CD4+ T-Cell Count Monitoring Does Not Accurately Identify HIV-Infected Adults With Virologic Failure Receiving Antiretroviral Therapy

Moore, David; Awor, Anna; Downing, Robert; Kaplan, Jonathan E.; Montaner, Julio S. G.; Hancock, John; Were, Willy; Mermin, Jonathan

doi:10.1097/qai.0b013e318186eb18

Cited by 105 publications

(83 citation statements)

References 14 publications

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“…In adults, the criteria have been shown to be insensitive measures for virologic outcomes [10,11], and a high prevalence of ARV resistance mutations has been documented in HIV-infected adults by the time they progress to meet the WHO criteria for ARV therapy switch [12]. A recent report showed same similarity in pediatric WHO guidelines, where it has been found to offer an insensitive measure of virologic failure [13].…”

Section: Research Articlementioning

confidence: 78%

First and Second Line Highly Active Anti-Retroviral Therapy Failure in HIV Infected Nigerian Children at University of Abuja Teaching Hospital Gwagwalada, Nigeria

Aa¹

2015

J HIV Clin Sci Res

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Background: In high-income countries, viral load is routinely used for monitoring HIV patients on antiretroviral therapy for early detection of drug failure. This is not the case in most resource limited settings like ours where only WHO immunological and clinical criteria are used for monitoring. This study is aimed at determining the rate/time of failure to 1 st and 2 nd antiretroviral drugs in children in our centers.Method: Is a retrospective study of children ≤18 years switched to 2 nd line antiretroviral regimen and those requiring third line drugs from Jan 2006 to June 2015 in our health institution. Data analysis was conducted using SPSS version 16.0 software and statistical significance set at p < 0.05. Result:Sixteen percent (82/514) of children on 1 st line medication were switched to 2 nd line drugs with switch over rate of 9 persons/year, and 6/82 (7.3%) required 3 rd line medication. The median switch over time was 31.3 months (IQR 26.4-36.2) for 2 nd line medication, and 42.6 months (IQR 40.1-44.3) from time of switch to 2 nd line drugs for those requiring 3 rd line regimen. Over 90% of patients switched to 2 nd line drugs were between 9-18 years, none was an infant. The mean CD4 cell count and viral load before switch to 2 nd line drugs were 109.09±29.23 cell/mm 3 and 180,480.29±35,303 copies/ ml, and 89.42±28.67 cell/mm 3 / 237,337.5±64,619 copies/ml for those requiring 3 rd line medications. There was over 450 fold increase in viral load from the expected undetectable level of 400 copies/ml after 6 months on medication before patients were switch to 2 nd line drugs, and over 590 folds increase for those that require 3 rd line medications. Significant difference was seen in the mean CD4 cell count and weight of those with adherence of ≥ 95% and ≤ 95% (p values were <0.05). Conclusion:WHO immunological and clinical criteria were found not to be ideal for monitoring of children on antiretroviral therapy. Six monthly viral load monitoring and resistance testing should be introduced in Nigerian guideline for managing HIV children for better therapeutic and pharmacoeconomic outcomes. Third line medication should also be made available in the country and intensification of adherence is required in adolescent age group.

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Section: Research Articlementioning

confidence: 78%

First and Second Line Highly Active Anti-Retroviral Therapy Failure in HIV Infected Nigerian Children at University of Abuja Teaching Hospital Gwagwalada, Nigeria

Aa¹

2015

J HIV Clin Sci Res

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“…Frequent misclassification of virological failure in adult patients has been reported, leading to early ART switch or late failure diagnosis. [3][4][5] In the latter circumstances, by the time treatment failure is recognized, patients may have already accumulated drug resistance mutations and high-level cross-resistance to subsequent antiretroviral regimens. [6][7][8] Minimizing resistance is particularly important in RLS with limited ART options, usually restricted to first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line protease inhibitor (PI)-based regimens.…”

Section: Introductionmentioning

confidence: 99%

Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

Coetzer

Westley

DeLong

et al. 2013

AIDS Research and Human Retroviruses

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Antiretroviral therapy in resource-limited settings is monitored clinically and immunologically according to WHO guidelines. Frequent misclassification of virologic failure is reported, mostly in adults, leading to early therapy switch or late failure diagnosis. Pediatric treatment monitoring and resistance data upon first-line failure are limited, particularly when the 2010-WHO pediatric guidelines are used without routine viral load monitoring. We previously reported high treatment failure misclassification rates by pediatric 2010 guidelines in Cambodian children on first-line therapy. Here we determine the extent and patterns of resistance, with yearly viral load and 6-monthly CD4. Drug resistance mutations were determined using the IAS-USA 2011 list. Predicted resistance interpretation was determined with Stanford Database tools. Fifty-one children with available genotypes met inclusion criteria. All but one (subtype B) were CRF01_AE. The most common regimen was stavudine, lamivudine, and nevirapine (96%), taken for a median of 2.2 years. Resistance was seen in 98%; 96% to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs); 51% with ‡ 4 mutations. The most common NRTI mutations were 184V/I and 67N and the most common NNRTI mutations were 181C/Y/I/V and 190A/S. A total of 22% had multiresistant mutations and 18% had predicted high-level resistance to subsequent therapy options didanosine, abacavir, etravirine, and tenofovir. In 98% of Cambodian children misclassified as nonfailing first-line therapy by 2010 guidelines, 51% had extensive drug resistance to current and 18% to subsequent antiretroviral therapy. Affordable routine viral load monitoring allowing for early and more accurate treatment failure diagnosis is desperately needed in resource-limited settings.

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“…Neither clinical findings nor CD4 cell counts are adequate predictors of viral suppression, and in fact management by CD4 cell counts alone can lead to unnecessary treatment changes (1). VL testing is the only reliable marker for the early detection of the failure of antiretroviral therapy (17,20).…”

mentioning

confidence: 99%

Comparative Evaluation of the ExaVir Load Version 3 Reverse Transcriptase Assay for Measurement of Human Immunodeficiency Virus Type 1 Plasma Load

Labbett¹,

Garcı́a-Dı́az²,

Fox³

et al. 2009

J Clin Microbiol

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In resource-limited settings, the virological monitoring of antiretroviral therapy is limited by high cost and the lack of infrastructure. The Cavidi ExaVir Load assay employs a simple and inexpensive enzyme-linked immunosorbent assay format to measure human immunodeficiency virus (HIV) reverse transcriptase activity, which correlates with plasma RNA load. The version 3 assay has been described as having improved precision and sensitivity. There are limited data on its performance relative to those of current real-time assays

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CD4+ T-Cell Count Monitoring Does Not Accurately Identify HIV-Infected Adults With Virologic Failure Receiving Antiretroviral Therapy

Abstract: CD4 cell count monitoring does not accurately identify individuals with virologic failure among patients taking ART.

Cited by 105 publications

References 14 publications

First and Second Line Highly Active Anti-Retroviral Therapy Failure in HIV Infected Nigerian Children at University of Abuja Teaching Hospital Gwagwalada, Nigeria

First and Second Line Highly Active Anti-Retroviral Therapy Failure in HIV Infected Nigerian Children at University of Abuja Teaching Hospital Gwagwalada, Nigeria

Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

Comparative Evaluation of the ExaVir Load Version 3 Reverse Transcriptase Assay for Measurement of Human Immunodeficiency Virus Type 1 Plasma Load

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