Hypertension in patients with HIV associated with obesity, fat loss and previous treatment with stavudine

Patients with HIV have a higher prevalence of hypertension than closely matched HIV-negative controls, investigators from the Netherlands report in the online edition of Clinical Infectious Diseases. Moreover, hypertension in patients with HIV was associated with changes in body composition, including both abdominal obesity and fat wasting associated with stavudine, an older nucleoside reverse transcriptase (NRTI) inhibitor, which although now little used in richer countries was until recently a mainstay of antiretroviral regimens in resource-limited settings.

“Hypertension is highly prevalent among predominantly virologically suppressed HIV-1-infected individuals,” write the investigators. “Unfavourable changes in body compostion, i.e. abdominal obesity among HIV-1-infected individuals and lipoatrophy among those with prior stavudine exposure, may contribute to the pathogenesis of the increased risk of hypertension among HIV-1-infected individuals.”

Several studies have shown that patients with HIV have an increased risk of cardiovascular disease. Hypertension is an important contributor to this increased risk. Research suggests that between 13 and 49% of HIV-positive individuals have hypertension. Possible risk factors for hypertension in the context of HIV-infection include age, gender, BMI, immune activation and inflammation, immune deficiency and the use of antiretroviral therapy.

Glossary

hypertension

When blood pressure (the force of blood pushing against the arteries) is consistently too high. Raises the risk of heart disease, stroke, kidney failure, cognitive impairment, sight problems and erectile dysfunction.

abdomen

The part of the body below the chest, including the stomach, liver, intestines, kidneys, bladder, ovaries and uterus. The word ‘abdominal’ relates to pain or other problems in that area.

diastolic blood pressure

The lowest level of blood pressure – when the heart relaxes between beats. It is the second of the two numbers in a blood pressure reading (above 140/90 mmHg is high blood pressure).

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

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. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.

To gain a further understanding of these issues, investigators from the AGEhIV Cohort Study in Amsterdam designed a cross-sectional study involving HIV-positive patients and well-matched HIV-negative controls. They had three aims:

  • To determine the prevalence of hypertension in middle-aged HIV-positive patients, most of who were taking antiretrovirals
  • To assess whether HIV infection is independently associated with hypertension, and if so –
  • To identify the HIV-related factors that might explain the higher prevalence of hypertension among HIV-positive individuals.

The study population consisted of 527 HIV-positive individuals and 517 HIV-negative controls. Baseline visits occurred between 2010 and 2012. Assessments included measurement of resting blood pressure, and hypertension was defined as systolic blood pressure of 140 mmHg or above, diastolic blood pressure of 90 mmHg or above, and/or self-reported use of anti-hypertensive medication.

Patients and controls had a median age of approximately 53 years and 87% were male.

Nearly all the HIV-positive patients were taking antiretroviral therapy, had an undetectable viral load and median CD4 cell count was 570 cells/mm3. A fifth of patients had taken mono/dual NRTI therapy before the availability of potent treatment and 37% had a history of therapy with stavudine, a drug which is now known to be associated with significant toxicities, especially changes in body fat composition.

Prevalence of hypertension was significantly higher among HIV-positive compared to HIV-negative participants (48% vs. 36%, respectively; OR = 1.63, 95% CI, 1.27-2.09).

Infection with HIV remained significantly associated with increased prevalence of hypertension after controlling for age, gender and ethnicity (OR = 1.52; 95% CI, 1.17-1.98; p = 0.002), and also after adjustment for common risk factors for hypertension such as smoking, alcohol use, BMI and physical activity (p < 0.001).

After adjustment for hip-to-waist ratio, the association between HIV and hypertension was weakened and ceased to be significant.

Restricting analysis to the HIV-positive patients showed there was a significant negative association between hip circumference and hypertension (OR = 0.93 per 1cm greater hip circumference; 95% CI, 0.88-0.98; p = 0.004). The negative association between hip circumference and hypertension was significant among patients with previous exposure to stavudine (p < 0.001), but not among patients who had not taken this drug. Treatment with stavudine remained associated with hypertension after controlling for established risk factors for hypertension (OR = 1.54; 95% CI, 1.04-2.30; p = 0.033). However, this relationship was weakened and ceased to be significant after adjustment for waist-to-hip ratio and hip circumference, but not after taking into account waist circumference.

Infection with HIV continued to be associated with increased prevalence of hypertension in an analysis that excluded patients with a history of mono/dual NRTI therapy and which also controlled for tradition risk factors (OR, 1.44; 95% CI, 1.07-1.94; p = 0.015). However, once again, the relationship between HIV and hypertension ceased to be significant after adjustment for waist-to-hip ratio. Nor was there a relationship with hip circumference. Moreover, the association of hypertension with previous use of stavudine was no longer significant among patients who did not have a history of mono/dual NRTI therapy.

“A change in body composition in HIV-1-infected individuals may be an important contributor to the association between HIV and hypertension,” comment the authors. “The negative association between hip circumference and hypertension among HIV-1-infected individuals appears to be driven by prior exposure to stavudine.”

The investigators believe that both abdominal fat accumulation and peripheral fat loss have a role in the development of hypertension in patients with HIV.

They conclude, “our results underline the importance of avoiding stavudine as well as limiting the occurrence of abdominal obesity in preventing and managing hypertension and cardiovascular risk among HIV-1-infected patients.”

References

Van Zoest R et al. Higher prevalence of hypertension in HIV-1-infected patients on combination antiretroviral therapy is associated with changes in body composition and prior stavudine exposure. Clin Infect Dis, online edition, 2016.