Abstract
BACKGROUND: Pretreatment HIV drug resistance (PDR) can impair virological response to ART, jeopardizing effective treatment for children.
METHODS: Children aged ≤12 years initiated first-line ART in Uganda during 2010-11. Baseline and 6 monthly viral load (VL) and genotypic resistance testing if VL >1000 copies/mL was done. The 2015 IAS-USA mutation list and Stanford algorithm were used to score drug resistance mutations (DRMs) and susceptibility. Virological failure (VF) was defined as two consecutive VLs >1000 copies/mL or death after 6 months of ART. Factors associated with failure and acquired drug resistance (ADR) were assessed in a logistic regression analysis.
RESULTS: Among 317 children enrolled, median age was 4.9 years and 91.5% received NNRTI-based regimens. PDR was detected in 47/278 (16.9%) children, of whom 22 (7.9%) had resistance against their first-line regimen and were therefore on a partially active regimen. After 24 months of follow-up, 92/287 (32.1%) had experienced VF. Children with PDR had a higher risk of VF (OR 15.25, P < 0.001) and ADR (OR 3.58, P = 0.01).
CONCLUSIONS: Almost one-third of children experienced VF within 24 months of NNRTI-based first-line treatment. PDR was the strongest predictor of VF and ADR, and therefore presents a major threat in children. There is a need for ART regimens that maximize effectiveness of first-line therapy for long-term treatment success in the presence of PDR or incorporation of routine VL testing to detect VF and change treatment in time, in order to prevent clinical deterioration and accumulation of additional drug resistance. Children ≤3 years should be initiated on a PI-based regimen as per WHO guidelines.
| Original language | English |
|---|---|
| Pages (from-to) | 2587-2595 |
| Number of pages | 9 |
| Journal | The Journal of antimicrobial chemotherapy |
| Volume | 72 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1 Sept 2017 |
Bibliographical note
© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.Funding
This work was supported by the European & Developing Countries Clinical Trials Partnership (EDCTP) and The Netherlands African Partnership for Capacity Development and Clinical Interventions against Poverty Related Diseases (NACCAP) program of The Netherlands Organisation for Scientific Research (NWO)-Science for Global Development (WOTRO). We thank all study participants and their caregivers, doctors and nurses, and support staff at JCRC and AIGHD: Annet Nandudu, James Nkalubo, Isaac Egau and Lincoln Mugarura (JCRC Kampala); Michael Owor, Christine Matama and Florence Nambaziira (JCRC Fort Portal); Mary Abwola, Fred Senono, Ronald Namisi and Sylivia Nakusi (JCRC Mbale); Cees Hesp and John Dekker (PharmAccess); Corry Manting, Desiree Lathouwers, Nadine Pakker, Bram Prins, Elske van Schijndel and Marloes Nijboer (AIGHD-Amsterdam); Cathy Nalubwama and Martin Omello (AIGHD-Kampala). This work was partially presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2016, Abstract 849, Boston, MA, USA, 22-25 February 2016, and the 10th INTEREST Workshop 2016, Yaounde, Cameroon, 3-6 May 2016, Abstract 3
| Funders | Funder number |
|---|---|
| AIGHD-Amsterdam | |
| AIGHD-Kampala | |
| Cathy Nalubwama and Martin Omello | |
| Cees Hesp and John Dekker | |
| NACCAP | |
| Netherlands African Partnership for Capacity Development and Clinical Interventions against Poverty Related Diseases | |
| European and Developing Countries Clinical Trials Partnership | |
| Nederlandse Organisatie voor Wetenschappelijk Onderzoek |
Keywords
- Anti-HIV Agents/pharmacology
- Black People
- Child
- Child, Preschool
- Drug Resistance, Viral/genetics
- Female
- Genotype
- HIV Infections/drug therapy
- HIV-1/drug effects
- Humans
- Male
- Mutation
- Treatment Failure
- Treatment Outcome
- Uganda/epidemiology
- Viral Load/drug effects