Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

Reddi, A. Hari; Leeper, Sarah; Grobler, Anneke; Geddes, Rosemary; Dorse, Gillian L.; Vlok, Willem J.; Mntambo, Mbali.; Thomas, M.; Nixon, Krystal-Lee.; Holst, Helga; Karim, Quarraisha Abdool; Rollins, Nigel; Coovadia, Hoosen; Giddy, Janet

doi:10.1186/1471-2431-7-13

Cited by 170 publications

(173 citation statements)

References 40 publications

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“…This was similar to the reported rate in some other resource limited settings were HIV RNA VL assays was not routinely used in the monitoring of patients on ART; 13% in Uganda children [9], 16% in South Africa [21], 16% in Thailand [22], but fair much lower than 33% in Kenya [23], and 44% in Mali [24]. It was however higher than 9.1% reported from another South African study [25], and 0.8% from a multicenter study in Africa and Asia [26].…”

Section: Discussionsupporting

confidence: 71%

“…Failure to 1 st line ART has been documented in 13% of HIV-infected Uganda children [9], 16% in South Africa [21], 16% in Thailand [22], 33% in Kenya [23], 44% in Mali [24], 9.1% in another South African study [25], and 0.8% from a multi-center study in Africa and Asia [26]. Adherence to ARV therapy has a major role of achieving good viral suppression on HIV patients.…”

Section: Research Articlementioning

confidence: 99%

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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: Discussionsupporting

confidence: 71%

Section: Research Articlementioning

confidence: 99%

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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“…A treatment interruption due to poor adherence was defined as three or more consecutive missed daily doses of ARV medications in a treatment month after enrolment on HAART. Treatment failure that resulted in a change in HAART regimen was defined as a viral load greater than 5000 copies of HIV RNA/mL, for greater than 6 months, and resulting in an immunological decline [14].…”

Section: Patients and Settingsmentioning

confidence: 99%

Adverse Events in HIV- infected Children on Antiretroviral Therapy at a Teaching Hospital in Lagos, Nigeria: A Retrospective Study

Oshikoya¹

2012

Adv Pharmacoepidem Drug Safety

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Background: Highly active antiretroviral therapy (HAART) program requires adequate monitoring of the potential adverse events to the antiretroviral (ARV) drugs. We investigated the ARV drug combinations prescribed for HIV-infected children and their suspected adverse events.Methods: This is a retrospective and descriptive study involving HIV-infected children less than 15 years old who received treatment at the APIN clinic, Lagos University Teaching Hospital (LUTH) in Nigeria. The case files of 80 patients initiated on HAART, between January 2008 and December 2009, were reviewed. Their demographics, clinical details and medication use, the prescribed HAART regimen, and the suspected clinical and laboratory adverse events were extracted. Results:The patients were female (46; 57.5%) preponderant with a median age of 3 (IQR: 1.1-6.0) years. Zidovudine-lamivudine-nevirapine (AZT-3TC-NVP) combination (74; 92.5%) was the most frequently prescribed first-line regimen. Thirty three patients changed their first-line HAART to abacavir-lamivudine-lopinavir boosted with ritonavir (ABC-3TC-LVP/r) (11; 33.3%), and zidovudine-lamivudine-abacavir-lopinavir boosted with ritonavir (AZT-3TC-ABC-LVP/r) (8; 24.2%) combinations. Of the 80 patients included in the study, 38(47.7%) experienced 142 adverse events. The most frequently experienced clinical adverse events were nevirapine-induced skin rashes (93; 65.5%), vomiting (19; 13.4%), and pallor (12; 8.5%). Macrocytosis (22/72; 30.6%), anaemia (6/72; 8.3%), and thrombocytopenia (2/72; 2.8%) were the commonest haematological adverse events associated with zidovudine. Conclusions:The HAART regimens used for HIV-infected children in this study have a good safety profile. Their few adverse events suggest a need for prospective pharmacovigilance to effectively monitor the toxicities of ARV drugs.

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“…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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Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

Abstract: Background: Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa.

Cited by 170 publications

References 40 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

Adverse Events in HIV- infected Children on Antiretroviral Therapy at a Teaching Hospital in Lagos, Nigeria: A Retrospective Study

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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