Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial

Chéret, Antoine; Nembot, Georges; Mélard, Adeline; Lascoux, C.; Slama, Laurence; Miailhes, Patrick; Yéni, Patrick; Abel, Sylvie; Avettand-Fènoël, Véronique; Venet, Alain; Chaix, Marie‐Laure; Molina, Jean‐Michel; Katlama, Christine; Goujard, Cécile; Tamalet, Catherine; Raffi, François; Lafeuillade, Alain; Reynes, Jacques; Ravaux, Isabelle; Hoën, Bruno; Delfraissy, Jean‐François; Meyer, Laurence; Rouzioux, Christine

doi:10.1016/s1473-3099(15)70021-6

Cited by 63 publications

(56 citation statements)

References 30 publications

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“…This has been previously described and was not found to be associated with any differences in the measurable HIV reservoir after 24 weeks of therapy [9]. Similarly, addition of raltegravir and maraviroc to protease inhibitor-based regimens has been shown to result in rapid reduction of plasma viremia without long-term effect on HIV reservoirs when ART is initiated during primary HIV infection [24,25]. In prior studies, adherence to the intensified five-drug regimens tended to be worse and virologic failure was more common [24,25].…”

Section: Discussionsupporting

confidence: 52%

“…Similarly, addition of raltegravir and maraviroc to protease inhibitor-based regimens has been shown to result in rapid reduction of plasma viremia without long-term effect on HIV reservoirs when ART is initiated during primary HIV infection [24,25]. In prior studies, adherence to the intensified five-drug regimens tended to be worse and virologic failure was more common [24,25]. Interestingly, three of the four participants with virologic failure at week 24 in this study were prescribed the intensified five-drug regimen.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, participants who achieved a two-log decline in HIV RNA after four weeks of ART demonstrated a shorter time to virologic suppression (12 [8][9][10][11][12][13][14][15][16] vs. 24 [12][13][14][15][16][17][18][19][20][21][22][23][24] weeks, p<0.001; Figure 3B). blips, compared to four of 29 (13.8%) in the group that did not achieve this viral load target (p=1.00).…”

Section: Time To Virologic Suppressionmentioning

confidence: 98%

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Virologic failure is uncommon after treatment initiation during acute HIV infection

Crowell

Phanuphak

Pinyakorn

et al. 2016

Aids

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Time To Virologic Suppressionmentioning

confidence: 98%

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Virologic failure is uncommon after treatment initiation during acute HIV infection

Crowell

Phanuphak

Pinyakorn

et al. 2016

Aids

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“…The decline in total blood HIV DNA in patients adherent to cART has been extensively studied in both adults and children (57,77,78,82,(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109). This decline varies among patients.…”

Section: Decline In Total Hiv Dna During Cartmentioning

confidence: 99%

“…The OPTIPRIM randomized trial, in which total HIV DNA decay was the primary endpoint, recently showed that standard triple-drug therapy reduced total HIV DNA load in PBMC as effectively as a five-drug regimen when initiated during PHI (109). No decrease in total HIV DNA levels has been observed with intensification strategies using the integrase inhibitor raltegravir, for example, in patients treated during CHI with controlled plasma viremia (42, 225).…”

Section: Total Hiv Dna Can Be Used To Evaluate Treatment Strategies mentioning

confidence: 99%

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

et al. 2016

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SUMMARYHIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis.

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Impact of genotypic susceptibility score on cART outcomes during primary HIV infection

Giacomelli

Fabbiani

Benedetto

et al. 2019

Journal of Medical Virology

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To assess the impact of genotypic susceptibility score (GSS) on combined antiretroviral therapy (cART) outcomes during primary HIV infection (PHI) we retrospectively enrolled patients with PHI diagnosed between 2008 and 2015 at 9/24 Italian Network ACuTe HIV InfectiON centers. One hundred‐seventy‐six patients were enrolled. Of these, 55 (32.9%) patients started with more than three drugs and 11 (7.2%) started with a GSS < 3. Regimen's GSS (per 1 point increase) (adjusted odds ratio [aOR], 4.82; 95% confidence interval [CI], 1.62‐14.28; P = .005) and baseline HIV‐RNA (per 1 log10 increase) (aOR, 2.02; 95% CI, 1.09‐3.73; P = .025) resulted associated with early cART initiation. In conclusion, regimen's GSS resulted to be associated to the time to cART initiation during PHI.

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Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial

Cited by 63 publications

References 30 publications

Virologic failure is uncommon after treatment initiation during acute HIV infection

Virologic failure is uncommon after treatment initiation during acute HIV infection

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

Impact of genotypic susceptibility score on cART outcomes during primary HIV infection

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