Acute and early HIV infection: Treatment
- Paul E Sax, MD
Paul E Sax, MD
- Section Editor — HIV
- Clinical Director, Division of Infectious Diseases
- Brigham and Women's Hospital
- Professor of Medicine
- Harvard Medical School
The first description of acute HIV infection, a "mononucleosis-like" illness, based upon the clinical records of 12 men with documented seroconversion to HIV during the preceding six months, was published in 1985 . Since then, the early period following acquisition of HIV has been a subject of tremendous clinical and research interest, yet many challenges remain in its diagnosis, management, and impact on public health.
Difficulties in identifying patients with early HIV infection have hindered the performance of trials to evaluate the long-term clinical benefits of initiation of antiretroviral therapy during this stage of infection. Thus, decisions for treatment initiation during this period must balance the potential benefits based on indirect evidence, including effects on surrogate markers, and the potential risks of earlier therapy. In addition, the general trend in treatment guidelines in favor of treating all individuals with HIV infection influences the approach in early infection toward treatment .
The treatment of early HIV infection will be reviewed here. The pathogenesis, epidemiology, clinical manifestations, and diagnosis of acute and early infection with HIV are discussed separately. (See "Acute and early HIV infection: Pathogenesis and epidemiology" and "Acute and early HIV infection: Clinical manifestations and diagnosis".)
Different terms, including acute, recent, primary, and early HIV infection, have been used in the literature to refer to variable intervals following initial infection with the virus. In this topic, we use the term "early HIV infection" to refer to the approximate six-month period following HIV acquisition. We use the term "acute HIV infection," to refer to symptomatic early infection, as this reflects common usage in clinical care.
DECISION TO INITIATE ANTIRETROVIRAL THERAPY DURING EARLY HIV INFECTION
For chronically infected HIV patients, a growing body of evidence from trials and large observational studies that demonstrate a reduction in AIDS and non-AIDS morbidity and mortality with antiretroviral therapy (ART) across a wide range of CD4 cell counts has led to the recommendation by many experts for ART initiation regardless of CD4 cell count. (See "When to initiate antiretroviral therapy in HIV-infected patients", section on 'Benefits of antiretroviral therapy'.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Cooper DA, Gold J, Maclean P, et al. Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. Lancet 1985; 1:537.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf (Accessed on May 01, 2014).
- Daar ES, Pilcher CD, Hecht FM. Clinical presentation and diagnosis of primary HIV-1 infection. Curr Opin HIV AIDS 2008; 3:10.
- Kelley CF, Barbour JD, Hecht FM. The relation between symptoms, viral load, and viral load set point in primary HIV infection. J Acquir Immune Defic Syndr 2007; 45:445.
- Lavreys L, Baeten JM, Chohan V, et al. Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women. Clin Infect Dis 2006; 42:1333.
- Kassutto S, Maghsoudi K, Johnston MN, et al. Longitudinal analysis of clinical markers following antiretroviral therapy initiated during acute or early HIV type 1 infection. Clin Infect Dis 2006; 42:1024.
- Le T, Wright EJ, Smith DM, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013; 368:218.
- Phillips AN, Gazzard B, Gilson R, et al. Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count. AIDS 2007; 21:1717.
- HIV-CAUSAL Collaboration, Ray M, Logan R, et al. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS 2010; 24:123.
- Sabine C, Antiretroviral Therapy (ART) Cohort Collaboration. AIDS events among individuals initiating HAART: do some patients experience a greater benefit from HAART than others? AIDS 2005; 19:1995.
- Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009; 360:1815.
- Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011; 365:493.
- Minga AK, Lewden C, Gabillard D, et al. CD4 cell eligibility thresholds: an analysis of the time to antiretroviral treatment in HIV-1 seroconverters. AIDS 2011; 25:819.
- Lodi S, Phillips A, Touloumi G, et al. Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count thresholds <200, <350, and <500 Cells/mm³: assessment of need following changes in treatment guidelines. Clin Infect Dis 2011; 53:817.
- 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.
- Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005; 191:1403.
- Cohen MS, Shaw GM, McMichael AJ, Haynes BF. Acute HIV-1 Infection. N Engl J Med 2011; 364:1943.
- Pilcher CD, Tien HC, Eron JJ Jr, et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004; 189:1785.
- Xiridou M, Geskus R, de Wit J, et al. Primary HIV infection as source of HIV transmission within steady and casual partnerships among homosexual men. AIDS 2004; 18:1311.
- Abu-Raddad LJ, Longini IM Jr. No HIV stage is dominant in driving the HIV epidemic in sub-Saharan Africa. AIDS 2008; 22:1055.
- Brenner BG, Roger M, Routy JP, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 2007; 195:951.
- O'Brien M, Markowitz M. Should we treat acute HIV infection? Curr HIV/AIDS Rep 2012; 9:101.
- Volz EM, Ionides E, Romero-Severson EO, et al. HIV-1 transmission during early infection in men who have sex with men: a phylodynamic analysis. PLoS Med 2013; 10:e1001568; discussion e1001568.
- 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.
- Chun TW, Justement JS, Moir S, et al. Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: implications for eradication of virus. J Infect Dis 2007; 195:1762.
- Jain V, Hartogensis W, Bacchetti P, et al. Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J Infect Dis 2013; 208:1202.
