Table 2 Relevant studies describing the use of hair and plasma as methods to estimate adherence and sustained drug concentrations in patients in South Africa

Correlation of hair and plasma efavirenz concentrations in HIV-positive South Africans

Western Cape

Median efavirenz concentrations for extensive, intermediate and slow metabolising genotypes were 3.54, 5.11 and 10.66 ng mg⁻¹, respectively. A strong correlation was observed between the efavirenz concentrations measured in hair and plasma samples (Spearman’s correlation coefficients, 0.672–0.741, p < 0.0001). This shows hair could be used a matrix for measuring antiretroviral concentrations as markers of adherence

[41]

A comparison of plasma efavirenz and tenofovir, dried blood spot tenofovir-diphosphate, and self-reported adherence to predict virologic suppression among South African women

Western Cape

Dried blood spot TFV-DP [0.926 (95% CI: 0.876 to 0.976)] had a higher area under the curve than plasma TFV [0.864 (0.797 to 0.932); p = 0.006], plasma EFV [0.903 (0.839–0.967)] was not significantly different from DBS TFV-DP (p = 0.138) or plasma TFV (p = 0.140); all ARV assays performed better than self-report. The association of EFV, TFV, and DBS TFV-DP were seen as strong predictors of virologic suppression. Data shows that EFV or TFV assays have potential for development as point-of-care assays for use in more objective adherence measurement in resource-limited settings

[42]

A validated liquid chromatography tandem mass spectrometry method for the analysis of efavirenz in 0.2 mg hair samples from HIV-infected patients

Western Cape

Using ten times less hair than in a previously published method, the lower limit of quantitation (LLOQ) was validated at 0.625 ng mg⁻¹. This paper perhaps reports the first quantitative method for the determination of efavirenz in hair in South Africa. The validated method was used to successfully monitor efavirenz concentration in hair collected from HIV-infected patients

[85]

CYP2B6*6 and CYP2B6*18 predict long-term efavirenz exposure measured in hair samples in HIV-positive South African women

Western Cape

The predictive value of EFV levels in hair and selected variants in CYP2B6 on virologic treatment outcomes was assessed. Previously described alleles (CYP2B6*2, CYP2B6*5, CYP2B6*6, CYP2B6*17, and CYP2B6*18), as well as two novel alleles (CYP2B6*31 and CYP2B6*32), were detected in the study. Compared to noncarriers, individuals homozygous for CYP2B6*6 had ∼109% increased EFV levels in hair (p = 0.016) and CYP2B6*18 heterozygotes demonstrated 82% higher EFV hair levels (p = 0.0006)

[39]

Random lopinavir concentrations predict resistance to lopinavir-based antiretroviral therapy

Western Cape and KwaZulu Natal

A random lopinavir concentration above the recommended minimum trough of 1 μg mL⁻¹ [adjusted odds ratio (aOR) = 5.81, 95%, CI: 2.04–16.50; p = 0.001] and male sex (aOR = 3.19, 95% CI 1.22–8.33; p = 0.018) were predictive of the presence of at least one major PI resistance mutation. Random lopinavir concentrations of < 1 μg mL⁻¹ had a negative predictive value of 91% for major PI resistance mutations. Random lopinavir concentrations are strongly associated with the presence of major PI resistance mutations

[38]

Plasma lopinavir concentrations predict virological failure in a cohort of South African children initiating a protease-inhibitor-based regimen

Gauteng

Median (IQR) lopinavir concentrations were 8.00 mg L⁻¹ (4.11–12.42) at median (IQR) 3.50 h (2.67–4.25) after the dose. The hazard of viral load > 400 copies mL⁻¹ was increased with lopinavir concentrations < 1 versus ≥ 1 mg L⁻¹ (adjusted hazard ratio 2.3 [95% CI 1.63, 3.26]), and lower height-for-age z-scores. Low lopinavir concentrations (< 1 mg L⁻¹) were associated with viraemia in children. This measure could be used as a proxy for adherence and to identify children more likely to fail treatment

[37]

Low lopinavir plasma or hair concentrations explain second line protease inhibitor failures in a resource-limited setting

Western Cape

The probability of failure with lopinavir plasma concentration > 1 μg mL⁻¹ or hair concentrations > 3.63 ng mg⁻¹ for virologic failure were 86 and 89%; and positive predictive values of low concentrations 73 and 79%, respectively, whereas all virologic failures with HIV RNA loads above 1000 copies mL⁻¹, of patients without protease inhibitor resistance, could be explained by either having a low lopinavir concentration in plasma or hair

[36]