Short-term Risk of HIV Disease Progression and Death in Ugandan Children Not Eligible for Antiretroviral Therapy

Overview

Journal J Acquir Immune Defic Syndr

Specialty Infectious Diseases

Date 2010 Jul 2

PMID 20592617

Citations 5

Authors

Edwin D Charlebois

Theodore D Ruel

Anne F Gasasira

Jane Achan

Frederick Kateera

Caroline Akello

Huyen Cao

Grant Dorsey

Philip J Rosenthal

Isaac Ssewanyana

Moses R Kamya

Diane V Havlir

Affiliations

Soon will be listed here.

Abstract

Background: Increasing numbers of HIV-infected children not yet eligible for antiretroviral therapy (ART) are entering health care in Africa. We sought to characterize the risk of short-term disease progression in this population.

Methods: In a cohort of HIV-infected ART-naive and -ineligible Ugandan children older than 1 year, the rates of clinical/immunologic progression within 2 years were assessed using Kaplan-Meier survival analysis and multivariate Cox proportional-hazards modeling.

Results: Among 192 children (mean age: 6.4 years, CD4%:25), 19% progressed within 2 years by World Health Organization stage 3/4 event (n = 22), death (n = 3), or World Health Organization-defined CD4 threshold for ART initiation (n = 12). Significant univariate predictors were CD4% [hazard ratio (HR) = 2.0 per 10% decrease, P = 0.005], HIV RNA level (HR = 2.4 per log10 increase, P = 0.002), male gender (HR = 2.0, P = 0.04), age < 3 years (HR = 3.7, P = 0.001), CD4 activation (%CD4+ CD38+ HLADR+) (HR = 1.6 per 10% increase, P = 0.05), and CD8 activation (%CD8+ CD38+ HLADR+) (HR = 1.3 per 10% increase, P = 0.05] (HR = 1.3, P = 0.5). In multivariate analysis, CD4% (HR = 2.0, P = 0.034), HIV RNA level (HR = 1.8, P = 0.013), and age < 3 years (HR = 3.0, P = 0.008) were independently predictive. Children with HIV RNA >10 copies per milliliter and CD4% <25 had progression rates of 29% (1 year) and 34% (2 years).

Conclusions: Even with frequent CD4 monitoring, HIV-infected Ugandan children experienced significant clinical events while ineligible for ART per WHO 2006 guidelines.

Citing Articles

They are likely to be there: using a family-centered index testing approach to identify children living with HIV in Kenya.

Okoko N, Kulzer J, Ohe K, Mburu M, Muttai H, Abuogi L Int J STD AIDS. 2020; 31(11):1028-1033.

PMID: 32693739 PMC: 7530071. DOI: 10.1177/0956462420926344.

Factors Determining Survival and Retention among HIV-Infected Children and Adolescents in a Community Home-Based Care and a Facility-Based Family-Centred Approach in Kampala, Uganda: A Cohort Study.

Massavon W, Barlow-Mosha L, Mugenyi L, McFarland W, Gray G, Lundin R ISRN AIDS. 2014; 2014:852489.

PMID: 25006529 PMC: 4003865. DOI: 10.1155/2014/852489.

Beyond early infant diagnosis: case finding strategies for identification of HIV-infected infants and children.

Ahmed S, Kim M, Sugandhi N, Phelps B, Sabelli R, Diallo M AIDS. 2013; 27 Suppl 2:S235-45.

PMID: 24361633 PMC: 4122794. DOI: 10.1097/QAD.0000000000000099.

Paediatric HIV care in sub-Saharan Africa: clinical presentation and 2-year outcomes stratified by age group.

Ben-Farhat J, Gale M, Szumilin E, Balkan S, Poulet E, Pujades-Rodriguez M Trop Med Int Health. 2013; 18(9):1065-1074.

PMID: 23782065 PMC: 4285230. DOI: 10.1111/tmi.12142.

Risk factors for pre-treatment mortality among HIV-infected children in rural Zambia: a cohort study.

Sutcliffe C, van Dijk J, Munsanje B, Hamangaba F, Siniwymaanzi P, Thuma P PLoS One. 2012; 6(12):e29294.

PMID: 22216237 PMC: 3244458. DOI: 10.1371/journal.pone.0029294.

