Abstract

Introduction: The morbidity and mortality of HIV infection has dropped since the introduction of antiretroviral therapy (ART). Being a combination therapy made up of three different molecules, antiretrovirals effectively reduce viral load but may also lead other complications such as renal and hepatic dysfunction. This study therefore compares liver and kidney function markers to first- and second-line antiretroviral therapy.

Method: A cross-sectional observational and analytical study was conducted among HIV infected adults on first- or second-line ART at the laquintinie HIV reference center in April 2021. Following a convenient sampling, blood samples were collected for measurement of alanine aminotransaminase (ALT) and serum creatinine. The proportion of renal and hepatic dysfunction were compared between ART regimen and p-values < 0.05 were considered statistically significant.

Results: Among the 118 ART experienced patients (median and IQR age: 50.50[43.00- 74.00] years). The rate of hepatotoxicity was (10.169%) and the rate of nephrotoxicity was (19.49%). According to this ART regimen, hepatotoxicity was higher in first line compared to second line respectively (10.3% vs 9.52% p-value=0.914) while the rate of nephrotoxicity was higher in second line compared to first line respectively (42.85% vs 14.43% p- value=0.011).

Conclusion: The risk of nephrotoxicity for patients on second line ART appears to be higher, while hepatotoxicity is slightly higher for patients on first line ART regimen. Thus, as patients move from first to second line ART, a closer monitoring of kidney function should be implemented.

CHAPTER ONE

INTRODUCTION

Background

Worldwide HIV/AIDS is a major health problem. As of 2017 over 36 million people where living with HIV/AIDS. Africa being the most affected continent had 25.7 million (70%) of the people living with HIV/AIDS [1]. Drug toxicity is the degree to which a substance (drug type) can cause harm to humans or animals causing harmful effects over an extended period of time [2].

It is important to note that HIV been a long term therapy, complications associated with HIV/AIDS do not only come as a result once’s HIV status but may also come as a result of the treatment used to remedy the situation [3].

Hepatotoxicity also known as toxic hepatitis or liver toxicity or toxic liver disease is a term used to describe chemical driven liver damage. Liver injuries accounts for 2 million deaths per year worldwide [4].

Drug induced liver injury accounts for 13.9-24.0 per 100,000 inhabitants globally [5]. In Africa, 30% of individuals suffer from DILI as a result of antiretroviral and antituberculosis treatment. This has led to 14-18% death among HIV infected persons only [6].

Drug induced nephrotoxicity terns to be more common among certain patients in specific clinical situation and patient related risk factors such as age, underlying renal insufficiency, diabetes, heart failure and sepsis [7]. The HAART and other medical therapies for HIV related infections have also been associated with this toxicity.

ART can contribute to renal disfunction directly by inducing acute tubular necrosis, renal interstitial nephritis, crystal nephropathy and renal tubular disorders or indirectly via drug interactions [8].

Given the high rate of blood flow through the proximal tubule and consequently the high level of toxins it has to process, this portion of the nephron is at a particular risk of developing drug-related damage.

The HAART which involving a cocktail of antiretroviral drugs therefore increases the risk of kidney damage [9]. However, ARV nephrotoxic effects accounts for 14% late onset kidney injury with Tenofovir being the drug with most common effects [8].

Rationale

Cameroon first line ART containing preferentially TDF and DTG as part of the ARVs. Second line containing preferentially PI/r and AZT or TDF as part of the drug combination. Previous findings have shown association between TDF and risk of nephrotoxicity.

However, an appraisal of such effects within each drug combination remains limited. This is particularly true in a context like Cameroon where DTG-containing regiments are the preferred option for first-line ART.

It would therefore be clinically relevant to unveil the risk of nephrotoxicity by ART regimens in order to establish regimens that require a closer monitoring in routine practice.

Hypothesis

 

Antiretrovirals have significant hepatotoxic and nephrotoxic effects on patients under antiretroviral therapy.

General Objectives

To compare the rate of hepatotoxicity and nephrotoxicity in patients on first versus second line patients on antiretroviral drug therapy

Specific objectives

1. To evaluate the rate of hepatotoxicity among patients on first- and second-line antiretroviral drug therapy
2. To evaluate the rate of nephrotoxicity among patients on first- and second-line antiretroviral drug therapy
3. To compare the risk of hepatotoxicity and nephrotoxicity between patients on first versus second line ART
4. To study other factors associated with hepatotoxicity or nephrotoxicity