Primary Care Issues in HIV

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Primary Care Issues in HIV
David H. Spach, MD
DH Spach, MD.Presented at IASUSA/RWCA Clinical
Conference, June 2005.
The International AIDS SocietyUSA
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Primary Care Issues in HIV

• Hepatitis B Vaccination
• Hepatitis A Vaccination
• Screening for Cervical Abnormalities
• Evaluation of Renal Disease
• Adverse Drug Effects Case Studies

DHS/HIV//PP
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• Hepatitis A and B Vaccination

DHS/HIV/PP
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Hepatitis A B Vaccination Practices for
Ambulatory Patients with HIV-Infection
Study Design
Results

• Methods- 9 Clinic (HOPS) Sites- N 1071 in
  study- Analysis of HOPS data base

From Tedalid EM et al. Clin Infect Dis
2004381478-84.
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Hepatitis A B Vaccination Practices for
Ambulatory Patients with HIV-Infection Provider
Reasons for Not Vaccinating

• (1) Patient did not regularly attend clinic
• (2) Patient not considered high risk
• (3) CD4 cell count considered too low
• (4) Insurance would not pay for immunization

From Tedalid EM et al. Clin Infect Dis
2004381478-84.
DHS/HIV/PP
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Hepatitis A B Vaccination Practices for
Ambulatory Patients with HIV-Infection
Conclusions

• Although there were low rates of complete
  hepatitis vaccination in this cohort of
  ambulatory patients, prompt efforts to vaccinate
  patients entering care, receipt of antiretroviral
  therapy, and practice reminder systems may
  enhance vaccination practices.

From Tedalid EM et al. Clin Infect Dis
2004381478-84.
DHS/HIV/PP
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ACIP Hepatitis B Vaccine Recommendations
Indications Schedule
HBV anti-HBs Titers

• Vaccine Indications - All HIV-infected persons
  without evidence of prior HBV infection
• Vaccine Schedule (Adults) - ENGERIX-B 20 ug
  (0,1,6 m) - RECOMBIVAX HB 10 ug (0,1,6m) -
  TWINRIX 0,1,6m
• Post-Vaccine Antibody Testing - Test 1-6 months
  after series

TWINRIX HAVRIX 720 EL.U plus ENGERIX 20 ug
From CDC National Immunization Program.
2004-2005 ACIP Recommendations.
DHS//HIV/PP
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HBV Isolated anti-HBc

• Definition of Isolated anti-HBc-HBsAg
  negative-anti-HBs negative-anti-HBc positive
• Possible Explanations(1) False positive(2)
  Remote infection (resolved)(3) Remote infection
  (persistent/occult)(4) Acute infection IgM
  (window)

Hepatitis B Core (Capsid)
DHS/HIV/PP
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HBV Vaccine Naive Anamnestic Responses
Anamnestic Response
Naive Response
10 IU/L
HBV Vaccination Series
DHS/PP
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Isolated anti-HBc in HIV-Infected Persons
Study Design
Patients with Anamnestic Response

• Methods- N 69 HIV-infected adults- All
  HBsAg(-) and anti-HBs(-)- 40 (58) of 69
  anti-HBc(-)- 29 (42) of 69 anti-HBc()
  Approx 50 of anti-HBc() also anti-HBe()
• Intervention HBV Vaccine- Outcome Anamnestic
  Response

Defined as anti-HBs titer gt 10 IU/L within 4
weeks of vaccination
anti-HBc
From Gandi RT, et al. J Infect Dis
20051911435-41.
DHS/HIV//PP
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Isolated HBcAb in HIV-Infected Persons
Conclusions

• After hepatitis B vaccination, the anamnestic
  response rate in HIV-1positive subjects who
  tested positive for isolated anti-HBc but
  negative for anti-HBe was low and was comparable
  to that in subjects who tested negative for
  anti-HBc.
• This finding suggests that testing for anti-HBc
  alone may not be a reliable assessment of
  protection from HBV infection.

