Higher pulmonary artery systolic pressure levels – an independent risk factor for pulmonary arterial hypertension – have been found in an HIV-positive study group, as compared to HIV-negative controls. However, no association with human herpesvirus-8 (HHV-8) infection was found. The results were reported in the April 23rd issue of AIDS.
Pulmonary arterial hypertension is a condition in which the blood pressure in the pulmonary artery (which supplies blood to the lungs) rises far above normal, accompanied by a thickening of the walls of the pulmonary arteries. Pulmonary arterial hypertension makes it more difficult for the heart to supply blood to the lungs, and therefore oxygen to the rest of the body. High prevalence rates of PAH have been found in people with HIV, but this relationship has not been well characterised other than a known association with injection drug use (IDU) in the general population.
Human herpesvirus-8 (HHV-8), the virus associated with Kaposi's sarcoma, has also been linked with pulmonary arterial hypertension in the general population (Cool 2003). Due to the prevalence of HHV-8 in the HIV-positive population and the relatively poorly-studied link between HIV infection and pulmonary arterial hypertension, a research team based at San Francisco General Hospital compared rates of pulmonary arterial hypertension in HIV-positive patients and HIV-negative controls.
The team recruited a group of 196 HIV-positive participants from another ongoing cohort study based in the hospital HIV immunodeficiency clinic. A group of 52 HIV-negative controls was also recruited; controls were confirmed as HIV-antibody negative, but there were no other exclusion criteria of any kind for either group.
Demographics of both groups were similar: respectively, the HIV-positive participants and HIV-negative controls were a median of 47 vs. 45 years old, 83% vs. 88% were male, 54% vs. 67% were Caucasian, 25% vs. 8% were African-American, 34% vs. 35% had never smoked, and 35% vs. 25% were current smokers. IDU rates were higher in the HIV-positive group: 6% were current users and 32% were past users, while only 2% of the controls were past users and the rest had never used. Past or current history of stimulant use (cocaine, amphetamine and/or methamphetamine) was also higher in the HIV-positive group: 46% vs. 17%.
Most (82%) of the HIV-positive participants were on antiretroviral therapy; median duration of infection was 15 years, and the median CD4 count was 420 cells/mm3.
Pulmonary artery systolic pressure was calculated by echocardiogram in all participants in a blinded manner. Pulmonary artery systolic pressure was found to be higher in the HIV-positive participants, with a median pressure of 27.5 mmHg vs. 22 mmHg in the controls (p<.001). More of the HIV-positive participants (35.2%; 95% confidence interval [CI], 28.5–42.3%) than controls (7.7%; p<.001) had pulmonary artery systolic pressure greater than 30mmHg – a typical threshold for diagnosis of pulmonary arterial hypertension.
Pulmonary artery systolic pressure was also high (median 28 mmHg; 36.1% greater than 40 mmHg) in the 49 HIV-positive participants who had never used injection drugs or stimulants, were HCV-antibody negative, had never smoked, and had no history of heart problems.
After adjusting for age, gender, race, smoking, IDU, and stimulant use, HIV infection was still a significant independent risk factor. HIV-positive participants had 5.1 mmHg higher mean PASP (95% CI 3.1–7.0, p < 0.001) and seven-fold greater odds of having PASP more than 30 mmHg (95% CI 2.3–21, p < 0.001). Among the other variables examined, only age had a significant association with pulmonary artery systolic pressure.
The team did not find a significant association between pulmonary artery systolic pressure and HHV-8 infection in the HIV-positive participants. In unadjusted analyses, mean PASP was non-significantly lower in those who were antibody-positive for HHV-8, by 0.39 mmHg (95% CI, -3.2–2.4, p = 0.78), and the odds of pulmonary artery systolic pressure greater than 30 mmHg were 1.2-fold greater (95% CI, 0.67–2.3, p = 0.51). These associations remained insignificant after adjusting for other factors.
The researchers conclude that this study, the first to include a "well characterized contemporaneous HIV-uninfected… comparator group" and to account for the "critical confounding factor of IDU", still found that "HIV-infected persons have a high prevalence of elevated [pulmonary arterial systolic pressure], which is independent of other risk factors for [pulmonary arterial hypertension (PAH)]." This "suggests a causal role of HIV in PAH" and – since it is not yet known whether this increased prevalence will lead to clinical disease – "emphasizes the need to understand the natural history of PAH in this setting." Meanwhile, the potential role of HHV-8 as a risk factor "remains much less definitive."
Reference:
Hsue PY et al. Role of HIV and human herpesvirus-8 infection in pulmonary arterial hypertension. AIDS: 22:825-833, 2008.