NORTHWEST AIDS EDUCATION AND TRAINING CENTER Primary Care of the HIV Infected Patient: 2014 Robert D. Harrington, M.D.
Primary Care of the HIV Infected Patient: 2014 Primary Care Guidelines for the Management of Persons Infected with HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America (Clinical Infectious Diseases, November, 2013)
Primary Care of the HIV Infected Patient: 2013 The Initial Evaluation Opportunistic Infection Prophylaxis Starting Antiretroviral Therapy Follow-up Care Laboratory Cancer screening Vaccinations STD screening Metabolic disorders
The Initial Evaluation
Case 1 A 23 year old gay man presents after testing positive for HIV by rapid test at a night club. This is his first ever HIV test. He is sexually active with men exclusively, has ~ 10 partners per year and does not regularly use protection. He is well and without symptoms His PMH is notable for depression, a history of methamphetamine use, gonorrhea and syphilis He is a college graduate, works in retail, drinks 6 beers on weekend nights, smokes ½ ppd and no longer uses illicit drugs His physical exam is normal
Case 1 Elements of a comprehensive HIV history and exam! Dates of HIV testing (negative and first positive) ARV history (including adherence, drug resistance and drug intolerances), CD4 nadir and HIV RNA zenith HIV related illnesses Cardiac, renal and hepatic disease history TB exposure and risk Travel and residence history (exposure to dimorphic fungi) Mental health and substance abuse history Sexual and STD history Partner s HIV status Medications (watch for significant drug interactions) Physical exam particular attention to skin, mouth, lymphnodes, neurological and cognitive exam, anogenital exam, fat distribution and evidence for liver disease
Case 1 What laboratory testing is indicated at the initial visit?! HIV serology CD4 count (absolute and percent) HIV RNA level HIV genotypic resistance testing CBC, chemistries and urinalysis Fasting lipids G6PD level TST or IGRA Toxoplasma serology Syphilis serologies (IgG if no h/o disease, otherwise RPR or VDRL) Hepatitis B sag, sab, cab if isolated cab, check HBV DNA Hepatitis C AB (repeat annually if at risk), if AB+, check HCV RNA Hepatitis A AB CMV AB (if at low risk for infection, not MSM or IDU)
Occult HBV infection with isolated HBcAb Swiss cohort study: 57 patients with isolated HBcAb: Over time HBV DNA + in 51/57 (89.5%) (Eur J Clin Microbiol Infect Dis, 1998) Range in other studies from 0.6 to 83.3% - Khamduang, Clin Infect Dis, 2013 24% - Karaosmanoglu, HIV Clin Triala, 2013 7.5% - DiLello, Enferm Infecc Microbiol Clin, 2012 0.7% - N Dri-Yoman, Antivir Ther, 2010 10% - Ramia, Int J STD AIDS, 2008 83.3% - Azadmanesh, Intervirology, 2008 13.6% - Neau, Clin Infect Dis, 2005 0.6%
Case 1 What about an STD evaluation? - All women should be screen for Trichomoniasis - Men and women should be screened for GC and Chlamydia - Anyone testing + for GC or Chlamydia or Trichomoniasis should be retested in 3 months due to high rates of re-infection Cervical cancer screening? - Pap smear on presentation and a second one 6 months later then annually (if normal). If abnormal (any abnormality), refer for colposcopy Anal cancer screening? - Anyone practicing RAI or with a h/o genital warts and women with abnormal pap smears should have an anal pap smear (weak recommendation, moderate quality evidence) Testosterone testing? - In men with decreased libido, ED, reduced bone mass, hot flashes: test morning testosterone levels
Follow-up Care Cancer screening Women: pap smears annually Women: mammograms annually > age 50 and individualized for those 40-49 Colon cancer screening: > 50; colonoscopy every 5-10 years or annual FOBT Anal cancer screening?
Anal Pap Smears? High anal cancer rates (up to 137/100,000 py in MSM)! High rates of anal HPV + SIL in HIV+ women with cervical SIL! High grade SIL can progress to invasive cancer! Anal Pap smears can detect anal dysplasia (sensitivity ~69-93%)! IRC provides a safe and effective means to treat lesions (AIN2-3)! Survival from anal cancer is much improved if detected early!! Anal dysplasia rates 41-97% (M) and 14-28% (W)! Anal dysplasia can regress spontaneously! Anal Pap smear specificity 32-59%! Variable correlation between cytology and Bx results! No evidence that anal Paps improve outcomes! Low availability of HRA and IRC! Calore, Diagnostic Cytol 2010! Hessol AIDS 2013! Tandon Am J OBGYN 2010! Berry Int J Cancer 2014! Sirera AIDS 2013! Nathan AIDS 2010! Chiao, CID, 2006!