References

Ruel T, Ssewanyana I, Achan J, Gasasira A, Kamya M, Kekitiinwa A . Dynamics of T cell activation accompanying CD4 recovery in antiretroviral treated HIV-infected Ugandan children. Clin Immunol. 2009; 131(3):410-4. PMC: 3032795. DOI: 10.1016/j.clim.2009.01.016. View

Mocroft A, Bofill M, Lipman M, Medina E, Borthwick N, Timms A . CD8+,CD38+ lymphocyte percent: a useful immunological marker for monitoring HIV-1-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1997; 14(2):158-62. DOI: 10.1097/00042560-199702010-00009. View

Violari A, Cotton M, Gibb D, Babiker A, Steyn J, Madhi S . Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008; 359(21):2233-44. PMC: 2950021. DOI: 10.1056/NEJMoa0800971. View

Rizzardini G, Trabattoni D, Saresella M, Piconi S, Lukwiya M, Declich S . Immune activation in HIV-infected African individuals. Italian-Ugandan AIDS cooperation program. AIDS. 1999; 12(18):2387-96. DOI: 10.1097/00002030-199818000-00007. View

Liu Z, Hultin L, Cumberland W, Hultin P, Schmid I, Matud J . Elevated relative fluorescence intensity of CD38 antigen expression on CD8+ T cells is a marker of poor prognosis in HIV infection: results of 6 years of follow-up. Cytometry. 1996; 26(1):1-7. DOI: 10.1002/(SICI)1097-0320(19960315)26:1<1::AID-CYTO1>3.0.CO;2-L. View

Taha T, Graham S, Kumwenda N, Broadhead R, Hoover D, Markakis D . Morbidity among human immunodeficiency virus-1-infected and -uninfected African children. Pediatrics. 2000; 106(6):E77. DOI: 10.1542/peds.106.6.e77. View

Dunn D . Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis. Lancet. 2003; 362(9396):1605-11. DOI: 10.1016/s0140-6736(03)14793-9. View

. Markers for predicting mortality in untreated HIV-infected children in resource-limited settings: a meta-analysis. AIDS. 2007; 22(1):97-105. DOI: 10.1097/01.aids.0000302262.51286.a5. View

Ssewanyana I, Elrefaei M, Dorsey G, Ruel T, Jones N, Gasasira A . Profile of T cell immune responses in HIV-infected children from Uganda. J Infect Dis. 2007; 196(11):1667-70. DOI: 10.1086/522013. View

10.

Hunt P, Martin J, Sinclair E, Bredt B, Hagos E, Lampiris H . T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003; 187(10):1534-43. DOI: 10.1086/374786. View

11.

Taha T, Kumwenda N, Hoover D, Biggar R, Broadhead R, Cassol S . Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age. AIDS. 2000; 14(4):453-9. DOI: 10.1097/00002030-200003100-00021. View

12.

Palumbo P, Raskino C, Fiscus S, Pahwa S, Fowler M, Spector S . Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA. 1998; 279(10):756-61. DOI: 10.1001/jama.279.10.756. View

13.

Were W, Mermin J, Wamai N, Awor A, Bechange S, Moss S . Undiagnosed HIV infection and couple HIV discordance among household members of HIV-infected people receiving antiretroviral therapy in Uganda. J Acquir Immune Defic Syndr. 2006; 43(1):91-5. DOI: 10.1097/01.qai.0000225021.81384.28. View

14.

Rouet F, Sakarovitch C, Msellati P, Elenga N, Montcho C, Viho I . Pediatric viral human immunodeficiency virus type 1 RNA levels, timing of infection, and disease progression in African HIV-1-infected children. Pediatrics. 2003; 112(4):e289. DOI: 10.1542/peds.112.4.e289. View

15.

Resino S, Correa R, Bellon J, Munoz-Fernandez M . Preserved immune system in long-term asymptomatic vertically HIV-1 infected children. Clin Exp Immunol. 2003; 132(1):105-12. PMC: 1808687. DOI: 10.1046/j.1365-2249.2003.02116.x. View

16.

Mofenson L, Korelitz J, Meyer 3rd W, Bethel J, Rich K, Pahwa S . The relationship between serum human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 lymphocyte percent, and long-term mortality risk in HIV-1-infected children. National Institute of Child Health and Human Development Intravenous.... J Infect Dis. 1997; 175(5):1029-38. DOI: 10.1086/516441. View

17.

Abrams E . The unanswered question: when to initiate antiretroviral therapy in children with HIV infection. Curr Opin HIV AIDS. 2009; 2(5):416-25. DOI: 10.1097/COH.0b013e3282cef1ee. View

18.

Resino S, Seoane E, Gutierrez M, Leon J, Munoz-Fernandez M . CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2006; 42(3):269-76. DOI: 10.1097/01.qai.0000222287.90201.d7. View

19.

Giorgi J, Liu Z, Hultin L, Cumberland W, Hennessey K, Detels R . Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr (1988). 1993; 6(8):904-12. View

20.

Kamya M, Gasasira A, Achan J, Mebrahtu T, Ruel T, Kekitiinwa A . Effects of trimethoprim-sulfamethoxazole and insecticide-treated bednets on malaria among HIV-infected Ugandan children. AIDS. 2007; 21(15):2059-66. DOI: 10.1097/QAD.0b013e3282ef6da1. View