Prevalence of anaemia in hiv infected children at the university of abuja teaching hospital, gwagwalada

ORIGINAL ARTICLE
Prevalence of Anaemia in HIV-Infected Children at the
University of Abuja Teaching Hospital, Gwagwalada
*Okechukwu A A FMC Paed *Gambo D MBBS **Okechukwu I O MPH, Adherence
*Department Of Paediatrics, **Paediatric Outpatient Special Treatment Clinic, University Of Abuja Teaching Hospital,Gwagwalada Abstract
Background:
Use of highly active antiretroviral All patients were started on co-trimoxazole therapy (HAART) has remained the only regimen prophylaxis with the exception of 6 (3.5%) patients potent enough to reduce viral replication in HIV- because of drug reaction. The mean PCV of infected individuals. Its combination with co- patients on ZDV containing combination with co- trimoxazole has also been recommended in those trimoxazole decreased from 30.2 ± 5.5% to 29.0 ± with CD4% of less than 15%. The use of HAART 2.3%, with a net decrease of 1.2% after one year containing zidovudine (ZDV) in combination with treatment, those on stavudine containing co-trimoxazole carries the risk of anaemia in combination with co-trimoxazole instead showed already anaemic predisposed individuals from HIV an increased from initial PCV of 28.3 ± 4.2% to 34.2 infections, opportunistic infections, parasitic ± 3.0% with a net increase of 5.9% after the same infestations, sickle cell anaemia, and malnutrition. duration of treatment, ( p>0.05). While patients The aim of the study is to document the effect of use on ZDV combination alone without co-trimoxazole of combination of HAART containing ZDV with co- prophylaxis had a minimal decrease of 0.9% in trimoxazole in haemoglobin profile of HIV-infected their PCV level after one year treatment, those on children after one year of its administration at the stavudine combination alone without any University of Abuja Teaching Hospital (UATH), prophylaxis instead showed an increase of 6.8% in Gwagwalada. It is also aimed at comparing the their PCV after the same duration of treatment. result obtained with those on stavudine containingHAART with co-trimoxazole. Conclusion: A combination of HAART containing
ZDV plus co-trimoxazole carries risk of anaemia
Method : A two year prospective study of HIV-
than that of stavudine containing combination infected children on treatment with HAART in with co-trimoxazole. Such combination should combination with co-trimoxazole, and attending therefore not be given to anaemic patients. the paediatric outpatient special treatment clinic Regular check in PCV of patients on HAART (POSTC) for HIV infected children at the UATH, combination with ZDV and additional co- trimoxazole prophylaxis is required for early 2008, was carried out to determine effect of these detection of significant drop in PCV level. drug combinations in the haemoglobin profile ofinfected children. Three monthly PCV level was Key words: Highly active antiretroviral therapy,
carried out using haematocrit centrifuge and zidovudine, stavudine, co-trimoxazole, anaemia. Date Accepted for publication: 10th October
Results: A total of 173 patients were started on
2010
HAART during the first year recruitment period, 90 Nig J Med 2010; 50-57
(52.0%) were males, while 83 (48.0%) females, Copyright 2010 Nigerian Journal of Medicine
giving a male to female ratio of 1.1:1. One hundredand seventeen (67.7%) of patients were on ZDVcontaining HAART, while 56 (32.3%) were onstavudine containing combination. Correspondence to Dr Adline A Ok
echukwu P M B 228, FCT – Abuja
Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010 Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada:Okechukwu A A Gambo
echukwu I O
Introduction
HIV infected children are saddled with problem of Anaemia is a common condition in HIV infected opportunistic infections for which co-trimoxazole children and contributes significantly to its ( c o m b i n a t i o n o f t r i m e t h o p r i m a n d determined to a large extent to the prevailing prophylaxis. The trimethoprim component of co- conditions that cause anaemia in the environment trimoxazole is an anti-foliate metabolite that like malaria, sickle cell anaemia, helminthiasis, inhibits the enzymic reduction of folate to folinic malnutrition and micro-nutrient deficiencies.4-6 acid via the dihydro-reductase pathway. This The basic pathology in the anaemia of HIV infection inhibitory process eventually leads to loss of p u r i n e a n d h e n c e p o o r s y n t h e s i s o f inflammatory cytokines during the chronic disease deoxyribonucleic acid (DNA) in the human cell, process which not only inhibits erythropoiesis by with subsequent megaloblastic changes in the blunting the erythropoietin response, but also marrow and manifestation of megaloblastic reduces the red blood cell survival via the haemo- phagocytic mechanism as well as preventing therelease of iron from the reticuloedothelial system.2- This singular effect is expected to worsen the anaemia of patients on ZDV. Thus HIV infected Despite the survival benefits of antiretroviral drugs children in this environment and on treatment (ARD) in patients living with HIV, the clinical with HAART containing ZDV plus co-trimoxazole, management of the disease presents a major are saddled with problems of anaemia from challenge for both clinicians and patients.7-11 nutritional causes, micro-nutrient deficiencies, Treatment of HIV infection with ARD is aimed at preventing progression of the disease to AIDS and i n fe c t i o n s / i n fe s t a t i o n s , b o n e m a r r o w death by reducing the plasma HIV ribonucleic acid suppressive effect of ZDV, as well as anti-folate activity of co-trimoxazole. The aim of the present eradication of HIV from an individual is not study is to document the prevalence of anaemia considered possible with the a single ARD, 10 and in HIV/AIDS in children on treatment with HAART.
