Pediatr Blood Cancer 2010;54:657–658

HIGHLIGHTby Alan Davidson, FCPaed, MPhil*

Kaposi Sarcoma: The African HIV Epidemic’s Partner in Crime(Commentary on Gantt et al., page 670)

A bout 370,000 children younger than 15 years became

infected with HIV in 2007, bringing the number living with

HIV worldwide to about 2 million [1]. Almost 90% live in sub-

Saharan Africa. While advances in prevention and treatment have

stabilized HIV prevalences in Europe and North America, less than

one quarter of HIV-infected people in sub-Saharan Africa who

need antiretroviral therapy (ART) are receiving it, and only about

6% of those on treatment are children [2]. This has led to a

dramatic increase in Kaposi Sarcoma (KS) in the region.

AIDS-related Non-Hodgkin’s Lymphoma (ARL) and KS are the

most common AIDS-defining malignancies. KS is the result of

uncontrolled expression of human herpesvirus-8 (HHV8) in

endothelial cells usually secondary to immunosuppression. Although

KS was already endemic in parts of sub-Saharan Africa, where the

seroprevalence of HHV8 in the population often exceeds 50% [3], the

incidence has risen dramatically in the wake of the HIV epidemic.

Data from Malawi [4], Uganda [5] and South Africa [6,7] suggest a

modest increase in Burkitt lymphoma compared to a 10-fold or more

increase in KS, making KS one of the commonest childhood cancers

in the region today. This is in sharp contrast to the United States where

the incidence of KS among adults has declined by a factor of 7 [8], and

where few pediatric cases are reported [9].

The article by Gantt et al. in this issue of Pediatric Blood &

Cancer describes KS in a cohort of HIV-positive Ugandan children,

focusing attention on the HIV virus’ partner in crime, human

herpesvirus-8. The authors documented the clinical presentation

and response to treatment in 73 children who presented to the

Uganda Cancer Institute in Kampala between 2004 and 2007. The

median age (based on data from 56 cases) was 10.1 years, and the

commonest sites (based on data from 42 cases) were nodal (60%)

and cutaneous (48%) with few KS presenting in the oral cavity

(21%) or viscera (12%). With CD4 values available for 35 cases

(48%), the median count (210 cells/ml) and percent (7.4%) were

both suppressed. Eight patients had recently been started on ART

but there was no difference between these patients and those who

were ART-naı̈ve in terms of CD4 values. Patients with lymphade-

nopathic KS had higher absolute CD4 values than those without

lymphadenopathy. They were also noted to be 3.7 years younger on

univariate analysis, but this trend was negated by multivariate

logistic regression analysis, based on the fact that the natural

decline in CD4 counts that occurs with age is more pronounced

among HIV-infected children.

Thirty-six children were documented to have received chemo-

therapy (vincristine and/or bleomycin), 41 children received ART

and 26 from each group were treated with both. Of the 32 patients,

where outcome data was available, 62.5% had a complete response

(CR). When comparing children receiving chemotherapy to those

who did not, there was no difference in the proportion achieving CR.

There was, however, a higher proportion of CRs in the group who

received ART compared to the group who were treated without

ART.

Despite the limitations imposed by an incomplete dataset, the

authors make a few valuable observations in terms of the clinical

presentation of HIV-associated KS. The relative rarity of cutaneous

and oral lesions has been confirmed in Malawi [4] but the

relationship between site and CD4 values reported in this study

raises an interesting possibility. The authors suggest that lympha-

denopathic disease may be the result of recent HHV8 infection with

a rapid progression to malignancy, since the virus is tropic for lymph

nodes during seroconversion. HHV8 transmission is not fully

understood, but is believed to be mainly horizontal through saliva

and semen rather than vertical. Malope et al. [10] showed that

while children of HHV8-seropositive mothers are at risk for HHV8

infection, seroprevalence of children was half that of their mothers,

supporting the notion that seroprevalence increases with age. It may

simply be the timing of the HHV8 infection that determines clinical

presentation. While some children may be infected with HHV8

prior to HIV infection, which is the case in most adults where

immunological control of HHV8 is lost as immunosuppression

worsens, many will be infected subsequent to vertical transmission

of HIV with a consequent inability to control the virus ab initio.

These are two related, but separate, epidemics. While HHV8-

positive mothers and children are more likely to be HIV-positive,

maternal HIV-seropositivity does not, in itself, confer a risk of

HHV8 infection on the children [10]. There is no evidence that the

HIVepidemic has changed the epidemiology of HHV8 [3] but it has

certainly changed the incidence of KS.

Clearly, KS can have a favorable outcome notwithstanding lack

of access to drugs such as liposomal doxorubicin. In the absence of

disseminated disease, a critical airway or a life-threatening

haemorrhage, there is an option to start ART and defer chemo-

therapy until the response to immune reconstitution can be assessed.

Data from South Africa [7] suggest that most patients will

eventually require chemotherapy to achieve CR, but this study

supports ART monotherapy as a viable first-line strategy in

resource-limited settings.

� 2010 Wiley-Liss, Inc.DOI 10.1002/pbc.22412Published online 11 January 2010 in Wiley InterScience(www.interscience.wiley.com)

——————Haematology/Oncology Service, Department of Child and Adolescent

Health, Red Cross Children’s Hospital, University of Cape Town, Cape

Town, South Africa

*Correspondence to: Dr. Alan Davidson, Haematology/Oncology

Service, Department of Child and Adolescent Health, Red Cross

Children’s Hospital, University of Cape Town, Cape Town, South

Africa. E-mail: alan.davidson@uct.ac.za

Received 30 November 2009; Accepted 30 November 2009

The degree to which antiviral agents specific for HHV8 might

play a role in prevention and treatment of KS is being explored.

Ganciclovir used to treat cytomegalovirus disease in patients with

AIDS decreases the risk of KS but does not achieve the responses in

established disease that have been observed in multicentric

Castlemen’s disease, which is an HHV8-associated lymphoproli-

ferative disorder [11]. This is probably because most cells are

latently infected and do not support lytic replication. Valproate may

be able to induce lytic replication rendering KS amenable to

antiviral therapy [11].

As Gantt et al. suggest much remains to be done. Improved

access to ART will decrease this preventable malignancy, while

prospective trials need to be initiated to study appropriate

therapeutic combinations. We have promises to keep, and miles to

go before we sleep.

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Pediatr Blood Cancer DOI 10.1002/pbc

658 Davidson