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Acute HIV Infection

Acute HIV Infection. September 13, 2007 H. Nina Kim MD, MS I-TECH/University of Washington Distance Learning Clinical Seminar Series. Case. 25 yo sexually active woman presents with a 3-week hx fever, fatigue, HA, mild sore throat. On physical exam, the patient is alert & oriented.

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Acute HIV Infection

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  1. Acute HIV Infection September 13, 2007 H. Nina Kim MD, MS I-TECH/University of Washington Distance Learning Clinical Seminar Series

  2. Case • 25 yo sexually active woman presents with a 3-week hx fever, fatigue, HA, mild sore throat. • On physical exam, the patient is alert & oriented. • T 38.2 C. A maculopapular rash is present over trunk & face. A few ulcers are seen on soft palate. • Cervical lymph nodes are slightly enlarged, and her neck is stiff. Pelvic exam shows mild cervicitis. • WBC 3.6, Hct 34%, platelets 90,000. Monospot & serum RPR are negative. A cervical swab reveals Neisseria gonorrhoeae by DNA probe.

  3. Case Which of the following is the most likely diagnosis? • Acute HIV infection • Cytomegalovirus mononucleosis • Primary herpes simplex virus infection • Secondary syphilis • Disseminated gonococcal infection

  4. Acute HIV Infection • Epidemiology • Clinical Features • Differential • Diagnosis • (Treatment)

  5. Epidemiology • 4.3 million people newly infected with HIV in 2006 per UNAIDS estimates

  6. Important to capture acute HIV infection • Early entry into clinical care &/or study • Public health implications – Reduce secondary transmission: • Patients with acute HIV infection (AHI) higher-risk behavior • AHI index cases reported 4.85 partners per 6 months • CHI “controls” reported 1.1 partners per 6 months Pilcher et. al. CROI 2006; Abstract #371. • Patients with AHI have higher viral levels in plasma and genital secretions

  7. Risk of HIV Transmission byStage of Infection Cohen & Pilcher. J Infect Dis 2005;191(9):1391-3..

  8. High Per-Partnership Transmission

  9. A Missed Opportunity… • But detection of acute HIV not common: • Among 46 prospectively identified recent seroconverters, 41 (89%) recalled symptoms of acute retroviral syndrome. Only 25% were diagnosed acute HIV at the 1st presentation. Schacker et. al. Ann Intern Med 1996;125:257. • In another study, among 50 recent seroconverters who were symptomatic & presented to medical care, only 8 (16%) correctly diagnosed. Celum et. al. J Infect Dis 2001;183:23.

  10. Why Missed? • Wide range in clinical manifestations • Non-specific signs & symptoms • Lack of clinical suspicion • Asking difficult questions: You need to elicit exposure history! • Diagnostic Testing: • Not readily available • Lack of understanding

  11. A “Flu-like” Illness • 1985, a “mononucleosis-like” syndrome preceding seroconversion described • 11 of 12 men who had sex w/ men (MSM) • Sudden onset, lasting from 3-14 days • Clinical features: • Fever/sweats • Headaches, malaise, anorexia • Lethargy, myalgias/arthralgias • Generalized LAN • Rash: “erythematous maculopapular truncal eruption” DA Cooper et.al., Lancet 1985;1:537.

  12. Signs & Symptoms JO Kahn & B Walker, N Engl J Med 1998;339:35.

  13. JO Kahn & B Walker, N Engl J Med 1998;339:36.

  14. Differential Diagnosis • Infectious mononucleosis (primary acute EBV, CMV) • Secondary syphilis • Hepatitis A or B (acute infection) • Malaria • Typhoid fever • Toxoplasmosis • Aseptic meningitis • Viral pharyngitis; influenza • Drug reaction

  15. E Daar et.al., Ann Intern Med 2001;134:25-9.

  16. Predictors of Acute HIV • Prospective study of 1053 HIV-negative female sex workers in Mombasa, Kenya • N=162 women seroconverted • Clinical scoring system: ≥2 S/Sx  51% sensitivity & 83% specificity for detecting acute HIV L Lavreys et.al., Clin Infect Dis 2000;30:488.

  17. Timeline of Events Viral Set point

  18. Diagnostic Tests • Acute or Primary HIV Infection • Negative ELISA + positive HIV viral RNA • Negative ELISA + positive p24 antigen • Early HIV Infection • Positive ELISA + indeterminate Western Blot • Positive ELISA + evolving Western Blot • Positive ELISA + negative “detuned” Ab test • Positive ELISA + negative ELISA x 6 mon ago

  19. Time Course Pilcher C et al, J Clin Investigation 2004;113:937.

  20. Evolution of Tests during Acute  Early HIV Infection E Fiebig et.al., AIDS 2003;17:1871-9.

  21. Evolving Western Blots TC Quinn, JAMA 1997;278:59.

  22. HIV p24 Antigen CD Pilcher et. al, Ann Intern Med 2002;136:488.

  23. HIV Viral Load TW Schacker et al, Ann Intern Med 1998;128:615.

  24. Screening by Pooled HIV RNA CD Pilcher, et. al. JAMA 2002;288:216.

  25. Resolution Testing A Individual testing on 10 specimens 10 pools of 10 screened 20 Screening Pools Tested N=2000

  26. Low Complexity TestingOptions for Resource-Limited Settings • Dried blood spots with central HIV RNA testing in major lab centers (Uganda, Brazil) • p24 Ag EIAs • Fourth generation EIA (p24 Ag/Ab combo) • Dual rapid antibody testing • Point-of-care rapid NAAT …

  27. Viral Setpoints & Outcome Multicenter AIDS Cohort Study RH Lyles et. al. J Infect Dis 2000;181:878.

  28. Symptoms of Acute Retroviral Syndrome & Outcome Prospective cohort study of Kenyan women L Lavreys et. al. Clin Infect Dis 2006;42:1333.

  29. Why Study Acute HIV Infection?Because Treatment may: • Alter initial viral set point & delay disease progression • Lower viral diversification • Reduce severity of acute retroviral sx’s • Diminish 2° HIV transmission • Preserve critical immune function

  30. But Treatment of Acute HIV may also come with Risks: • Medication toxicities extended over longer duration • Impact on quality of life • Drug resistance • ? Duration of therapy

  31. Remaining Questions • Can early treatment & viral suppression provide longterm immune preservation? • How soon must Tx be initiated to observe sustained immunologic benefits? • What is optimal duration of Tx? • Safety & adherence in this early group?

  32. Signs & Symptoms Suggesting Acute HIV? • Most predictive • Fever • Rash • Myalgias/Arthralgias • Lymphadenopathy • Pharyngitis • Less suggestive • Cough • Coryza • Helpful • Leukopenia, Thrombocytopenia Risk Factors & Exposures • Unprotected Sexual Intercourse (oral, anal, vaginal) • Sharing needles (injection drug use) • Has HIV-infected sexual or IVDU partner • Men who have sex with men (MSM) • Partner of MSM • Hx STDs or ulcerative oral/genital lesions HIV Ab Test(s), p24 Ag, HIV viral RNA

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