people undergoing treatment for HIV disease must It is also aimed at determining the effect of take a daily regimen of at least three ARD HAART containing ZDV plus co-trimoxazole on combinations otherwise known as highly active haemoglobin profile of infected children, and comparing the result with those on HAARTcontaining stavudine (whose major side effect is HAART is the only regimen potent enough to drastically reduce viral replication, prevent theemergence of resistance, restore immune status, slows HIV disease progression, has durable The prospective study was conducted at the therapeutic responses, improve quality of life and paediatric outpatient special treatment clinic promotes normal growth and development in (POSTC) for HIV/AIDS children at the UATH, children.11-13 Zidovudine or stavudine is commonly paired with lamivudine or abacavir as the November 2006 to October 2008. The subjects nucleoside components of HAART regimen.6,10,13 were paediatric HIV/AIDS patients on HAART with Zidovudine is well known for its bone marrow or without co-trimoxazole. Patients were aged between two months to 15 years and positive for related to marrow reserve, dosage of the drug, HIV infection either by serology method or by duration of treatment and the stage of HIV deoxyribonucleic acid (DNA) polymerase chain disease.6,10,13 Anaemia is one of the major bone reaction (PCR) test. For children 18 months of age marrow suppressive effect of ZDV and is commonly and above, the sera were screened for the seen 4 to 6 weeks of its commencement.10,13 presence of HIV-I or 2 using commercially Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010 Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada:Okechukwu A A Gambo
echukwu I O
available recombinant antigen based double rapid The study was carried out after approval from the test (STATPAK by Chembio-Diagnostic System Inc, ethics committee of the hospital, and informed New York, and DETERMINE by Abbot laboratories Japan), with sensitivity and specificity of 100%. For those less than 18 months of age diagnosis was explanation on the implication of the study, in the based on use of DNA PCR test. DNA PCR test amplifies and detects the HIV pro-viral DNA Paediatric patients who met the World Health sequences within the mono-nuclear cells in the Organization (WHO)/ National guideline for blood, and is 100% sensitive after 4 to 6 weeks of HAART were started on the drugs. They includepatients greater than 3 years whose CD4 cell Blood for PCV was collected for all patients by the percentage were less than 15%, those between 1- 3 years with CD4 percentage of less than 20%, recruitment, and subsequently at a three monthly intervals for the one year follow up period. Samples were collected at the dorsum of the right or left All infected infants, older children with hand with 5 ml syringe after wiping the area with 2% symptomatic HIV disease or an AIDS defining alcohol spirit swab. The collected sample was illness or those with CD4 of less than 20% for age centrifuged using a haematocrit centrifuge 1-3years, or less than 15% for older children were (Hawksley micro-haematocrit centrifuge, made in all started on co-trimoxazole prophylaxis.6,10,13 On England by Hawksley & sons Limited) at 2,000 recruitment of patients which lasted for one year, rovers per minute for 5 minutes. The PCV value was clinical, immunological and haematological read with haematocrit reader (Hawksley micro- assessments were carried out. This included general physical examination, anthropometricmeasurements (body weight, recumbent length Information collected at recruitment includes age o r h e i g h t a n d h e a d c i r c u m f e r e n c e ) , of the patient, sex and body weight. CD4 cell count immunological assessment (CD4 cell count and and its percentage, WHO clinical staging of the its percentages), haematological profile (full patients and their intial PCV level were also blood count and differential, packed cell volume), collected at recruitment. First line HAART regimens and blood chemistry (liver function test, used for the patients were combinations of ZDV or urea/creatinine, and lipid profile).
stavudine plus lamivudine and nevirapine (NVP) orefevarenz (EFZ) depending on whether the patient For the purpose of the study, the patients were was receiving anti-tuberculous therapy. Those on anti-tuberculous medication with rifampicin were nucleoside reverse transcriptase inhibitors given EFV instead of NVP when age is greater than 3 years or weight >10kg. When age is less than 3 years results at recruitment, as well as use or non- use or weight <10kg, NVP was replaced with abacavir.
of co-trimoxazole prophylaxis. The summary of Second line HAART regimen used were combination of ZDV or stavudine, plus lamivudine and lopinavir/ *Group 1 - HAART (ZDV) patients without co-
trimoxazole.
