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

•  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

Elements of a comprehensive HIV history and exam !

Case 1

•  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)

What laboratory testing is indicated at the initial visit? !

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! !

Calore, Diagnostic Cytol 2010!Hessol AIDS 2013!Tandon Am J OBGYN 2010!Berry Int J Cancer 2014!Sirera AIDS 2013!

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 !

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 semi-annual 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

TMP/SMX or dapsone or atovaquone or aerolsolized pentamidine

Tuberculosis PPD > 5 mm INH Toxoplasmosis IgG+ and CD4 <

100 TMP/SMX or dapsone + pyrimethamine + leukovorin

MAC CD4 < 50 Azithromycin VZV CD4 > 200 Vaccine HAV Vaccine HBV Vaccine Streptococcus pneumoniae

Vaccine

Influenza 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

Leidl Eur Respir J 2010: ;35:619-26!

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 (▪).!

HIV Superinfection?

Redd AD, Lancet Infectious Diseases, Volume 13, Issue 7, 2013, 622 - 628 !

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!

Questions!