Transactions of the Royal Society of Tropical Medicine and Hygiene (2006) 100, 19—23

SOCIETY MEETING PAPER

Addressing the paediatric HIV epidemic:a perspective from the Western CapeRegion of South Africa�

Brian Eley ∗

Red Cross Children’s Hospital and the School of Child and Adolescent Health, University of Cape Town,Klipfontein Road, Rondebosch, 7701, South Africa

Received 6 January 2005; received in revised form 11 April 2005; accepted 12 April 2005A

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vailable online 9 September 2005

KEYWORDSHIV;Mother-to-child-transmission;Prevention;ART;HAART;Nevirapine;Zidovudine;South Africa

Abstract In the Western Cape province of South Africa, a prevention of mother-to-child-transmission (PMTCT) intervention programme, based on short-course nevi-rapine, achieved universal coverage in 2003. Despite this programme, an estimated1400—1650 HIV-infected children were born in the province in that year. These crudeestimates suggest that there are many children in the province who need medicalcare. Several strategies could collectively reduce the size of the paediatric epidemicand improve the outcome of HIV-infected children in the region, including intensi-fication of the existing PMTCT programme and provision of antiretroviral therapy(ART) for children with moderate or severe disease. Progress towards implementingthese interventions is discussed. Future challenges include understanding the factorsthat favour long-term survival of children on highly active antiretroviral therapy inresource-limited settings, identifying appropriate treatment for the metabolic com-plications of ART, and the provision of adolescent services for long-term survivors.Developments over the next few years will determine whether these challenges canbe met.© 2005 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd.All rights reserved.

� Based on a presentation to the Royal Society of Tropicaledicine and Hygiene Meeting at the Liverpool School of Tropicaledicine, Liverpool, 18 November 2004, entitled ‘Challenges inaediatric HIV Care in Resource Poor Countries’.∗ Tel.: +27 21 658 5111; fax: +27 21 689 1287.E-mail address: beley@ich.uct.ac.za.

1. Introduction

The National Department of Health’s annual sero-prevalence surveys conducted among pregnantwomen aged 15—49 years provide important infor-mation regarding the HIV epidemic in South Africa.These studies have been conducted since 1990. Themost recent survey, completed in October 2003,indicated that the national average HIV prevalence

035-9203/$ — see front matter © 2005 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.oi:10.1016/j.trstmh.2005.04.015

20 B. Eley

rate among pregnant women was 27.9% (95% CI26.8—28.9). The prevalence rate was highest inKwaZulu-Natal (37.5%, 95% CI 35.2—39.8) andlowest in the Western Cape province (13.1%, 95% CI8.5—17.7%). Assuming a mother-to-child transmis-sion (MTCT) rate of 30% in the absence of perinataltransmission interventions, approximately 96 000new paediatric infections occurred in South Africain 2003 alone (Department of Health, 2004).The Western Cape has a population of approxi-

mately 4.57 million people, of whom approximately70% live in the Cape Town Metropolitan Region(Statistics South Africa, 2004). An estimated 70 000pregnancies occur in the province per annum. Thus,in 2003 more than 9000 HIV-infected pregnancieswere managed in the province. The Western Capeis divided into 25 health districts. In 2003, the dis-trict HIV survey showed that the prevalence of HIVinfection among pregnant women ranged from 1.1%to 28.1%. The HIV prevalence in 7 of the 25 districtswas higher than the provincial average of 13.1%.Furthermore, the average HIV prevalence amongpregnant women in the urban health districts was14.7% and in rural health districts was 8.3% (N.Shaikh, personal communication).

an estimated 1400—1650 HIV-infected childrenwere born in the province. These crude estimatessuggest that there is a large number of HIV-infectedchildren in the province who need medical care,including antiretroviral therapy (ART). The numberof infected children in the province is probably inexcess of 4000.

2. Responding to the paediatricepidemic

Several strategies have been identified that couldcollectively reduce the size of the paediatric epi-demic and improve the quality of life and outcomeof children with HIV infection. Curtailment of het-erosexual transmission is an important aspect. From1990 onwards, Uganda reduced the size of its HIVepidemic from a peak prevalence in urban areas of31% to less than 5% as a consequence of implement-ing a range of successful measures, including strongpolitical leadership in advocating and supportingHIV/AIDS interventions (Buve et al., 2002; Okwareet al., 2001; Parkhurst and Lush, 2004). The recentantenatal surveys in South Africa showed that therieth

