HIV-related Pulmonary Arterial Hypertension Research Articles

HIV-derived proteins contribute to the development of pulmonary arterial hypertension in mice

Pulmonary arterial hypertension (PAH) is a life-threatening lung disease caused by remodeling of pulmonary vascular walls which is associated with a sustained elevation in pulmonary arterial pressure leading to RV failure and ultimately death. HIV infection increases the risk of developing severe PAH and HIV-associated PAH has a poor prognosis with elevated mortality. Despite significant effort to understand its pathophysiology, the identification of signaling pathways involved in HIV-mediated onset and progression of PAH remains scarce. The aim of the present study is to unravel the mechanistic links between HIV and PAH and to investigate how HIV-derived proteins contribute to the pathological processes of pulmonary vascular remodeling (PVR) of PAH and right ventricle (RV) hypertrophy. Three different HIV mouse models have been used to answer these questions. Our results showed that transgenic HIV-1 Tg26 mice, which mimics people living with HIV (PLWH) with low viremia and without progression to AIDS, exhibit increased right ventricular systolic pressure (RVSP), Fulton-index and thickness of pulmonary arterial wall indicating PVR and RV hypertrophy in these mice. More importantly, transfer of bone marrow (BMT) from Tg26 to wild-type (WT) mice and chronic treatment with HIV-encoded Tat protein induce development of PAH and RV hypertrophy in WT mice indicating that HIV-derived proteins contribute to the pathogenesis of PAH in mouse models of HIV. In order to explore signaling pathways involved in the HIV-related PAH, RNA sequencing and qPCR were performed using lung samples from control/Tg26 mice and BMT mice. We found increased expression of the proliferative marker Ki67 in Tg26 lung endothelial cells (EC). In Tg26 lung vascular smooth muscle cells (VSMC), markers of contractile SMC phenotype (SM22, SM MHC) were decreased while markers for synthetic SMC phenotype (Vimentin, Rbp-1) were upregulated suggesting increased EC proliferation and SMC de-differentiation in Tg26 mice. Moreover, we identified ten genes which expression levels were up/ downregulated in the lungs of Tg26 mice which can potentially contribute to the development of HIV-associated PAH. In conclusion, we have established a novel model of HIV, the BMT Tg26 to WT mice, to study the contribution of immune cell derived viral proteins to PAH and demonstrated that at least one viral protein, the HIV-Tat, is involved in the development of PAH and RV hypertrophy associated with HIV. Additional studies are needed to further elucidate the role of these signaling mechanisms in HIV-induced PAH in order to develop effective therapy for the prevention and treatment of this lung disorder. Supported by NIH NHLBI 1R01HL147639 (EBdC) and Augusta University IGP IGPP00030 (LK). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

HIV transgene expression impairs K+ channel function in the pulmonary vasculature.

Human immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH); however, the pathogenesis of HIV-related PAH remains unclear. Since K+ channel dysfunction is a common marker in most forms of PAH, our aim was to analyze whether the expression of HIV proteins is associated with impairment of K+ channel function in the pulmonary vascular bed. HIV transgenic mice (Tg26) expressing seven of the nine HIV viral proteins and wild-type (WT) mice were used. Hemodynamic assessment was performed by echocardiography and catheterization. Vascular reactivity was studied in endothelium-intact pulmonary arteries. K+ currents were recorded in freshly isolated pulmonary artery smooth muscle cells (PASMC) using the patch-clamp technique. Gene expression was assessed using quantitative RT-PCR. PASMC from Tg26 mice had reduced K+ currents and were more depolarized than those from WT. Whereas voltage-gated K+ channel 1.5 (Kv1.5) currents were preserved, pH-sensitive noninactivating background currents ( IKN) were nearly abolished in PASMC from Tg26 mice. Tg26 mice had reduced lung expression of Kv7.1 and Kv7.4 channels and decreased responses to the Kv7.1 channel activator L-364,373 assessed by vascular reactivity and patch-clamp experimental approaches. Although we found pulmonary vascular remodeling and endothelial dysfunction in Tg26 mice, this was not accompanied by changes in hemodynamic parameters. In conclusion, the expression of HIV proteins in vivo impairs pH-sensitive IKN and Kv7 currents. This negative impact of HIV proteins in K+ channels was not sufficient to induce PAH, at least in mice, but may play a permissive or accessory role in the pathophysiology of HIV-associated PAH.

