Patterns and risk factors for alanine transaminase elevation among HIV positive patients on nevirapine regimens at Kenyatta national hospital

Abstract

Background: Human immunodeficiency infected patients frequently present with elevated level s of serum transaminases. This is often been attributed to hepatic effects of antiretroviral drugs. The introduction of life prolonging anti - retroviral therapy has drastically reduced the morbidity and mortality associated with HIV . Because of im proved life expectancy, non - HIV/AIDS defining diseases and drug related toxicities have emerged as key issues in the management and care of people living with HIV /AIDS . Nevirapine is associated with asymptom atic elevations of alanine transaminase (ALT ) levels , and at times life threatening, clinical liver hepatotoxicity . Hepatotoxicity can be fatal when not recognized early an d when treatment not interrupted in time. Objective : This study aimed to determine the pattern and risk factors for alanine transamina se elevation among HIV positive adult patients on nevirapine containing anti - retroviral regimen s at Kenyatta National Hospital. Methodology : We obtained e thical approval to c arry out this study from the KNH - Uo N research and ethics committee . We conduct ed a retrospective cohort study of HIV positive patients on nevirapine containing regimens who attended the KNH Comprehensive Care Clinic between May and August 2014. We performed generalized linear regression to establish patterns and predictors for ALT elevation. D ata obtained from the patient interviews and abstraction of patient files , were analyzed using STATA version 10. R esults : Two hundred and forty one patients took part in the study . One hundred and sixty two (67.2%) had normal ALT levels t hroughout the study, s eventy - two (29.9%) had mild elevation and seven (2.9%) developed moderate hepatotoxicity. None of the participants developed severe or very severe hepatotoxicity . In patients with normal ALT at baseline, the pattern of ALT change was cyclical with peaks and troughs. The peak levels seemed to increase with time. Very sharp peaks were noted from the 5 th year of therapy onward. Among patients who had elevated ALT levels at baseline the trend was a gradual decline in ALT levels until a bout 6 years of therapy, thereafter the AL T levels started rising progressively . Risk factors for ALT elevation differed across sex. P redictor variables that were significantly associated with ALT elevation i n both sexes included; elevated baseline ALT le vel [ 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 ren al 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; sm oking (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 Alanine transaminase elevation might occur in up to one third of HIV /AIDS positive ad u lt patients taking nevirapine based ART . N one of the patients developed severe or very severe hepatotoxicity in this cohort xiv In setting where transaminase testing is available, monitoring should focus on delayed hepatotoxicity, patients with abnormal bas eline ALT and those with impaired renal functioning. All HIV - infected patients should be screened for liver disease at the time entry into care