ArticlesIntensive 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
Introduction
In France, guidelines now recommend initiation of combination antiretroviral therapy (cART) during primary HIV-1 infection,1 which is when HIV reservoirs are established.2 The resulting viral invasion leads to harmful activation of the immune system, and the extent of this activation is related to disease progression.3 HIV-DNA loads in peripheral blood mononuclear cells (PBMC) give an estimation of the size of HIV reservoirs, and are predictive of both immunological and clinical outcomes in people infected with HIV.4, 5, 6 Early treatment during primary HIV-1 infection might restrict the size of HIV reservoirs,6, 7 ensuring optimal immune restoration7 and lessening T-cell activation.8
HIV blood reservoirs are generally larger at primary HIV-1 infection9 than during the chronic phase, but the same first-line drugs are recommended for both situations. One challenge is to develop treatment strategies for primary HIV-1 infection that can block HIV expansion and attenuate the so-called cytokine storm.10
The OPTIPRIM–Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) 147 trial was designed to establish whether intensive cART—specifically, darunavir, ritonavir, tenofovir disoproxil fumarate plus emtricitabine, raltegravir, and maraviroc—started early during primary HIV-1 infection has a greater effect on HIV reservoir status than does the recommended triple-drug regimen. We also aimed to assess whether patients receiving the intensive cART regimen could achieve so-called post-treatment controller status after interruption of a 2 year treatment course. We chose raltegravir for its potent antiviral effect11 and maraviroc for both its antiviral activity and its positive effect on the CD4+ T-cell count.12
Section snippets
Study design and participants
OPTIPRIM was a randomised, open-label, phase 3 trial done in 33 French hospitals (appendix). Recruitment began in April, 2010, for a planned period of 2 years.
Patients were eligible for the trial if they presented with primary HIV-1 infection with either symptoms or a CD4+ cell count below 500 cells per μL (ie, they met criteria to receive treatment as recommended by the 2010 national guidelines).13 Primary HIV-1 infection was defined as detectable plasma HIV-RNA and an incomplete HIV-1 western
Results
Between April 26, 2010, and July 13, 2011, 110 patients were enrolled, of whom 92 were randomly assigned to a treatment group. Two patients in the intensive cART group dropped out before starting treatment, so 45 patients in each group were analysed in the modified intention-to-treat population (figure 1).
A symptomatic primary HIV-1 infection was noted in 87 (97%) of 90 patients, a median of 20 days (IQR 13–28) after symptoms onset (table 1). The median time from the estimated date of infection
Discussion
Compared with early standard cART, early intensive cART including raltegravir and maraviroc had no additional effect on HIV-DNA load after 24 months of treatment. A marked decline in the size of HIV blood reservoirs was reported at month 24 in both groups—larger than previously reported in patients with chronic HIV on treatment.19 At month 12, the median change in HIV-DNA load was −1·26 (IQR −1·43 to −0·98) log10 copies per 106 PBMC in the intensive cART group and −1·24 (−1·51 to −0·96) log10
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Factors associated with post-treatment control of viral load in HIV-infected patients: a systematic review and meta-analysis
2023, International Journal of Infectious DiseasesLong-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study
2021, The Lancet MicrobeCitation Excerpt :Although early ART initiation does not prevent establishment of the HIV reservoir, several observational studies have suggested that prompt ART initiation (ie, within 1–6 months of infection) might be associated with a more rapid decay in the pool of infected cells compared with delayed ART initiation (ie, >6 months after infection),10–16,19 which could accelerate reservoir clearance when combined with other eradication strategies. Several groups have described a biphasic decay of the HIV DNA reservoir on ART initiation, with a rapid initial decline followed by a second slower decay.13,24–26 Even though HIV DNA dynamics follow a similar two-phase decay pattern in early or chronically treated individuals, early ART initiation could be associated with a more rapid initial clearance of the HIV reservoir and a slower but continuous decay after long-term therapy compared with delayed ART initiation.13,16,19,27
Residual immune dysfunction under antiretroviral therapy
2021, Seminars in ImmunologyReasons for noncompliance with the national guidelines for initial antiretroviral therapy of HIV-infected patients in Spain, 2010–2015
2019, Enfermedades Infecciosas y Microbiologia ClinicaCitation Excerpt :These patients received intensified regimens with four or five drugs between the years 2013–2015 in different centres and most were likely to have primary HIV infection. This has also been found in another French study,26 and it suggests that some clinicians still feel that high viral loads in primary infection need the prescription of additional drugs associated to the recommended regimens, despite the guideline recommendations and the evidence showing that these regimens are not more effective than three-drug treatments for primary infection.27 In multivariable analysis, prescription of nonrecommended treatments was significantly associated with male sex, heterosexual mode of transmission (compared to MSM), low viral loads and more recent years (compared to 2010).
Time spent with residual viraemia after virological suppression below 50 HIV-RNA copies/mL according to type of first-line antiretroviral regimen
2018, International Journal of Antimicrobial AgentsCitation Excerpt :However, these results are in line with previous studies regarding antiretroviral-naïve patients with chronic HIV infection or patients with primary HIV infection [17–19]. Possible explanations for the lack of a superior virological efficacy of regimens based on more than three drugs include poorer adherence to therapy in patients treated with more complex regimens, and an unfavourable effect of maraviroc on persistent low-level replication [18]. On the contrary, the use of some NNRTI-based regimens has been associated with a lower risk of RV [3,9,10]; in particular, patients treated with nevirapine had VL<1 copy/mL more frequently than those treated with efavirenz in one study [20].