Patterns and Risk Factors of Alanine Transaminase elevation among HIV positive patients on Nevirapine regimens at Kenyatta National Hospital
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ABSTRACT

Background: The introduction of life prolonging anti-retroviral therapy has drastically reduced the morbidity and mortality associated with HIV AIDs. Because of improved life expectancy, non-HIV AIDs defining diseases and drug related toxicities have emerged key issues in the management and care of people living with HIV/AIDs.

All classes of antiretroviral have been associated with asymptomatic elevations of alanine transaminases (ALT) levels, and much less frequently with serious, and at times life threatening, clinical liver hepatotoxicity.  Nevirapine is one of the recommended first line anti-retroviral drugs and forms the backbone in HIV management. However, nevirapine can cause potentially life-threatening skin reactions and hepatotoxicity. Screening for hepatotoxicity during ART is primarily based on serum levels of alanine transaminase, a liver enzyme which serves as a “proxy” for liver inflammation and damage. Hepatotoxicity can be fatal when not recognized early and when treatment is not interrupted in time.

Objective: To determine the pattern and risk factors for alanine transaminase elevation in HIVpositive patients on Nevirapine based regimens.

Methodology: Ethical approval to carry out this study was obtained from the KNH-UoN research and ethics committee. A retrospective cohort study on HIV infected patients on nevirapine containing regimens who attended the Clinic between May and August 2014 was performed.Patients who met the inclusion criteria and were willing to participate were required to give a written informed consent. Data was obtained through patient interviews and abstraction of their files.

Generalized linear models were used to establish predictors for development of ALT elevation. All variables with a P-value lower than 0.20 at bivariable analysis were entered into a multivariable model (if clinically meaningful) and model building was conducted using forward stepwise selection method.Patients were dichotomized as having normal or elevated ALT level if their fold increase was less or greater than1.25 upper limit of the normal (ULN). The severity of liver toxicity was further graded using the AIDs Clinical Trial Group (ACTG) system.  All analyses were performed using STATA version 10 (StataCorp 4905 Lakeway Drive College Station, Texas 77845 USA).

Results: A median band plot was generated to examine the patterns of ALT levels with time in patients with normal baseline values.The pattern looked cyclical with peaks and troughs.  The peak levels seemed to increase with time. In patients who had abnormal ALT levels, lowess plots were generate to establish the trend.   In this group of patients the trend was a gradual decline in ALT levels till about 6 years of therapy, thereafter the ALT levels started rising steadily.

Risk factors for ALT elevation differed across sex.  Predictor variables that were significantly associated with ALT elevation in both sexes included; elevated baseline ALT level [β=10.14 (95%CI 7.34- 12.96); P<0.001], [β=13.52(95%CI 9.36 –17.68); P < 0.001] and renal disease [β=5.44 (95%CI 2.62 – 8.25); P <0.001],[β=11.52 (95%CI 3.46 – 19.60); P = 0.005] in females and males respectively.Ethnicity had a protective effect in both sexes; [β-6.61(95%CI-9.28, -3.93); P< 0.001] in males and [β-1.20(95% CI-2.39, -0.01); P= 0.048] in females. Among the different ethnic groups,Nilotes and Cushites had lower ALT levels compared to Bantus.

Other factors that were significant included; smoking (P=0.001), concurrent illnesses (P=0.045), previous adverse drug reactions (P=0.040) in females and a longer duration of anti-retroviral therapy [β 1.81(95%CI 0.89 – 2.73); P < 0.001] in males.  Poor adherence had a protective effect [β -1.62(95%CI -3.20, -0.04); P=0.045] among females, whereas initiation on AZT+3TC+NVP had a significant protective effect [β-7.80 (95%CI -13.96, -1.63); P=0.013] in males.

Conclusion: Creatinine and transaminase testing should be done routinely to mitigate delayed hepatotoxicity in patients with abnormal ALT baseline levels.

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