Nevirapine Resistance in Previously Nevirapine-Unexposed HIV-1-Infected Kenyan Infants Initiating Early Antiretroviral Therapy

Chohan, Bhavna; Tapia, Kenneth; Benki-Nugent, Sarah; Khasimwa, Brian; Ngayo, Musa Otieno; Maleche‐Obimbo, Elizabeth; Wamalwa, Dalton; Overbaugh, Julie; John‐Stewart, Grace

doi:10.1089/aid.2014.0370

Cited by 7 publications

(3 citation statements)

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“…In Mali, baseline NNRTI resistance was common in children without reported PMTCT drug exposure and was associated with increased risk of treatment failure [ 33 ]. Reports from Central African Republic [ 35 ] and Kenya [ 34 ] show drug resistance in as high as 90% of children with detectable viral loads. We found few children achieved virologic suppression after failure was detected but the odds of virologic suppression were significantly higher for children on a PI-based versus NNRTI regimen.…”

Section: Discussionmentioning

confidence: 99%

Adoption of routine virologic testing and predictors of virologic failure among HIV-infected children on antiretroviral treatment in western Kenya

et al. 2018

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BackgroundAccess to routine virologic monitoring, critical to ensuring treatment success, remains limited in low- and middle-income countries. We report on implementation of routine viral load (VL) monitoring and risk factors for virologic failure among HIV-infected children on antiretroviral treatment (ART) in Western Kenya.MethodsRoutine VL testing was introduced in western Kenya in November 2013. We performed a case-control study among 1190 HIV-infected children ≤15 years on ART who underwent routine VL testing June 2014–May 2015. A random sample of 98 cases (virologic failure define as VL >1000 cps/mL) and 201 controls (VL <1000 cps/mL) from five facilities in three high HIV prevalence counties in Kenya were followed for a minimum of 12 months. Data from patient charts were analyzed using logistic regression to determine factors associated with failure to attain virologic suppression at initial routine and subsequent VL testing among cases.ResultsOverall, 1190 (94%) children with a median age of 8 years underwent routine VL testing of whom (37%) had virological failure. Among the 299 cases and controls, WHO stage, baseline CD4 count and time since ART initiation were not associated with virologic failure during the follow-up period. In multivariable analysis, unsuppressed children at initial test were more likely to be male (adjusted Odds Ratio (aOR) 2.1, 95% Confidence Interval (CI) 2.1–3.6) and have had an ART regimen change (aOR 2.0, CI 1.0–3.7) than controls. Of the two-thirds of children 201/299 who had a subsequent VL performed, VL suppression was greater among those suppressed at initial test 126/135 (93.3%) compared to children with virologic failure 15/66 (22.7%, p<0.0001). Among those failing at first test who achieved viral suppression in follow up, 12/15 (80%) were on a protease inhibitor (PI)-based regimen. In the multivariable analysis of children with subsequent VL testing, children on PI-based 2nd line regimens were 10-fold more likely to achieve viral suppression than children on first-line NNRTI-based ART (adjusted Odds Ratio [aOR] 0.1; 95%CI 0.0–0.4).ConclusionCoverage of initial routine viral load testing among children on ART in western Kenya is high. However, subsequent testing and virologic suppression are low in children with virologic failure on initial routine viral load test. There is an urgent need to improve management and viral load monitoring of children living with HIV experiencing treatment failure to ensure improved long-term outcomes.

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Section: Discussionmentioning

confidence: 99%

Adoption of routine virologic testing and predictors of virologic failure among HIV-infected children on antiretroviral treatment in western Kenya

et al. 2018

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“…Guidelines provide for drug resistance testing, a vital component in management of treatment failure (52) and subsequently prevents pragmatic drug switches that could lead to drug resistance. Studies have reported that upto 60-90% children who don’t attain viral suppression tend to have drug resistance (53) (54), especially mutations to PI drugs which may hinder success of HIV care interventions in children. In this study amongst the CYALHIV who had been switched from PI to DTG based regimen as a result of non-suppression, only 33% had received drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Viral load monitoring practices and correlates of viral non-suppression among children and young adolescents living with HIV in level five hospitals in Kiambu county, Kenya

