Immediate start of antiretroviral treatment (ART) among non-hospitalized outpatient children living with HIV may improve or worsen clinical outcomes due to immune reconstitution.
Objective
Role of immediate versus post-stabilization start of antiretroviral treatment in children and youths living with HIV on CD4 count and viral load suppression.
Methods
This was a single blinded, randomized controlled trial conducted on outpatients attending a tertiary care hospital associated HIV clinic in North India. We enrolled ART-naive children and youths living with HIV aged 18 months to 21 years in a 1:1 ratio. Block randomization was done using computerized software. Children and youths living with HIV were either started with ART on diagnosis immediately within 24 h (Group A) or post stabilization at 2 weeks (Group B) as per National AIDS Control Organization (NACO) India guidelines. Both groups were comparable for baseline characteristics.
Results
There was no significant difference seen in CD4 counts between two groups at 6 months follow up. CD4 count increased significantly in immediate group but not in post-stabilization group at 6 months. No significant changes/differences was seen in WHO clinical staging or anthropometry; one patient developed tuberculosis in both groups. Viral load at 6 months in both the groups did not differ significantly.
Conclusion
Immediate ART in children and youths living with HIV results in significant increase in CD4 count at 6 months follow up exemplifying immunological response to ART.
Government of India, Ministry of Health & Family Welfare and National AIDS Control Organization. An ethno-epidemiological study to assess early infant diagnosis of HIV infection programme. New Delhi: National AIDS Control Organization. 2015. Accessed January 01, 2023. Available from:https://naco.gov.in/sites/default/files/Technical_Brief_on_EID.pdf
4.
ViolariACottonMFGibbDM, et al.Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med2008; 359(21): 2233–2244.
5.
NjugunaINCranmerLMOtienoVO, et al.Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial. Lancet HIV2018; 5(1): e12–e22.
World Health Organization. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease inadults and children. Geneva: WHO. 2022. Accessed January 01, 2023. Available from:https://apps.who.int/iris/handle/10665/4369
9.
World Health Organization. Manual on paediatric HIV care and treatment for district hospitals: addendum to the pocket book of hospital care of children. Diagnosis of HIV infection in infants and children. Geneva: WHO. 2022. Accessed January 01, 2023. Available from:https://whqlibdoc.who.int/publications/2011/9789241501026eng.pdf
10.
GibertCL. Treatment guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents: an update. Fed Pract2016; 33(Suppl 3): 31S–36S.
11.
HoDD. Time to hit HIV, early and hard. N Engl J Med1995; 333(7): 450–451.
12.
GatellJM. When and why to start antiretroviral therapy?J Antimicrob Chemother2010; 65(3): 383–385.
13.
CarpenterCCFischlMAHammerSM, et al.Antiretroviral therapy for HIV infection in 1996: recommendations of an international panel. Int AIDS Soc–USA. JAMA1996; 276(2): 146–154.
14.
WeiXGhoshSKTaylorME, et al.Viral dynamics in human immunodeficiency virus type 1 infection. Nature1995; 373(6510): 117–122.
15.
HoDDNeumannAUPerelsonAS, et al.Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature1995; 373: 123–126.
16.
EronJBenoitSJemsekJ, et al.A randomized double-blind multicenter comparative trial of lamivudine (3TC) monotherapy vs. zidovudine (ZDV) monotherapy vs. 3TC ZDV combination in naïve patients with CD4 cell counts of 200–500/mm3. In: Program and abstracts of the Second National Conference on Human Retroviruses and Related Infections. Washington, DC, February 1 1995 Jan 29.
17.
MauskopfJKitahataMKaufT, et al.HIV antiretroviral treatment: early versus later. J Acquir Immune Defic Syndr2005; 39(5): 562–569.
18.
KaganJMSanchezAMLandayA, et al.A brief chronicle of CD4 as a biomarker for HIV/AIDS: a tribute to the memory of john L. Fahey. Onco Ther2015; 6(1-2): 55–64.
19.
