Effects of antiretroviral treatment and nadir CD4 count in progression to cardiovascular events and related comorbidities in a HIV Brazilian cohort: a multi-stage approach

ABSTRACT

The use of highly active antiretroviral therapy has resulted in changes of comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS-related events. The occurrence of cardiovascular events is greater in PLHIV, but the mechanism responsible for it is still controversial. This article aimed to investigate factors associated with the progression to cardiovascular events in PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio de Janeiro-Brazil. Clinical progression was stratified in five states: No comorbidities (s₁), arterial hypertension (s₂), lipid abnormalities (s₃), hypertension and lipid abnormalities (s₄) and major cardiovascular events (stroke, coronary artery disease, thrombosis or death) (s₅). Semi-Markov models evaluated the effects of cardiovascular traditional factors, treatment and clinical covariates on transitions between these states. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided. In addition to traditional factors (age, sex, educational level and skin color), the development of one comorbidity (lipid abnormalities or hypertension) increased in patients with low nadir CD4 (<50 cells/mm³), (HR = 1.59, CI 1.11–2.28 and 1.36, CI 1.11–1.66, respectively). The risk to experience a second comorbidity (s₃→s₄) increased 75% with low nadir CD4. Age was the only factor that increased the risk of major cardiovascular events once having lipid abnormalities with or without hypertension (s₃,s₄→s₅). The prolonged use of certain antiretroviral drugs (abacavir, didanosine, ritonavir, lopinavir, amprenavir and fosamprenavir) increased the risk of direct transition (s₁→s₅) to major cardiovascular events (HR = 5.29, CI 1.16–24.05). This analysis suggests that prolonged use of certain antiretroviral drugs led directly to major cardiovascular events, while low nadir CD4 only affected the occurrence of lipid abnormalities and hypertension. Management strategies, including rational use of complex exams (such as, computed-tomography angiography), statins and antihypertensives, should be developed based on the distinct roles of antiretroviral use and of HIV infection itself on the progression to cardiovascular events.

KEYWORDS:

• Cardiovascular events
• progression
• HIV/AIDS
• multi-stage model
• cohort study

Acknowledgments

We thank the professionals involved in the PLHIV care, the staff at the Hospital Information Service for maintaining the database and Eduardo Furtado for the proofreading service.

Disclosure statement

No potential conflict of interest was reported by the authors.

ORCID

Raquel de Vasconcellos Carvalhaes de Oliveira http://orcid.org/0000-0001-9387-8645

Silvia Emiko Shimakura http://orcid.org/0000-0002-5468-2516

Dayse Pereira Campos http://orcid.org/0000-0002-8965-534X

Yara Hahr Marques Hokerberg http://orcid.org/0000-0001-7140-7172

Flaviana Pavan Victoriano http://orcid.org/0000-0002-5149-9441

Sayonara Ribeiro http://orcid.org/0000-0003-0461-9735

Valdiléa Gonçalves Veloso http://orcid.org/0000-0002-6622-3165

Beatriz Grinsztejn http://orcid.org/0000-0003-3692-5155

Marilia Sá Carvalho http://orcid.org/0000-0002-9566-0284