Role of HIV and human herpesvirus-8 infection in pulmonary arterial hypertension

Background: Previous work has found a high prevalence of pulmonary arterial hypertension in HIV-infected persons, but establishment of a causal relationship has been limited by the lack of well characterized contemporaneous HIV-uninfected comparator groups. Among HIV-uninfected persons, human herpesvirus-8 (HHV-8) has also been linked to pulmonary arterial hypertension (PAH), but whether this relationship occurs among HIV-infected persons - who have among the highest prevalence of HHV-8 infection - has not been examined. Methods and results: We echocardiographically calculated pulmonary artery systolic pressure and measured HHV-8 antibodies in HIV-infected and HIV-uninfected adults. Among the 196 HIV-infected participants, the median pulmonary artery systolic pressure (PASP) was 27.5 mmHg and 35.2% had PASP greater than 30 mmHg. This compared to a median of 22 mmHg among 52 HIV-uninfected participants in whom 7.7% had a PASP greater than 30 mmHg (P < 0.001). After adjustment for injecting drug and stimulant use, smoking, age, and gender, HIV-infected participants had 5.1 mmHg higher mean PASP and seven fold greater odds of having a PASP greater than 30 mmHg (P<0.001). Although we found no association between HHV-8 and PAH among all HIV-infected participants, a borderline relationship was present when restricting to those without risk factors for PAH. Conclusion: HIV-infected persons have a high prevalence of elevated PASP, which is independent of other risk factors for PAH. This suggests a causal role of HIV in PAH and emphasizes the need to understand the natural history of PAH in this setting. A role for HHV-8 infection in PAH remains much less definitive. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.