High nonnucleoside reverse transcriptase inhibitor resistance levels in HIV-1-infected Zambian mother-infant pairs.

OBJECTIVE(S): To elucidate relationships in antiretroviral resistance between HIV-1-infected mother-infant pairs by defining the resistance profiles in the mothers and infants and quantifying drug resistance prevalence in the pairs post-Option B+ implementation. DESIGN: Collection of dried blood spots from mother-infant pairs during routine HIV-1 screens in Lusaka, Zambia from 2015 to 2018. METHODS: DNA was extracted from the dried blood spots, the HIV-1 pol region was amplified, and the purified proviral DNA was sequenced using Sanger sequencing. Drug resistance mutations (DRM) were identified in sequenced DNA using the Stanford HIVdb (https://hivdb.stanford.edu/). RESULTS: DRM were detected in 45% (44/97) of samples, and these samples were found to harbor resistance to at least two antiretrovirals. The prevalence of nonnucleoside reverse transcriptase inhibitor resistance was significantly higher than that of other antiretroviral classes. DRM were detected disproportionately in infants (67%; 33/49) compared with mothers (23%; 11/48), but the magnitude of resistance did not differ when resistance was detected. The disparity in drug resistance profiles was reinforced in pairwise comparison of resistance profiles in mother-infant pairs. CONCLUSION: While Option B+ is effective in reducing mother-to-child transmission, in cases where this regimen fails, high-level nonnucleoside reverse transcriptase inhibitor resistance is frequently detected in infants. This underscores the importance of pretreatment drug resistance screening in both mothers and infants and emphasizes the necessary change to protease inhibitor-based and integrase inhibitor-based regimens for treatment of HIV-1-infected infants and mothers.

Performance Characteristics of Kidney Injury Molecule-1 In Relation to Creatinine, Urea, and Microalbuminuria in the Diagnosis of Kidney Disease.

CONTEXT: The diagnosis and evaluation of impaired renal function remains a challenge owing to lack of reliable biomarker for assessment of kidney function. The existing panel of biomarkers currently displays several limitations, and recently kidney injury molecule-1 (KIM-1) has been suggested as a sensitive biomarker of renal function and proposed to enter clinical practice. AIMS: This study was conducted to determine the diagnostic value of serum creatinine, urea, and microalbuminuria (MAU) in relation to the novel biomarker, KIM-1. MATERIALS AND METHODS: Serum creatinine, urea, MAU, and KIM-1 were measured in forty individuals with and forty without kidney disease. Data were analyzed using multivariate methods of assessing diagnostic efficiency, test agreement, condition effects, and variability. RESULTS: The area under the receiver-operator characteristic curve revealed a diagnostic advantage of creatinine (0.924 ± 0.0066) and urea (0.925 ± 0.0068) over MAU (0.880 ± 0.078) and KIM-1 (0.35 ± 0.124). Overall diagnostic efficiency was higher for creatinine and urea (89.5% and 90.9%, respectively), followed by MAU (85.7%) and then KIM-1 (56.3%). Logistic regression analysis showed that creatinine and urea (R2 = 0.75 and R2 = 0.72, respectively, P < 0.001 for both) were better predictors of kidney disease than MAU (R2 = 0.64, P < 0.001) and KIM-1 (R2 = 0.046, P = 0.116). Further analysis of agreement showed that urea had an excellent agreement with creatinine (kappa r = 0.835, P < 0.001), with KIM-1 (kappa r = -0.198, P = 0.087) showing a poor agreement with creatinine. CONCLUSION: Our results indicate that elevated serum creatinine and urea above specific cutoff points reliably identifies patients with acute kidney injury or chronic kidney disease. However, more researches are warranted to further validate the diagnostic efficiency and application of MAU and for KIM-1 before its implementation in clinical practice.

Kidney injury molecule-1 and microalbuminuria levels in Zambian population: biomarkers of kidney injury.

INTRODUCTION: Kidney injury affects renal excretion of plasma analytes and metabolic waste products with grave pathologic consequences. Early detection, thus of kidney injury is essential for injury specific intervention that may avert permanent renal damage and delay progression of kidney injury. We aimed to evaluate Kidney Injury Molecule-1 (KIM-1) and Microalbuminuria (MAU), as biomarkers of kidney injury, in comparison with creatinine. METHODS: We compared the levels of urine MAU, urine KIM-1 and other plasma biochemical tests in specimens from 80 individuals with and without kidney disease. RESULTS: We found no difference in KIM-1 levels between the kidney disease group (2.82± 1.36ng/mL) and controls (3.29 ± 1.14ng/mL), p = 0.122. MAU was higher in participants with kidney disease (130.809± 84.744 µg/mL) than the controls (15.983± 20.442µg/mL), p ?0.001. KIM-1 showed a weak negative correlation with creatinine (r = -0.279, p = 0.09), whereas MAU was positively correlated with creatinine in participants with kidney disease with statistical significance (r = 0.556, p = 0.001). CONCLUSION: The study demonstrated that in Zambian setting MAU and creatinine are sensitive biomarkers in the diagnosis of kidney damage. We moreover propose further evaluation of KIM-1 as a biomarker of kidney injury.