Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

Acute Disease Adult Anti-HIV Agents / pharmacology CD4 Lymphocyte Count Central Nervous System Diseases / etiology Female HIV Infections / blood HIV-1 / drug effects Humans Italy Male Middle Aged RNA, Viral / genetics Regression Analysis Retrospective Studies Risk Factors Treatment Failure Viral Load / drug effects

acute HIV infection blip early antiretroviral treatment incomplete viral response virologic failure

Journal

HIV medicine

ISSN: 1468-1293

Titre abrégé: HIV Med

Pays: England

ID NLM: 100897392

Informations de publication

Date de publication:
09 2020

Historique:

accepted: 13 05 2020

pubmed: 25 6 2020

medline: 1 12 2021

entrez: 25 6 2020

Statut: ppublish

Résumé

The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

Identifiants

DOI: 10.1111/hiv.12885 PMID: 32578947

pubmed: 32578947

doi: 10.1111/hiv.12885

doi:

Substances chimiques

Anti-HIV Agents 0

RNA, Viral 0

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

523-535

Subventions

Organisme : Gilead Sciences

Organisme : ANLAIDS sezione Lombardia

Informations de copyright

Références

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (accessed 22 August 2019).

Hogan CM, Degruttola V, Sun X et al. The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals. J Infect Dis 2012; 205: 87-96.

Grijsen ML, Steingrover R, Wit FW et al. No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial. PLoS Med 2012; 9: e1001196.

Hamlyn E, Ewings FM, Porter K et al. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection. PLoS One 2012; 7: e43754.

Strain MC, Little SJ, Daar ES et al. Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis 2005; 191: 1410-1418.

SPARTAC Trial Investigators, Fidler S, Porter K et al. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med 2013; 368: 207-217.

Rosenberg ES, Altfeld M, Poon SH et al. Immune control of HIV-1 after early treatment of acute infection. Nature 2000; 407: 523-526.

Schuetz A, Deleage C, Sereti I et al. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog 2014; 10: e1004543.

Mehandru S, Poles MA, Tenner-Racz K et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004; 200: 761-770.

Guadalupe M, Reay E, Sankaran S et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol 2003; 77: 11708-11717.

Ananworanich J, Chomont N, Eller LA et al. HIV DNA set point is rapidly established in acute HIV infection and dramatically reduced by early ART. EBioMedicine 2016; 11: 68-72.

Wawer MJ, Sewankambo NK, Serwadda D et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Lancet 1999; 353: 525-535.

Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection. J Infect Dis 2008; 198: 687-693.

Cohen MS, Shaw GM, McMichael AJ, Haynes BF. Acute HIV-1 Infection. N Engl J Med 2011; 364: 1943-1954.

Hoen B, Cooper DA, Lampe FC et al. Predictors of virological outcome and safety in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005. Clin Infect Dis 2007; 45: 381-390.

Smith MK, Rutstein SE, Powers KA et al. The detection and management of early HIV infection: a clinical and public health emergency. J Acquir Immune Defic Syndr 2013; 63: S187-S199.

Goujard C, Emilie D, Roussillon C et al. Continuous versus intermittent treatment strategies during primary HIV-1 infection: the randomized ANRS INTERPRIM trial. AIDS 2012; 26: 1895-1905.

Crowell TA, Pinyakorn S, Sacdalan Cet al. Viral Blips After Treatment Initiation During Acute HIV Infection. CROI Conference, Seattle 2019, Abstract number # 522. Available at http://www.croiconference.org/sessions/viral-blips-after-treatment-initiation-during-acute-hiv-infection (accessed 23 August 2019).

Ford N, Migone C, Calmy A et al. Benefits and risks of rapid initiation of antiretroviral therapy. AIDS 2018; 32: 17-23.

Antinori A, Di Biagio A, Marcotullio S et al. Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. Update 2016. New Microbiol 2017; 40: 86-98.

Ostrowski M, Benko E, Yue FY et al. Intensifying antiretroviral therapy with raltegravir and maraviroc during early human immunodeficiency virus (HIV) infection does not accelerate hiv reservoir reduction. Open Forum Infect Dis 2015; 2: ofv138.

