Long-Term Follow-up of Human Immunodeficiency Virus-Associated Pulmonary Hypertension: Clinical Features and Survival Outcomes of the Pan Africa Pulmonary Hypertension Cohort (PAPUCO)

Abstract

Aims Data characterizing risk factors and long-term outcome studies on HIV-associated pulmonary hypertension (PH) in Africa are lacking. Methods The Pan African Pulmonary Hypertension Cohort, a multinational registry of 254 consecutive patients diagnosed with PH (97% of African descent) from nine centres in four African countries was implemented. We compared baseline characteristics and three-year survival of an HIV-infected cohort newly diagnosed with PH (PH/HIV+) to an HIV-uninfected cohort with PH (PH/HIV-). Results 134 participants with PH completed follow-up (47 PH/HIV + and 87 PH/HIV-; age/median 36 vs 44 years; p = 0.0004). Cardiovascular risk factors and co-morbidities were similar except for previous tuberculosis (62% vs 18%, p < 0.0001). Six-minute walk distance (6MWD) < 300 meters was common in PH/HIV- (p = 0.0030), but PH/HIV + had higher heart (p = 0.0160) and respiratory (p = 0.0374) rates. Thirty-six percent of PH/HIV + and 15% of PH/HIV- presented with pulmonary arterial hypertension (PAH) (p = 0.0084), whereas 36% of PH/HIV + and 72% of PH/HIV- exhibited PH due to left heart disease (PHLHD) (p = 0.0009). PH due to lung diseases and hypoxia (PHLD) was frequent in PH/HIV + (36% vs 15%) but did not reach statistical significance. HIV-associated PAH tended to have a poorer survival rate compared to PHLHD/PHLD in HIV-infected patients. Conclusion PH/HIV + patients were younger and commonly had previous tuberculosis compared to PH/HIV- patients. Despite a better 6MWD at presentation, they had more signs and symptoms of early onset heart failure and a worse survival rate. Early echocardiography assessment should be performed in HIV-infected patients with history of tuberculosis who present with signs and symptoms of heart failure or post-tuberculosis lung disease.

The prevalence of pulmonary hypertension in post-tuberculosis and active tuberculosis populations: a systematic review and meta-analysis

“…A total of 95 full-text articles were assessed for eligibility. Articles assessed to have the incorrect denominator or no clear numerator were excluded as these missing elements would have precluded us from finding prevalence estimates [ 13 , 14 , 24 , 25 ].…”

“…The pooled cohort with active TB in this systematic review had a relatively young age, were less frequently smokers than the post-TB group and, although numbers are small, had a relatively high HIV prevalence (15% versus 11% in the global TB population) [ 1 ]. Data from the Pan African Pulmonary Hypertension Cohort (PAPUCO) showed that 5–7% of PH patients had active TB at the time of PH diagnosis, rising to 13% in the HIV population [ 13 , 14 ]. Although HIV may cause PH in its own right in approximately 0.5% of cases, the critical interplay between these two chronic infectious diseases and the combined effect on the pulmonary vasculature is unknown and is an important area of research [ 53 , 54 ].…”

“…The pooled cohort with active TB in this systematic review had a relatively young age, were less frequently smokers than the post-TB group and, although numbers are small, had a relatively high HIV prevalence (15% versus 11% in the global TB population) [1]. Data from the Pan African Pulmonary Hypertension Cohort (PAPUCO) showed that 5-7% of PH patients had active TB at the time of PH diagnosis, rising to 13% in the HIV population [13,14].…”

“…Irrespective of the underlying aetiology and clinical group, the development of PH is often associated with poor outcomes and increased mortality [8,9]. Both active and previously treated pulmonary TB are associated with the development of PH, possibly through distinct pathophysiological mechanisms [10][11][12][13]. In high TB burden countries, post-TB lung disease (PTLD) has been found to be one of the most common causes of group III PH (PH associated with lung diseases and/or hypoxia) and, when cohorts of patients with PH from African countries were studied, previous or current TB was identified in 23% of patients [14,15].…”

Effects of post tuberculosis lung disease on survival in HIV-infected individuals with pulmonary hypertension: Insights from the Pan African Pulmonary Hypertension Cohort (PAPUCO) study

“…In this secondary analysis study of the Pan African Pulmonary Hypertension Cohort, a unique contemporary multi-country registry available to the continent [12][13][14][15] , we aimed to assess the effect of TB history on the prevalence and hazards of death associated with PH in the region with an important burden of HIV/TB coinfection, while also considering other emerging TB risk factors such as diabetes and chronic lung diseases on the rise on the continent. Our findings should rekindle debate about the proper management of noncommunicable diseases associated with TB care, as well as the need for effective universal health care to address the intersection of chronic communicable diseases and NCDs in Africa and other regions.…”