S474 • JID 2007:196 (Suppl 3) • Meyers et al.
S U P P L E M E N T A R T I C L E
CSE Global Theme Issue on Poverty and Human Development
Challenges to Pediatric HIV Care and Treatment
in South Africa
Tammy Meyers,1,2Harry Moultrie,1,2Kimesh Naidoo,4Mark Cotton,5Brian Eley,6and Gayle Sherman2,3
1Harriet Shezi Children’s Clinic, Chris Hani Baragwanath Hospital,2Wits Paediatric HIV Clinics, University of the Witwatersrand, and3Department
of Molecular Medicine and Haematology, National Health Laboratory Service, Johannesburg,4Department of Health KwaZulu-Natal, King Edward
VIII Hospital, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban,5Department of Paediatrics and Child Health, Children’s
Infectious Diseases Research Unit, Tygerberg Children’s Hospital and Stellenbosch University, Stellenbosch, and6Red Cross Children’s Hospital
and the School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa
It is estimated that almost 300,000 children in South Africa have human immunodeficiency virus(HIV)infection.
The disease is responsible for reversing decreases in child mortality. Few data exist evaluating the outcomes of
the prevention of mother-to-child transmission of HIV (PMTCT) program, although PMTCT coverage appears
to be low. Hospitals are still witnessing large numbers of admissions of HIV-infected children. Postnatal trans-
mission of HIV is high, reflecting poor education of and support for women in their infant feeding choices. Too
few infants and children are entering care through early diagnosis, which should be widely available. Cotri-
moxazole prophylaxis coverage is inadequate, contributing to high morbidity and mortality in infants. The
number of children receiving antiretroviral therapy (ART) is increasing steadily. However, significantinequalities
in access to ART exist between and within provinces. Challenges for pediatric ART include a lack of sufficiently
trained health care personnel and inadequate facilities, as well as the complexity of drug regimens and formu-
lations. The compartmentalization of the ART rollout program hindersPMTCT and makesitdifficultforchildren
to be identified and referred into appropriate services. This article delineates the challenges to pediatric HIV
care in South Africa and provides some practical recommendations to improve it.
In 2004, 29.5% (95% confidence interval [CI], 28.5%–
30.5%) of women attending public antenatal facilities
in South Africa were HIV positive . There are, un-
fortunately, no reliable data on the national coverage
and efficacy of the prevention of mother-to-childtrans-
mission of HIV (PMTCT) program, which makes the
incidence of HIV infection in children difficult to
Potential conflicts of interest: none reported.
Presented in part: The Realities of ART Roll-Out: Overcoming Challenges to
Successful Implementation, Durban, South Africa, October 2006.
Financial support: Elizabeth Glaser Pediatric AIDS Foundation, the President’s
Emergency Plan for AIDS Relief, and the United Nations Children’s Fund (support
to T.M., H.M., and G.S.). Supplement sponsorship is detailed in the Ac-
Reprints or correspondence: Dr. Tammy Meyers, Harriet Shezi Clinic, Dept. of
Paediatrics, Chris Hani Baragwanath Hospital, PO Bertsham 2013, Johannesburg,
South Africa (firstname.lastname@example.org).
The Journal of Infectious Diseases
? 2007 by the Infectious Diseases Society of America. All rights reserved.
The Actuarial Society of South Africa AIDS and De-
mographic Model (ASSA2003), which provides the
most plausible estimates of the prevalence of HIV in-
fection among children in South Africa, estimates that
there were 275,000 HIV-infected children in mid-2005,
increasing to 293,000 in mid-2006 .aThe estimated
numbers of HIV-infected children in each province
range from !3000 in the Northern Cape to nearly
100,000 in KwaZulu-Natal (figure 1).
The proportion of these HIV-infected children re-
quiring antiretroviral therapy (ART) is unknown. Pro-
gression to AIDS is more rapid in children than adults,
and it is likely that a large proportion of HIV-infected
children are urgently in need of access to ART.
