Self-reported HIV/HAART-associated Lipodystrophy and Modifiable Risk Factors for Cardiovascular Disease

Abstract Background Patient self-report is the most common diagnostic tool in the literature to detect HIV/HAART-associated lipodystrophy. However, data on the association of cardiovascular risk factors with HIV/HAART-associated lipodystrophy assessed by self-report are still missing. Objectives To determine the prevalence of self-reported HIV/HAART-associated lipodystrophy and to identify independent associations between traditional modifiable cardiovascular risk factors and self-reported lipodystrophy. Methods We conducted a retrospective observational study at an outpatient infectious disease clinic in the Central-West of Brazil to identify the association between traditional modifiable cardiovascular risk factors and self-reported lipodystrophy. Sedentary lifestyle, smoking status, family history of cardiovascular disease, hypertension, diabetes, dyslipidemia, increased waist circumference and overweight were the cardiovascular risk factors assessed. Self-reported HIV/HART-associated lipodystrophy was categorized as: mild (noticeable by patients' close inspection), moderate (easily noticeable by patient and physician) or severe (readily noticeable by a casual observer). Prevalence ratio (PR) and 95% confidence interval (CI95%) were calculated. Multivariate Poisson's regression was used to analyze factors associated to HIV/HAART-associated lipodystrophy assessed by self-report considering a significance level of 5%. Results A total of 183 patients were included, with a mean age of 39.3±10.9 years. Most of the sample were male (77.6%), non-white (50.8%) and single (53.0%). The overall prevalence of HIV/HAART-associated lipodystrophy was 52.5% (95% CI 44.96 - 59.88). Severe lipodystrophy was observed in more than half patients (55.2%). No traditional modifiable cardiovascular risk factor was independently associated with lipodystrophy. Female sex (PR 1.49; 95% CI 1.15 - 1.95; p =0.003), time of HIV infection diagnosis of 1-3 years (PR 1.83; 95% CI 1.09 - 3.08; p =0.002) and a positive family history of CVD (PR 1.62; 95% CI 1.11 - 2.36; p <0.001) were independently associated with lipodystrophy. Conclusion HIV/HAART-associated lipodystrophy assessed by patient self-report was not associated with traditional modifiable cardiovascular risk factors. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Lipid profile of HIV-infected patients in relation to antiretroviral therapy: a review / Perfil lipídico de pacientes infectados pelo HIV em relação à terapia antirretroviral: uma revisão

This study reviewed the lipid profile of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in relation to use of antiretroviral therapy (ART), and its different classes of drugs. A total of 190 articles published in peer-reviewed journals were retrieved from PubMed and LILACS databases; 88 of them met the selection criteria and were included in the review. Patients with HIV/AIDS without ART presented an increase of triglycerides and decreases of total cholesterol, low density lipoprotein (LDL-c), and high density lipoprotein (HDL-c) levels. Distinct ART regimens appear to promote different alterations in lipid metabolism. Protease inhibitors, particularly indinavir and lopinavir, were commonly associated with hypercholesterolemia, high LDL-c, low HDL-c, and hypertriglyceridemia. The protease inhibitor atazanavir is apparently associated with a more advantageous lipid profile. Some nucleoside reverse-transcriptase inhibitors (didanosine, stavudine, and zidovudine) induced lipoatrophy and hypertriglyceridemia, whereas abacavir increased the risk of cardiovascular diseases even in the absence of apparent lipid disorders, and tenofovir resulted in lower levels of cholesterol and triglycerides. Although non-nucleoside reverse-transcriptase inhibitors predisposed to hypertriglyceridemia and hypercholesterolemia, nevirapine was particularly associated with high HDL-c levels, a protective factor against cardiovascular diseases. Therefore, the infection itself, different classes of drugs, and some drugs from the same class of ART appear to exert distinct alterations in lipid metabolism.