*Group 11 - HAART (ZDV) with co-trimoxazole.
University of Abuja Teaching Hospital is a 350 bed *Group 111 - HAART (stavudine) patients without
capacity referral centre sub serving FCT and neighbouring states like Nassarawa, Kogi, Benue, *Group 1V – HAART (stavudine) with co-
Niger, and parts of Kaduna. It is one of the centers in the country that offers free medical services to Patients were assigned to ZDV or stavudine group HIV/AIDS patients courtesy of United State Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010 Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada:Okechukwu A A Gambo
echukwu I O
When PCV was found to be greater than 30%, There was also statistical significant difference patients were assigned to ZDV group, but when less between mean PCV of stage 2 and stage 3 disease than 30% they will be assigned to stavudine group.
(35.0% Vs 32.3%, p = 0.034). It was also noted that 30% PCV level was chosen because this is the level 18/56 (32.1%) of patients in stage 4, 12/83 that signifies moderate anaemia.23 Patients with (14.5%) in stage 3, 2/34 (5.9%) in stage 2 moderate to severe anaemia were not assigned to presented with PCV of less than 21% signifying ZDV group because of possibility of ZDV worsening severe anaemia. There is a positive correlation the anaemia from its bone marrow suppressive between the level of PCV and the degree of effect.6,13 They were instead assigned to stavudine immune suppression ( r=0.48, p=0.06).
group. Because all infants were expected to be on Table 111 shows the changes in PCV level during co-trimoxazole prophylaxis irrespective of CD4 cell one year treatment with different regimen of count and its percentage, they were not assigned to HAART. While there was a net increase in PCV of groups 1 & 111. Data entry and analysis was carried 6.8% from a baseline value of 28.3% to 35.1% out using SPSS programme version 7.5 that after one year treatment for those on stavudine provided frequency distribution, means, standard deviations, and correlation coefficient.
patients on ZDV containing combination withoutco-trimoxazole prophylaxis had a slight decrease in PCV value from 30.5% to 29.6%, (0.9%). The A total of 173 patients were stared on HAART sample size of the two groups were however too during the one year recruitment period, 90 (52.0%) small for any meaningful statistical comparism (4 were males and 83 (48.0%) females giving a male to female ratio of 1.1:1. One hundred and sixty seven(167) of 173 recruited patients (96.5%) were on co- trimoxazole prophylaxis, while 6 (3.5%) were not HAART plus co-trimoxazole, and ZDV containing because of drug reaction, and alternative drug HAART with co-trimoxazole, that of ZDV group (dapsone) was used instead. Significant number of with co-trimoxazole showed a non significant recruited patients 117 (67.6%) were also on ZDV decrease in PCV value from 30.2±5.5 to 29.0±2.3, combination as against 56 (32.3%) on stavudine (p< (1.2% decrease), p>0.05, after one year 0.05). Of the 117 patients on ZDV, 113 (96.6%) were treatment, while that of stavudine with co- also on additional co-trimoxazole prophylaxis, 4 trimoxazole instead showed a significant increase (3.4%) were not, and of the 56 patients on from 28.3±4.2 to 34.2±3.0, (5.9% increase), p< stavudine, 54 (96.4%) were on co-trimoxazole, 0.01. In summary, while there was a net decrease in PCV value of 1.2% in ZDV group with co-trimoxazole, stavudine combination with co- The mean age of the patients at recruitment was trimoxazole showed an increase of 5.9%, p< 0.05 4.1 ± 1.2 years, while there mean CD4 cell count, It is also obvious from the data that while patients CD4 percentage and WHO clinical staging were 216.9 ± 104.2cells/ml, 11.7%, and stages 3 respectively, all signifying advanced immune decrease in their PCV (0.9%) after one year of suppression at recruitment, (table I). Table II shows treatment, those in the same regimen with WHO clinical staging and PCV values of recruited additional co-trimoxazole prophylaxis instead patients.A total of 56/173 (32.4%) of the patients showed a decrease in their PCV (1.2%), after the were at WHO stage 4, 83/173 (48.0%) in stage 3, same duration of treatment. In the same vain, the 34/173 (19.7%) in stage 2 disease, and none in increase in PCV for patients on stavudine asymptomatic stage 1. When compared to stage 2 containing HAART alone without co-trimoxazole patients, there is a statistical significant difference was higher (6.8%), while those on stavudine between their mean PCV and that of stage 4 containing regimen with co-trimoxazole had an disease (35.0% Vs 20.7%, p = 0.002).
Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010 Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada:Okechukwu A A Gambo
echukwu I O
Six patients died in the first year recruitment phase, with a mortality of 4.6%. At the end of the study, two of which was from severe pneumonia, two 150 patients (86.7%) were alive and on first line from severe jaundice with positive antibody to anti retroviral treatment, 3 (1.7%) were alive and hepatitis B surface antigen, one from HIV on second line drugs, 10 (5.7%) were lost to follow encephalopathy, and the remaining one from up, while 2 (1.2%) discontinued ARD, as a result of severe anaemia with septicemia. An additional two adherence failure following several serious patients died during the second year from severe malaria and meningitis, making a total of 8 patients, Table I : Characteristics of Recruited Patients
Variables
Total (%)
Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010 Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada:Okechukwu A A Gambo
echukwu I O
Table II: World Health Organization Clinical Staging and Packed Cell Volume of Recruited
Infants at Recruitment.
WHO clinical
Mean PCV (%)
Percentage with
Mean Age (Years)
severe anaemia
PCV < 21%
Table III: Packed Cell Volume Changes during One Year Treatment on HAART.
Drug Regimen
PCV at one
recruitment
HAART – Highly Active Antiretroviral Therapy Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010 Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada:Okechukwu A A Gambo
echukwu I O
Discussion
In addition to the adduced reasons highlighted previously as the causes of high prevalence of infection in children.1-4,14 This is evident in this study anaemia in HIV infected individuals, which where 129/173 ( 74.6%) of the patients seen worsen as the disease progresses, the parvovirus presented with mild to moderate anaemia, (PCV of B19 induce chronic anaemia in HIV infected may less than 30%), 32/173 (18.5%) with features of also be an additional factor.19-21 HIV infected severe anaemia, (PCV of less than 21%), and 12/173 individual with severe immune suppression lacks (6.9%) with no features of anaemia. The findings the ability to mount antibody against the were similar with reports from Jos (73.7%) 16 and structural proteins of B19 parvovirus, a well South Africa (72.0%).5 The high prevalence of anaemia seen in HIV infected children in the present and other studies is to a large extent notonly due to both direct and indirect effect of HIV Zidovdine, stavudine and lamivudine are the infection on erythropioesis, but also as a result nucleotide reverse transcriptase inhibitors excessive destruction, erythropoietic factor (NRTIs) component of HAART used in this study.
deficiencies, and other co-existing disease They act by incorporating themselves into the conditions as highlighted in the introductory part of DNA of HIV virus formed, thus stopping the this article. The incidence of anaemia in HIV disease building process and formation of the new is dependent on the severity of HIV disease as well and major side effect of ZDV, suppression beingrelated to the marrow reserve, dosage of the In a survey by the Centre for Disease Control (CDC) drug, duration of treatment and stage of HIV in the United State of America (USA),4 among 3,200 disease. Stavudine is noted for its peripheral adolescents and adults with HIV infection and on neuropathy from mitochondrial toxicity.
treatment with the ARD, the prevalence of Marrow suppression or anaemia is not its major moderate anaemia with Hb of <10g/dL was found to be 31.6% in patients with CD4 cell count of<200cells/ml, and 4.5% in those with cells of Trimethoprim and sulphametoxazole, are the >200cells/ml. The same study showed prevalence two drug combinations in co-trimoxazole used as of mild to moderate anaemia of Hb of 10-14g/dL to prophylaxis against most opportunistic infections be present in 31.3% of patients with AIDS and in HIV infected individuals. Both drugs act at two 26.6% in those without AIDS.4 The present study levels in the biosynthesis of tetra-hydrofolic acid, noted severe anaemia of PCV of < 21% to be a precursor in the synthesis of folic acid and present in 32.1% of WHO stage 4 disease of severe purine. While sulphametoxazole inhibits the immune suppression, and 5.9% in those in stage 2 incorporation of para-amino benzoic acid (PABA) of mild to moderate immune suppression.
