Background:
Human immunodeficiency infected patients frequently present with elevated levels 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 improved 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 asymptomatic elevations of alanine transaminase (ALT)
levels, and at times life threatening, clinical liver hepatotoxicity. Hepatotoxicity can be
fatal when not recognized early and when treatment not interrupted in time.
Objective:
This study aimed to determine the pattern and risk factors for alanine transaminase
elevation among HIV positive adult patients on nevirapine containing anti-retroviral
regimens at Kenyatta National Hospital.
Methodology:
We obtained ethical approval to carry out this study from the KNH-UoN research and
ethics committee. We conducted 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. Data obtained from the patient interviews and
abstraction of patient files, were analyzed using STATA version 10.
Results:
Two hundred and forty one patients took part in the study. One hundred and sixty two
(67.2%) had normal ALT levels throughout the study, seventy-two (29.9%) had mild
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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 5th year of therapy onward. Among patients who had elevated ALT levels
at baseline the trend was a gradual decline in ALT levels until about 6 years of therapy,
thereafter the ALT levels started rising progressively.
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
Alanine transaminase elevation might occur in up to one third of HIV/AIDS positive
adult patients taking nevirapine based ART. None of the patients developed severe or
very severe hepatotoxicity in this cohort.
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In setting where transaminase testing is available, monitoring should focus on delayed
hepatotoxicity, patients with abnormal baseline ALT and those with impaired renal
functioning.
All HIV-infected patients should be screened for liver disease at the time entry into care