Effect of 6-min Walk Test on pro-BNP Levels in Patients with Pulmonary Arterial Hypertension.

Plasma pro-BNP (brain natriuretic peptide) levels are often elevated in response to right ventricular (RV) volume and pressure overload, parameters potentially affected by exercise. Plasma pro-BNP levels change in association with long-term changes in pulmonary hemodynamics, thereby serving as a potential biomarker in pulmonary arterial hypertension (PAH). The 6-min Walk Test (6MWT) and pro-BNP level are often checked in a single office visit. There is no universal standard for measuring Pro-BNP levels relative to the timing of the 6MWT. Based on the studies in normal subjects indicating that pro-BNP levels changes after exercise, we hypothesized that the pro-BNP might rise after the 6MWT in PAH patients, potentially impacting clinical decisions. Patients at our center with WHO Group 1 PAH on active therapy at a stable dose for 30days or more were enrolled. After resting the patient for 30min, blood was drawn for baseline pro-BNP and a 6MWT was performed. Pro-BNP levels were drawn immediately after the 6MWT and 1 and 2h later. Pro-BNP was measured using a commercially available ELISA kit. The levels before exercise and after exercise were compared using student's paired t tests. There were 17 females and 3 male subjects. The mean age was 53±11years. Seven patients had systemic lupus erythematosus-related PAH, six had idiopathic PAH, three had scleroderma, three had portopulmonary hypertension, and one had HIV-related PAH. The mean PA pressure was 50±15mmHg with a mean pulmonary vascular resistance of 10±4Wood units. The majority of the patients were on multimodality PAH therapy, including parenteral prostacyclins. Mean 6MWT distance was 377±140m. In 14/20 patients, the pro-BNP level increased immediately after the 6MWT; in 12/20 patients, the pro-BNP level was elevated at 1h post exercise. In the majority of the patients, the pro-BNP fell to baseline 2h post 6MWT. There appears to be a trend of pro-BNP level increasing immediately after exercise and continuing to be elevated at 1h. Pro-BNP levels then return to baseline at 2h post 6MWT.

Early Right Ventricular Dysfunction in Highly Selected (Totally Free from Cardiovascular Risk Factors and Other Comorbidities) Human Immunodeficiency Virus Patients: A Pilot Study with Advanced Echocardiography.

Objective:Human immunodeficiency virus (HIV) infection may also be associated with cardiac dysfunction, thus negatively affecting patients’ morbidity and mortality. This preliminary study aimed at evaluating whether bi-and three-dimensional (3D) strain echocardiographic facilities were able to identify alterations in the right ventricular (RV) function in highly selected – because free from cardiovascular risk factors and other comorbidities – HIV patients.Materials and Methods:Eight of these specific HIV patients (age: 32.0 ± 3.6 years; 7 months) treated with highly active antiretroviral therapy (HAART) were enrolled and compared with 8 sex-, age-, and cardiovascular risk profile-matched healthy individuals. All underwent clinical evaluation and transthoracic echocardiography coupled with tissue Doppler, two-dimensional (2D), and 3D speckle tracking imaging to examine their RV function.Results:All standard echocardiographic parameters resulted in the normal range, with no significant differences between HIV and controls. On the contrary, 2D longitudinal strain (16.1% ±1.6% vs. 17.8% ±0.9%, P = 0.02) and Global 3D strain (28.5% ±3.6% vs. 33.5% ±1.9%, P = 0.0002) were reduced in the HIV group. Moreover, Global 3D strain values showed a direct correlation with RV fractional area change values (r = 0.66, P = 0.005).Conclusions:2D longitudinal and 3D Global strain can identify an early asymptomatic RV impairment in HIV patients free from other risk factors and comorbidities. These findings seem to imply that also in treated with HAART and well-controlled HIV patients an early asymptomatic systolic RV dysfunction is present, as a distinctive and separated pathological entity compared with classic HIV-related pulmonary arterial hypertension and left ventricular dysfunction. In these patients, RV dysfunction is not revealed by standard echocardiography.

