Can
People in Low-income Countries Benefit from Antiretroviral Therapy without Routine
Laboratory Monitoring?
 | Antiretroviral
therapy (ART) should not be withheld from HIV patients in medium- and low-income
countries due to lack of laboratory monitoring, according to results of the Development
of Antiretroviral Therapy (DART) in Africa trial, presented last week at the 5th
International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention
in Cape Town, South Africa. The researchers also concluded that first-line treatment
regimens can be given to people in resource-limited countries without the need
for routine laboratory monitoring of toxicity. |
 Because
of high costs, ART often is
not accompanied by routine laboratory monitoring in low-income countries, and
the clinical outcomes of this strategy have not been well studied. The objective
of the DART trial was to discover whether the absence of routine monitoring led
to poor outcomes.
 The
DART trial -- the largest clinical study ever conducted in sub-Saharan Africa
-- enrolled 3316 previously untreated adults in Uganda and Zimbabwe with a median
CD4 count of 86 cells/mm3 and World Health Organization (WHO) adverse event stages
2/3/4 (20%, 56%, and 23%, respectively).
Participants
were randomized into 2 groups, the Laboratory and Clinical Monitoring (LCM) arm
or the Clinically Driven Monitoring (CDM) arm, and were followed for a median
of 4.9 years. Participants
started ART using 1 of 3 treatment regimens:  Tenofovir
(Viread) plus zidovudine/lamivudine (Combivir):
74%;
Nevirapine (Viramune) plus
Combivir (16%);
Abacavir (Ziagen) plus Combivir:
9%.
Patients
switched to second-line therapy after new or recurrent WHO stage 3/4 events or
(in the LCM arm only) reaching a CD4 count below 100cells/mm3. In
the 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 CDM, only grade 4 toxicity results were returned, but tests
other than CD4 count could be requested if clinically indicated.
Results | 459
patients (28%) in the CDM group versus 356 participants (22%) in the LCM group
experienced a new WHO stage 4 event or died. | | Death
rates per 100 person years (PY) were 2.94 in the CDM group versus 2.18 in the
LCM group. | | An
estimated 130 PY of laboratory monitoring was needed to prevent 1 death. | | Differences
between the 2 monitoring strategies occurred from the third year on ART. | | Lower
likelihood of switching to second-line ART in the CDM arm occurred from the second
year. | | There
were no significant differences between the 2 strategies with regard to time to
first serious adverse event, grade 4 toxicity, or ART-modifying toxicity. |
In
conclusion, the investigators stated, "Overall survival at 5 years (CDM:
87%; LCM: 90%) was excellent, strongly reinforcing WHO guidelines that ART should
never be withheld due to lack of laboratory monitoring." They
noted that the differences in survival free of WHO 4 events were small, "but
suggest a role for targeted CD4 monitoring to guide switching from the second
year on ART." "First-line
regimens used in DART can be given without need for routine toxicity laboratory
monitoring, even in advanced disease," they concluded, adding that a cost-effectiveness
analysis would also help to determine ART policy in these settings. Joint
Clinical Research Centre, Kampala, Uganda; MRC Clinical Trials Unit, London, UK;
University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe; MRC/UVRI Uganda
Research Unit on AIDS, Entebbe, Uganda; Infectious Diseases Institute, Kampala,
Uganda; UNAIDS, New Delhi, India; Imperial College, London, UK. 7/31/09 Reference
P
Mugyeny, S Walker, J Hakim, and others (on behalf of The DART Trial Team). Impact
of routine laboratory monitoring over 5 years after antiretroviral therapy (ART)
initiation on clinical disease progression of HIV-infected African adults: the
DART Trial final results. 5th International AIDS Society Conference on HIV Pathogenesis,
Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa.
Abstract
TuSS102.
|
|