- Ananworanich J, Vandergeeten C, Chomchey N, et al. Early ART intervention restricts the seeding of the HIV reservoir in long-lived central memory CD4 T cells. Presented at the 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, March 3-6, 2013. Abstract 47.
- Henrich TJ, Gandhi RT. Early treatment and HIV-1 reservoirs: a stitch in time? J Infect Dis 2013; 208:1189.
- Hey-Cunningham WJ, Murray JM, Natarajan V, et al. Early antiretroviral therapy with raltegravir generates sustained reductions in HIV reservoirs but not lower T-cell activation levels. AIDS 2015; 29:911.
- Martínez-Bonet M, Puertas MC, Fortuny C, et al. Establishment and Replenishment of the Viral Reservoir in Perinatally HIV-1-infected Children Initiating Very Early Antiretroviral Therapy. Clin Infect Dis 2015; 61:1169.
- 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.
- Rosenberg ES, Altfeld M, Poon SH, et al. Immune control of HIV-1 after early treatment of acute infection. Nature 2000; 407:523.
- Oxenius A, Price DA, Easterbrook PJ, et al. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc Natl Acad Sci U S A 2000; 97:3382.
- Titanji K, Chiodi F, Bellocco R, et al. Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions. AIDS 2005; 19:1947.
- Günthard HF, Aberg JA, Eron JJ, et al. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA 2014; 312:410.
- Yanik EL, Napravnik S, Hurt CB, et al. Prevalence of transmitted antiretroviral drug resistance differs between acutely and chronically HIV-infected patients. J Acquir Immune Defic Syndr 2012; 61:258.
- Jain V, Liegler T, Vittinghoff E, et al. Transmitted drug resistance in persons with acute/early HIV-1 in San Francisco, 2002-2009. PLoS One 2010; 5:e15510.
- Hurt CB, McCoy SI, Kuruc J, et al. Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. Antivir Ther 2009; 14:673.
- Metzner KJ, Rauch P, von Wyl V, et al. Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy. J Infect Dis 2010; 201:1063.
- 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.
- 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.
- Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283.
- Danel C, Moh R, Minga A, et al. CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial. Lancet 2006; 367:1981.
- 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.
- Luzuriaga K, Tabak B, Garber M, et al. HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment. J Infect Dis 2014; 210:1529.
- Hatano H et al. Lack of detectable HIV DNA in a PrEP study participant treated during “hyperacute” HIV infection. Presented at the 21st Conference on Retroviruses and Opportunistic Infections, Boston, MA, March 3-6, 2014. Abstract #397LB
- Sáez-Cirión A, Bacchus C, Hocqueloux L, et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog 2013; 9:e1003211.
- Persaud D, Gay H, Ziemniak C, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med 2013; 369:1828.
- Luzuriaga K, Gay H, Ziemniak C, et al. Viremic relapse after HIV-1 remission in a perinatally infected child. N Engl J Med 2015; 372:786.
- 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.
- Fidler S and the SPARTAC Trials investigators. The effect of short-course antiretroviral therapy in primary HIV infection: final results from an international randomised controlled trial; SPARTAC. Presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention, Rome, Italy, July 17-20, 2011, #WELBX06
- 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.
- Volberding P, Demeter L, Bosch RJ, et al. Antiretroviral therapy in acute and recent HIV infection: a prospective multicenter stratified trial of intentionally interrupted treatment. AIDS 2009; 23:1987.
- Hecht FM, Wang L, Collier A, et al. A multicenter observational study of the potential benefits of initiating combination antiretroviral therapy during acute HIV infection. J Infect Dis 2006; 194:725.
- Seng R, Goujard C, Desquilbet L, et al. Rapid CD4+ cell decrease after transient cART initiated during primary HIV infection (ANRS PRIMO and SEROCO cohorts). J Acquir Immune Defic Syndr 2008; 49:251.
- Pantazis N, Touloumi G, Vanhems P, et al. The effect of antiretroviral treatment of different durations in primary HIV infection. AIDS 2008; 22:2441.
- Lodi S, Meyer L, Kelleher AD, et al. Immunovirologic control 24 months after interruption of antiretroviral therapy initiated close to HIV seroconversion. Arch Intern Med 2012; 172:1252.
- Hoen B, Fournier I, Lacabaratz C, et al. Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial. J Acquir Immune Defic Syndr 2005; 40:307.
- SPARTAC Trial Investigators, Fidler S, Porter K, et al. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med 2013; 368:207.
- DECISION TO INITIATE ANTIRETROVIRAL THERAPY DURING EARLY HIV INFECTION
- Rationale for initiation of ART in early infection
- - Effect on symptomatic disease
- - Improved clinical markers of disease
- - Interval until treatment criteria are met is short
- - Decreased risk of transmission
- - Decreased viral reservoir and improved markers of immune cell function
- Potential risks
- Recommendations from expert groups
- Our approach
- MANAGEMENT OF EARLY HIV INFECTION
- Patients who initiate antiretroviral therapy
- - Treatment setting
- - Selection of antiretroviral regimen
- - Monitoring during antiretroviral therapy
- - Duration of treatment
- Patients who defer antiretroviral therapy
- CAN ART IN EARLY INFECTION ALTER DISEASE COURSE?
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS