Agaba

Beatrice Mwagomba

Dalitso Misinde

Di Lorenzo

Jones

Kathryn Chu

Krown

Makombe

Meditz

Mills

Moses Massaquoi

Murdaca

Nasti

Nathan Ford

Olesi Pasulani

Rony Zachariah

Schopper

Zachariah

English

Chu, Kathryn

Misinde, Dalitso

Massaquoi, Moses

Pasulani, Olesi

Mwagomba, Beatrice

Ford, Nathan

Zachariah, Rony

MSF Field Research

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http://www.elsevier.com/copyrightAuthor's personal copy
International Health 2 (2010) 99–102
Contents lists available at ScienceDirect
International Health
journal homepage: http://www.elsevier.com/locate/inhe
Risk factors for mortality in AIDS-associated Kaposi sarcoma in a
primary care antiretroviral treatment program in Malawi
Kathryn Chua,b,∗, Dalitso Misindec, Moses Massaquoic, Olesi Pasulanic,
Beatrice Mwagombad, Nathan Forda, Rony Zachariahe
a Médecins Sans Frontières, 49 Jorissen St, Braamfontein 2017, Johannesburg, South Africa
b Department of International Health, Johns Hopkins M, Baltimore, MD, USA
c Médecins Sans Frontières, Thyolo, Malawi
d Ministry of Health, Thyolo, Malawi
e Médecins Sans Frontières, Medical Department, (Operational Research Unit), Brussels, Belgium
article info
Article history:
Received 19 November 2009
Received in revised form 25 February 2010
Accepted 7 April 2010
Keywords:
AIDS
Kaposi sarcoma
mortality
risk factors
Africa
abstract
AIDS-associated Kaposi sarcoma (AIDS-KS) is the most common HIV-related malignancy.
The majority of cases are found in sub-Saharan Africa. This retrospective cohort study
describes characteristics of patients with AIDS-KS and factors associated with mortality
in an antiretroviral treatment (ART) program in rural Malawi. Of 11 122 patients enrolled
onART,830(7%)hadAIDS-KS.PatientswithAIDS-KSweremorelikelytobelosttofollow-up
(22% versus 14%, P<0.001) and showed a higher mortality (22% versus 10%, P<0.001) com-
pared to patients without AIDS-KS. A CD4 count ≤150 cells/l, advanced stage AIDS-KS,
and absence of bleomycin chemotherapy were associated with increased mortality. Ear-
lier diagnosis and improved treatment of AIDS-KS are urgently needed in order to reduce
mortality.
© 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All
rights reserved.
1. Introduction
AIDS-associated Kaposi sarcoma (AIDS-KS) is the most
commonHIV-relatedmalignancy.Themajorityofcasesare
found in sub-Saharan Africa, where the disease is associ-
atedwithincreasedmortality.1,2 However,thereisadearth
of published information on risk factors associated with
mortality among AIDS-KS patients.
In the developed world, treatment with highly active
antiretroviral therapy (HAART) has led to a sharp decline
in the incidence of AIDS-KS3 and to increased survival.4
HAART can result in regression and even complete remis-
∗ Corresponding author at: Unit 23B, No 14, Waverly Business Park,
Wyecroft Road, Mowbray 7700, Cape Town, South Africa.
Tel.: +27 79 895 2489; fax: +27 21 448 3128.
E-mail address: kathryn.chu@joburg.msf.org (K. Chu).
sion of KS lesions.5 Unfortunately HAART is still not widely
availableinthedevelopingworldwhereAIDS-KSmortality
remains high.2 Moreover, in many settings KS is a visible
and potentially stigmatising sign of AIDS that is known
to the community. In this respect, KS-related mortality
may undermine public health objectives by supporting the
notion that, despite substantial advances, AIDS is still a
death sentence.
Data from resource-rich settings suggest that adju-
vant systemic chemotherapy can improve outcomes in
advanced cases, and newer chemotherapeutic agents such
as liposomal anthracyclines and taxanes have improved
efﬁcacy and tolerability compared to older drugs such
as bleomycin, doxorubicin, vincristine, vinblastine, or
