Virological and immunological characteristics of HIV treatment failure

BackgroundResistance to antiretroviral treatment is prevalent. There is limited knowledge of the determinants of disease evolution in subjects infected with multidrug-resistant HIV (MDR-HIV). MethodsInfectivity, replication, chemokine receptor usage, and env, gag, protease and reverse transcriptase sequence analysis was performed for MDR-HIV isolates from 14 HIV-infected individuals and compared to wild-type HIV isolates from individuals naive to antiretroviral treatment. Expression of CD45RO/RA, Ki67 and interferon-γ and CD4 proliferative response to various antigens was determined for individuals infected with MDR-HIV and compared to that in individuals with optimal suppression of viral replication. ResultsInfectivity and replication are diminished for various MDR-HIV isolates, usually in the context of an increase in CD4 and CD4+CD45RA+ T-cell counts. However, a number of MDR-HIV isolates are associated with high in vivo viraemia and pronounced immunosuppression, and display in vitro levels of infectivity and replication comparable to those of wild-type strains. No specific genetic sequence or chemokine receptor usage predicted the fitness of an MDR isolate. ConclusionsDespite the biological diversity of resistant viruses and the range of host responses observed, our descriptive analysis indicates that viral factors play a role in determining the degree of immune damage observed in the context of MDR-HIV infection.

[1]  A. Telenti,et al.  Heterogeneity in the Response to Antiretroviral Therapy , 2001 .

[2]  A. Telenti,et al.  Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors. , 2000, AIDS research and human retroviruses.

[3]  C. Verhofstede,et al.  Interruption of reverse transcriptase inhibitors or a switch from reverse transcriptase to protease inhibitors resulted in a fast reappearance of virus strains with a reverse transcriptase inhibitor-sensitive genotype. , 1999, AIDS.

[4]  M. Youle,et al.  Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy. , 1999, AIDS.

[5]  C. Boucher,et al.  Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. , 1999, AIDS.

[6]  H. Furrer,et al.  HAART in HIV-infected patients: restoration of antigen-specific CD4 T-cell responses in vitro is correlated with CD4 memory T-cell reconstitution, whereas improvement in delayed type hypersensitivity is related to a decrease in viraemia. , 1999, AIDS.

[7]  Richard A. Loftus,et al.  HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. , 1999, AIDS.

[8]  A. Telenti,et al.  Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study , 1999, The Lancet.

[9]  Louis J. Picker,et al.  Changes in thymic function with age and during the treatment of HIV infection , 1998, Nature.

[10]  F. Mammano,et al.  Resistance-Associated Loss of Viral Fitness in Human Immunodeficiency Virus Type 1: Phenotypic Analysis of Protease andgag Coevolution in Protease Inhibitor-Treated Patients , 1998, Journal of Virology.

[11]  P. Schnyder,et al.  Limited CD4+ T-cell renewal in early HIV-1 infection: Effect of highly active antiretroviral therapy , 1998, Nature Medicine.

[12]  A. Telenti,et al.  HIV treatment failure: testing for HIV resistance in clinical practice. , 1998, Science.

[13]  Alan S. Perelson,et al.  Turnover of CD4+ and CD8+ T Lymphocytes in HIV-1 Infection as Measured by Ki-67 Antigen , 1998, The Journal of experimental medicine.

[14]  Amalio Telenti,et al.  CD4-cell count in HIV-1-infected individuals remaining viraemic with highly active antiretroviral therapy (HAART) , 1998, The Lancet.

[15]  S. Yerly,et al.  Detection of low HIV-1 RNA levels in plasma. , 1997, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[16]  A. Bahnson,et al.  Centrifugal enhancement of retroviral mediated gene transfer. , 1995, Journal of virological methods.