Predictors of Long-Term Viral Failure Among Ugandan Children and Adults Treated With Antiretroviral Therapy

Kamya, Moses R.; Mayanja‐Kizza, Harriet; Kambugu, Andrew; Bakeera-Kitaka, Sabrina; Semitala, Fred; Mwebaze-Songa, Patricia; Castelnuovo, Barbara; Schaefer, Petra; Spacek, Lisa A.; Gasasira, Anne; Katabira, Elly; Colebunders, Robert; Quinn, Thomas C.; Ronald, Allan; Thomas, David L.; Kekitiinwa, Adeodata

doi:10.1097/qai.0b013e31814278c0

Cited by 201 publications

(178 citation statements)

References 25 publications

(22 reference statements)

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“…The median age, viral load, CD4 count, and CD4% at VL rebound were 10·6 years [5·6-13·4], 3·6 log 10 c/ml [3·1-4·2], 550 cells/μl , and 24% [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], respectively, and three-quarters of children initiated on a NNRTI-based regimen. Fifty one (30%) had already experienced some ART modifications not meeting the definition of switch prior to VL rebound.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies of children, primarily on NNRTI-based regimens, have shown similar rates of virological failure at 12 months, although some of these studies used different definitions of failure (single elevated viral load measurements) 21,23,24 . Among patients who switched to second-line therapy in our study, we found a median [IQR] time from VL rebound to switch of 4·9 months [1·7-13·4] which is comparable or slightly shorter than studies in resource limited settings 21,25 .…”

Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 99%

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Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

et al. 2015

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Section: Resultsmentioning

confidence: 99%

Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 99%

Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

et al. 2015

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“…28 Predictors of VF in HIV-infected children reported in other studies include physician documentation of poor adherence, lower baseline CD4%, male gender, and treatment with nevirapine versus efavirenz-based HAART, and being an orphan. 25,26,29,30 In US children, reporting a barrier to adherence in the PACTG adherence questionnaire was significantly associated with elevated HIV-RNA. 10 VF was significantly associated with reporting any barrier in the PACTG questionnaire in our study, so this tool could be useful for helping physicians to identify children at risk for VF, and address specific barriers that prevent them from adhering to their treatment regimens.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Adherence Monitoring Tools and Correlation to Virologic Failure in a Pediatric HIV Clinical Trial

Intasan

Bunupuradah²,

Saphonn³

et al. 2014

AIDS Patient Care and STDs

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There is no consensus on a gold standard for monitoring adherence to antiretroviral therapy (ART). We compared different adherence monitoring tools in predicting virologic failure as part of a clinical trial. HIV-infected Thai and Cambodian children aged 1-12 years (N = 207) were randomized to immediate-ART or deferred-ART until CD4% < 15%. Virologic failure (VF) was defined as HIV-RNA > 1000 copies/mL after ‡ 6 months of ART. Adherence monitoring tools were: (1) announced pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and (3) child self-report (self-reporting from children or caregivers to direct questioning by investigators during the clinic visit) of any missed doses in the last 3 days and in the period since the last visit. The Kappa statistic was used to describe agreement between each tool. The median age at ART initiation was 7 years with median CD4% 17% and HIV-RNA 5.0 log 10 copies/mL and 92% received zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by announced pill count before VF in VF children was 92% compared to 98% in children without VF ( p = 0.03). Kappa statistics indicated slight to fair agreement between tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and caregiver education, significant predictors of VF were poor adherence by announced pill count (OR 4.56;, reporting any barrier to adherence in the PACTG adherence questionnaire (OR 7.08;, and reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR 8.64;). In conclusion, we recommend the child self-report of any missed doses since last visit for use in HIV research and in routine care settings, because it is easy and quick to administer and a strong association with development of VF.

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“…7,9,10 Children are twice as likely to experience virological failure to ART compared with adults. 11 Furthermore, a large proportion of HIV-infected children (13-53%) are expected to experience virological failure within the first year of treatment and are therefore at a higher risk of developing drug resistance if failure is diagnosed late. 7,10,[12][13][14] Such resistance may have important consequences for second-line treatment strategies, particularly in children with reduced treatment options and formularies.…”

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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Predictors of Long-Term Viral Failure Among Ugandan Children and Adults Treated With Antiretroviral Therapy

Cited by 201 publications

References 25 publications

Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

Comparison of Adherence Monitoring Tools and Correlation to Virologic Failure in a Pediatric HIV Clinical Trial

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

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