adriamycin.6 Unfortunately, these medications are rarely
available in sub-Saharan Africa, mainly because of their
high cost.
1876-3413/$ – see front matter © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.inhe.2010.04.001Author's personal copy
100 K. Chu et al. / International Health 2 (2010) 99–102
Inthisretrospectivestudywedescribecharacteristicsof
patientswithAIDS-KSandriskfactorsassociatedwithmor-
tality within a routine HIV/AIDS care program in Thyolo,
rural Malawi.
2. Methods
ThyoloDistrictHospitalinsouthernMalawihasacatch-
ment area of about 500 000 people. HIV-positive patients
are managed by Medecins Sans Frontieres (MSF) and the
Ministry of Health as described before.7 All patients start-
ingHAARTfromthebeginningoftheprograminApril2003
to June 2009 were included in this study.
Initial KS stage was determined using the AIDS Clin-
ical Trials Group staging system which classiﬁes tumor
(T), immune (I), and systemic illness (S) into good and
poor risk. Immune status was subsequently dropped fol-
lowing a study that found it not to be a good predictor
of outcome.8 T0 disease was deﬁned as <10 cutaneous
lesions and one or fewer oral lesions and T1 disease as
>10 cutaneous lesions and/or extensive oral or visceral
disease. S0 disease was deﬁned as no history of oppor-
tunistic infections, no B symptoms (unexplained night
sweats or fever), and a Karnofsky score >70%. S1 disease
was deﬁned as history of opportunistic infection, B symp-
toms, or a Karnofsky score <70%. Patients with T1S1 were
considered to have advanced disease. In 2004, bleomycin
became available in Malawi for treatment of AIDS-KS
patients with T1 disease and this was provided per pro-
tocol (15mg intramuscular injections every two weeks for
10 cycles, then for an additional 10 cycles if there was no
improvement).
Information on baseline characteristics, ART, mortality,
loss-to-follow-up (LTFU), AIDS-KS diagnosis, KS staging,
and chemotherapy were extracted from an electronic
database maintained for routine monitoring and evalua-
tion.Baselinecharacteristicsweredescribedusingmedians
and interquartile ranges (IQRs) for continuous variables
and counts and percentages for categorical data. Patient
time to loss to follow up was calculated from date of
HAART initiation. Outcomes were censored on 1 July 2009.
Differences between groups were compared using the 2
test for categorical variables and the Student t-test for
continuous variables. Cox proportional hazards were used
to identify risk factors for mortality in AIDS-KS patients.
Kaplan-Meier analysis was used to estimate cumulative
survival for patients with and without AIDS-KS. Variables
considered in the analysis included age, gender, baseline
CD4 count (less or greater than 150 cells/ul), KS stage, and
use of bleomycin chemotherapy. Factors with a P <0.1 on
univariate analysis were included in a multivariate model.
Alltestsandconﬁdenceintervalswereconsideredtobesig-
niﬁcant at a P ≤ 0.05. All statistical analysis was performed
using STATA 10 (College Station, TX, USA).
2.1. Ethics
The study received ethical approval from the Ethics
Review Board, Médecins Sans Frontières, Geneva,
Switzerland.9
3. Results
Of 11 122 patients enrolled on ART during the study
period, 830 (7%) had AIDS-KS. Baseline characteristics for
patients with and without AIDS-KS are shown in Table 1.
The median follow-up for AIDS-KS patients was 397 days
(IQR,118-868) compared to 569 days (IQR,169-1043) for
non-AIDS-KS patients (P<0.001). A greater proportion of
AIDS-KS patients were deceased (19%, n=161) and lost to
follow-up(16%,n=136)atoneyearcomparedtonon-AIDS-
KS patients (8%, n=855, P<0.001 and 9%, n=904, P<0.001
respectively). Of deaths and LTFU in the ﬁrst year, 56%
occurred in the ﬁrst three months. Cumulative survival of
