Noninfectious HIV-related Comorbidities and HAART Toxicities: Choosing Alternative Antiretroviral Strategies

Lidia Gazzola; Camilla Tincati; Antonella d'Arminio Monforte


HIV Ther. 2010;4(5):553-565. 

In This Article

Noninfectious HIV-related Comorbidities: The Premature aging Process in HIV-infected People

In the HAART era, most patients taking medication achieve a complete and most likely lifelong virologic suppression, and thus, the classic AIDS-related conditions are becoming less common, with a dramatic drop in overall mortality.[1–3]

However, despite the apparently full control of HIV infection by HAART, clinical evidence has demonstrated that HAART does not completely restore health in HIV-infected patients, who are affected by an increased risk of several non-AIDS complications.[4]

A twofold increase in the relative risk of myocardial infarction (MI) has been observed in the HIV-positive population compared with HIV-uninfected patients,[5–7] as well as a three-times greater prevalence of osteoporosis.[8] Furthermore, renal diseases affect HIV-infected people: black HIV-positive patients are more likely to develop chronic kidney failure, and HIV-infected individuals have a decreased glomerular filtration rate and increased prevalence of microalbuminuria than matched HIV-uninfected controls.[9]

These noninfectious HIV-related comorbidities are tied together and are the expression of a physiologic aging process, even though they occur at an earlier age, undermining life expectancy in the HIV-infected population.[10]

These clinical findings probably arise from the failure of HAART to repair all immune damage consequent to HIV infection. Indeed, HIV-infected patients undergoing HAART, despite full virologic control, maintain a hyper-activated immunological profile, which is sustained by HIV and non-HIV-related antigens and is associated with reduced naive and central memory subsets, in favor of T-cell senescence.[11–13] These immunological alterations are similar to those associated with age in the HIV-uninfected elderly population, and have led to hypotheses that an accelerated process of immune senescence and inflammatory aging takes place during HIV infection, as evidenced by the increased risk of age-related diseases and 'frailty'.[14,15]

As treating clinicians, we have to deal with the changing spectrum of HIV-associated disease, and modifications in the medical management of HIV infection are thus advocated. In particular, there is an increasing need to strictly consider premature age-associated complications when choosing a tailored antiretroviral (ARV) therapy regimen. This article aims to explore the impact of standard HAART regimens on the different noninfectious HIV-related comorbidities. Metabolic, cardiovascular, bone and renal diseases, with the exclusion of liver complications, will be assessed together with the currently available and more recent alternative ARV strategies in order to summarize the state of the art and its clinical implications.


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