From Gandi RT, et al. J Infect Dis
20051911435-41.
DHS/HIV/PP
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HIV and Hepatitis B VaccineStandard Dose versus
Double Dose
Study Design
Seroconversion Rate

• Methods - N 210 HIV-infected adults - HBV
  negatives
• HBV Vaccine (Engerix) Dosing - Standard 20 ug
  at 0,1, 6 m - Double dose 40 ug at 0,1 6m
• Major Measurement - anti-HBsAb

Standard

100
Double
-
Dose

80
64
60
47
Patients ()
39
40
34
26
24
20
0
All
CD4 gt 350
CD4 lt 350
From Fonseca MO, et al. Vaccine 2005232902-8.
Anti-HBsAB titer gt 10 IU/L
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ACIP Hepatitis A Vaccine Recommendations
Indications Schedule
Protective Titers Used In Studies

• Vaccine Indications - Travel to endemic
  region - Male-male sex - Injection-drug use
  - Chronic liver disease - Clotting factor
  disorders
• Vaccine Schedule (Adults) - HAVRIX 1440 EL.U
  (0, 6-12m) - VAQTA 50 U (0, 6-12m) - TWINRIX
  0,1,6m

Cut-Off, Range 20-33(Modified Enzyme Immunoassay)
Cut-Off, Range 10-20 (Radioimmunoassay)
TWINRIX HAVRIX 720 EL.U plus ENGERIX 20 ug
From CDC National Immunization Program.
2004-2005 ACIP Recommendations.
DHS/PP
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Hepatitis A Vaccine in HIV-Infected Adults
Study Design
HAV Seroconversion

• Methods - N 133 HIV-infected adults - HAV
  seronegative
• Study Groups (0, 6 months) - HAV vaccine
  (HAVRIX)1440 EIU - Saline placebo
• Outcomes - Vaccine responses - Affect on HIV
  RNA CD4

Anti-HAV antibody titer gt 33 mIU/mlVaccine had
no effect on HIV RNA or CD4 count
From Kemper CA et al. JID 20031871327-31.
DHS/HIV/PP
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Hepatitis A Vaccine in HIV-Infected Adults
Study Design
HAV Seroconversion Week 28

• Methods - N 90 HIV-infected adults - N
  90 HIV-seronegative adults - HAV seronegative
• Study Groups (0, 6 months) - HAV vaccine
  (VAQTA)50 EIU - Saline placebo
• Outcomes - Vaccine responses - Affect on HIV
  RNA CD4

Anti-HAV antibody titer gt 10 mIU/mlVaccine had
no effect on HIV RNA or CD4 count
From Wallace MR, et al. CID 2004391207-13.
DHS/HIV/PP
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• Screening for Cervical Abnormalities

DHS/HIV/PP
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HIV Classification HPV-Related Conditions

• Category B Conditions- Cervical Dysplasia
  (Moderate or Severe)- Cervical Carcinoma in Situ
• Category C Conditions- Invasive Cervical Cancer

Cancer
From CDC Prevention. MMWR. 199241
(RR-17)1-19.
DHS/PP
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PAP Smears in HIV-Infected PersonsRecommendations
from IDSA OI Prophylaxis Guidelines
Initial Evaluation Twice in First Year after HIV
Diagnosis
Normal
Abnormal
Manage According to NCI Consensus Panel Interim
Guidelines for Abnormal Cervical Cytology
Annual Screening
Abnormal
Normal

Rescreen Annually
Picture
From 2001 USPHS/IDSA Prevention of OI Guidelines
www.aidsinfo.nih.org
DHS/PP
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Guidelines for Approach to Abnormal Cervical
Cytology
From 2001 USPHS/IDSA Prevention of OI Guidelines
www.aidsinfo.nih.org
DHS/HIV//PP
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HIV Women Frequency of Pap Smears
ASCUS atypical squamous cells of undetermined
significance LGSIL low grade squamous
intraepithelial lesion
A Guide to the Clinical Care of Women with
HIV/AIDS lt http//hab.hrsa.gov/publications/women
care.htmgt
DHS/HIV/Women/PP
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HIV WomenImproving Screening for Cervical
Abnormalities

• Incorporate into Quality Improvement Project
• Computerized Records with Reminders
• Feedback to Providers
• Incorporate Quality Improvement with Provider
  Performance Indicators

Information on Quality Improvement in HIV
Clinicslthttp//hab.hrsa.gov/tools/primarycaregui
degt
DHS/HIV/Women/PP
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HPV-16 Vaccine in Women
Study Design
Persistent HPV-16 Infection

• Background - N 2392 - Females aged 16-23
  - Randomized, double-blind - F/U Median
  17.4 months
• Vaccines (0, 2, and 6 months) - HPV-16
  Vaccine 40 ug - Placebo

P lt 0.001
HPV virus-like particle vaccine
Cervical Intraepithelial Neoplasia- Placebo 9
cases - Vaccine 0 cases
From Koutsky L et al. N Engl J Med
20023471645-51.
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HPV-16 HPV-18 Vaccine in Women
Study Design
Persistent HPV-16/18 Infection