patients with and without AIDS-KS is shown in Figure 1.
Of those with AIDS-KS, 396 (47%) had advanced (T1S1)
disease and 636 (77%) received bleomycin chemother-
apy. A CD4 count ≤150 cells/l (adjusted HR (AHR)=1.3,
P=0.053), advanced stage KS (AHR=1.8, P=0.002) and lack
of treatment with bleomycin chemotherapy (AHR=2.0,
P=0.001) were associated with increased mortality
(Table 2).
4. Discussion
We report on a large series of AIDS-KS patients from a
primary care HAART program in Malawi. Overall, the pro-
portion of patients with AIDS-KS that died or were lost
to follow up was signiﬁcantly higher than those without
AIDS-KS. It can be expected that the higher lost to fol-
low up is associated with higher mortality, as a tracing
study from Malawi demonstrated that 50% patients LTFU
in HAART programs had died, most (58%) within the ﬁrst
three months.10 In sub-Saharan Africa, despite the intro-
Table 1
Characteristics of patients with and without Kaposi sarcoma on antiretroviral therapy in Thyolo, Malawi.
KS non-KS
n=830 n=10292 P value*
Males 485 (58) 3884 (38) 0.001
Age on starting ART, years 33 (28–39) 33 (27–40) 0.696
Median baseline CD4+ count, cell/l 136 (56–243) 147 (70–248) <0.001
Median follow-up time, days 397 (118–868) 569 (169–1043) <0.001
Deaths 182 (22) 1028 (10) <0.001
Lost to follow-up 185 (22) 1427 (14) <0.001
KS: Kaposi sarcoma. ART: antiretroviral therapy.
Continous variables are given as medians (interquartile range). Ordinal and discrete variables are given as n (%).
* 2 for categorical variables and Wilson rank-sum test for continous variables.Author's personal copy
K. Chu et al. / International Health 2 (2010) 99–102 101
Figure 1. Cumulative survival in patients with and without AIDS-KS.
CumulativesurvivalinpatientswithAIDS-KSislowerthatthosewithoutAIDS-KS.Thenumberatriskateachtimepointisdisplayedwiththecorresponding
number of deaths.
duction of HAART, AIDS-KS remains associated with higher
mortality.2 Contributing factors likely include late diagno-
sisofKSdisease,lateaccesstoHAART,andpooravailability
of chemotherapy. Earlier HIV diagnosis and HAART initia-
tion,andimprovedretentionincare,especiallyforpatients
with AIDS-KS, are needed.
Nearly half of the AIDS-KS patients in our study pre-
sented with advanced stage KS (T1S1), with corresponding
high mortality. Other studies have also demonstrated that
patients with advanced KS have a poorer prognosis.11
Lower baseline CD4 was also associated with increased
mortality, again pointing to the need for earlier enrolment
into HIV care and therefore earlier diagnosis of KS. If AIDS-
KS can be detected early in the community and patients
come forward for HIV testing and care, the prognosis is
likely to improve. The earliest signs of KS which can be
easily diagnosed by patients, family relatives or commu-
nity volunteers include violet discolouration or plaques in
the oral cavity or skin. Individuals could be screened for
such a condition at the community level and immediately
referred to health facilities for appropriate care as has been
suggested recently.12 Increasing awareness through spe-
ciﬁcinformationandeducationcampaignsfocusedonearly
recognitionofKSatcommunitylevelwouldalsobehelpful.
Our HAART program enrolled more women which
reﬂects the general trend that uptake of HIV services
by men is poor.13 However, men were more likely to
have AIDS-KS than women which is consistent with other
studies14 probably in part because men tend to be diag-
nosed and treated for HIV at a later stage when prevalence
of opportunistic infections is higher. There is a need to
increase uptake of services in this vulnerable population.
Table 2
Associations with mortality in AIDS-KS patients.
Deaths/Total % Unadjusted Adjusted
