Predicting Virologic Failure Among HIV-1-Infected Children Receiving Antiretroviral Therapy in Tanzania: a Cross-Sectional Study

Emmett, Susan D.; Cunningham, Coleen K.; Mmbaga, Blandina T; Kinabo, Grace D.; Schimana, Werner; Swai, Mark; Bartlett, John A.; Crump, John A.; Reddy, Elizabeth

doi:10.1097/qai.0b013e3181cf4882

Cited by 74 publications

(74 citation statements)

References 22 publications

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“…The rate of virological failure in this study was high (57%) compared with those reported in previous studies: 20% in Thailand, [8] 26% in Uganda, [9] 32% in the Kilimanjaro region, Tanzania, [10] and 50% in Cote d'Ivoire. [11] The differences observed between the current and previous studies could be explained by the different viral load cut-off points used, e.g.…”

Section: Discussionmentioning

confidence: 35%

Detecting virological failure in HIV-infected Tanzanian children

2014

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Background. The performance of clinical and immunological criteria to predict virological failure in HIV-infected children receiving antiretroviral therapy (ART) is not well documented. Objective. To determine the validity of clinical and immunological monitoring in detecting virological failure in children on ART. Methods. A total of 218 children were included in the study. All were from care and treatment clinics in Dar es Salaam, Tanzania. Their mean age was 10.6 years, 122 (56.0%) were males, and the mean time on ART was 40.9 months. The study was conducted from August 2011 to March 2012. Data on sociodemographic and clinical characteristics and immunological and virological failure were based on World Health Organization definitions. Blood samples were collected for CD4 + T-cell count and viral load tests. Results. Of 217 children with available viral load results, 124 (57.1%) had virological failure (>400 copies/mL), 25.0% immunological failure and 11.5% clinical failure. The sensitivity, specificity, positive predictive value and negative predictive value of clinical criteria were 12.9%, 90.3%, 64.0% and 43.8%, respectively, those for immunological criteria 22.6%, 73.1%, 53.3% and 41.4%, and those for the combination of clinical and immunological monitoring 25.8%, 69.9%, 53.3% and 41.4%. Children who received nevirapine (NVP)-based regimens were two times more likely (odds ratio 2.0; 95% confidence interval 1.20 -3.64) to have virological failure than those on efavirenz and protease inhibitor-based regimens. Conclusions. The study demonstrated poor performance of currently recommended clinical and immunological criteria for monitoring HIV-infected children on ART. Moreover, children on NVP-based regimens had a higher risk of developing virological failure than those on other regimens.

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Section: Discussionmentioning

confidence: 35%

Detecting virological failure in HIV-infected Tanzanian children

2014

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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]. This was confirmed in Ugandan study by Ruel et al [9], and additionally demonstrated that the HIV-infected African children with ongoing undetected virologic failure develop ARVmutations that could compromise future therapeutic options.…”

Section: Research Articlementioning

confidence: 72%

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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“…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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Predicting Virologic Failure Among HIV-1-Infected Children Receiving Antiretroviral Therapy in Tanzania: a Cross-Sectional Study

Cited by 74 publications

References 22 publications

Detecting virological failure in HIV-infected Tanzanian children

Detecting virological failure in HIV-infected Tanzanian children

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

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

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