The under-5 mortality rate and the infant mortality
aFigures are rounded to nearest 1000 to avoid spurious accuracy. If the PMTCT
uptake rates for all population groups in the ASSA2003 model are decreased to
60% of pregnant women tested and 90% of these receiving nevirapine,ASSA2003
generates estimates of 287,000 infected in July 2005 and 309,000 in mid-2006.
Because of the change in assumptions, the figures in this footnote do not represent
the views of the Actuarial Society of South Africa.
Pediatric HIV Treatment • JID 2007:196 (Suppl 3) • S475
South Africa, by province, mid-2006. Data are from Actuarial Society of
South Africa AIDS and Demographic Model (ASSA2003) .
Estimated nos. of HIV-infected children !15 years of age in
years of age in South Africa, 1997–2004.
Increase in nos. of reported deaths of children !15
Year Reported deaths
Increase from 1997 to 2004
are from Statistics South Africa .
Data are no. of reported deaths, unless otherwise indicated, and
rate in South Africa decreased from 1975 to 1994 [3, 4]. Data
from the 1998 South African Demographic and Health Survey
are that mortality rates among infants and among children !5
years of age are continuing to rise [4–6]. Reported deaths
among children !15 years of age increased by 72.9% between
1997 and 2004 (table 1) . Much of the increase in mortality
is attributable to HIV/AIDS, although registration of deathshas
improved during this period.
It is impossible to discuss care for HIV-infected children in
South Africa without focusing on PMTCT, because pediatric
HIV infection is a preventable condition [8, 9]. In 2002, South
Africa set a goal to reduce the proportion of infants infected
with HIV by 20% by 2005 . There is no reliableinformation
to assess whether this has been achieved.
The uptake of voluntary counseling and testing (VCT) at
antenatal services is reportedly low, with !50% of women at-
tending PMTCT sites being tested nationally (PMTCT Task
Team, Concerned Child Health Workers, unpublished report).
Current approaches to VCT adhere to “opt-in” principles, al-
though opt-out strategies appear to dramatically increase up-
take of testing .
Pregnant women have a higher risk of acquiring HIV infec-
tion than do nonpregnant women . The risk of transmis-
sion to infants is increased in women with high viral loads,
particularly in those with acute primary HIV infection .
There is concern that women who experience seroconversion
during pregnancy may miss the opportunity for PMTCT if they
are not retested late in pregnancy.
HIV transmission to infants occurs through breastfeeding,
although exclusive breastfeeding for the first few months of life
is associated with lowertransmissionratesthanismixedfeeding
[14, 15]. Replacement feeding is available as an option for
infants up to 6 months of age through the national PMTCT
program. As a result of inadequate counseling, support, and
education of women, late transmission of HIV to children
through mixed feeding is reversing some of the effects of an-
tiretroviral intervention .
Single-dose nevirapine given to mothers and babies has been
the standard of PMTCT care in South Africa since 2003. Al-
though simple and cost-effective, its efficacy is, at best, 50%
. Reports indicate that nevirapine coverage for HIV-in-
fected pregnant women is no more than 30% (PMTCT Task
Team, Concerned Child Health Workers, unpublished report).
In some urban facilities, where more women choose to for-
mula feed, perinatal HIV transmission rates with single-dose
nevirapine have been reported to be∼9% [18,19].Theaddition
of zidovudine to single-dose nevirapine reduces the transmis-
sion rate to !2% for formula-fed infants [20–22]. The World
Health Organization, in updated guidelines, recommends and
advocates that countries consider implementing combination
therapy when feasible . The Western Capehasimplemented
DIAGNOSIS OF HIV INFECTION IN INFANTS
Early identification of HIV-infected children is vital for their
entry into comprehensive care and for evaluation of theefficacy
of PMTCT programs. HIV DNA polymerase chain reaction
(PCR) testing was introduced in 2004 for early diagnosis of
HIV infection in infants from 6 weeks of age [24, 25]. Thirty
percent of the ∼1 million infants born in South Africa annually
are estimated to be HIV exposed, requiring a laboratory ca-
pacity to perform 300,000 PCR tests per annum. In June 2006,
∼6750 PCR tests were performed nationally at 6 sites, equalling
27% of the total capacity required for that month. The National
Health Laboratory Service is scaling up the number of HIV
DNA PCR laboratories nationally, to improve equity and
S476 • JID 2007:196 (Suppl 3) • Meyers et al.
roviral therapy (ART), by province, in mid-2006 (public sector).
