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.

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.

Multi-state models for defining degrees of chronicity related to HIV-infected patient therapy adherence.

Few studies on AIDS that evaluate factors associated with treatment failure have considered the slow evolution of the disease and multiple health state transitions following the use of antiretrovirals. In this article we study factors associated with the progression between different stages of the disease, focusing on therapy adherence using a sample of 722 HIV+ patients followed up for 3 years. States were defined using the following classifications of the CD4 cell count: s1 (CD4 ≥ 500); s2 (350 ≤ CD4 < 500); and s3 (CD4 < 350). The transitions between states were modeled using multi-state models. Antiretroviral therapy adherence and disease duration were associated with transitions between immune states during follow-up. Low adherence increased the hazard ratio of a transition between s1 to s2 and intermediate adherence increased the hazard ratio of a transition between s2 to s3. On the other hand, older age and disease duration between two and four years are protective factors for AIDS progression. Multi-state modeling is a powerful approach for studying chronic diseases and estimating factors associated with transitions between each stage of progression, thus enabling the use of more individualized and effective interventions.

Multi-state models for defining degrees of chronicity related to HIV-infected patient therapy adherence / Modelos multiestado para determinação dos graus de cronicidade de acordo com a adesão de paciente infectado pelo HIV / Modelos multi-estado para la determinación de los grados de cronicidad, de acuerdo con la adhesión del paciente infectado por el VIH

Few studies on AIDS that evaluate factors associated with treatment failure have considered the slow evolution of the disease and multiple health state transitions following the use of antiretrovirals. In this article we study factors associated with the progression between different stages of the disease, focusing on therapy adherence using a sample of 722 HIV+ patients followed up for 3 years. States were defined using the following classifications of the CD4 cell count: s1 (CD4 ≥ 500); s2 (350 ≤ CD4 < 500); and s3 (CD4 < 350). The transitions between states were modeled using multi-state models. Antiretroviral therapy adherence and disease duration were associated with transitions between immune states during follow-up. Low adherence increased the hazard ratio of a transition between s1 to s2 and intermediate adherence increased the hazard ratio of a transition between s2 to s3. On the other hand, older age and disease duration between two and four years are protective factors for AIDS progression. Multi-state modeling is a powerful approach for studying chronic diseases and estimating factors associated with transitions between each stage of progression, thus enabling the use of more individualized and effective interventions.

Poucos estudos sobre AIDS que avaliam fatores associados à falha terapêutica consideram sua evolução lenta, com a passagem por múltiplos estados de saúde, consequência do uso de antirretrovirais. Nesse artigo foram estudados fatores associados à progressão entre estados imunes, enfocando adesão, em 722 pacientes HIV+ acompanhados por 3 anos. O desfecho foi a contagem de células CD4 classificada em s1 (CD4 ≥ 500), s2 (350 ≤ CD4 < 500) e s3 (CD4 < 350). As transições entre estados foram modeladas por modelos multiestado. A adesão à terapia antirretroviral e o tempo de doença estão associados diferentemente à mudança do estado imune vivido pelo paciente. Baixa adesão à terapia aumentou o risco de s1→s2 e adesão intermediária aumentou o de s2→s3. Por outro lado, idades elevadas e tempo de doença de 2 a 4 anos se apresentam como fatores de proteção na progressão da AIDS. A modelagem multiestado é uma abordagem poderosa no estudo de doenças crônicas, por estimar os fatores associados a cada etapa da evolução de doenças crônicas, possibilitando a adoção de intervenções mais individualizadas e eficazes.

Existen pocos estudios sobre el SIDA que evalúan factores asociados al fallo terapéutico, consideran su evolución lenta, con el pasaje por múltiples estados de salud, consecuencia del uso de antirretrovirales. En ese artículo se estudiaron factores asociados a la progresión entre estados inmunes, enfocando adhesión, en 722 pacientes VIH+ acompañados durante 3 años. El desenlace fue el cómputo de células CD4, clasificado en s1 (CD4 ≥ 500), s2 (350 ≤ CD4 < 500) y s3 (CD4 < 350). Las transiciones entre estados se modelaron por modelos multi-estado. La adhesión a la terapia antirretroviral y el tiempo de enfermedad están asociados diferentemente al cambio del estado inmune vivido por el paciente. Baja adhesión a la terapia aumentó el riesgo de s1→s2 y una adhesión intermedia aumentó de un s2→s3. Por otro lado, edades elevadas y tiempo de enfermedad de 2 a 4 años se presentan como factores de protección en la progresión del SIDA. El modelo multi-estado es un enfoque poderoso en el estudio de enfermedades crónicas, por estimar los factores asociados a cada etapa de la evolución de enfermedades crónicas, posibilitando la adopción de intervenciones más individualizadas y eficaces.