Este estudo faz uma revisão sobre o perfil lipídico de pacientes com vírus da imunodeficiência humana/síndrome da imunodeficiência adquirida (HIV/AIDS) em relação ao uso da terapia antirretroviral (TARV), e suas diferentes classes de fármacos. Um total de 190 artigos publicados em revistas indexadas foram selecionados das bases de dados PubMed e LILACS; 88 deles preencheram os critérios de seleção e foram incluídos nesta revisão. Pacientes com HIV/AIDS sem uso de TARV apresentaram aumento de triglicérides e diminuição dos níveis de colesterol total, lipoproteína de baixa densidade (LDL-c) e lipoproteína de alta densidade (HDL-c). Distintos regimes de TARV promoveram diferentes alterações no metabolismo lipídico. Inibidores de protease, particularmente indinavir e lopinavir, foram comumente associados com hipercolesterolemia, aumento de LDL-c, diminuição de HDL-c e hipertrigliceridemia. O inibidor de protease atazanavir aparentemente está associado a menores alterações do perfil lipídico. Alguns inibidores da transcripitase reversa análogos de nucleosídeos (didanosina, estavudina e zidovudina), induziram lipoatrofia e hipertrigliceridemia, enquanto o abacavir aumentou o risco cardiovascular mesmo na ausência de aparentes distúrbios lipídicos, e o tenofovir resultou em menores níveis de colesterol e triglicérides. Embora os inibidores da transcriptase reversa não análogos de nucleosídeos possam predispor a hipertrigliceridemia e hipercolesterolemia, a nevirapina, particularmente, foi associada a maiores níveis de HDL-c, um fator de proteção contra doenças cardiovasculares. Portanto, a própria infecção, diferentes classes de fármacos e alguns fármacos da mesma classe de TARV podem exercer distintas alterações no metabolismo lipídico.

Lipodistrofia en pacientes con VIH/SIDA: Estudio descriptivo, prospectivo, transversal sobre la incidencia de lipodistrofia en pacientes pediátricos con VIH/SIDA que reciben terapia antirretroviral en clínica de atención integral de VIH/SIDA, Hospital Regional de Occidente San Juan de Dios durante mayo a junio de 2011 / ILipodistrofia in patients with HIV / AIDS: a descriptive, prospective, cross-sectional study on the prevalence of lipodystrophy in pediatric patients with HIV / AIDS receiving antiretroviral therapy clinic comprehensive HIV / AIDS, Western Regional Hospital San Juan de Dios in may june 2011

El uso de la terapia antirretroviral ha mejorado la calidad de vida de los niños. El inicio de estos fármacos ha sido muy positivo en la lucha contra la pandemia de VIH/sida, hasta el momento es la única con la que se cuenta para el control de la infección pero la introducción en el organismo de estos fármacos con actividad enzimática supone en muchos casos una reacción adversa al propio cuerpo. Así se describen numerosos efectos secundarios asociados al uso de estos medicamentos...

Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids: [revisão] / Gonadotrophic axis dysfunction in men with HIV-infection/Aids: [review]

A disfunção do eixo gonadotrófico é frequentemente observada em pacientes infectados pelo HIV. A patogênese é multifatorial e está relacionada à duração da infecção pelo HIV, aos efeitos citopáticos diretos do vírus, ao uso de drogas gonadotóxicas, às infecções oportunistas, às neoplasias, à desnutrição, entre outros fatores. Em homens, a redução dos níveis de testosterona está associada à perda de massa e de força muscular, à redução da densidade mineral óssea, à lipodistrofia, à depressão, à astenia, à fadiga e à disfunção sexual. Em pacientes infectados pelo HIV com hipogonadismo, inúmeros estudos têm comprovado os efeitos benéficos da reposição de testosterona sobre o perfil metabólico e a distribuição da gordura corporal, com aumento da massa corporal magra, além de promover melhora da qualidade de vida, reduzir a perda de massa óssea e reduzir os índices de depressão. Assim, esta revisão teve como objetivo trazer uma breve atualização sobre o presente tema, abordando dados epidemiológicos, mecanismos fisiopatológicos e estratégias terapêuticas para as principais anormalidades do eixo gonadotrófico masculino associadas à infecção pelo HIV e ao seu tratamento.