Breakdown of nos. of children !14 years of age receiving antiret-
receiving ART, no.
Children receiving ART,
no. (% of total patients
receiving ART) Date
Data are from the Department of Health, South Africa .
The clinical capacity needed to perform HIV DNA PCR
testing on infants at health care services, particularly outside
of the major cities, is limited. Facilities are poorly staffed, and
individuals with the skills required for pediatric venipuncture
are scarce. Dried blood spots from heel pricks are easier to
obtain than liquid blood, and health care workers are already
trained to do this for other indications. HIV DNA PCR tests
performed on dried blood spots and liquid blood samples have
comparable accuracy, although it is more labor intensive to
process dried blood spots in the laboratory [26–28]. Efforts are
under way to massively scale up the use of dried blood spots
nationally to improve the accessibility of diagnosis in the field.
Many older HIV-infected children have yet to be identified.
The clinical features of HIV infection in children are too non-
specific to enable health care workers to reliably diagnose HIV
infection on clinical grounds alone . Opportunities fortest-
ing for and diagnosing HIV infection in children attending
immunization programs, TB services, or in- and outpatient
pediatric services, as well as in children of adults attendingVCT
services, are being missed. Only 63% of children admitted to
Kalafong, a regional hospital in Gauteng, were tested for HIV
infection . In a nationwide report on in-hospital pediatric
mortality, there was no confirmatory HIV infection diagnosis
in 22% of deaths reported as being HIV/AIDS related .
PROPHYLAXIS AGAINST OPPORTUNISTIC
Cotrimoxazole (CTZ) prophylaxis for preventing Pneumocystis
jirovecii pneumonia and other commonly acquired infections
reduces mortality among HIV-infected children by as much as
43% . P. jirovecii pneumonia has a peak incidence in early
infancy with a very high associated mortality . South Africa
follows World Health Organization guidelines in recommend-
ing CTZ prophylaxis from 4 to 6 weeks of age for all HIV-
exposed infants, continuing in those with a definitive diagnosis
of HIV infection until such time as a favorable CD4 cell re-
sponse to ART is demonstrated .
In 2001, only a third of clinics in South Africa reported
routine administration of CTZ to HIV-exposed children, and
the majority of those providing CTZ were administering in-
appropriate doses . Although good CTZ coverage has been
reported in the Cape Town area, there are few data from else-
where. Anecdotal reports indicate that CTZ coverage is still
inadequate in other places.
Highly active ART (HAART) has become increasingly available
since the implementation of the South African Comprehensive
HIV and AIDS Care, Management and Treatment Plan in 2004.
During the first year, very few children were accessing ART.
The number of children receiving ART has, however, increased
from !3000 in February 2005  to 121,000 by September
2006 . The total number of children receiving treatment
through private projects outside of the public health system is
unknown, although it is anticipated to be low.
Despite the scaling up of ART access for children, marked
inequities persist. The National Department of Health has
called on provincial HIV/AIDS, sexually transmitted infection,
and tuberculosis (HAST) directorates to ensure that at least
15% of all patients receiving ART are children. Most provinces
have not yet achieved this target (table 2). Furthermore, there
is considerable variability in access to pediatric ART between
districts within the same province. For example, although
KwaZulu-Natal has successfully increased the proportion of
patients receiving ART who are children from !5% in Novem-
ber 2004  to 110% in early 2006, the absolute numbers
and percentages of children receiving ART across health dis-
tricts vary considerably (table 3).