Gachoka,

Njoroge

2024

Preprint

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BackgroundHIV has been a major global public health issue among children and young adolescents living with HIV (CYALHIV), their viral suppression rates being lower compared to adults. Follow up through viral load monitoring may influence their health outcomes.ObjectiveIn a cross-sectional study we determined viral load monitoring practices and correlates of viral non-suppression of all CYALHIV in three level five hospitals in Kiambu county, KenyaMethodsWe abstracted data from electronic and paper medical records. Multivariable log binomial regression was used to estimate prevalence ratios (PR) and assess correlates of non-suppression. Adherence to viral load testing guidelines was assessed. Viral non-suppression was defined as a VL >1000c/ml.ResultsOf the 252 CYALHIV, the median age was 11 (IQR: 7-13) years. Fourteen had non-suppression at last assessment. Correlates of non-suppression included having previously had TB [aPR=4.25; 95% CI=1.41-12.8; p=0.01], ART side effects [aPR=3.01; 95% CI=1.37-6.62 p=0.006] and having received enhanced adherence counselling [aPR =5.32; 95% CI=2.00-14.15; p=0.001]. Being on Dolutegravir was significantly associated with a lower likelihood of non-suppression (aPR=0.35; CI:0.15-0.85: p = 0.021). Timing of baseline VL tests improved through the years though there were gaps in routine VL monitoring and follow-up on unsuppressed results.ConclusionAt most current VL, 14% children were non-suppressed, higher than the 5% UNAIDS 2030 target. Special strategies on assessing and addressing corelates of non-suppression are essential for ART programs. Routine VL monitoring as per the guidelines was suboptimal despite increased access to VL testing, suggesting other barriers to VL monitoring.

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“…Neonatal drug resistance can result from either maternal exposure to nevirapine 18 or after neonatal administration. 18,19 Preparation of the infant raltegravir formulation is difficult, and raltegravir has a complex dosing regimen with multiple changes in dose and frequency within the first 2 months of life to avoid high exposures and potential toxicity. 6 Lopinavir/ritonavir and dolutegravir have been shown to be safe and efficacious when used in combination regimens in older infants, but reports of neonatal toxicity and/or lack of formulations with adequate neonatal pharmacokinetic and safety data 20 restrict their use to infants over 2 21 and 4 weeks 22 of postnatal age, respectively.…”

Section: Discussionmentioning

confidence: 99%

Maraviroc Population Pharmacokinetics Within the First 6 Weeks of Life

Liyanage

Nikanjam

McFadyen

et al. 2022

Pediatric Infectious Disease Journal

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Background: Treatment and prophylaxis options for neonatal HIV are limited. This study aimed to develop a population pharmacokinetic model to characterize the disposition of maraviroc in neonates to inform dosing regimens and expand available options. Methods: Using maraviroc concentrations from neonates who received either a single dose or multiple doses of 8 mg/kg of maraviroc in the first 6 weeks of life, a population pharmacokinetic model was developed to determine the effects of age, sex, maternal efavirenz exposure and concomitant ARV therapy on maraviroc disposition. The final model was used in Monte Carlo simulations to generate expected exposures with recommended dosing regimens. Results: A total of 396 maraviroc concentrations, collected in the first 4 days of life, at 1 week, at 4 weeks and at 6 weeks, from 44 neonates were included in the analysis. After allometrically scaling for weight, age less than 4 days was associated with a 44% decreased apparent clearance compared with participants 7 days to 6 weeks of life. There were no differences identified in apparent clearance or volume of distribution from ages 7 days to 6 weeks, sex, maternal efavirenz exposure or concomitant nevirapine therapy. Monte Carlo simulations with FDA-approved weight band dosing resulted in the majority of simulated patients (84.3%) achieving an average concentration of ≥75 ng/mL. Conclusions: While maraviroc apparent clearance is decreased in the first few days of life, the current FDA-approved maraviroc weight band dosing provides maraviroc exposures for neonates in the first 6 weeks of life, which were consistent with adult maraviroc exposure range. Maraviroc provides another antiretroviral treatment option for very young infants.

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Nevirapine Resistance in Previously Nevirapine-Unexposed HIV-1-Infected Kenyan Infants Initiating Early Antiretroviral Therapy

Cited by 7 publications

References 24 publications

Adoption of routine virologic testing and predictors of virologic failure among HIV-infected children on antiretroviral treatment in western Kenya

Adoption of routine virologic testing and predictors of virologic failure among HIV-infected children on antiretroviral treatment in western Kenya

Viral load monitoring practices and correlates of viral non-suppression among children and young adolescents living with HIV in level five hospitals in Kiambu county, Kenya

Maraviroc Population Pharmacokinetics Within the First 6 Weeks of Life

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