There are about 2.1 million children infected with HIV globally and about 120,000 deaths annually. Nigeria has one of the highest rates of pediatric HIV infection globally. Pretreatment HIV drug resistance data inform the choice of first- and second-line antiretroviral therapy (ART) regimens. This study investigated the prevalence of HIV drug-resistant strains among ART-naive children in Ibadan, Nigeria. A total of 20 children aged <15 years were enrolled. Demographic, clinical, and laboratory data were documented. Total nucleic acid was extracted from blood samples after which amplification of HIV-1 pol gene was done using polymerase chain reaction. Amplified gene was sequenced using big dye sequencing method. The sequenced HIV-1 pol gene was typed and analyzed for identification of mutations indicative of drug resistance across the different classes of ART. HIV-1 RNA pol gene was successfully amplified in 12/20 (60%) children. All were identified as HIV-1 and the subtypes were G and CRF 02AG, recombinant of 02_AG/G and recombinant of 02_AG/A1. Drug-resistant mutations (DRMs) were identified in 4/12 (33%). Three out of the four mutations were identified as non-nucleoside reverse transcriptase inhibitors DRM (K103N), whereas the fourth had nucleoside reverse transcriptase inhibitors DRM (M184V). Results from this preliminary study show that drug resistance among ART-naive children is a problem in Ibadan. Pretreatment drug resistance testing is desirable in children before initiation of ART to guide effective treatment.
Get full access to this article
View all access options for this article.
References
1.
UNICEF: Paediatric care and treatment—UNICEF DATA [Internet]. Available at https://data.unicef.org/topic/hivaids/paediatric-treatment-and-care, accessed October26, 2020.
2.
SlogroveAL, PowisKM, JohnsonLF, StoverJ, MahyM: Estimates of the global population of children who are HIV-exposed and uninfected, 2000–18: A modelling study. Lancet Glob Heal, 2020; 8:e67–e75.
3.
Federal Ministry of Health: Integrated guidelines for HIV prevention treatment and care. Vol. 1, National AIDs/STI Control Programme, 2014.
4.
(UNAIDS) JUNP on HIV: The Gap Report. UNAIDS, Geneva, 2014, pp. 1–16.
5.
WHO: The Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. WHO, Geneva, 2016.
6.
WilliamsPL, JessonJ: Growth and pubertal development in HIV-infected adolescents. Curr Opin HIV AIDS, 2018; 13:179–186.
7.
GsponerT, WeigelR, DaviesMA, et al.: Variability of growth in children starting antiretroviral treatment in Southern Africa. Pediatrics, 2012; 130:e966.
8.
McGrathCJ, DienerL, RichardsonBA, Peacock-ChambersE, John-StewartGC: Growth reconstitution following antiretroviral therapy and nutritional supplementation: Systematic review and meta-analysis. AIDS, 2015; 29:2009–2023.
9.
Barlow-MoshaL, MusiimeV, DaviesMA, et al.: Universal antiretroviral therapy for HIV-infected children: A review of the benefits and risks to consider during implementation. J Int AIDS Soc, 2017; 20:21552.
10.
FMOH: National Guidelines for HIV Prevention Treatment and Care National [Internet]. 2016, p. 173. Available at www.naco.gov.in/upload/2016">www.naco.gov.in/upload/2016/Data/LS/National-Guidelines-for-HIV-Testing_21Apr2016.pdf, accessed July4, 2021.
11.
Global AIDS update 2019—Communities at the centre | UNAIDS [Internet]. Available at https://www.unaids.org/en/resources/documents/2019/2019-global-AIDS-update, accessed October28, 2020.
12.
VairoF, NicastriE, LiuzziG, et al.: HIV-1 drug resistance in recently HIV-infected pregnant mother's naïve to antiretroviral therapy in Dodoma urban, Tanzania. BMC Infect Dis, 2013; 13:439.
13.
KityoC, SigaloffKCE, BoenderTS, et al.: HIV drug resistance among children initiating first-line antiretroviral treatment in Uganda. AIDS Res Hum Retroviruses, 2016; 32:628–635.
14.
HIV Drug Resistance Report 2017 Trends Quality Action. [Internet]. 2017, p.82. Available at https://apps.who.int/iris/bitstream/handle/10665/255896/9789241512831-eng.pdf;sequence=1, accessed July4, 2021.
15.
