Study: ART Not Responsible for Hypertension in Patients with HIV

Camilla Hatleberg, MD, PhD

Antiretroviral drug treatment (ART) was not found to be a cause of the higher prevalence of hypertension in persons infected with HIV in an analysis from the largest surveillance study of ART and cardiovascular disease.

The most recent findings from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study implicated traditional cardiovascular disease risk factors rather than antiretroviral drugs as predictors of hypertension.

"It is reassuring that we do not find any strong associations between several antiretroviral drugs from the 3 most widely used ART classes and the risk of hypertension, based on data from the largest prospective cohort study that has so far considered this question," Camilla Hatleberg, MD, PhD, Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark, told MD Magazine®.

Hatleberg and colleagues explained that there has been uncertainty over whether exposure to ART poses an additional risk for developing hypertension, but that the studies which have suggested the association have examined smaller populations over shorter periods and considered fewer potential confounders than the present analysis.

In their new assessment from the D:A:D study, an observational, multinational cohort collaboration across the US, Europe and Australia, Hatleberg and colleagues examined data collected prospectively at routine clinic visits of over 33,000 persons treated for HIV who were enrolled beginning in January 1999.

Subjects included in the study were normotensive without antihypertensive drugs at baseline, not diagnosed with hypertension within 6 months after baseline, and had at least two blood pressure measurements in their record. They were followed through the earlier of either the study end in February 2013, receiving a diagnosis of hypertension at least 6 months after baseline, or for a period of 6 months after their last clinic visit.

The investigators determined the incidence of new hypertension in the cohort overall, and in analysis stratified by demographics, metabolic and HIV-related physiologic changes, and by cumulative exposure to each of the 18 most commonly prescribed individual antiretroviral drugs in the combination ART regimens.

The investigators were able to access D:A:D data on ART exposure prior to the start of this study, to include several agents in the analysis which were not in widespread use later in the investigation. Hatleberg notes, however, that several agents have been introduced subsequently, and were not available for this analysis.

"Due to limited follow-up, we have not been able to study any drugs from the newer classes, such as integrase-inhibitors and entry inhibitors," Hatleberg commented, "and hence cannot exclude the possibility that these drugs may play a contributing role in the development of hypertension."

In the initial, univariable analyses, the investigators found significant association between cumulative exposure to almost all ART and the risk of hypertension. In the multivariable analysis which included adjustment for all 18 antiretroviral drugs, 12 continued to be independently associated with hypertension. Several dropped from the association with adjustment for demographic factors not on the causal pathway.

After further adjusting for metabolic factors considered to be on the causal pathway and factoring in latest viral load and CD4 count, a small but statistically significant contribution to hypertension risk remained only with indinavir plus ritonavir (rate ratio 1.12 per 5 years; 95% CI: 1.04 - 1.20) and with nevirapine (Viramune) (rate ratio 1.07 per 5 years; 95% CI: 1.04 - 1.13).

The strongest independent predictors of hypertension were male gender, older age, black-African ethnicity, diabetes, dylipidemia, use of lipid-lowering drugs, high body mass index (BMI), renal impairment, and low CD4 count.

"Our findings suggest that people living with HIV should follow the same recommendations as those for HIV-negative people," Hatleberg recommended. "In particular, they should attempt to reduce cardiovascular risk by minimizing modifiable risk factors.”

Such efforts, Hatleberg cited, include stopping smoking, following a healthy diet, exercising regularly, and ensuring that their blood pressure, lipids and blood sugar levels are checked regularly.

The study, "Association between exposure to antiretroviral drugs and the incidence of hypertension in HIV‐positive persons: the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) study," was published online in HIV Medicine.