Pediatric HIV Treatment • JID 2007:196 (Suppl 3) • S477
district in KwaZulu-Natal, March 2006.
Children !14 years of age receiving antiretroviral therapy (ART), by
ART facilities, no.
Children receiving ART,
no. (% of total patients
Data are from the KwaZulu-Natal Department of Health.
gently need antiretroviral therapy (ART) and are receiving it, by province,
2006. Data are compiled from mid-2006 estimates extracted from Ac-
tuarial Society of South Africa AIDS and Demographic Model(ASSA2003)
 and table 3, under the assumption that 40% of HIV-infected children
Estimated percentages of children in South Africa who ur-
The provinces with the lowest estimated numbers of HIV-
infected children, particularly the Western Cape and Northern
Cape, are faring much better in meeting the demand for pe-
diatric ART. Figure 2 depicts the differences in proportions of
children accessing ART by province, under the assumptionthat
at least 40% of children require ART. Although the percentage
of coverage for each province is roughly calculated, it is clear
that there are very large inequities among provinces. For ex-
ample, a child with advanced disease in the Western Cape has
an ∼14-fold higher chance of receiving ART than does a child
Most HIV-infected children in Gauteng are receiving care at
tertiary care facilities (figure 3). The scale up of ART at primary
care and secondarycarefacilitiesinGautenghasbeenhampered
by limited human resources and inadequate pediatric clinical
skills. Many facilities lack physicians, and primary health care
nurses have not been trained to manage patients receivingART.
At Chris Hani Baragwanath Hospital in Soweto, primaryhealth
care nurses have been adequately trained and are successfully
initiating ART in children and managing children receiving
ART under the supervision of physicians.
The Western Cape has made progress with the decentrali-
zation of pediatric ART. As evidence of this, the proportion of
children receiving ART at the 3 academic hospitals has declined
from 78.4% to 38% between March 2004 and September 2006
(B. Eley, University of Cape Town, personal communication,
No national data on the outcomes of children receiving ART
in South Africa are available. In countries with adequate re-
sources, ART has allowed children to have healthy and pro-
ductive lives well into adolescence and early adulthood [38,
39]. Programs in countries with fewer resources have also doc-
umented good outcomes for children receiving ART—for in-
stance, in the Ivory Coast, a 2-year survival rate of 98% was
reported among children with a CD4 cell percentage of ?5%.
. Although some South African ART facilities have pub-
lished data demonstrating the early benefits of ART in children
enrolled in the program [41–44], routine data on adherence,
retention, viral load suppression, clinical status, mortality, and
adverse effects are required to assess the impact of the program.
CHALLENGES OF SCALING UP PEDIATRIC ART
The integration of ART with primary health care services has
been very limited, with vertical programs independently man-
aging PMTCT, immunization, integrated managementofchild-
S478 • JID 2007:196 (Suppl 3) • Meyers et al.
by health facility level, in Gauteng, South Africa. Data were provided by
the Gauteng Department of Health. CHC, community health center; hosp,
hood illnesses, tuberculosis, diagnosis of HIV infection in in-
fants, wellness, and ART services. The functionalandfrequently
structural separation of these servicesfromeachotherprecludes
continuity of care for children and results in high leakage rates
between the component services and in numerous missed op-
portunities. Furthermore, ART services for adults and children
are frequently separated by clinic day or even location, with
few family-based clinic services.
Human-resource challenges include (1) shortages of staff
comfortable managing general medical problems in children
; (2) the isolation of medical staff, frequently with only 1
physician appointed to each site, which results in poor staff
morale and logistical difficulties, because training staff off-site
leads to service interruptions; (3) the lack of a nationally stan-
dardized training program in pediatric ART; and (4) the fact
that there is little on-site mentorship of physicians and nurses.
