Blunted response to combination antiretroviral therapy in HIV elite controllers: an international HIV controller collaboration.
OBJECTIVE
HIV "elite controllers" (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs).


METHODS
ECs were defined as patients with at least ≥5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (<1 year) ART-naïve HIV-1-infected adults. CD4 T-cell count dynamics after cART initiation in both groups were modelled with piecewise mixed linear models.


RESULTS
After cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63√CD4/month), followed by +0.19√CD4/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm(3), the estimated mean CD4 T-cell gain during the first 12 months was 139/mm(3) in VIRs and 80/mm(3) in ECs (p = 0.048).


CONCLUSIONS
cART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients.
Inserm, CESP Centre for research in Epidemiology and Population Health, Epidemiology of HIV and STI Team, le Kremlin-Bicêtre, France ; Univ Paris-Sud, Le Kremlin Bicêtre, France.
Faroudy
F
Boufassa
Univ Paris-Sud, Le Kremlin Bicêtre, France.
Jérome
J
Lechenadec
Inserm, CESP Centre for research in Epidemiology and Population Health, Epidemiology of HIV and STI Team, le Kremlin-Bicêtre, France ; Univ Paris-Sud, Le Kremlin Bicêtre, France ; AP-HP, Service de Santé Publique, Hôpital de Bicêtre, le Kremlin Bicêtre, France.
Laurence
L
Meyer
UPMC Univ Paris 06, Paris, France ; INSERM, Paris, France.
Dominique
D
Costagliola
Laboratory Medicine, Departments of Medicine, Epidemiology, and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
Peter W
PW
Hunt
The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts, United States of America.
Florencia
F
Pereyra
Laboratory Medicine, Departments of Medicine, Epidemiology, and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
Steve
S
Deeks
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
Gianfranco
G
Pancino
Hôpital Saint-Louis, Paris, France.
Olivier
O
Taulera
Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Mathias
M
Lichterfeld
Service des Maladies Infectieuses et Tropicales, Hôpital Purpan, Toulouse, France ; INSERM, Toulouse, France.
Pierre
P
Delobel
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
Asier
A
Saez-Cirion
AP-HP, Service de Médecine Interne, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Olivier
O
Lambotte
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007391:International Cooperation; D007700:Kinetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D014766:Viremia / Q000821:virology