Paper # 676 
A Single CD4 Test with Threshold >250 Cells/mm3 Can Markedly Reduce Switching to Second-line ART in African Patients Managed without CD4 or Viral Monitoring
Charles Gilks*1, S Walker2, P Munderi3, C Kityo4, A Reid5, E Katabira6, H Grosskurth3, P Mugyenyi4, D Gibb2, J Hakim5, and DART Trial Team
1Imperial Coll London, UK; 2MRC Clin Trials Unit, London, UK; 3MRC/Uganda Virus Res Inst, Entebbe; 4Joint Clin Res Ctr, Kampala, Uganda; 5Univ of Zimbabwe Clin Res Ctr, Harare; and 6Infectious Disease Inst, Makerere Univ, Kampala, Uganda
Background: In Africa, many patients on ART are
managed without routine CD4/viral load monitoring. Using clinical failure alone
to trigger switching may result in unnecessary use of more costly second-line
therapy. Low-cost point-of-care CD4 tests are likely to be available soon.
Methods: The Development of AntiRetroviral Therapy in Africa (DART) randomized 3316 African participants to first-line ART with
clinically driven (CDM) or laboratory and clinical monitoring (LCM) and
followed them for median 5 years. The relationship between CD4 at switch and
main failure criterion (new/recurrent WHO stage 4 event, single or multiple WHO
3 events; and CD4 <100 or other CD4 reason in LCM only) was investigated in
all 675 (361 LCM, 314 CDM) participants switching during follow-up under a randomized
strategy. Retrospective viral loads were available in 221 (33%) participants
enrolled in second-line studies in DART.
Results:
In LCM, 265 of 361(73%) participants failed with CD4 <100 cells/mm3;
43 (12%) for other CD4 reasons; 37 (10%) with WHO 4; 10 (3%) and 6 (2%) with
single or multiple WHO 3 events, respectively. With no CD4 counts in CDM, 206
of 314 (66%) participants failed with WHO 4 events, and 76 (24%) or 32(10%) for
single or multiple WHO 3 events, respectively. Failure triggered switching in 7
(2%) LCM participants with CD4 ≥250 cells/mm3 (3 WHO 4; 1
single WHO 3; 3 other CD4) compared to 64 (20%) in CDM (p <0.001). Without CD4 monitoring (CDM group), failure/switching
determined by a single WHO 3 event was significantly more likely to occur with
CD4 ≥250 cells/mm3 (27/76; 36%) compared to multiple WHO 3
(4/32; 12%) or WHO 4 (33/206; 16%) events (p
= 0.001). Overall, 108 LCM and 113 CDM participants had viral load available at
failure/switch: 15 (14%) and 32 (28%)
were <400 copies/mL, respectively (p
= 0.009). In CDM, 25/31 (81%) with clinical failure and CD4 ≥250 cells/mm3
had viral load <400 copies/mL vs 7/82 (9%) with CD4 <250 cells/mm3
(p <0.001); with a non-significant
trend to more CDM participants failing/switching for single WHO 3 events with viral
load <400 copies/mL (17/46, 33%) vs multiple WHO 3 (3/16, 19%) or WHO 4
(12/51, 24%) events (p = 0.22).
Conclusions: A
CD4 “tie breaker” at a ≥250 cells/mm3 threshold for patients
clinically monitored and failing first-line therapy could identify as many as
80% (with viral load <400copies/mL) who are unlikely to benefit from
second-line therapy. Nearly 40% of participants in DART failing ART clinically
with a single WHO stage 3 event had CD4 >250 cells/mm3:
targeting this group would be
particularly likely to avoid premature and costly switching to second-line.
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