AIDS defining diseases were recruited between November 1998 and August '99. Patients were randomly assigned to one of 2 twice daily regimens: Combivir (AZT 300mg, 3TC 150mg) + nelfinavir  1250mg bid, or Combivir + nevirapine 200mg bid. Although the presenter did not show data at this time ongoing substudies include VL in reservoirs (LT, CSF, semen), immunologic changes, lipid metabolism changes, resistance, and quality of life scores. A poster of a substudy was presented from the Spain group reporting on metabolic and anthropometric assessments and their findings will be reviewed below.

BASELINE CHARACTERISTICS:

There did not appear to be much difference between the 2 arms.

CD4:

• Nelfinavir (NFV) mean & median- 347 & 375

• Nevirapine (NVP) mean & median- 351 & 361

HIV Viral Load:

• NFV mean & median- 164,000 & 66,000 copies/ml

• NVP mean & median- 119,000 & 60,000 copies/ml

About 30% had >100,000 copies/ml viral load: 26 (37%) in NFV arm and 21 (29%) in NVP arm.

% <200 copies/ml at 9 months (ITT)

% <200 at 9 months (On-Treatment analysis)

% <20 copies/ml at 9 months (ITT)

% <20 copies/ml at 9 months (On Treatment analysis)

% Undetectable at 9 months with baseline HIV-RNA >100,000 copies/ml

On Treatment Analysis

Alhough the NFV arm had a bigger increase in CD4s it was not statistically significant. Nelfinavir arm was 347 Cd4s at baseline and 519 at 9 months for an increase of 172. Nevirapine arm was 375 CD4s at  and 491 at 9 months for an increase of 116.

About 39% (56/142) total patients stopped therapy: 45% (32/70) in NFV arm and 33% (24/72) in the NVP arm. About 20% stopped due to intolerance: 22% in NVP arm but 2 were lost to follow-up and 18% in the NFV arm. 19% in total were lost to follow-up: 24% in the NFV arm and 13% in the NVP arm.

Discontinuations Due To Adverse Events

GI symptoms (diarrhea & vomiting) were the most common cause of discontinuation in the NFV arm (10 vs 1 in the NVP arm). Surprisingly, anemia and/or neutropenia were the most common AE in the NVP arm (6 vs 1 in the NFV arm; AZT was switched to d4T). The author reported 5 (5/72) discontinuations due to hepatitis in the NVP arm (vs 1 in the NFV arm) although its unsure if they stopped due to elevated LFTs or some other reason. There were 4 discontinuations due to rash in the NVP arm and 1 in the NFV arm.

Preliminary Results of Anthropometric and Metabolic Changes Observed in HIV-infected Patients Treated with Combivir (ZDV/3TC) Plus Nelfinavir or Nevirapine (a Substudy of the COMBINE-study)

The Spain research group reported in a poster on  this whose purpose was to look at body composition and metabolic alterations in a subgroup of HIV-infected naive patients in the COMBINE Study. They reported that after 6 months fasting total cholesterol increased significantly (p<0.05) in the NFV (4.89 at baseline to 5.69 mmol/L at month 6), and with no-significance in the CNr group (4.81 at baseline to 4.98 mmol/L). At baseline no anthropometric or biochemical differences were observed between groups. In the NFV group a 1.34 fold non-significant increase in triglycerides levels was observed. Comparing NFV with NVP significant differences in LDLc (3.85 vs. 2.74 mmol/L) and HDLc (1.32 vs. 1.65 mmol/L, respectively) have occurred at month 6. At the time of data analysis no glucose metabolism alterations or lipodystrophy onset have been detected.