MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

Abstract

In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50 years, and in that regard, the use of ART has transformed HIV into a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear but may be related to a complex interaction between long-term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors (PIs) and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer PIs, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks.

Prevalência de excesso de peso, obesidade central e risco de comorbidades metabólicas em adultos com HIV/AIDS sem terapia antirretroviral

“…Estudo realizado com 14.084 PVHA provenientes de 17 coortes, demonstrou que, após três anos do início da terapia ARV, 22% e 18% dos indivíduos com IMC normal (18,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)9 kg /m 2 ) tinham sido reclassificados com excesso de peso (IMC 25,0-29,9 kg /m 2 ) e obesidade (IMC≥30 kg /m 2 ), respectivamente (23) . O presente estudo utilizou o GAPB (20) O GAPB considera que o consumo diário de, pelo menos, 400g de frutas, legumes e verduras (FVL) é possivelmente a mais importante de todas as diretrizes, pois, além de contribuir para a variedade e oferta de nutrientes, pode colaborar na redução do consumo de alimentos com alto teor de gordura, sal e açúcar (20) .…”

“…O estado nutricional debilitado é um dos fatores que elevam o risco do PVHA desenvolver doenças crônicas (3,6) . Embora o ganho de peso beneficie o sistema imune e atenue o impacto de doenças oportunistas destes indivíduos, o aumento de gordura corporal, especialmente abdominal, pode ser fonte crônica de proteínas pró-inflamatórias que influenciam o curso da doença e o envelhecimento precoce (7,8) .…”

Clinical Outcomes Associated with Single Tablet Regimens: Relationship between Antiretroviral Therapy Pill Burden and Control of Concomitant Comorbidities among HIV-Infected Patients

“…This Article is available in: http://hiv.imedpub.com drugs, especially older classes of drugs, have significant metabolic adverse effects as well as potential interactions with agents used in the treatment of cardiometabolic comorbidities [19,20]. Our study was not powered to observe differences in outcomes between drugs classes utilized in MTR patients; thus, unobserved class-specific effects on cardiometabolic outcomes may have influenced these results.…”

“…Our study was not powered to observe differences in outcomes between drugs classes utilized in MTR patients; thus, unobserved class-specific effects on cardiometabolic outcomes may have influenced these results. Newer drug formulations have generally demonstrated more favorable metabolic profiles [20]. Many of these formulations have only become commercially available recently and were not available for the majority of the study period.…”

“…This formulation was utilized by most STR patients in our study population. However, regimens containing efavirenz have been associated with select adverse effects and reduced therapy longevity compared to STR formulations that have subsequently become available [20,22]. Furthermore, newer formulations have shown improved adherence and are increasingly being utilized [23].…”