BishopJDDeShieldsSCunninghamT, et al.CD4 count recovery after initiation of antiretroviral therapy in patients infected with human immunodeficiency virus. Am J Med Sci2016; 352(3): 239–244.
20.
BabikerADarbyshireJPezzottiP, et al.Short-term CD4 cell response after highly active antiretroviral therapy initiated at different times from seroconversion in 1,500 seroconverters. J Acquir Immune Defic Syndr2003; 32(3): 303–310.
21.
MrudulaNDSuwarnaUPKhadseR, et al.Statistical analysis and evaluation of CD4 count after 6 months on ART. Indian J Community Med2012; 37(4): 266–267.
22.
FrangePMontangeTLe ChenadecJ, et al.Impact of early versus late antiretroviral treatment initiation on naive T lymphocytes in HIV-1-Infected children and adolescents–the-ANRS-EP59-CLEAC study. Front Immunol2021; 12: 662894.
23.
SaluzzoSPandeyRVGailLM, et al.Delayed antiretroviral therapy in HIV-infected individuals leads to irreversible depletion of skin- and mucosa-resident memory T cells. Immunity2021; 54(12): 2842.e5–2858.e5.
24.
WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2nd ed.Geneva: World Health Organization, 2016.
25.
ShahI. Adverse effects of antiretroviral therapy in HIV-1 infected children. J Trop Pediatr2006; 52(4): 244–248.
26.
OpokuSSakyiSAAyisi-BoatengNK, et al.Factors associated with viral suppression and rebound among adult HIV patients on treatment: a retrospective study in Ghana. AIDS Res Ther2022; 19(1): 21.
27.
ZeruMA. Prevalence and associated factors of HIV-TB co-infection among HIV patients: a retrospective Study. Afr Health Sci2021; 21(3): 1003–1009.
28.
NegussieADebalkeDBelachewT, et al.Tuberculosis co-infection and its associated factors among People living with HIV/AIDS attending antiretroviral therapy clinic in southern Ethiopia: a facility based retrospective study. BMC Res Notes2018; 11(1): 417.
29.
KibretKTYalewAWBelainehBG, et al.Determinant factors associated with occurrence of tuberculosis among adult people living with HIV after antiretroviral treatment initiation in Addis Ababa, Ethiopia: a case control study. PLoS One2013; 8(5): e64488.
30.
MbithiAGichangiAKimAA, et al.Tuberculosis and HIV at the national level in Kenya: results from the second Kenya AIDS indicator survey. J Acquir Immune Defic Syndr. 2014; 66(Suppl 1): S106–S115.
31.
MitkuAADessieZGMulunehEK, et al.Prevalence and associated factors of TB/HIV co-infection among HIV Infected patients in Amhara region, Ethiopia. Afr Health Sci2016; 16(2): 588–595.
32.
PuthanakitTSaphonnVAnanworanichJ, et al.Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial. Lancet Infect Dis2012; 12(12): 933–941.
33.
MangiliAMurmanDHZampiniAM, et al.Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort. Clin Infect Dis2006; 42(6): 836–842.
34.
WankeCASilvaMKnoxTA, et al.Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis2000; 31(3): 803–805.
35.
MounzerKBrunetLHsuR, et al.Changes in body mass index associated with antiretroviral regimen switch among treatment-experienced, virologically suppressed people living with HIV in the United States. AIDS Res Hum Retrovir2021; 37(11): 852–861.
36.
CalzaLColangeliVBorderiM, et al.Weight gain in antiretroviral therapy-naive HIV-1-infected patients starting a regimen including an integrase strand transfer inhibitor or darunavir/ritonavir. Infection2020; 48(2): 213–221.
37.
AchappaBMadiDBhaskaranU, et al.Adherence to antiretroviral therapy among people living with HIV. N Am J Med Sci2013; 5(3): 220–223.
38.
PatersonDLSwindellsSMohrJ, et al.Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med2000; 133: 21–30.
39.
SinghMVSiddiquiSA. Impact mitigation of COVID-19 pandemic on pediatric HIV care. Indian J Pediatr2021; 88(7): 719.
