The renal safety profile of tenofovir as used in combination antiretroviral therapy
Abstract
Background: Tenofovir disoproxil fumarate (TDF) is the prodrug of tenofovir and is currently first-line therapy in adolescents above the age of 15 and adults, according to the consolidated guidelines on the use of antiretroviral therapy (ARV) in South Africa. TDF has proven to be an effective drug in the fight against human immunodeficiency virus (HIV) and is utilised in the treatment of Hepatitis B. Tenofovir disoproxil fumarate is effective and efficient as used in combination for post-exposure prophylaxis and to prevent HIV transmission in heterosexual, serodiscordant couples. However, the renal safety profile of tenofovir remains a contentious issue in the African context. This study investigated the renal function outcome of HIV-positive patients exposed to tenofovir-based antiretroviral therapy. Method: The study was a retrospective, partial prospective observational cohort analysis of serum creatinine (SCr), CD4 count, viral load (VL) and body mass index (BMI) data of 66 black patients attending the clinic in Newcastle, KwaZulu-Natal. This study group was subdivided into two age groups (≥20 - <30 years and ≥30 - ≤40 years), and into male and female. The renal function was evaluated by calculating the creatinine clearance (CrCl) by means of the Cockcroft-Gault (CG) equation at baseline (before TDF commencement) and at 12 months post-TDF commencement.
The independent t-test was applied to investigate differences in SCr, CrCl, CD4 count and BMI by comparing female vs male participants at baseline and at 12 months post-TDF commencement. The Mann-Whitney test was utilised as the non-parametric equivalent of the independent t-test. The dependent t-test was used to investigate the changes on SCr, CrCl, CD4 count and BMI from baseline to 12 months (female vs. male). The Wilcoxon signed-rank test was utilised as the non-parametric equivalent of the dependent t-test. Ethical approval was obtained from The Human Research Ethics Committee of the North-West University on the 18th of August 2015 (NWU 00044-15-A1) and from the KwaZulu-Natal Department of Health (KZ_2015_RP40-426) on the 7th of September 2015 to conduct this study.
Results: Thirty-five female (mean age 30.43 [4.69] years) and 31 males (mean age 30.32 [4.60] years) patients consented to participate in the study. The BMI and CD4 count improved in all age and gender groups at 12-month follow-up data. There was no statistically significant change in the SCr from baseline to follow-up in any of the age groups but the ≥20 - <30 year age group showed an improvement in CrCl at 12-month follow-up data (p = 0.15 and p = 0.020) for the female and male group respectively. A higher mean SCr value was established for the male group but a higher mean CrCl value was seen in the female group. The ≥30 - ≤40 year age group depicted a minor decline in CrCl at 12-month follow-up (p = 0.176 and p = 0.941) for female and males respectively. The immunological outcome is depicted by the CD4 count. The female group stratified according to age ≥20 - <30 and ≥30 -≤40 years, displayed a statistically significant difference in CD4 count at 12 months post-TDF commencement, with a large practical significance (p < 0.001 [0.94], p = 0.002 [0.87]). The mean increase in CD4 count was 174 cells/mm3 and 208.75 cells/mm3. The pooled female group (≥20 - ≤40 years) displayed a mean increase in CD4 count of 196.06 cells/mm3. The VL was suppressed in majority of the patients at 12-month follow-up data.
Conclusion: Virological suppression was seen in majority of the patients at 12 months post-TDF commencement. The immunological outcome improved in this study population. Selecting a younger age group reduced the risk of age-related degeneration of kidney function. The CrCl in the younger age group (≥20 - <30years) exhibited an increase in CrCl at 12 months post-TDF commencement. The older age group (≥30 - ≤40 years) displayed a decrease in CrCl at 12 months post-TDF commencement for females and males. The BMI improved in all age and gender groups investigated. The renal function exhibited a positive outcome for all patients in this study population. This study supports the use of TDF as first-line therapy in South Africa. This study also supports the existing evidence that age and gender, influence kidney function.
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