HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

I am convinced that our mitochondria are affected even after years off Zerit, DDI or AZT. Mitochondrial dysfunction has been widely reported with D drugs (D4T, DDI) and AZT and has been linked to lipoatrophy and metabolic problems.  But I think what we ignore is the permanent effects on the mitochondria even after years of stopping those drugs. 

 Although mitochondria DNA in fat and muscle cells gets better after switching from Zerit or AZT to tenofovir (the most widely used nucleoside analog used in HIV), it never returns to normal (compared to healthy controls).  HIV in itself is known to affect mitochondria function.

Can fatigue get better by improving mitochondrial function with supplementation? We do not have much data on this. In fact, fatigue related research in HIV is almost non existent.  Except for researchers like Dr Judith Rabkin in NY, almost no one is looking at this problem commonly reported in clinical studies of new HIV drugs. Fatigue is one of the top quality of life issues reported by most HIV long term survivors and even in those with early disease.

Note: Fatigue can also have other causes: http://bit.ly/P168QB

This study concludes: Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue.

HIV Med. 2012 Sep 23. doi: 10.1111/j.1468-1293.2012.01050.x. [Epub ahead of print]

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

Source

Department of Infection and Tropical Medicine, Royal Victo, ria Infirmary, Newcastle-upon-Tyne, UK; Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.

Abstract

OBJECTIVE:

The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART).

METHODS:

A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME).

RESULTS:

Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001).

CONCLUSIONS:

Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis.Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared therapeutic approach.
© 2012 British HIV Association.

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