The lack of capacity in the healthsystemtoprovidetreatment
to all those who need it could be contributing to the indirect
rationing of treatment to certain groups, such as those who are
better informed, live closer to treatment sites, have time to wait
in queues every month, or have a higher socioeconomic status
[46, 47]. The concentration of children receiving ART in ter-
tiary/regional facilities results in inappropriate utilization of
highly skilled staff to manage well children. These experienced
staff will increasingly be needed to attend to more complicated
cases related to adverse reactions and treatment failure as the
provision of ART matures.
In addition, provision of ART to HIV-infected children is
more complex than provision to adults, because
CD4 cell percentage, rather than the absolute CD4 cell
count, is used in children, and the cutoff for initiating
therapy differs according to the age of the child;
drug doses need to be regularly reviewed to keep up with
no guidance is provided in the South African guidelines
for infants !6 months of age, because few formulations
have been studied in this age group, and, because mor-
tality is so high, these young infants deserve special
even for older children, fewer formulations exist than for
adults, and palatability is generally poor; and
elderly caregivers often have practical difficulties in dis-
pensing medication—for example, drawing up solutions
requires good vision and basic arithmetic skills.
Recommendations to improve PMTCT.
sures are recommended to improve PMTCT ( and PMTCT
Task Team, Concerned Child Health Workers, unpublished re-
Incorporation of VCT into family-planning activitiesand
incorporation of family planning into VCT services
Implementation of an opt-out approach to VCT at an-
Implementation of repeated testing for HIV-negative
pregnant women in the third trimester
Implementation of routine testing for infants presenting
to immunization clinics at 6 weeks of age (the potential
for negative impact on routine immunization uptake ex-
ists and should be evaluated)
Training of all nursing staff who interact with pregnant
women or mothers of young infants to provide infor-
mation on PMTCT, infant feeding choices, CTZ pro-
phylaxis, and infant diagnosis and treatment
Improvement of counselor training, with regular review
and monitoring of messages provided by counselors
Immediate CD4 cell count determination for allpregnant
women testing HIV positive, to assess whether ART is
indicated (point-of-service CD4 cell count machines
should be introduced at PMTCT sites)
Provision of ART to pregnant women with CD4 cell
counts !200 cells/mm3, as a matter of urgency, with sys-
tems put in place to expedite this intervention
Inclusion of zidovudine with nevirapine for PMTCT, in
accordance with World Health Organization recommen-
Provision of nutritional support for women who decide
to breastfeed for the first 6 months
Sentinel surveillance at health care facilities and population-
based prevalence surveys that include children !2 years of age
are required from all provinces to monitor and evaluate the
coverage and impact of the PMTCT program and the rollout
of ART, because routinely collected data are currently inade-
quate. Improving the tracking and follow-up of infants at and
between primary health care facilities is necessary to obtain
better routine data of the coverage and impact of the PMTCT
Recommendations for the scaling up of pediatric diagnosis.
At the clinical level, a diagnostic service has to be commenced.
This will require the following:
Identification of facilities where pediatric diagnosis can
be performed (e.g., PMTCT programs, immunization
clinics, TB clinics, and inpatient facilities)
The following mea-
Pediatric HIV Treatment • JID 2007:196 (Suppl 3) • S479
Provision of appropriate staffing at these facilities (e.g.,
phlebotomists, counselors, and laboratory staff)
Training of staff in blood sampling, laboratory logistics,
record keeping, and tracking and interpretation of test
Procurement and distribution of consumables to enable
dry blood spot testing
Laboratory space for new instruments
Research and development to increase laboratory capac-
ity—for example, automation with careful qualitycontrol
Validation of algorithms that utilize rapid HIV tests is re-
quired to improve diagnosis. Key indicators must be docu-
mented to assess service, and monthly HIV DNA PCR test
statistics should be made available. A system for feedback from
clinics for central monitoring of, for instance, service issues
and quality control should be established.
