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.
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.”