LockmanS, ShapiroRL, SmeatonLM, et al.: Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med, 2007; 356:135–147.
16.
MoorthyA, KuhnL, CoovadiaA, et al.: Induction therapy with protease-inhibitors modifies the effect of nevirapine resistance on virologic response to nevirapine-based HAART in children. Clin Infect Dis, 2011; 52:514–521.
17.
IyidoganP, AndersonKS: Current perspectives on HIV-1 antiretroviral drug resistance. Viruses, 2014; 6:4095–4139.
18.
GuptaRK, JordanMR, SultanBJ, et al.: Global trends in antiretroviral resistance in treatment-naïve individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: A global collaborative study and meta-regression analysis. Lancet, 2012; 380:1250–1258.
19.
GregsonJ, TangM, NdembiN, et al.: Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: A multicentre retrospective cohort study. Lancet Infect Dis, 2016; 16:565–575.
20.
Stanford HIV Drug Resistance Database Major HIV-1 Drug Resistance Mutations. [Internet]. Available at https://hivdb.stanford.edu/, accessed July4, 2021.
21.
HIV Circulating Recombinant Forms (CRFs) [Internet]: Available at https://www.hiv.lanl.gov/content/sequence/HIV/CRFs/CRFs.html, accessed July4, 2021.
22.
BbosaN, KaleebuP, SsemwangaD: HIV subtype diversity worldwide. Curr Opin HIV AIDS, 2019; 14:153–160.
23.
OlusolaBA, OlaleyeDO, OdaiboGN: Early HIV infection among persons referred for malaria parasite testing in Nigeria. Arch Virol, 2017; 163:439–445.
24.
SantoroMM, AlteriC, RongaL, et al.: Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02-AG) in Italy. AIDS Res Hum Retroviruses, 2012; 28:1285–1293.
25.
ChaplinB, EisenG, IdokoJ, et al.: Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy. AIDS Res Hum Retrovir, 2011; 27:71–80.
26.
DialloK, ZhengD-P, RottinghausEK, BasseyO, YangC: Viral genetic diversity and polymorphisms in a cohort of HIV-1-infected patients eligible for initiation of antiretroviral therapy in Abuja, Nigeria. AIDS Res Hum Retroviruses, 2015; 31:564–575.
27.
WickhamH. Wickham H: Ggplot2 Elegant Graphics for Data Analysis, 2nd Edition. Springer, New York, 2009.
28.
OmoniAO, NtoziniR, EvansC, et al.: Child growth according to maternal and child HIV status in Zimbabwe. Pediatr Infect Dis J, 2017; 36:869–876.
29.
McHenryMS, ApondiE, AyayaSO, et al.: Growth of young HIV-infected and HIV-exposed children in western Kenya: A retrospective chart review. Madiba S, editor. PLoS One, 2019; 14:e0224295.
30.
LentoorA: Nutritional status of perinatally HIV-infected children on antiretroviral therapy from a resource-poor rural South African community. African J Med Heal Sci, 2018; 17:1.
31.
SimmsV, RylanceS, BandasonT, et al.: CD4+ cell count recovery following initiation of HIV antiretroviral therapy in older childhood and adolescence. AIDS, 2018; 32:1977–1982.
32.
SchomakerM, LeroyV, WolfsT, et al.: Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: A multiregional analysis from Southern Africa, West Africa and Europe. Int J Epidemiol, 2017; 46:453–465.
33.
PicatMQ, LewisJ, MusiimeV, et al.: Predicting patterns of long-term CD4 reconstitution in HIV-infected children starting antiretroviral therapy in Sub-Saharan Africa: A cohort-based modelling study. PLoS Med, 2013; 10:e1001542.
34.
LewisJ, WalkerAS, CastroH, et al.: Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: Effects on long-term T-cell reconstitution. J Infect Dis, 2012; 205:548–556.
35.
UNAIDS: Children and HIV. Media, 2016; 296:2006–2007.
36.
ArchinNM, SungJM, GarridoC, Soriano-SarabiaN, MargolisDM: Eradicating HIV-1 infection: Seeking to clear a persistent pathogen. Nat Rev Microbiol, 2014; 12:750–764.
37.
ArchinNM, VaidyaNK, KurucJD, et al.: From the Cover: Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proc Natl Acad Sci USA, 2012; 109:9523–9528.
38.
