Nevirapine matches atazanavir/ritonavir in 48-week study

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Nevirapine has equivalent efficacy to atazanavir/ritonavir when combined with tenofovir and FTC in treatment-naive patients, results from the ARTEN study show.

The findings, presented by Dr Vincent Soriano last week at the Fifth International AIDS Society conference in Cape Town, also showed that patients who received nevirapine had fewer lipid elevations than those who received atazanavir/ritonavir.

Nevirapine is one of the cheapest agents for use in antiretroviral therapy, is well tolerated after the first weeks of treatment and does not cause increases in lipid levels.

Glossary

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

rash

A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

naive

In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

However its popularity has declined in the developed world since data emerged in 2001 showing that use of the drug in women with CD4 counts above 250 cells/mm3 and men with counts above 400 cells/mm3 carried a higher risk of liver toxicity. Treatment guidelines in the United States and Europe no longer describe nevirapine as a 'preferred' option for first-line treatment.

There have also been concerns about use of nevirapine in combination with tenofovir due to unusually high failure rates in several small studies, and as tenofovir has displaced AZT and d4T as the agent of choice in first-line nucleoside analogue backbones, physicians have become reluctant to use nevirapine as frequently as in the past.

The ARTEN study was designed to evaluate the use of nevirapine in combination with Truvada (tenofovir and FTC) and in comparison with atazanavir/ritonavir, the drug considered most lipid-friendly apart from nevirapine.

The study recruited treatment-naive patients in Europe, Mexico and Argentina with a mean CD4 count of around 180 cells/mm3. Around 65% of patients had a viral load above 100,000 copies/ml.

The study randomised patients to receive nevirapine once (400mg qd) (n=188) or twice daily (200mg bid) (n=188), or to receive atazanavir/ritonavir (300/100mg) (n=196), in combination with tenofovir and FTC (Truvada).

The primary endpoint of the study was the proportion of patients with viral load below 50 copies/ml at week 48, and time to loss of virologic response (TLOVR) at week 48. The

At week 48 almost equal proportions in the nevirapine and atazanavir groups had viral load below 50 copies/ml by intent to treat analysis (67 vs 65%), and there was no difference between the once- and twice-daily nevirapine dosage groups in the performance when compared to atazanavir.

Virologic failure rates were also similar between the treatment arms at week 48 (11.2% in the nevirapine qd arm, 12.8% in the nevirapine bid arm and 14% in the atazanavir/ritonavir arm).

On-treatment analysis showed that 93.4% of patients taking nevirapine at week 48 had a viral load below 50 copies/ml, compared to 88% of the atazanavir group.

In all arms of the study the proportion of patients with viral load below 50 copies/ml was greater when considering only those with viral load below 100,000 copies/ml. In patients with viral load above 100,000 copies/ml there was a trend towards a greater frequency of viral load suppression in nevirapine-treated patients (60 vs 52%).

The overall rate of serious adverse events was similar between the two drugs (9.6% in the nevirapine arms, 8.8% in the atazanavir arm), but discontinuations due to adverse events were more frequent in the nevirapine arm (13.6 vs 3.6%). Discontinuations in the nevirapine arms were chiefly due to rash (5.1%), hepatitis or liver enzyme elevation, but there were no grade 4 rashes and no cases of Stevens-Johnson syndrome. Of note, rash was reported in 12.4% of patients who received atazanavir.

At week 48, patients in the nevirapine group experienced a mean decline in their total cholesterol to HDL ratio of -0.24, indicating an improvement in lipid profile. In contrast the total cholesterol: HDL cholesterol ratio rose slightly in atazanavir-treated patients, rising by +0.13 (p = 0.001).

This difference appears to have been driven by a much greater HDL cholesterol increase in nevirapine-treated patients (+9.7% vs +3.9%, p

The authors do not report the baseline lipid levels in the study population, nor the proportion of patients who became eligible for lipid-lowering drugs or other cholesterol-lowering interventions during the study. In addition, the size of the decrease in total cholesterol: HDL cholesterol ratio seen in this study would be considered very marginal, and is difficult to interpret without information on baseline levels.