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In January 1999, the Western Cape ProvincialHealth Department implemented a pilot pre-vention of mother-to-child-transmission (PMTCT)programme in the Khayalitsha health district. Thisprogramme was based on the original Thailandshort-course zidovudine regimen. It demonstratedthat PMTCT interventions were acceptable andcould be implemented in a high-prevalence, peri-urban setting in South Africa (Abdullah et al., 2001;Shaffer et al., 1999). The intervention was shownto be effective in reducing MTCT. Consequently,in 2001 the Western Cape Department of Healthbegan implementing a province-wide PMTCTprogramme based on the HIVNET 012 nevirapineregimen and the provision of milk powder to allinfants of mothers who elected to formula-feedtheir offspring. Milk power was provided for thefirst 6 months of life (Guay et al., 1999). Thisprogramme achieved universal coverage in March2003.The PMTCT programme is predominantly admin-

istered at primary level, by community midwifeobstetric units (MOU) located in most health dis-tricts in the province. The MOUs are managed byprofessional nurses. Obstetric departments locatedat regional hospitals staffed by medical officers andspecialists provide the necessary consultation andreferral support for the care of pregnant women,including the PMTCT programme.In the year 2003, in the presence of a PMTCT pro-

gramme that was between 40% and 50% effective,

ate of increase of the HIV epidemic is slowing downn South Africa (Department of Health, 2004). How-ver, a similar comprehensive approach is requiredo reverse the heterosexual transmission rate andence the paediatric HIV burden in South Africa.A complete review of interventions that could

mprove the outcome of paediatric HIV infection iseyond the scope of this paper; instead, progress inmplementing selected interventions is discussed.

.1. Intensification of PMTCT

lthough the effectiveness of the initial PMTCTrogramme in the Western Cape has never beenomprehensively evaluated, a recent study fromauteng province reported an HIV MTCT rate of.9% at 3 months of age. The population studiedas similar to that managed in the public sectorn the Western Cape. The PMTCT programmen Gauteng is virtually identical to the initialrogramme introduced in the Western Cape in001, and includes the HIVNET 012 nevirapineegimen and provision of formula milk for the firstmonths of life as the main components of the pro-ramme. This study therefore demonstrated thatevirapine-based interventions can be effective inouth Africa (Sherman et al., 2004).Because the HIV prevalence rates are extremely

igh in sub-Saharan Africa, intensification of PMTCTrogrammes is essential to reduce the overall size

Addressing the paediatric HIV epidemic 21

of the paediatric HIV burden. Therefore, to improvethe effectiveness of the PMTCT programme, theWestern Cape Department of Health began imple-menting an intensified programme in mid 2004.The new programme is based on evaluating theCD4 count of all HIV-infected pregnant women will-ing to receive PMTCT interventions. Those womenwith a CD4 count ≤200 cells/�l will be treatedwith highly active antiretroviral therapy (HAART).Mother—infant pairs with a maternal CD4 count>200 cells/�l will be given a combination of zidovu-dine (from 36 weeks gestation until delivery in thepregnant women, and for 7 d from birth in the new-born infant) together with single-dose nevirapine(a single maternal dose at the onset of labour fol-lowed by a single dose to the newborn infant). Whenfully implemented, it is hoped that this strategy willreduce MTCT to less than 6% (Dabis et al., 2002).A recent publication showed that by commencingantenatal zidovudine at 28 weeks gestation, a com-bination of zidovudine and nevirapine could reduceHIV transmission to approximately 2% (Lallemantet al., 2004). This improved strategy is currentlybeing adopted by the Western Cape Department ofHealth.

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were receiving ART at 18 public health facilitiesin the Western Cape. These institutions comprise11 regional hospitals, including 4 in Cape Town,and 7 primary-level community ART clinics withinthe Cape Town Metropolitan Region with wellestablished referral links to regional hospitals.Approximately 75% of children were being treatedat three academic hospitals in Cape Town: Red CrossChildren’s Hospital, Groote Schuur Hospital andTygerberg Hospital. HIV-infected children live inboth urban and rural settings throughout the West-ern Cape, yet 89.4% of the children on treatmentwere being treated at 12 health facilities in thegreater Cape Town region (P. Bock, Western CapeDepartment of Health, personal communication).At Red Cross Children’s Hospital, a donor-funded

ART programme for public sector patients began inAugust 2002 (Eley et al., 2004a). The programme ismanaged by medical doctors and led by a specialistpaediatrician. Preliminary results based on an anal-ysis of the routine data of all children entered intothe programme showed that the children respondedwell during the first 48 weeks of HAART: growth,particularly the prevalence of children who wereunderweight-for-age, improved significantly, andt>aaaHimesc9irterds