Recommendations to scale up and improve pediatric ART
resources between provinces and districts require that local so-
lutions tailored to local conditions be found. District-level
health provider networks with community representation
should be formed to coordinate services and test strategies to
improve the functional integration of services. Appointing staff
employed for the ART rollout program to a district-based clus-
ter could provide staff flexibility, facilitate outreach training
and support from the larger ART sites, and improve com-
This district strategy needs to be tested.
In addition, the following is recommended:
Clear targets for treating children with ART should be
set at provincial and district levels. These targets should
be calculated according to the number of children who
need ART rather than as a percentage of the total number
of adults and children receiving ART.
Primary health care nurses should become the key per-
sonnel to manage and prescribe treatment for patients
receiving ART whose conditions are stable. Pharmacist
assistants should likewise be utilized.
Family-oriented services should be established at all ART
facilities, with at least 1 day/week being assigned for
Theoretical training for nursing and medical students
lines for children.
Outreach from sites with experience in treating children
to inexperienced sites should be encouraged, to provide
An expert advisory team should be appointed by the
Department of Health to regularly update guidelines. A
strategy for dissemination of updated guidelines needs to
A standardized patient management tool to support both
the care of patients and the reporting of indicators needs
to be developed and piloted. Ideally, the system needs to
support the tracking of patients across the vertical pro-
grams (VCT, PMTCT, infant diagnosis, and ART) and
Program managers need to be trained to use available
data to improve the efficiency and effectiveness of their
The following has been recommended (Pharmacology Task
Team, Concerned Child Health Workers, unpublished report)
to address some of the concerns regarding pharmacological
challenges with pediatric treatment:
Stavudine 15 mg is not widely procured for the ART
rollout program; although higher-strength capsules are
available, the 15-mg strength of stavudine formulation is
very helpful for pediatric use, and we recommend that
it become readily available at all sites.
The Medicines Control Council should fast-track thereg-
istration of pediatric (i.e., chewable or dispersible) fixed-
dose drug combinations.
Even distribution of the active ingredient within adult
formulations and scoring tablets to facilitate use in older
children should be ensured.
The thermostability and palatability of pediatricsolutions
should be improved.
The color coding of individual antiretroviral agents
should be standardized country-wide.
Attention needs to be paid to the care of infants !6
months of age; infants should be monitored at least
monthly for clinical deterioration and should have ART
commenced as soon as there is any indication to do so.
District Child Care Forums, involving the health sector,
social welfare, businesses, nongovernmental organiza-
tions, and community-based organizations, need to be
strengthened; a registry of highly vulnerable children
should be kept in each district to coordinate support.
Adolescent-friendly clinic services should be made avail-
able in every district; adolescent-focused training mate-
rials, such as those developed by the NationalAdolescent-
Friendly Clinic Initiative, need to be updated to include
information on ART and disseminated.
Psychosocial issues for children need to be considered,
and, where possible, a multidisciplinary approach should
be implemented to deal with these issues—for example,
disclosure of HIV infection status.
The implementation of the PMTCT program and the Com-
prehensive HIV and AIDS Care, Management and Treatment
Plan has made some progress toward alleviating the burden of
S480 • JID 2007:196 (Suppl 3) • Meyers et al.
the pediatric HIV epidemic in South Africa. However, both the
technical content and the implementation of these programs
need to be strengthened if South Africa is to succeed in achiev-
ing the Millennium Development Goals. In the absence of
good-quality monitoring and evaluation demonstratingtheim-
pact on the pediatric epidemic, there is little to guide the pro-
gram. It is essential that a focus on the plight of children be
maintained, so that their needs not be subsumed to the over-
whelmingly large adult program. Equity of care must be ad-
dressed urgently, so that all children in the country may benefit
equally from services that they deserve and to which they have
plement entitled “The Realities of Antiretroviral Therapy Rollout: Chal-
lenges to Successful ProgrammaticImplementation,”sponsoredbytheHar-
vard Medical School Division of AIDS, the Harvard University Center for
AIDS Research, and the Harvard Initiative for Global Health.
This article was published as part of a sup-
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