The impact of transmitted drug resistance on the natural history of HIV infection and response to first-line therapy.
BACKGROUND
Transmission of drug-resistant HIV-1 is well recognized. However, the impact of such transmission on natural history of infection remains unknown.


METHODS
Three hundred HIV-1-infected, antiretroviral-naive individuals, recruited between 1987 and 1993, and with resistance tests undertaken within 18 months of infection were assessed. We estimated the impact of transmitted drug resistance (TDR) on subsequent CD4 cell count decline in the absence of treatment. We also used Kaplan-Meier methods to assess the response to antiretroviral therapy based on the number of active drugs utilized (according to genotypic resistance results).


RESULTS
Infection with any form of drug-resistant HIV-1 was associated with a steeper decline of CD4 cell count over the first year of infection. Estimated rates of decline in the first year were 5.0 [95% confidence interval (CI), 2.8-7.3] and 1.7 (95% CI, 0.8-2.6) radicalCD4 cells per year for TDR and no TDR, respectively (P = 0.005). For an individual at a CD4 cell count of 500 cells/microl at seroconversion, these rates correspond to a CD4 cell loss of 199 and 73 cells/microl, respectively, in the first year. Thereafter we found no evidence of a difference in the rate of CD4 cell decline (P = 0.32). Initiation of HAART after calendar year 2000, but not number of active drugs, was associated with improved responses.


CONCLUSIONS
The impact of transmitted HIV-1 drug resistance on CD4 cell decline is time dependent, with greater rates of decline in the first year following infection. We found no evidence of a longer term effect of TDR on natural history of HIV-1 infection.
Pillay
Deenan
D
Centre for Virology, Division of Infection and Immunity, Royal Free and University College Medical School, Windeyer Institute, 46 Cleveland Street, London W1T 4JF, UK. d.pillay@ucl.ac.uk
Bhaskaran
Krishnan
K
Jurriaans
Suzanne
S
Prins
Maria
M
Masquelier
Bernard
B
Dabis
Francois
F
Gifford
Robert
R
Nielsen
Claus
C
Pedersen
Court
C
Balotta
Claudia
C
Rezza
Giovanni
G
Ortiz
Marta
M
de Mendoza
Carmen
C
Kücherer
Claudia
C
Poggensee
Gabriele
G
Gill
John
J
Porter
Kholoud
K
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D013997:Time Factors; D019562:Viral Load
D012367:RNA, Viral