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Intensification of PMTCT programmes presentsew challenges, including increased budgetaryressures, the need to retrain nursing and medi-al personnel, improving transport and laboratoryupport to ensure that CD4 counts are processedfficiently, overcoming the challenges of adminis-ering complex regimens to patients with limitedcholastic achievement, and improving the referralystems between obstetric clinics and ART clinicso ensure that enrolment of pregnant women withdvanced HIV infection on to HAART is completedn a timely manner. The HIVNET 012 regimen istrikingly simplistic and affordable. However, inten-ification is possible and necessary in regions infrica with relatively good health infrastructure.mproved PMTCT regimens will reduce the size ofhe paediatric HIV burden and may ultimately leado improved care for children with established HIVnfection.

.2. ART

he South African government approved therovision of ART in the public sector as part of aomprehensive strategy to combat HIV and AIDSn November 2003 (Tshabalala-Msimang, 2003).owever, through partnerships with various donors,IV-infected children managed within the publicector began receiving ART in the Western Caperom 2001 onwards (Medecins Sans Frontieres,002). At the end of December 2004, 1175 children

he proportion of children with a CD4 percentage20% increased from 12.3% at baseline to 41.7%t 48 weeks (P < 0.001). Of 47 children, 66% hadn undetectable viral load and a further 19% hadviral load <5000 copies/ml after 48 weeks ofAART. Adherence greater than 95% was achievedn 60—80% of children at each 4-weekly visit for theain antiretrovirals used in the programme (Eleyt al., 2004b). The children in this early analy-is originated from poverty-stricken communitiesharacterised by high unemployment. More than0% had advanced clinical disease and/or severemmunosuppression at enrolment. The children alleceived triple combination regimens comprisingwo nucleoside reverse transcriptase inhibitors plusither a protease inhibitor or a non-nucleosideeverse transcriptase inhibitor. These resultsemonstrated that it was possible to treat childrenuccessfully in an urban setting in South Africa.More recently, the initial programme has pro-

ided further clinical insights. Preliminary analysisf survival determined by the Kaplan—Meierethod showed an overall survival of approxi-ately 80% at 48 weeks. Survival of children withDC clinical category B disease at the start ofAART was significantly better than those withategory C disease (P = 0.001). Approximately 73%f children with category C disease survive to 48eeks, implying that HAART is beneficial in childrenith advanced disease in resource-limited settingsuch as South Africa. Serious medical complications

22 B. Eley

requiring hospitalisation during the first 6 months ofHAART occurred in 25.4% of children. The most fre-quent diagnoses were acute respiratory infections,diarrhoeal disease and septicaemia. The frequencyof hospitalisation during the early stages of HAART,particularly in children with advanced disease,implies that paediatric programmes in sub-SaharanAfrica will have to make provision for inpatient ser-vices to ensure that children on HAART are treatedcomprehensively (Eley et al., 2004a, 2004b).Analysis of other aspects of this programme,including factors influencing adherence and themanagement of HIV/tuberculosis co-infection, isongoing.

2.3. Paediatric HIV services

To improve the care of HIV-infected childrenthroughout the Western Cape, the provincial healthdepartment and the three academic paediatricinstitutions in Cape Town have recently initiated anoutreach programme whereby treatment capacitywill be developed at sentinel community clinicsand regional hospitals throughout the province toensure that all children with HIV infection have

the next few years will determine whether thehealth system is able to meet these challenges.

Conflicts of interest statementThe author has no conflicts of interest concerningthe work reported in this paper.

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3. Future challenges

There are many challenges that have to beovercome to ensure that all HIV-exposed and HIV-infected children in the Western Cape are givenopportunities to access improved care. Of priority isthe universal implementation of the interventionsdiscussed in this paper. Paediatric HIV infectionis an extension of a family illness. Therefore, thetreatment of children is probably best managed ina family setting led by a family practitioner. Familymodels of care need to be developed and evaluatedin South Africa to determine whether this will leadto improved care of HIV-infected children. Devel-oping the expertise to address adolescent-specificissues will strengthen current initiatives. Thereis a need to understand the long-term survival ofHIV-infected children treated with ART as well asthe factors that predict long-term survival in sub-Saharan Africa. Low-cost salvage regimens and viralresistance testing should be developed to ensurethat children can be managed beyond second-linetherapy. Furthermore, appropriate interventionsfor the treatment of the long-term complicationsof ART, including dyslipidaemias and lipodystro-phy syndrome, should be devised (Deeks, 2003;McComsey and Leonard, 2004). Developments over

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