Impact
of Adverse Events on Survival of African HIV Patients in the DART Trial
 | Due
to cost, there is often limited access to laboratory testing in middle- and low-income
countries. In these settings, World Health Organization (WHO) stage 3/4 adverse
events are used to determine the success or failure of antiretroviral therapy
(ART). As reported at the 5th International AIDS Society Conference on HIV Pathogenesis,
Treatment, and Prevention last week in Cape Town, South Africa, some WHO stage
3 events have a more significant impact on survival than stage 4 events, and further
evaluation is needed to determine the effects of switching to second-line therapy
after a survival risk event. |
 The
Development of Antiretroviral Therapy
in Africa (DART) trial, a randomized comparison of antiretroviral management strategies,
was conducted at medical centers in Uganda and Zimbabwe. Participants were symptomatic
African adults with CD4 counts < 200 cells/mm3 who had no prior treatment with
ART.
Participants
initiating combination antiretroviral therapy and were randomly assigned to 2
management strategy arms. In the Laboratory and Clinical Monitoring (LCM) arm,
routine CD4 cell tests and hematology and biochemistry monitoring for toxicity
were performed every 3 months, with results returned to patients' clinicians.
In the Clinically Driven Monitoring (CDM) arm, only grade 4 toxicity results were
returned, but tests other than CD4 count could be requested if clinically indicated. In
the present analysis, the researchers aimed to estimate the effect on survival
of WHO stage 3/4 events. A total of 3179 participants contributed 11236 years
of follow-up data.
Results
 | A
total of 281 deaths occurred during the follow-up period. | | 518
participants (16%) switched to second-line therapy, and 43 of the deaths occurred
while on second-line ART. | | Among
participants on first-line ART, 123 developed cryptococcosis, 177 had pulmonary
tuberculosis, 110 had extrapulmonary tuberculosis, 178 had esophageal candidiasis,
and 405 had oral candidiasis. | | Among
patients on second-line treatment, 6 developed cryptococcosis, 9 developed pulmonary
tuberculosis, 8 developed extrapulmonary tuberculosis, 3 had esophageal candidiasis,
and 7 had oral candidiasis (59 deaths). | | There
were 48 deaths due to cryptococcosis, 40 due to pulmonary tuberculosis, 19 due
to extrapulmonary tuberculosis, 25 due to esophageal candidiasis, and 59 due to
oral candidiasis. | | As
expected, WHO stage 3/4 events occurred more frequently among participants with
lower CD4 counts, lower hemoglobin levels, recent weight loss, and a history of
other WHO 3/4 events. | | Overall
(including patients on both first-line and second-line ART), cryptococcosis increased
all-cause mortality risk by 6.01-fold, pulmonary tuberculosis by 2.84-fold, extrapulmonary
tuberculosis by 1.61-fold, oral candidiasis by 1.98-fold, and esophageal candidiasis
by 0.91-fold. | | The
risk of death was higher in the 12 weeks following cryptococcosis (25 deaths)
than subsequently (23 deaths). | | Increased
mortality risk in the 12 weeks following an event were also observed for pulmonary
tuberculosis, extrapulmonary tuberculosis, and oral candidiasis. |
"Mortality
rates following a WHO stage 3/4 event vary considerably with diagnosis; of note,
some WHO 3 events have greater mortality impact than WHO 4 events," the investigators
concluded. "More work is needed to evaluate the impact of switching to second-line
therapy following an event on mortality risk." Download
the e-Poster Joint
Clinical Research Centre, Kampala, Uganda; MRC Clinical Trials Unit, London, UK;
University of Zimbabwe, Harare, Zimbabwe; MRC/UVRI Uganda Research Unit on AIDS,
Entebbe, Uganda; Infectious Diseases Institute, Makerere University, Mulago, Uganda;
Imperial College, London, UK.
7/31/09 Reference
C Kityo, D Ford, AS Walker, and others (on behalf of The DART Trial Team).
Effect of WHO stage 3/4 events after ART initiation on survival of HIV-infected
African adults in the DART trial. 5th International AIDS Society Conference on
HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape
Town, South Africa. Abstract
MoPeB003.
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