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Journal Club: Post-treatment HIV-1 controllers with a long term virological remission after the interruption of early initiated antiretroviral therapy

Article reviewed

Sáez-Cirión, A., Bacchus, C., Hocqueloux, L., Avettand-Fenoel, V., Girault, I., Lecuroux, C., and Rouzioux, C. (2013). Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study. PLoS Pathogens, 9(3), e1003211.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003211

Purpose of study

To investigate 14 HIV-1 infected patients who achieved durable viral control after the interruption of effective combined ART initiated during primary infection with HIV, and to compare them to HIV Controllers.

Methods

Post-Treatment Controllers (PTCs) were defined as those who initiated ART within 10 weeks of a primary infection, and whose plasma HIV RNA levels were <400 copies/mL for at least 24 months after treatment interruption. The 14 patients were identified from previous study cohorts and from patient follow-up. Several mechanisms of viremic control were investigated and compared to HIV-Controllers (HICs). HICs were patients from previous study cohorts who had been infected for more than 5 years, naïve of any ART, and had their last 4 consecutive plasma HIV RNA levels at <400 copies/mL.

Results

HIV specific CD8+ T cell response was very weak in PTCs, with a high prevalence of risk alleles and no over-representation of protective HLA subtypes. T cell activation status was similarly lower in PTCs compared to HICs. Both groups had low HIV reservoir levels, however PTCs had minimal contributions from long-lived CD4+ T cells and a predominance of the transitional memory cell subset.

The probability of viral control 12 months after interruption of long-term treatment that was initiated in the primary infection was estimated to be 15%.

Impact on clinical practice

Early initiation of therapy and a prolonged treatment period may be associated with viral control after treatment interruption. These findings may have important implications for the possibility of a functional HIV cure.

Further information

  1. Autran, B., Descours, B., Avettand-Fenoel, V., & Rouzioux, C. (2011). Elite controllers as a model of functional cure. Current Opinion in HIV and AIDS, 6(3), 181.
  2. Okulicz, J. F., & Lambotte, O. (2011). Epidemiology and clinical characteristics of elite controllers. Current Opinion in HIV and AIDS, 6(3), 163.

Acknowledgements

Dr. Richard Lester, Medical Head, STI/HIV Control, Clinical Prevention Services, BCCDC

Categories: Journal club

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