Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.
Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.
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DOI：
10.1371/journal.ppat.1006792
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发表时间：
2018-01
期刊：
影响因子：
6.7
通讯作者：
Chun TW
中科院分区：
文献类型：
--
作者：
Clarridge KE;Blazkova J;Einkauf K;Petrone M;Refsland EW;Justement JS;Shi V;Huiting ED;Seamon CA;Lee GQ;Yu XG;Moir S;Sneller MC;Lichterfeld M;Chun TW
Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals. Here, we show a significant increase of HIV burden in the CD4+ T cells of infected individuals during ATI that was correlated with the level of plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters, including markers of exhaustion and activation, returned to pre-ATI levels 6–12 months after the study participants resumed ART. Of note, the proportions of near full-length, genome-intact and structurally defective HIV proviral DNA sequences were similar prior to ATI and following reinitiation of ART. In addition, there was no evidence of emergence of antiretroviral drug resistance mutations within intact HIV proviral DNA sequences following reinitiation of ART. These data demonstrate that short-term ATI does not necessarily lead to expansion of the persistent HIV reservoir nor irreparable damages to the immune system in the peripheral blood, warranting the inclusion of ATI in future clinical trials evaluating curative strategies. While we have made considerable advancements in the treatment of HIV, most infected individuals require life-long treatment to suppress plasma viremia, underscoring the need for the development of additional therapeutic strategies that would allow durable virologic remission in the absence of antiretroviral therapy (ART). While a definitive cure has not yet been identified, the field is moving in a promising direction, and with continued efforts we may arrive at a clinically acceptable alternative to ART. Clinical validation of new treatment options likely requires patients to stop therapy while monitoring for viral rebound, but the effect of treatment interruption and its precise impact on immunologic and virologic parameters in HIV-infected individuals has not been fully delineated. In this work, we measured a significant increase of HIV burden in the CD4+ T cells of infected individuals who underwent ATI with subsequent plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters returned to pre-ATI levels 6–12 months after the participants resumed ART. These data suggest ATI does not lead to expansion of the persistent HIV reservoir nor irreversible damages to the immune system in the peripheral blood.
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DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
15.9
作者：
Lee, Guinevere Q.;Orlova-Fink, Nina;Lichterfeld, Mathias
通讯作者：
Lichterfeld, Mathias
影响因子：
50.3
作者：
Johnston, Robert J.;Comps-Agrar, Laetitia;Grogan, Jane L.
通讯作者：
Grogan, Jane L.
影响因子：
6.7
作者：
Rotger M;Dang KK;Fellay J;Heinzen EL;Feng S;Descombes P;Shianna KV;Ge D;Günthard HF;Goldstein DB;Telenti A;Swiss HIV Cohort Study;Center for HIV/AIDS Vaccine Immunology
通讯作者：
Center for HIV/AIDS Vaccine Immunology
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.