Enhanced autophagy in pulmonary endothelial cells on exposure to HIV-Tat and morphine: Role in HIV-related pulmonary arterial hypertension

ABSTRACTIntravenous drug use is one of the major risk factors for HIV-infection in HIV-related pulmonary arterial hypertension patients. We previously demonstrated exaggerated pulmonary vascular remodeling with enhanced apoptosis followed by increased proliferation of pulmonary endothelial cells on simultaneous exposure to both opioids and HIV protein(s). Here we hypothesize that the exacerbation of autophagy may be involved in the switching of endothelial cells from an early apoptotic state to later hyper-proliferative state. Treatment of human pulmonary microvascular endothelial cells (HPMECs) with both the HIV-protein Tat and morphine resulted in an oxidative stress-dependent increase in the expression of various markers of autophagy and formation of autophagosomes when compared to either Tat or morphine monotreatments as demonstrated by western blot, transmission electron microscopy and immunofluorescence. Autophagy flux experiments suggested increased formation rather than decreased clearance of autolysosomes. Inhibition of autophagy resulted in a significant increase in apoptosis and reduction in proliferation of HPMECs with combined morphine and Tat (M+T) treatment compared to monotreatments whereas stimulation of autophagy resulted in opposite effects. Significant increases in the expression of autophagy markers as well as the number of autophagosomes and autolysosomes was observed in the lungs of SIV-infected macaques and HIV-infected humans exposed to opioids. Overall our findings indicate that morphine in combination with viral protein(s) results in the induction of autophagy in pulmonary endothelial cells that may lead to an increase in severity of angio-proliferative remodeling of the pulmonary vasculature on simian and human immunodeficiency virus infection in the presence of opioids.

HIV related pulmonary arterial hypertension: epidemiology in Africa, physiopathology, and role of antiretroviral treatment.

The development of HIV related pulmonary arterial hypertension (PAH) reduces the probability of survival by half as compared with HIV-infected individuals without HIV related PAH. HIV infected patients have a greater incidence of PAH compared to general population and have a 2500-fold increased risk of developing PAH. It is therefore important to have a recent overview of the problem in Africa, the most HIV affected part of the world (70 % of all HIV infection in the world). First, we discussed the epidemiology of HIV-related PAH in Africa. Second, the current understanding of the HIV-related PAH pathogenesis has been covered. Third, role of highly active antiretroviral therapy on HIV-related PAH has been revisited. There are few data concerning epidemiology of HIV related pulmonary hypertension in Africa leading to necessity to conduct further prospective large studies. The prevalence of PAH among HIV infected people in Africa varies from 5 to 13 %. The prevalence of HIV-related PAH in Africa is notably high compared to those in developed countries and in general population. The pathogenesis of PAH is clearly complex, and probably results from the interaction of multiple modulating genes with environmental factors. The physiopathology includes cytokines secretion increase which induces dysregulation of endothelial and vascular smooth muscle cell growth and imbalance of endogenous vasodilators and constrictors; HIV viral proteins which induces vascular oxidative stress, smooth myocyte proliferation and migration, and endothelial injury and genetic predisposition due to some major histocompatibility complex alleles, particularly HDL-DR6 and HLA-DR5. Histologically, HIV related PAH has the same characteristics with other types PAH. Antiretroviral therapy have a beneficial effect on the outcome of HIV related pulmonary hypertension, but it lacks evidence from large prospective studies.

Prevalence and severity of ventricular dysfunction in patients with HIV-related pulmonary arterial hypertension

ObjectivesTo evaluate the occurrence of ventricular systolic dysfunction in human immunodeficiency virus (HIV)-related pulmonary arterial hypertension (PAH). BackgroundPatients with HIV-related PAH may develop ventricular systolic dysfunction both as a consequence of PAH progression or of the myocardial involvement from the HIV infection itself. MethodsCardiac magnetic resonance imaging was applied to measure ejection fraction for the left ventricle and the right ventricle in patients with HIV-related PAH (n = 27) and in patients with PAH from other aetiologies (n = 115). ResultsIn HIV-related PAH, ejection fraction values were lower and a higher proportion of patients presented with an advanced stage of ventricular dysfunction (55% vs. 25%; p = 0.009). In a multivariate model, PAH related to HIV infection remained independently associated with advanced ventricular dysfunction (p = 0.011). ConclusionsPatients with HIV-related PAH have more prevalent and severe ventricular systolic dysfunction compared to patients with PAH from other aetiologies.