Anal cancer screening: Madison Clinic Routine anal Pap smears are not done. Individuals with a h/o anal warts need annual DRE and anoscopy Individuals with ongoing anal symptoms needs semiannual DRE and anoscopy Individuals with a h/o anal cancer or anal dysplasia on previous studies should be referred for HRA
Case 1 Vaccinations? - Influenza (inactivated) annually - S. pneumonia: PCV-13 once and Pnvax 23 twice, 5 years apart - HPV: women 9-26, men 9-21 and consider 22-26 - HAV: if HAV AB negative test for seroconversion and re-vaccinate if NR - HBV: (40ug Recombivax x 3 OR 2-20ug doses of Energix B x 4) if sag negative and sab < 10. Consider, if isolated cab+ and HBV DNA negative - MMR: if not immune and CD4 > 200 - TDAP: once as an adult - Varicella: if not immune and CD4 > 200 - Zoster vaccine: consider in those > 60 and with CD4 > 200
Vaccinations Hepatitis A vaccine - Sero-reversion to negative happens in ~ 10% of patients. Hepatitis B vaccine - IDSA vaccination guidelines say consideration of the higher (40 ug) dosing - Better response rates are reported with 40 ug dose When patients are on ART with a suppressed viral load At higher CD4 count - Isolated HBcAb: check for HBV DNA: if negative then vaccinate with 3 dose series Zoster vaccine - Listed as contraindicated in HIV+ persons in the IDSA vaccination guidelines - Preliminary results of zoster vaccination of 286 HIV+ persons on stable ART showed safety and immunogenicity
Opportunistic Infection Prophylaxis
Primary Prophylaxis Infection Criteria Treatment PCP CD4 < 200 or CD4% < 14 or Thrush or ADI Tuberculosis PPD > 5 mm INH Toxoplasmosis IgG+ and CD4 < 100 MAC CD4 < 50 Azithromycin VZV CD4 > 200 Vaccine HAV HBV Streptococcus pneumoniae Influenza TMP/SMX or dapsone or atovaquone or aerolsolized pentamidine TMP/SMX or dapsone + pyrimethamine + leukovorin Vaccine Vaccine Vaccine Vaccine
Follow-up Care
Follow-up Care Laboratory HIV RNA: every 3-4 months, may be extended to every 6 months if suppressed for 2-3 years CD4: every 3-4 months, may be extended to every 6-12 months in those with good CD4 reconstitution HCV AB testing annually for those at risk Repeat TST or IGRA for those who tested negative initially and had low CD4 counts and who now have CD4 > 200 Special tests: CCR5 testing of virus (if considering maraviroc) and HLA-B5701 testing (if considering abacavir) Repeat genotype resistance if there has been a delay since initial visit (superinfection) Vaccinations Influenza (inactivated) annually S. pneumonia: PCV-13 (once lifetime) and Pnvax23 (once and repeat in 5 years) STD screening Annual testing for those at risk Re-testing 3 months after any positive test for GC, CT or Trichomonas Metabolic disorders FBS, A1C and fasting lipids before and 1-3 months after starting ART Bone densitometry: in post menopausal women and men > 50
IGRA Results and CD4 Count Prospective longitudinal study of 830 HIV+ patients at a single center Distribution of QuantiFERON-TB Gold In Tube assay results according to the actual CD4>+ T cell count and the CD4>+ T cell nadir. *P<.001 and **P<.05, Indeterminate test results at lower CD4 counts Aichelburg M C et al. Clin Infect Dis. 2009;48:954-962
Tuberculosis Immune Responses and CD4 Count Frequencies of positive immune responses in HIV-infected persons from Kampala Uganda, with <100, 100 250 and >250 CD4+ T-cells and HIV-uninfected controls T-Spot.TB test ( ), QuantiFERON-TB ( ;), TST 5 mm ( ), 10 mm ( ) 15mm ( ).! Leidl Eur Respir J 2010: ;35:619-26!
HIV Superinfection? Worldwide cases of HIV-1 superinfection! Rates of superinfection 0 to 7.7 % per yr! More common early after infection but has been! reported up to 2 years post-infection! Redd AD, Lancet Infectious Diseases, Volume 13, Issue 7, 2013, 622-628
Questions!