The impact of transmitted drug resistance on the natural history of HIV infection and response to first-line therapy
- 2 January 2006
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in AIDS
- Vol. 20 (1), 21-28
- https://doi.org/10.1097/01.aids.0000196172.35056.b7
Abstract
Transmission of drug-resistant HIV-1 is well recognized. However, the impact of such transmission on natural history of infection remains unknown. 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). 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. 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.Keywords
This publication has 20 references indexed in Scilit:
- French National Sentinel Survey of Antiretroviral Drug Resistance in Patients With HIV-1 Primary Infection and in Antiretroviral-Naive Chronically Infected Patients in 2001-2002JAIDS Journal of Acquired Immune Deficiency Syndromes, 2005
- Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infectionNature, 2005
- Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case reportThe Lancet, 2005
- The Epidemiology of Antiretroviral Drug Resistance among Drug‐Naive HIV‐1–Infected Persons in 10 US CitiesThe Journal of Infectious Diseases, 2004
- T Cell Dynamics in HIV-1 InfectionAnnual Review of Immunology, 2003
- Antiretroviral-Drug Resistance among Patients Recently Infected with HIVNew England Journal of Medicine, 2002
- Flexible parametric proportional‐hazards and proportional‐odds models for censored survival data, with application to prognostic modelling and estimation of treatment effectsStatistics in Medicine, 2002
- Persistence and Fitness of Multidrug-Resistant Human Immunodeficiency Virus Type 1 Acquired in Primary InfectionJournal of Virology, 2002
- Analysis of prevalence of HIV-1 drug resistance in primary infections in the United KingdomBMJ, 2001
- Changes in the uptake of antiretroviral therapy and survival in people with known duration of HIV infection in Europe: results from CASCADEHIV Medicine, 2000