Studies examine effects of ART on metabolic outcomes, cancer in adults living with HIV
One study found that switching from tenofovir disoproxil fumarate to tenofovir alafenamide was associated with obesity and dyslipidemia, while another suggested that deferred antiretroviral therapy (ART) initiation was associated with a small increase in risk for AIDS-defining cancer.
Two recent studies published online on March 16 by Annals of Internal Medicine looked at the effects of antiretroviral therapy (ART) in people living with HIV.
The first study found that switching from tenofovir disoproxil fumarate to tenofovir alafenamide was associated with metabolic complications. Researchers assessed weight changes, the development of overweight or obesity, and changes in lipid levels 18 months after replacement of tenofovir disoproxil fumarate (after at least six months of therapy) with tenofovir alafenamide in participants in the Swiss HIV Cohort Study. To account for different changes in weight before the index visit, they included all weight measurements from 2.5 years before that date until the end of follow-up.
A total of 4,375 participants (median age, 50 years; 25.9% women; 51.7% with a normal body mass index [BMI]) were included in the analysis. Of these, 891 (20.4%) continued tenofovir disoproxil fumarate and 3,484 (79.6%) switched to tenofovir alafenamide. After 18 months, switching to tenofovir alafenamide was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg) compared to 0.7 kg (95% CI, 0.4 to 1.0 kg) with the continued use of tenofovir disoproxil fumarate (between-group difference, 1.1 kg [95% CI, 0.7 to 1.4 kg]). Among participants with a normal BMI, 13.8% of those who switched to tenofovir alafenamide became overweight or obese compared to 8.4% of those who continued tenofovir disoproxil fumarate (difference, 5.4 percentage points [95% CI, 2.1 to 8.8 percentage points]). Switching was also associated with increases in adjusted mean total cholesterol (9.5 mg/dL), high-density lipoprotein cholesterol (1.9 mg/dL), low-density lipoprotein cholesterol (4.7 mg/dL), and triglyceride (16.1 mg/dL) levels after 18 months.
The study was limited by its relatively short follow-up, the potential for confounding by indication, and self-reported information on physical activity and use of weight-modifying drugs, the authors noted. “Recommendations on the use of [tenofovir alafenamide] should balance its advantages (renal and bone safety) with its potential harms, including metabolic complications,” they concluded.
The second study found that deferred ART initiation is associated with a small increase in risk for AIDS-defining cancer. Researchers used data from the D:A:D (Data collection on Adverse events of anti-HIV Drugs) study to estimate the long-term risk for non-AIDS-defining and AIDS-defining cancer after immediate or deferred ART initiation (at CD4 counts <350 and <500 × 109 cells/L) in HIV-positive individuals from Europe, Australia, and the U.S. Participants included 8,318 HIV-positive individuals (median age, 36 years; 22.7% women) with at least one measurement each of CD4 cell count and viral load while ART-naive from 2006 to 2016.
During 64,021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among the participants. With immediate ART initiation, the 10-year risk was 2.97% (95% CI, 2.37% to 3.50%) for non-AIDS-defining cancer and 2.50% (95% CI, 2.37% to 3.38%) for AIDS-defining cancer. Compared with immediate ART, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (95% CI, −0.01 to 0.26 percentage point) and 0.29 percentage point (95% CI, −0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (95% CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (95% CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer.
The authors could not exclude the possibility that some participants with previous unreported cancer were included in the analysis, among other limitations. “In summary, we observed that strategies promoting deferral of ART initiation in ART-naive, HIV-positive persons are associated with a small increase in risk for AIDS-defining cancer,” they concluded. “The study adds further supportive evidence that early ART may reduce risk for non–AIDS-defining cancer.”