Hofstra LM, Sauvageot N, Albert J et al. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe. Clin Infect Dis 2016; 62: 655-663.

Fiebig EW, Wright DJ, Rawal BD et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 2003; 17: 1871-1879.

Saracino A, Lorenzini P, Lo Caputo S et al. Increased risk of virological failure to the first antiretroviral regimen in HIV-infected migrants compared to natives: data from the ICONA cohort. J Int AIDS Soc 2014; 17(4 S3): 19769.

Crowell TA, Phanuphak N, Pinyakorn S et al. Virologic failure is uncommon after treatment initiation during acute HIV infection. AIDS 2016; 30: 1943-1950.

Valcour VG, Spudich SS, Sailasuta N et al. Neurological response to cART vs. cART plus integrase inhibitor and CCR5 antagonist initiated during acute HIV. PLoS One 2015; 10: e0142600.

Markowitz M, Evering TH, Garmon D et al. A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals. J Acquir Immune Defic Syndr 2014; 66: 140-147.

Chéret A, Nembot G, Mélard A et al. 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. Lancet Infect Dis 2015; 15: 387-396.

Chen Y, Chen K, Kalichman SC. Barriers to HIV medication adherence as a function of regimen simplification. Ann Behav Med 2017; 51: 67-78.

Armenia D, Di Carlo D, Cozzi-Lepri A et al. Very high pre-therapy viral load is a predictor of virological rebound in HIV-1-infected patients starting a modern first-line regimen. Antivir Ther 2019; 24: 321-331.

Di Biagio A, Rusconi S, Marzocchetti A et al. The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy. J Med Virol 2014; 86: 1648-1655.

Rossetti B, Di Gianbenedetto S, Torti C et al. Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016. HIV Med 2018; 19: 619-628.

Hellmuth J, Fletcher JL, Valcour V et al. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology 2016; 87: 148-154.

Kore I, Ananworanich J, Valcour V et al. Neuropsychological impairment in acute HIV and the effect of immediate antiretroviral therapy. J Acquir Immune Defic Syndr 2015; 70: 393-399.

Mussini C, Lorenzini P, Cozzi-Lepri A et al. CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: an observational cohort study. Lancet HIV 2015; 2: e98-e106.

Ceccherini-Silberstein F, Cozzi Lepri A, Alteri C et al. Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART. J Antimicrob Chemother 2018; 73: 3460-3470.

Chan P, Patel P, Hellmuth J et al. Distribution of human immunodeficiency virus (HIV) ribonucleic acid in cerebrospinal fluid and blood is linked to CD4/CD8 ratio during acute HIV. J Infect Dis 2018; 218: 937-945.

Joya C, Won SH, Schofield C et al. Persistent low-level viremia while on antiretroviral therapy is an independent risk factor for virologic failure. Clin Infect Dis 2019; 69: 2145-2152.

Laprise C, de Pokomandy A, Baril JG, Dufresne S, Trottier H. Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation. Clin Infect Dis 2013; 57: 1489-1496.

Taramasso L, Magnasco L, Bruzzone B et al. How relevant is the HIV low level viremia and how is its management changing in the era of modern ART? A large cohort analysis. J Clin Virol 2020; 123: 104255.

Doyle T, Smith C, Vitiello P et al. Plasma HIV-1 RNA detection below 50 copies/ml and risk of virologic rebound in patients receiving highly active antiretroviral therapy. Clin Infect Dis 2012; 54: 724-732.

Maggiolo F, Callegaro A, Cologni G et al. Ultrasensitive assessment of residual low-level HIV viremia in HAART-treated patients and risk of virological failure. J Acquir Immune Defic Syndr 2012; 60: 473-482.

Gianotti N, Galli L, Salpietro S et al. Virological rebound in human immunodeficiency virus-infected patients with or without residual viraemia: results from an extended follow-up. Clin Microbiol Infect 2013; 19: E542-E544.