Introduction.

Malawi has one of the highest HIV prevalence rates in the world. National HIV adult prevalence in Malawi reached a high of 26% in 1998 and has since decreased to about 12% in 2010 [1]. According to the 2010 United Nations General Assembly Special Session (UNGASS) Country Progress Report, over 930,000 Malawians currently live with HIV and approximately 84,000 new HIV infections occur annually [2]. Since 2004, the Malawian Ministry of Health has provided free antiretroviral therapy (ART) to individuals living with HIV and eligible for treatment through the Global Fund to Fight AIDS [3].

Malawi's current first-line antiretroviral therapy and former prevention of mother-to-child transmission (PMTCT) regimen consists of stavudine, lamivudine and nevirapine. Stavudine has long-term side-effects such as lactic acidosis, hepatic steatosis and lipo-atrophy [4]. As such, the Malawian government plans to change the first-line ART regimen for all individuals living with HIV to tenofovir disoproxil fumarate (TDF)/lamivudine/Efavirenz as a fixed-dose, combination tablet in accordance with WHO guidelines, despite the uncertainty of possible negative health effects associated with efavirenz use during pregnancy [5]. TDF has an excellent safety profile with rare reports of nephrotoxicity, proteinuria, and renal tubular dysfunction with Fanconi syndrome [6], [7], and its safety as a first-line ARV medication has been demonstrated in other African countries [8].

A creatinine clearance (CrCl) rate ≥50 ml/min is recommended before starting TDF for efficient renal clearance [9], [10]. In Malawi, previous studies among individuals living with HIV suggest that approximately 18.8% have a CrCl of 30–59 ml/min and 2.2% have a CrCl less than 30 ml/min [11]. While recommendations exist for dose modification in patients with lower creatinine clearance [12], these modifications preclude the use of a convenient fixed-dose, combination tablet. Given the limited laboratory infrastructure in Malawi, performing routine baseline CrCl screening could hinder the implementation of TDF as a component of first-line ART. As such, the goal of the current analysis is to determine prevalence and predictors of CrCl<50 ml/min among HIV-infected, ART-naïve individuals in Lilongwe, Malawi.

Abstract.
Background.

The Malawian government recently changed its prevention of mother-to-child transmission (PMTCT) regimen and plans to change its first-line antiretroviral therapy (ART) regimen to Tenofovir(TDF)/Lamivudine/Efavirenz as a fixed-dose combination tablet. Implementation could be challenging if baseline creatinine clearance (CrCl) screening were required to assess renal function prior to TDF therapy. Our goal is to determine predictors of CrCl<50 ml/min among HIV-infected, ART-naïve individuals.

Methodology.

Data on HIV-infected, ART-naïve adults screened for enrollment into 5 HIV clinical trials in Lilongwe, Malawi were combined for a pooled analysis of predictors for CrCl<50 ml/min. CrCl was derived from the Cockroft-Gault equation. Multivariable logistic regression modeled the association of age, body mass index (BMI), hemoglobin, CD4 cell count <350 cells/mm3, gender, and pregnancy with CrCl<50 ml/min.

Results.

The analysis included 3508 patients with values for creatinine clearance. Most subjects were female (90.6%) with a median age of 26 years (IQR 22–29). The median CD4 cell count was 444 (IQR 298.0–561.0), and 85.2% percent of women in our study were pregnant. Few patients had CrCl<50 ml/min (n = 38, 1.1%). A BMI less than 18.5 in non-pregnant females (OR = 8.87, 95% CI = 2.45–32.09)) was associated with CrCl<50 ml/min. Hemoglobin level higher than 10 g/dL in males (OR = 0.69, 95% CI = 0.56–0.86) and non-pregnant females (OR = 0.21, 95% CI = 0.04–0.97) was protective against CrCl<50 ml/min.

Discussion.

Our findings indicate few patients would be excluded from a TDF-based antiretroviral regimen, suggesting baseline creatinine clearance assessment may not be necessary for implementation. However, in ART settings individuals with low BMI or anemia could potentially be at increased risk for lower CrCl.