Tenofovir with 3TC or FTC associated with lower lipid increases than other NRTI pairs

The combination of tenofovir and 3TC (or FTC) is associated with smaller increases in lipid levels than other pairs of NRTIs in patients starting HIV treatment for the first time, US researchers report in the online edition of AIDS.

Although tenofovir (Viread) with 3TC (lamivudine, Epivir) or FTC (emtricitabine, Emtriva) was associated with better total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels, it did not have a beneficial effect on high-density lipoprotein (HDL) cholesterol.

“Findings from this study demonstrate that comparisons of dyslipidemia and cardiovascular disease risk factors associated with antiretroviral medications should focus on individual agents rather than on class effect,” comment the investigators.

Cardiovascular disease is now an important cause of death in patients with HIV. The exact causes are unclear, but increases in lipid levels have been seen in patients after they start antiretroviral therapy.

Most of the research investigating the association between antiretrovirals and abnormal lipid levels has focused on the impact of the drug classes. Little attention has been paid to the effect of individual agents.

The majority HIV treatment combinations include a pair of drugs from the nucleoside reverse transcriptase inhibitor (NRTI) class of antiretrovirals. Investigators from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort monitored changes in the lipids of 2267 patients who started potent combination HIV therapy for the first time between 1995 and 2008. After controlling for the use of drugs from other antiretroviral classes, as well as demographic , behavioural and life-style characteristics, the impact of pairs of NRTIs on changes in lipids was compared.

Mean age for the patients was 38 years, 75% were men, 55% were African American, and 21% were co-infected with hepatitis C virus.

At the time potent HIV therapy was started, the patients had a mean CD4 cell count of 173 cells/mm³ and 54% had a peak viral load over 100,000 copies/ml.

The most popular NRTI pair was AZT (zidovudine, Retrovir)/3TC (40%). The next most common NRTI pair was tenofovir/3TC (26%), followed by d4T (stavudine, Zerit)/3TC (16%). Between 2% - 5% of patients took other combinations of NRTIs. A weakness of this study is the lack of patients taking abacavir/3TC, now the most commonly prescribed alternative nucleoside pair to tenofovir/FTC.

Lipid levels increased after HIV therapy was started. The most rapid increase was observed in the first two months of treatment.

Patients taking tenofovir combined with 3TC or FTC had lower lipid levels than patients treated with other NRTI pairs.

Total cholesterol levels were significantly higher (between 10 – 22mg/dl, p < 0.001 – 0.002) among patients receiving any other NRTI combination when compared with tenofovir and 3TC or FTC.

LDL cholesterol levels  were also higher for patients taking combinations other than tenofovir/3TC or FTC, and were significantly so for those treated with ddI (didadosine, Videx)/3TC (p = 0.03).

In addition, mean triglyceride levels were lower for patients taking tenofovir/3TC or tenofovir FTC.

However, therapy with tenofovir and FTC or 3TC did not have a beneficial impact on HDL cholesterol, so called “good” cholesterol. Indeed, patients taking any other pair of NRTIs had significantly higher HDL cholesterol than those taking tenofovir and FTC or 3TC (+ 3 – 11 mg/dl, p < 0.01 – 0.02).

Improvements in health appeared to be associated with lipid increases. Each 10 cells/mm³ increase in CD4 cell count was associated with significant increases in total cholesterol, LDL cholesterol, non-HDL cholesterol and triglycerides (p = 0.008 – 0.05).

In addition each kg/m² increase in body mass index (BMI) was associated with significant increases in total cholesterol (p = 0.02), LDL cholesterol (p = 0.006), triglycerides (p = 0.03), and non-HDL cholesterol (p = 0.009).

Smaller lipid increases were seen in patients co-infected with hepatitis C. But the investigators do not believe that this conferred any health benefits. They note, “despite having more favourable pro-atherogenic lipid profiles, HCV co-infected patients were recently shown to have higher rates of cardiovascular events among a study of US veterans.”

The investigators conclude that the study “provides additional evidence that the metabolic impact of most antiretroviral agents, particularly those used more commonly in initial regimens in the current ART era, are relatively modest.”