into folic acid, trimethoprim blocks the reductionof dihydrofolic acid to tetra-hydrofolic acid.14,15 All This findings appears similar with CDC survey this processes are needed in the synthesis of folic among adolescents and adults population,4 but acid and purine. Failure of purine and folic acid appeared much lower than the report from South synthesis results in megaloblastic changes in the African5 were severe anaemia of PCV of <21% was bone marrow. At the end of one year treatment, found to be present in 92%, and 76% of patients children on HAART containing stavudine had a with severe and moderate immune suppression. All these findings highlights not only the significant combination, even though the latter started off relationship between immunological status of HIV patients and their Hb level, but also the adverse effects of HIV infection on the haematopoietic trimoxazole prophylaxis: thus depicting the probable bone marrow suppressive effect of ZDV, Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010 Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada:Okechukwu A A Gambo
echukwu I O
as well as the anti-folate activities of co- that of stavudine containing HAART with co- trimoxazole which resulted in a slight drop in PCV trimoxazole. Such combinations may not be very value when ZDV plus co-trimoxazole combination.
advisable in anaemia patients. . Regular check inPCV of patients on HAART, especially those Conclusion
A combination of HAART containing ZDV plus co- trimoxazole prophylaxis is required for early trimoxazole carries a greater risk of anaemia than detection of significant drop in PCV level.
References
Hilgartner M . Haematological manifestations in 12.Montaner JS, Hogg R, Raboud J, Harrigan R,
HIV infected children. J Pediatr 1991, 119; 547 – O'Shaughnessy M. Antiretroviral Treatmentin 1998. Lancet 1998; 352: 1919 – 22.
Coyle TE ; Haematologic complications of human 13.Bartlett JG, Gallant JE.
management of HIV infection. Pg 313 – 328.
www.hopkins – aid .edu/mmhiv/order.hmail.
Allen UD, King S M, Gomez M P, Lapointe N, 14.Mc Vie JC. Antimicrobial Drugs: In Girdwood R.H
F o r b e s J C . S e r u m i m m u n e r e a c t i v e eds. Clinical Pharmacology 24th ed. A Bailliére erythropoietin levels and associated factors Tinda,l an affiliation of Macmillan Co. Inc, New amongst HIV – infected children. AIDS 1998, 12 : 15.Emdex. Based on WHO Model Formulary. The
Sullivan PS, Hanson DL, Chu SY, Jones JL, Ward JM.
complete drug formulary for Nigerian health Epidemiology of anaemia in HIV infected person: professionals with guide to drug administration.
results from the multistate adult and adolescent Lindoz Book Int'l, Mississauga, Canada. 2007 Pg spectrum of HIV disease surveillance project.
16.Angyo IA. Okpe ES, Onah J. Paediatric AIDS in Jos ,
Eley RS, Sire AA, Shuttleworth M, Hussey GD. A Nigeria. West African J Med 1998;17:268-72.
prospective cross – sectional study of anaemia 17.Odunukwe NN, Idigbe EO, Onwujekwe DI, Ezechi
and peripheral iron status in antiretroviral naïve HIV – infected children in Cape Town, South anaemia in HIV – 1 infected individuals accessing medicare at Nigerian Institute of medical Tindyebwa D, Kayita J, Eley B, Nduatti R, Coovadia conference on AIDS and STI'S in Africa, Abuja, H. In handbook on Paediatric AIDS in Africa by the African Network for the care of children affected 18. onald T, Mitsuyasa MD. The importance of
treating anaemia in HIV disease. Medscape Antiretroviral therapy for HIV infection 1996.
19.Van Eslacker-Niela AM, Kroon FP, Van der Enda
Recommendation of an international panel.
ME, Salimaris MM, Spaan WJ, Kroes AC.
Prevalence of parvovirus B19 infection in Chun TW, Fauci AS. Latent reservoirs of HIV : patients infected with HIV. Clin Infect Dis 1996: Obstacles to the eradication of virus. Proc Nati Acad Sci USA 1996, 96 : 10958 – 61.
20.Arista S, De Grazia S, Romano A, Miraglia PM,
Ickovics JR, Maede CS. Adherence to HAART Carlo P. Paediatric HIV infection revealed by among patients with HIV : breaking through and parvovirus B-19 induced anaemia. Ital J Peadiatr barriers. AIDS care 2002; 14: 309 –18.
10. Federal Ministry of Health Nigeria. National
21.Brown KE, Young NS. Parovirus B-19 infection
guidelines for paediatric HIV and AIDS, 2007.
and haemopoesis. Blood Rev 1995; 9:17-23.
11. Egger M, May M, Chene G. Prognosis of
HIV–infected patients starting highly activeantiretroviral therapy: A collaboration analysis ofprospective studies. Lancet 2002 : 360 ; 119 – 29.
Nigerian Journal of Medicine, Vol. 19, No. 1, January- March 2010

Source: http://nigerianjournalofmedicine.com/files/journals/1/articles/9/submission/review/9-28-1-RV.pdf