Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients

Abstract

Background and Objective: There may be possible association among use of HAART, oxidative stress and mitochondrial functions in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Parklane, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEUuur) in long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

Assessment of Oxidative Stress Level in HIV/AIDS Patients on HAART Treatments

“…Malondiadehyde (MDA) is an enzymatic indicator that shows the presence of high-level production of free radicals in the body leading to oxidative stress. The significantly increased level of MDA in HIV positive patients as observed in this study is in keeping with the generally high levels of MDA found in some studies including that of Ikekpeazu et al [9]. This increase was observed with decrease in the levels of antioxidant (SOD and GSH) which is indicative of oxidative stress and lipid peroxidation.…”

“…Highly active antiretroviral therapy (HAART) is presently the therapy of optimal considerations for HIV-infected patients [9]. However, despite the amazing viral replication suppression and immune response restoration, long-term HAART appears of limited use in many patients because of additional adverse effects and/or regimen adherence difficulties [10].…”

Neurocognitive and Neuroarchitectural Changes in the Prefrontal Cortex of Wistar Rats Treated with Highly Active Antiretroviral Therapy

“…Even though it might be premature to explain the exact mechanism responsible for the higher levels of GSH observed in the treatment groups, in contrast to the high MDA levels, it may possibly be as a result of the release of GSH into the extracellular microenvironment by astrocytes which then generates precursors for neuronal GSH synthesis (Hirrlinger et al 2002). Results from the present study showed that the lamivudine and tenofovir might adversely alter the histoarchitectural integrity of the prefrontal cortex, possibly due to increased mitochondrial damage, which is a source of free radicals (Ikekpeazu et al 2020). It should be noted that the NNRTIs have also been implicated in the oxidative stress hypothesis.…”

Mitochondrial DNA Profiling in A Cohort of Antiretroviral Treated HIV Patients in Lagos, Nigeria: Assessment of Long-Term Effects of cART on Life Quality of PLWH

“…This study did not find significant difference in the cf-mtDNA concentration of ART treated HIV+ patients compared with healthy controls, even when they were matched to their respective age groups. Some of the previous studies reported significant difference of mtDNA concentration between healthy individuals and ART-treated HIV infected patients or ART-prophylactic treated children [36]- [39] and [35] also reported a significant depletion of mtDNA copy number among ART treated HIV patients compared to healthy controls in Enugu, a South-eastern part of Nigeria. However, [32] did not find marked variation in a study involving a cohort of HIV infected and non-infected children.…”