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

Clinical and biochemical evaluation of HIV-related lipodystrophy in an ambulatory population from the Hospital Universitário Cassiano Antonio de Morais, Vitória, ES, Brazil

We designed a retrospective cohort study to identify factors associated with HIV-1 related lipodystrophy at a tertiary HIV-care center in Vitória, ES, Brazil. Inclusion criteria were documented HIV diagnosis, anti-retroviral therapy and age above 17 years. Highly active antiretroviral therapy (HAART) was initially the exposure variable, but a second analysis was also performed, as a nested case-control, based on the presence or absence of lipodystrophy. Use of protease inhibitors (PI) was associated with an increase in serum triglycerides (243.7 ± 189 mg/dL vs. 172.7 ± 131 mg/dL, p = 0.015), but not of total cholesterol (TC) or HDL fraction levels. Non-nucleoside reverse transcriptase inhibitors (NNRTI) were associated with an increase in serum TC (180.6 ± 46.8 mg/dL versus 162.4 ± 41.4 mg/dL; p= 0.018) and an increase in HDL cholesterol (47.3 ± 13.8 mg/dL versus 23.3 ± 24.3 mg/dL; p < 0.001), with no significant effect on triglyceride levels. Lipodystrophy was diagnosed in 59.3 percent of the patients, but exposure to PI versus NNRTI did not affect the frequency of this disorder (43.4 percent versus 37.2 percent; p = 0.68). Serum TC, but not HDL cholesterol or triglyceride levels, was higher among the lipodystrophy cases (183.8 ±47.5 mg/dL versus 162.1 ±35.7; p=0.006). Among the controls (patients without lipodystrophy), HDL cholesterol (45.3 ±14.4 mg/dL vs. 27.1 ±26.3; p=0.001)and triglyceride levels (178.3 ±146.3 mg/dL vs. 126.3 ±126.9; p=0.013) also increased, but not TC. In conclusion, lipodystrophy was highly prevalent in our series. Lipid disorders were also frequent and apparently were related to lipodystrophy, except for triglyceride levels.

O papel do hormônio de crescimento no tratamento dos distúrbios endócrino-metabólicos do paciente com a síndrome da imunodeficiência adquirida (Aids): [revisão] / The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (Aids) patients: [review]

As primeiras descrições da síndrome da imunodeficiência adquirida (Aids) associavam-se à síndrome de emaciamento, e os distúrbios metabólicos às alterações na composição corporal. Após a introdução da terapia anti-retroviral altamente ativa (HAART), houve declínio na desnutrição, e surge a lipodistrofia como importante distúrbio metabólico. A Aids também se caracteriza por distúrbios hormonais, principalmente no eixo hormônio de crescimento/fator de crescimento insulina-like tipo 1 (GH/IGF-1). O uso do GH recombinante humano (hrGH) foi inicialmente indicado na síndrome de emaciamento, a fim de aumentar a massa muscular. Embora também não existam dúvidas quanto aos efeitos do hrGH na lipodistrofia, a diminuição na sensibilidade à insulina limita o seu uso, o qual ainda não está oficialmente aprovado. A diversidade nos esquemas de tratamento é outro limitante do uso dessa medicação em pacientes com Aids. Esta revisão apresenta os principais distúrbios endócrino-metabólicos associados à Aids e ao uso do hrGH nessas condições.

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.

Improvement of fat redistribution, insulin resistance and hepatic fatty infiltration in HIV-associated lipodystrophy syndrome by pioglitazone: a case report.

HIV-associated lipodystrophy syndrome is a syndrome occurring in HIV-infected patients who were treated with highly-active antiretroviral therapy (HAART), especially regimen containing protease inhibitors. The syndrome consists of fat redistribution, with loss of subcutaneous fat and increase in visceral fat, and metabolic disturbances, including glucose intolerance or overt diabetes and dyslipidemia. No standard treatment has been established for this syndrome. Pioglitazone is an oral antidiabetic agent that acts primarily on adipose tissue to reduce insulin resistance. The authors report a 50-year old HIV-infected woman who developed HIV-associated lipodystrophy syndrome after 3 months of HAART. She had significant weight loss with obvious loss of subcutaneous fat, together with development of hypertension, diabetes and dyslipidemia. After treatment with 30 milligrams of pioglitazone daily, her body weight increased within the first month of treatment. Subcutaneous fat loss was restored. Improvement in glycemic and lipid control was also noted. CT scan of the abdomen revealed that fatty infiltration in the liver was markedly decreased. Visceral fat as assessed by CT scan had also decreased. Pioglitazone appeared to have beneficial effects in this patient.