Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.
BACKGROUND
Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.


RESULTS
The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm(3). The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p=0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p=0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.


CONCLUSIONS
The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.


BACKGROUND
ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.
Unité Mixte Internationale 174, Institut de Recherche pour le Développement (IRD)-Programs for HIV Prevention and Treatment (PHPT), Chiang Mai, Thailand.
Gonzague
G
Jourdain
Sophie
S
Le Cœur
Nicole
N
Ngo-Giang-Huong
Patrinee
P
Traisathit
Tim R
TR
Cressey
Federica
F
Fregonese
Baptiste
B
Leurent
Intira J
IJ
Collins
Malee
M
Techapornroong
Sukit
S
Banchongkit
Sudanee
S
Buranabanjasatean
Guttiga
G
Halue
Ampaipith
A
Nilmanat
Nuananong
N
Luekamlung
Virat
V
Klinbuayaem
Apichat
A
Chutanunta
Pacharee
P
Kantipong
Chureeratana
C
Bowonwatanuwong
Rittha
R
Lertkoonalak
Prattana
P
Leenasirimakul
Somboon
S
Tansuphasawasdikul
Pensiriwan
P
Sang-A-Gad
Panita
P
Pathipvanich
Srisuda
S
Thongbuaban
Pakorn
P
Wittayapraparat
Naree
N
Eiamsirikit
Yuwadee
Y
Buranawanitchakorn
Naruepon
N
Yutthakasemsunt
Narong
N
Winiyakul
Luc
L
Decker
Sylvaine
S
Barbier
Suporn
S
Koetsawang
Wasna
W
Sirirungsi
Kenneth
K
McIntosh
Sombat
S
Thanprasertsuk
Marc
M
Lallemant
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D013785:Thailand; D019562:Viral Load
D019380:Anti-HIV Agents