HIV-1/Cocaine Induced Oxidative Stress Disrupts Tight Junction Protein-1 in Human Pulmonary Microvascular Endothelial Cells: Role of Ras/ERK1/2 Pathway

Intravenous drug use (IVDU) is the major risk factor in the development of HIV-related pulmonary arterial hypertension (HRPAH); however, the pathogenesis of HRPAH in association with IVDU has yet to be characterized. Endothelial injury is considered to be an initiating factor for pulmonary vascular remodeling in animal models of PAH. Our previous study shows that simultaneous exposure to HIV-Trans-activator of transcription (Tat) and cocaine exacerbates both disruption of tight junction proteins and permeability of human pulmonary artery endothelial cells compared with either treatment alone. We here now demonstrate that this HIV-Tat and cocaine mediated endothelial dysfunction accompanies with increase in hydrogen peroxide and superoxide radicals generation and involves redox sensitive signaling pathway. Pretreatment with antioxidant cocktail attenuated the cocaine and Tat mediated disassembly of Zonula Occludens (ZO)-1 and enhancement of endothelial monolayer permeability. Furthermore, inhibition of NADPH oxidase by apocynin or siRNA-mediated knockdown of gp-91phox abolished the Tat/cocaine-induced reactive oxygen species (ROS) production, suggesting the NADPH oxidase mediated generation of oxidative radicals. In addition, ROS dependent activation of Ras and ERK1/2 Kinase was observed to be mediating the TJP-1 disassembly, and endothelial dysfunction in response to cocaine and Tat exposure. In conclusion, our findings demonstrate that Tat/cocaine -mediated production of ROS activate Ras/Raf/ERK1/2 pathway that contributes to disruption of tight junction protein leading to pulmonary endothelial dysfunction associated with pulmonary vascular remodeling.

Pulmonary arterial hypertension related to human immunodeficiency virus infection: A case series.

To present 18 new cases of human immunodeficiency virus (HIV)-related pulmonary arterial hypertension (PAH) with presenting features, treatment options and follow-up data. This is a single-centre, retrospective, observational study that used prospectively collected data, conducted during a 14-year period on HIV-related PAH patients who were referred to a pulmonary hypertension unit. All patients infected with HIV were consecutively admitted for an initial evaluation of PAH during the study period and included in our study. Right heart catheterisation was used for the diagnosis of PAH. Specific PAH treatment was started according to the physician's judgment and the recommendations for idiopathic PAH. The data collected included demographic characteristics, parameters related to both HIV infection and PAH and disease follow-up. Eighteen patients were included. Intravenous drug use was the major risk factor for HIV infection. Risk factors for PAH, other than HIV infection, were present in 55.5% patients. The elapsed time between HIV infection and PAH diagnoses was 12.2 ± 6.9 years. At PAH diagnosis, 94.1% patients had a CD4 cell count > 200 cells/μL. Highly active antiretroviral therapy (present in 47.1% patients) was associated with an accelerated onset of PAH. Survival rates were 93.8%, 92.9% and 85.7% at one, two and three years, respectively. Concerning specific therapy, 33.3% of the patients were started on a prostacyclin analogue, and the rest were on oral drugs, mainly phosphodiesterase-5 inhibitors. During the follow-up period, specific therapy was de-escalated to oral drugs in all of the living patients. The survival rates of HIV-related PAH patients were higher, most likely due to new aggressive specific therapy. The majority of patients were on oral specific therapy and clinically stable. Moreover, sildenafil appears to be a safe therapy for less severe HIV-related PAH.

Human Immunodeficiency Virus and Pulmonary Arterial Hypertension

Human immunodeficiency virus- (HIV-) related pulmonary arterial hypertension (PAH) is a rare complication of HIV infection. The pathophysiology of HIV-related PAH is complex, with viral proteins seeming to play the major role. However, other factors, such as coinfection with other microorganisms and HIV-related systemic inflammation, might also contribute. The clinical presentation of HIV-related PAH and diagnosis is similar to other forms of pulmonary hypertension. Both PAH-specific therapies and HAART are important in HIV-related PAH management. Future studies investigating the pathogenesis are needed to discover new therapeutic targets and treatments.

