Authors of a letter to the editor published in Infectious Diseases contributed to recent Swedish recommendations on the antiviral treatment of HIV infection via a discussion of the association of lowered efavirenz dosage and reduction in low-density lipoprotein (LDL) and total cholesterol, an approach that should be used in patients with metabolic or cardiovascular comorbidities.
Efavirenz is prescribed extensively at the fixed dose combination of 600 mg efavirenz with tenofovir disoproxil fumarate and emtricitabine (TDF) as first-line antiretroviral therapy for HIV-1 naive adults. This treatment has demonstrated efficacy in virologic suppression, but can lead to increased serum glucose and lipid levels. The researchers used an observational retrospective analysis on patients with HIV-1 at the outpatient treatment unit of the G.B. Rossi University Hospital in Verona to examine the impact of reducing 600 mg efavirenz to 400 mg, and 400 mg to 200 mg.
Both study groups were taking efavirenz in combination with 2 nucleotide analog reverse transcriptase inhibitors. All participants had achieved virologic suppression for at least 6 months prior to dose reduction, and none of the participants were taking lipid-lowering drugs. Over a period of 12 months, pre- and post-dose reduction levels of fasting plasma values of LDL, high-density lipoprotein, total cholesterol, glucose, and triglycerides were compared. Mean values with standard deviations were considered for all metabolic parameters, and 95% confidence intervals and Student’s t-test were used to compare mean differences at the 2 different times.
Forty-two patients were assigned the 600 mg to 400 mg group (group 1) and 32 patients were assigned to the 400 mg to 200 mg group (group 2). In addition, 29 patients in each group, slowly reduced their dosage from 600 to 200 mg. Total cholesterol was significantly reduced in both groups, and group 2 also saw significantly reduced LDL levels, whereas the LDL reduction in group 1 was at the statistical significance limit. When the data were considered together and participants were separated into those on TDF and those not on TDF (25 of 42 in group 1, and 20 of 32 in group 2), a mean total cholesterol reduction of 8.5 mg/dL (95% CI, -14.0 to -3.0) was seen in the TDF group compared with a reduction of 10.3 mg/dL (95% CI, -18.3 to -2.3) in the non-TDF group, and a mean LDL reduction in of 5.9 mg/dL (95% CI, 10.6-1.2) was seen in the TDF group compared with a 7.6 mg/dL reduction (95% CI, -13.8 to -1.2) in the non-TDF group. A statistically insignificant lower reduction of LDL and total cholesterol was seen in the TDF group compared with the non-TDF group, which investigators suggested may be due to TDF’s known lipid-lowering effect.
The researchers concluded that “a reduced dose of efavirenz (a 400 mg dose is now recommended as an alternative first-line regimen also by [World Health Organization] can lead to a significant decline in total cholesterol and LDL and should be used especially in patients with cardiovascular or metabolic comorbidities.”
Nicolè S, Lanzafame M, Lattuada E, et al. Efavirenz dose reduction is associated with improved lipid profile in HIV-1 infected patients [published online May 12, 2019]. Infect Dis (Lond). doi: 10.1080/23744235.2019.1609078