Treatment with modern antiretrovirals doesn't increase the risk of hypertension

There is no strong evidence that treatment with antiretrovirals significantly increases the risk of hypertension, investigators from the D:A:D study report in HIV Medicine. After taking into account demographic and traditional risk factors, only two older anti-HIV drugs had a significant association with hypertension.

“Using data from a large, heterogeneous cohort with information on a wide range of demographic, metabolic and HIV-related factors, we did not find any strong associations between specific ARV [antiretroviral] drugs and an increased risk of hypertension,” write the investigators.

“We did, however, document associations with many of the established risk factors for hypertension in the general population, such as older age, male gender, diabetes, high BMI, black African ethnicity, low eGFR, in addition to severe immunosuppression.” The investigators believe their findings should provide reassurance that screening policies and preventative measures for hypertension used in the general population are also applicable for people with HIV.

Glossary

hypertension

Raised blood pressure.

immunosuppression

A reduction in the ability of the immune system to fight infections or tumours.

lipodystrophy

A disruption to the way the body produces, uses and distributes fat. Different forms of lipodystrophy include lipoatrophy (loss of subcutaneous fat from an area) and lipohypertrophy (accumulation of fat in an area), which may occur in the same person.

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Many BMI calculators can be found on the internet.

Cardiovascular disease is now a leading cause of death among people with HIV. This is because many people with HIV are living well into old age and also due to the high prevalence of cardiovascular risk factors, such as hypertension, among HIV-positive individuals.

Hypertension in people with HIV has been associated with traditional risk factors as well as HIV-related characteristics including immunosuppression, inflammation and lipodystrophy. Whether antiretrovirals increase the risk of hypertension is open to question. Some studies have shown this to be the case. But in a paper published in 2005 researchers from the D:A:D study – an ongoing large multi-cohort observational study exploring the relationship between antiretrovirals and cardiovascular disease and other adverse events – found no clear relationship between antiretroviral use and hypertension.

D:A:D researchers wanted to update their earlier findings, extending the period of follow-up (1999 to 2013) and taking into account treatment with newer antiretrovirals.

The study population consisted of 33,278 HIV-positive people who received care in Europe, Australia and the US. The investigators gathered data on the incidence of hypertension in these people and factors potentially associated with this condition: therapy with 18 individual antiretroviral drugs; HIV-related factors such as immunosuppression and lipodystrophy; and traditional risk factors, such as older age, male sex, ethnicity, smoking, diabetes, high BMI, lipids and impaired kidney function.

Incident hypertension was defined as blood pressure above 140/90 mm/Hg and/or the use of medication to lower blood pressure.

Three-quarters of the participants were male, the median age at baseline was 38 years and approximately half were white. A fifth had a previous AIDS diagnosis and  44% were in the men who have sex with men risk group. The median CD4 cell count was 429 cells/mm3. Nearly 40% of people had an undetectable viral load and 68% had experience of antiretroviral therapy. There was a high prevalence of cardiovascular disease risk factors. Approximately 60% were current or former smokers, 16% had a BMI over 26kg/m2, 18% had lipodystrophy, 4% were on lipid-lowering therapy and 2% had diabetes.

A total of 7636 people (23%) developed hypertension during 223,000 person-years of follow-up, an incidence of 3.42 per 100 person-years.

In the first analysis, cumulative exposure to almost all antiretroviral drugs had a significant association with hypertension. The only exceptions were darunavir/ritonavir and emtricitabine.

After adjustment for demographic risk factors, the only antiretrovirals that retained an association with hypertension were abacavir, nevirapine, ritonavir and indinavir/ritonavir.

After taking into account metabolic risk factors, only use of indinavir/ritonavir (RR = 1.12; 95% CI, 1.04-1.20 per 5 years) and nevirapine (RR = 1.08; 95% CI, 1.02-1.14 per 5 years) still had an association with the development of hypertension.

“The lack of a direct association between cART [combination antiretroviral therapy] in our study provides reassurance that, in addition to preventing immunosuppression by prompt initiation of cART, screening policies and preventive measures used in the general population are also applicable in HIV-positive individuals,” comment the authors.

The most important risk factors for incident hypertension were male gender, older age, black African ethnicity, injecting drug use, a previous AIDS diagnosis, diabetes, high blood lipids, lipodystrophy, obesity and impaired kidney function.

“We did not find evidence for any significant clinically relevant independent associations between exposure to any of the investigated ARV drugs and hypertension risk, but did confirm the importance of traditional risk factors,” conclude the authors. “Our findings provide reassurance that, in addition to preventing immunosuppression in HIV-positive individuals, screening policies and preventive measures for hypertension in HIV-positive persons should follow algorithms used in the general population.”

References

Hastleberg CI et al. 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. HIV Med, online edition, DOI: 10.1111/hiv.12639 (2018).