Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients.

BACKGROUND & OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs) are known to cause mitochondrial toxicity. This study was done to estimate mitochondrial DNA (mtDNA) content of peripheral blood mononuclear cells (PBMCs) among human immunodeficiency virus (HIV) infected, NRTI treated and antiretroviral therapy (ART)-naïve patients and evaluate the utility of mtDNA content as a biomarker of mitochondrial toxicity. METHODS: mtDNA content in PBMCs of 57 HIV-infected ART untreated and 30 ART treated with stavudine (d4T) or zidovudine (AZT) containing regimen were compared against 24 low-risk healthy controls (LoRHC). RESULTS: There was a significant (P=0.01) reduction in mtDNA content among HIV-infected (104; 80-135) compared to LoRHC (127; 110-167), and it was the same in both the treated (104.8; 88-130) and untreated patients (104.7; 78-142). mtDNA significantly (P=0.014) declined in ART treated patients symptomatic for toxicity (97; 74-111) than the asymptomatic patients (128; 103- 153). INTERPRETATION & CONCLUSIONS: mtDNA depletion in PBMCs was evident among HIV-infected individuals on ART. Moreover, as mtDNA content was reduced among the patients symptomatic for toxicity than the asymptomatic in both the HIV-infected groups, the current study supports mtDNA content of PBMCs to serve as a biomarker of mitochondrial dysfunction induced by NRTI and HIV. Longitudinal studies with a large sample need to be done to confirm these findings.

Incidence of atazanavir- associated adverse drug reactions in second -line drugs treated south Indian HIV-1 infected patients.

BACKGROUND: Ritonavir-boosted atazanavir (ATV/r) is the preferred second-line protease inhibitor (PI) option for HIV patients in resource-limited settings; its pattern of adverse drug reactions (ADRs) has not been much reported from India; hence, in this study, we have analyzed the incidence of ATV/r-associated ADRs in Southern Indian HIV-1-infected patients. METHODS: In this prospective study, 111 HIV patients treated with ATV/r were included with at least 2 years follow-up visits for the emergence of hyperbilirubinemia, hypertransaminasemia, and serum creatinine elevation. The causality assessment was done based on the WHO scale for the causality assessment of suspected ADR. RESULTS: The incidence of severe hyperbilirubinemia, hypertransaminasemia, and creatinine elevation was 28.6, 0.76, and 1.62 cases/100 person years, respectively. 3TC/FTC + TDF (odds ratio [OR]: 6.07, confidence interval [CI]: 1.31-27.98, P = 0.015) nucleos (t) ide reverse transcriptase inhibitor backbone and male sex (OR: 18.64, CI: 2.13-162.93, P = 0.0082) were found to be significantly associated with hypertransaminasemia and creatinine elevation, respectively. The causality assessment of ADR was "possible" for all the participants. Kaplan-Meier analysis showed hyperbilirubinemia to emerge earlier (mean duration: 32.18 months, CI: 24.9-39.4 months) followed by hypertransaminasemia and creatinine elevation. Hyperbilirubinemia is an expected side effect associated with ATV/r which is benign, transient, and does not predispose to hypertransaminasemia. CONCLUSION: Our study results show that patients starting ATV/r should be counseled for a good adherence in spite of the emergence of hyperbilirubinemia which generally reverts to normal range.