Bosentan and antiretroviral therapy in an HIV/HBV/HCV coinfected Chinese patient with HIV-related pulmonary arterial hypertension

Bosentan and antiretroviral therapy in an HIV/HBV/HCV coinfected Chinese patient with HIV-related pulmonary arterial hypertension

Doppler echocardiography does not accurately estimate pulmonary artery systolic pressure in HIV-infected patients

Doppler echocardiography is used to screen for HIV-related pulmonary arterial hypertension (HRPAH). We studied patients with HIV infection to determine the accuracy of Doppler echocardiography-estimated pulmonary artery systolic pressure (PASP) compared with PASP measured during right heart catheterization. Doppler echocardiography-estimated PASP was inaccurate in 19.7% of cases. Using Doppler echocardiography-estimated PASP, one in three patients with HRPAH was missed. Doppler echocardiography estimates of PASP are not accurate in patients with HIV.

Epigastric pain as the initial presentation of undiagnosed HIV and its associated pulmonary arterial hypertension

Introduction: Due to increase in survival of HIV positive patients on antiretroviral therapies, longer term complications of HIV infection have started to surface including HIV related pulmonary arterial hypertension (HIV­PAH). In the 1990’s the occurrence of HIV­PAH was estimated to be at 0.5% (1:1200) in HIV positive patients which is 2500 times higher than in the general population (1­2:1,000,000) and seems to remain at the same level despite advances in diagnosis and treatment. Case Report: A case of a 28­year­old African­American female presenting with abdominal pain, increased abdominal girth, weigh gain, and lower extremity swelling of one week duration is presented. She was not previously diagnosed with HIV. Upon admission she was diagnosed with HIV related pulmonary arterial hypertension World Health Organization functional class III. Conclusion: What makes our case unique, is the rarity of the disease entity, unique gastro intestinal presentation, young age and newly diagnosed HIV and associated pulmonary arterial hypertension. The presence of epigastric pain and increased abdominal girth should increase the suspicion of PAH with right heart failure.

Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort

The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in this setting, HIV-related cases of CAD remain at historically low levels.

Pulmonary Vascular Lesions Are Common in SIV- and SHIV-env-Infected Macaques

The lack of animal models of HIV-related pulmonary arterial hypertension (HIV-PAH) severely limits investigation of this serious disease. While histological evidence of HIV-PAH has been demonstrated in macaques infected with simian immunodeficiency virus (SIV) as well as with chimeric simian/human immunodeficiency virus (SHIV) containing HIV-1-derived Nef protein, other primate models have not been studied. The objective was to document and describe the development of pulmonary vascular changes in macaques infected with SIV or with SIV containing HIV-1-derived envelope protein (SHIV-env). Lung tissue was obtained at necropsy from 13 SHIV (89.6P)-env-infected macaques and 10 SIV (ΔB670)-infected macaques. Pulmonary arterial pathology, including arterial hyperplasia and the presence of plexiform lesions, was compared to normal monkey lung. Pulmonary artery hyperplasia was present in 8 of 13 (62%) SHIV-env-infected macaques and 4/10 (36%) SIV-infected macaques. The most common histopathological lesions were intimal and medial hyperplasia of medium and large pulmonary arteries. Hyperplastic lesions were predominantly due to smooth muscle cell hyperplasia. This is the first report of pulmonary vascular lesions in SHIV-env-infected macaques and confirms prior reports of pulmonary vasculopathy in SIV-infected macaques. The finding of pulmonary arteriopathy in monkeys infected with SHIV not containing HIV-nef suggests that other factors might also be important in the development of HIV-PAH. This SHIV-env model provides a new means to investigate HIV-PAH.