KaleebuP, KirungiW, WateraC, et al.: Virological response and antiretroviral drug resistance emerging during antiretroviral therapy at three treatment centers in Uganda. PLoS One, 2015; 10:1–18.
39.
PeetersM: The genetic variability of HIV-1 and its implications. Transfus Clin Biol, 2001; 8:222–225.
40.
OlusolaBA, OlaleyeDO, OdaiboGN: New infections and HIV-1 subtypes among febrile persons and blood donors in Oyo State, Nigeria. J Med Virol, 2021; 93:4891–4900.
41.
UdezeAO, OlaleyeDO, OdaiboGN: Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Blackard J, editor. PLoS One, 2020; 15:e0231031.
42.
OdaiboGN, OkonkwoP, AdewoleIF, OlaleyeDO: Pattern of HIV-1 drug resistance among adults on ART. World J AIDS, 2013; 2013:327–334.
43.
HemelaarJ, GouwsE, GhysPD, OsmanovS: Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004. AIDS, 2006; 20:W13–W23.
44.
OlusolaBA, KabelitzD, OlaleyeDO, OdaiboGN: Early HIV infection is associated with reduced proportions of gamma delta T subsets as well as high creatinine and urea levels. Scand J Immunol, 2020; 91:e12868.
45.
OlusolaBA, OlaleyeDO, OdaiboGN: Non-synonymous Substitutions in HIV-1 GAG are frequent in epitopes outside the functionally conserved regions and associated with subtype differences. Front Microbiol, 2021; 11:3471.
46.
HamersR: Drug-resistant HIV-1 in sub-Saharan Africa: Clinical and public health studies [Internet]. Available at http://dare.uva.nl/en/record/436846 (2013), accessed July4, 2021.
47.
BoermaRS, BoenderTS, SigaloffKCE, et al.: High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children. J Int AIDS Soc, 2016; 19:1–8.
48.
InzauleSC, OsiSJ, AkinbiyiG, et al.: High prevalence of HIV drug resistance among newly diagnosed infants aged <18 months. JAIDS J Acquir Immune Defic Syndr, 2018; 77:e1–e7.
49.
SsemwangaD, LihanaRW, UgojiC, NkengasongJ, DakumP, NdembiN: Update on HIV-1 acquired and transmitted drug resistance in Africa. AIDS Rev, 2015; 17:3–20.
50.
CambianoV, BertagnolioS, JordanMR, LundgrenJD, PhillipsA: Transmission of drug resistant HIV and its potential impact on mortality and treatment outcomes in resource-limited settings. J Infect Dis, 2013; 207(Suppl. 2):57–62.
51.
InzauleSC, JordanMR, BelloG, et al.: High levels of resistance to nucleoside/nucleotide reverse transcriptase inhibitors in newly diagnosed antiretroviral treatment-naive children in sub-Saharan Africa. AIDS, 2020; 34:1567–1570.
52.
BoenderTS, HoenderboomBM, SigaloffKCE, et al.: Pretreatment HIV drug resistance increases regimen switches in sub- Saharan Africa. Clin Infect Dis, 2015; 61:1749–1758.
53.
Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf, accessed July4, 2021.
54.
CihlarT, FordyceM: Current status and prospects of HIV treatment. Curr Opin Virol, 2016; 18:50–56.
55.
HIV Drug Resistance Report 2019. Geneva, Switzerland: World Health Organization; 2019 (WHO/CDS/HIV/19.21). Licence: CC BY-NC-SA 3.0 IGO, accessed July4, 2021.
56.
PenazzatoM, PrendergastAJ, MuheLM, TindyebwaD, AbramsEJ: Optimization of antiretroviral therapy in HIV-infected children under 3 years of age: A systematic review. AIDS, 2014; 28:S137–S146.
57.
SebunyaR, MusiimeV, KitakaSB, NdeeziG: Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. AIDS Res Ther, 2013; 10:1.
58.
ClutterDS, JordanMR, BertagnolioS, ShaferRW: HIV-1 drug resistance and resistance testing. Infect Genet Evol, 2016; 46:292–307.
59.
Anejo-OkopiJA, AgbajiOO, AgabaPA, et al.: Human immunodeficiency virus type-1 (HIV-1) genetic diversity and prevalence of antiretroviral drug resistance mutations in treatment-naïve adults in Jos, North Central Nigeria. Afr J Biotechnol, 2013; 12:2279–2287.