HR 95% CI P HR 95% CI P
Gender
Female 77/345 (22) 1.00
Male 175/797 (21) 0.98 (0.73–1.31) 0.876
Age
≤18 years 6/33 (18) 1.00
>18 years 175/797 (22) 0.99 (0.98–1.01) 0.600
Baseline CD4 count
>150 cells/l 86/457 (19) 1.0
≤150 cells/l 95/373 (25) 1.4 (1.0–1.9) 0.029 1.3 (0.99–1.8) 0.053
KS Stage
Unstaged 48/147 (33)
T0S0 6/54 (11) 1.0
T0S1 6/42 (14) 1.4 (0.5–4.4) 0.548
T1S0 21/191 (11) 1.0 (0.4–2.5) 0.999
T1S1 100/396 (25) 2.4 (1.1–5.6) 0.034 1.8 (1.2–2.5) 0.002
Bleomycin Chemotherapy
Yes 132/636 (21) 1.0
No 49/194 (25) 1.4 (1.0–2.0) 0.032 2.0 (1.4–3.1) 0.001
KS: Kaposi sarcoma. HR: Hazards Ratio.Author's personal copy
102 K. Chu et al. / International Health 2 (2010) 99–102
Chemotherapy has been demonstrated to improve out-
comes for patients with advanced AIDS-KS. Liposomal
drugs, the backbone of treatment of advanced AIDS-KS
in Western settings, are not readily available in sub-
SaharanAfrica.Inourcohort,monotherapywithbleomycin
decreased mortality by half suggesting that although this
regimen is old, it can still be effective. However, mortal-
ity was still high. Currently, studies on efﬁcacy and safety
are underway comparing older regimens to newer taxane-
based therapies in sub-Saharan Africa. Improving access to
more effective adjuvant chemotherapy that can be admin-
istered safely in resource poor settings is a priority for
reducing KS mortality.
Ourstudyhadseverallimitations.PatientswithKSwere
identiﬁed through an electronic database used for routine
monitoring and evaluation. Using this methodology, we
may have underestimated the number of cases, especially
those with early or small lesions. The relatively high lost
to follow up and the known high mortality among patients
who are lost to care suggest that our mortality estimate
is likely to be underestimated. A considerable proportion
of patients were also not staged. In addition, the effects of
bleomycin therapy and HAART on the change in KS lesions
werenotanalyzed.Furtherstudiesareneededtodetermine
the efﬁcacy and safety of currently available therapies on
KS disease progression.
Nevertheless, in one of the largest case series of AIDS-
KS patients reported in the literature to date, we ﬁnd that
patients tend to present with advanced KS disease and
face high mortality despite starting HAART and receiving
bleomycin. This points to an urgent need for early diag-
nosis of HIV, KS and improved treatment of AIDS-KS in an
effort to reduce mortality.
Authors’ contributions
KC was responsible for the overall design, analysis, and
writing of the paper. DM, OP, and MM contributed to
the data analysis and interpretation. NF, RZ, and BM con-
tributed to the design of the study and drafting of the
manuscript. All authors were involved in critically review-
ingthemanuscriptforitsintellectualcontentandapproved
the ﬁnal version. KC is guarantor of the paper
Funding: None.
Conﬂicts of interest: None declared.
Ethical approval: The study received ethical approval
from the Ethics Review Board, Médecins Sans Frontières,
Geneva, Switzerland.
References
1. Agaba PA, Sule HM, Ojoh RO, Hassan Z, Apena L, Mu’azu MA, et al.
Presentation and survival of patients with AIDS-related Kaposi’s sar-
coma in Jos, Nigeria. Int J STD AIDS 2009;20:410–3.
2. Makombe SD, Harries AD, Yu JK, Hochgesang M, Mhango E, Weigel
R, et al. Outcomes of patients with Kaposi’s sarcoma who start
antiretroviral therapy under routine programme conditions in
Malawi. Trop Doct 2008;38:5–7.
3. Jones JL, Hanson DL, Dworkin MS, Jaffe HW. Incidence and trends in
Kaposi’ssarcomaintheeraofeffectiveantiretroviraltherapy.JAcquir
Immune Deﬁc Syndr 2000;24:270–4.
4. Tam HK, Zhang ZF, Jacobson LP, Margolick JB, Chmiel JS, Rinaldo C,
et al. Effect of highly active antiretroviral therapy on survival among
HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma.
Int J Cancer 2002;98:916–22.
5. Murdaca G, Campelli A, Setti M, Indiveri F, Puppo F. Complete
remission of AIDS/Kaposi’s sarcoma after treatment with a com-
bination of two nucleoside reverse transcriptase inhibitors and
one non-nucleoside reverse transcriptase inhibitor. Aids 2002;16:
304–5.
6. Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, Di Trolio R, De
Placido S, Dezube BJ. Management of AIDS-related Kaposi’s sarcoma.
Lancet Oncol 2007;8:167–76.
7. Zachariah R, Fitzgerald M, Massaquoi M, Pasulani O, Arnould L,
Makombe S, et al. Risk factors for high early mortality in patients
on antiretroviral treatment in a rural district of Malawi. Aids
2006;20:2355–60.
8. Nasti G, Talamini R, Antinori A, Martellotta F, Jacchetti G, Chiodo F, et
al. AIDS-related Kaposi’s sarcoma: evaluation of potential new prog-
nosticfactorsandassessmentoftheAIDSClinicalTrialGroupStaging
System in the Haart Era–the Italian Cooperative Group on AIDS and
TumorsandtheItalianCohortofPatientsNaiveFromAntiretrovirals.
J Clin Oncol 2003;21:2876–82.
9. Schopper D, Upshur R, Matthys F, Singh JA, Bandewar SS, Ahmad A,
van Dongen E. Research ethics review in humanitarian contexts: the
experience of the independent ethics review board of Medecins Sans
Frontieres. PLoS Med 2009;6:e1000115.
10. Yu JK, Chen SC, Wang KY, Chang CS, Makombe SD, Schouten EJ,
Harries AD. True outcomes for patients on antiretroviral therapy
who are “lost to follow-up” in Malawi. Bull World Health Organ
2007;85:550–4.
11. Krown SE. Highly active antiretroviral therapy in AIDS-associated
Kaposi’s sarcoma: implications for the design of therapeutic trials in
patients with advanced, symptomatic Kaposi’s sarcoma. J Clin Oncol
2004;22:399–402.
12. Zachariah R, Ford N, Philips M, Lynch S, Massaquoi M, Janssens V,
et al. Task shifting in HIV/AIDS: opportunities, challenges and pro-
posed actions for sub-Saharan Africa. Trans R Soc Trop Med Hyg
2009;103:549–58.
13. Mills EJ, Ford N, Mugyenyi P. Expanding HIV care in Africa: making
men matter. Lancet 2009;374:275–6.
14. Meditz AL, Borok M, MaWhinney S, Gudza I, Ndemera B, Gwanzura
L, et al. Gender differences in AIDS-associated Kaposi sarcoma in
Harare, Zimbabwe. J Acquir Immune Deﬁc Syndr 2007;44:306–8.

Complete remission of AIDS/Kaposi’s sarcoma after treatment with a combination of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor.

Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma.

Highly active antiretroviral therapy in AIDS-associated Kaposi’s sarcoma: implications for the design of therapeutic trials in patients with advanced, symptomatic Kaposi’s sarcoma.

Incidence and trends in Kaposi’s sarcoma in the era of effective antiretroviral therapy.

Management of AIDS-related Kaposi’s sarcoma. Lancet Oncol

Outcomes of patients with Kaposi’s sarcoma who start antiretroviral therapy under routine programme conditions in Malawi. Trop Doct

Presentation and survival of patients with AIDS-related Kaposi’s sarcoma in Jos,

Research ethics review in humanitarian contexts: the experience of the independent ethics review board of Medecins Sans Frontieres.

Risk factors for high early mortality in patients on antiretroviral treatment in a rural district of Malawi. Aids

True outcomes for patients on antiretroviral therapy who are “lost to follow-up” in Malawi. Bull World Health Organ

Risk factors for mortality in AIDS-associated Kaposi sarcoma in a primary care antiretroviral treatment program in Malawi

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Risk factors for mortality in AIDS-associated Kaposi sarcoma in a primary care antiretroviral treatment program in Malawi

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