Pulmonary Hypertension Associated With HIV Infection: Pulmonary Vascular Disease: The Global Perspective

The success of antiretroviral therapies in improving the survival of patients infected with HIV and reducing HIV-associated opportunistic infections is undisputed. Nevertheless, long-term outcomes such as noninfectious cardiovascular complications, including cardiomegaly, pericarditis, myocarditis, and pulmonary arterial hypertension, are now serious concerns. The lung is a frequent target organ for disorders associated with HIV infection. HIV-related pulmonary arterial hypertension (HRPAH) affects more individuals who are infected with HIV than individuals who are uninfected. Moreover, the long-standing estimated prevalence of HRPAH in developed countries (calculated at 0.5%) is increasing as more clinician-scientists unify their efforts to screen patients who are pulmonary asymptomatic for pulmonary arterial hypertension. In order to decrease mortality, efforts are directed at early detection, diagnosis, and therapeutic interventions before the disease compromises patients' quality of life. This article reviews the logistics of screening approaches for HRPAH and discusses the substantial disease burden currently faced by developing countries, where the prevalence of HIV infection is higher and complicated by hyperendemic risk factors, limited access to antiretrovirals, and lack of screening tools. We also present mechanistic insights into HRPAH, including the role of HIV proteins and their potential use as screening tools, and, finally, areas that still need intense research.

HIV and pulmonary arterial hypertension: a systematic review

HIV-related pulmonary arterial hypertension (PAH) is a rare entity but is associated with significant morbidity and mortality. The literature describing the outcomes of therapy for this disease is limited to case series and cohort studies. The objective of this study was to systematically review and synthesize the literature on HIV-related PAH. MEDLINE, EMBASE, PapersFirst, the Cochrane collaboration and the Cochrane Register of controlled trials were searched with pre-defined search terms. Randomized controlled trials, observational cohort studies, case-control studies and case reports were considered for inclusion in the qualitative analysis. A total of 180 case reports of PAH in HIV-infected patients were identified. Twenty-six were excluded and thus 154 case reports were included in the qualitative analysis. Thirteen cohort, one case series and two case-control studies were also identified and included in the review. The average baseline CD4 count at the time of diagnosis of PAH was 352 ± 304 cells/μL. The average time from diagnosis of HIV infection to diagnosis of PAH was 4.3 ± 4.0 years. Predominant chest X-ray findings included cardiomegaly (80%) and pulmonary arterial enlargement (75%). Highly active antiretroviral therapy, bosentan, and prostaglandin therapy have all been reported to be beneficial in improving haemodynamic and functional status in HIV-related PAH. HIV-related PAH is a rare entity with clinical, laboratory, imaging and pathological manifestations similar to those of idiopathic PAH. The evidence for various treatments is limited to cohort, case series and case-control studies. Randomized controlled trials are needed to properly assess the utility of these therapies in the treatment of HIV-related PAH.

Improvement of HIV-related pulmonary hypertension after the introduction of an antiretroviral therapy

To the Editors: The potential impact of combination antiretroviral therapy (CART) on HIV-related pulmonary arterial hypertension (PAH) remains controversial 1–4. We herein report the case of a dramatic improvement in PAH at the time of the inception of CART in a 19-yr-old female with HIV-1 infection due to mother-to-child transmission. HIV-related PAH was diagnosed in January 2006, when she was stable in stage A2 of the US Centers for Disease Control and Prevention classification without any antiretroviral therapy (table 1⇓). Specific PAH therapy with bosentan was started in January 2006, in combination with oral anticoagulant and diuretic therapy. CART was indicated at that time, but not prescribed owing to patient …

Successful switch to sitaxsentan in a patient with HIV-related pulmonary arterial hypertension and late intolerance to nonselective endothelin receptor blockade

Pulmonary arterial hypertension [PAH] is a rare but well-known cardiovascular condition potentially associated with human immunodeficiency virus [HIV] infection and is currently recognized to be one of the most ominous noninfectious HIV complications. Although there is no clear evidence supporting the use of any medication for the treatment of HIV-related PAH, many of the currently available agents have been shown to exert some clinical benefits HIV-PAH patients. To date, no data are available regarding the potential effects of sitaxsentan, a selective endothelin type-A receptor antagonist, in this peculiar patient population. We report the case of a successful switch to sitaxsentan in a HIV-infected patient with PAH initially receiving bosentan who developed a late treatment-related side-effect.

Prevalence of HIV-related Pulmonary Arterial Hypertension in the Current Antiretroviral Therapy Era

Prevalence of HIV-related Pulmonary Arterial Hypertension in the Current Antiretroviral Therapy Era