• Background - N 1113 - Females aged 15-25
  - Randomized, double-blind - F/U up to 27
  months
• Vaccines (0, 1, and 6 months) - HPV-16
  Vaccine 40 ug - Placebo

P lt 0.001
P lt 0.001
HPV virus-like particle vaccine
From Harper D et al. Lancet 20043641757-65.
DHS/PP
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• Evaluation Management of Renal Disease
  Recommendations from HIVMA-IDSA

DHS/HIV/PP
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Screening for Renal Disease in HIV-Infected
PersonsRecommendations from HIVMA-IDSA
Screening Studies at Initial Evaluation -
Urine analysis (for proteinuria) - Serum
Creatinine (to estimate Ccl or GFR)
Abnormal Value- Grade gt 1
proteinuria by dipstick- Ccl or GFR lt 60 mL/min
per 1.73m2
No Abnormal Value

Risk Factors Present - Rescreen Annually
Risk Factors Absent - Follow Clinically
Further Evaluation- Spot Urine Prot/Creat
Ratio- Renal Ultrasound - Consider Nephrology
Referral
Picture
From Gupta SK, et al. Clin Infect Dis
2005401559-85.
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Screening for Renal Disease in HIV-Infected
PersonsRecommendations from HIVMA-IDSA
Screening Studies at Initial Evaluation -
Urine analysis (for proteinuria) - Serum
Creatinine (to estimate Ccl or GFR)
No Abnormal Value
Risk Factors for DevelopingProteinuric Renal
Disease- African American- CD4 lt 200
cells/mm3- HIV RNA gt 4,000 copies/ml- Diabetes
mellitus- HTN- Chronic HCV Infection

Risk Factors Present - Rescreen Annually
Risk Factors Absent - Follow Clinically
Picture
From Gupta SK, et al. Clin Infect Dis
2005401559-85.
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Management of Nephropathy in HIV-Infected
PersonsKey Recommendations from HIVMA-IDSA

• 1. Control BP lt 125/75 mm Hg - Preferential
  use of ACE Inhibitors or ARBs if proteinuria -
  Avoid calcium-channel blockers if patient taking
  PI
• 2. Treat HIVAN with HAART at Diagnosis
• 3. Use Additional Therapies for HIVAN Refractory
  to HAART - ACE Inhibitors, ARBs,
  Corticosteroids
• 4. Perform Dialysis if Indicated
• 5. Consider Renal Transplant for ESRD

From Gupta SK, et al. Clin Infect Dis
2005401559-85.
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• Medication-Related Adverse Effects Case Studies

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Case History

• A 38-year-old HIV-infected man with a CD4 count
  of 188 cells/mm3 starts on a regimen of tenofovir
  plus lamivudine plus lopinavir-ritonavir. Other
  medications include inhaled fluticasone,
  montelukast, and trimethoprim-sulfamethoxazole.
• Three months later his HIV RNA is lt 50 copies/ml,
  but at the 3-month visit, he complains of new
  weakness in his upper arms and legs as well as
  puffy cheeks. He also has new onset hypertension
  and hyperglycemia.
• What do you think is the most likely cause of his
  new problems?1. Rapid onset protease
  inhibitor-related lipodystrophy2. Iatrogenic
  Cushings syndrome from fluticasone 3. Renal
  toxicity caused by tenofovir 4.
  Lopinavir-ritonavir hepatotoxicity

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Case History

• A 43-year-old HIV-infected woman with a CD4 count
  of 374 cells/mm3 is admitted to the hospital with
  a severe buttock MRSA abscess. The patient is
  discharged on a 7-day course of linezolid. Two
  days after leaving the hospital, the patient
  comes to the clinic with mental status changes,
  increased muscle tone, tremor, and diarrhea.
  Examination shows T 38.5, agitation,
  hyperreflexia, and clonus.
• Medications (Chronic)- Abacavir-lamivudine-
  Atazanavir- Citalopram- Methadone
• What do you think would best explain the clinical
  course in this patient?1. Linezolid-induced
  opiate withdrawal (decrease in methadone
  level)2. Abacavir hypersensitivity syndrome 3.
  Serotonin syndrome4. Malignant hyperthermia

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Case History

• A 29-year-old man has a CD4 count of 41 and an
  HIV RNA of 134,000 and is admitted to the
  hospital with moderately severe PCP (pO2 73).
  He has a history of Stevens-Johnson syndrome from
  TMP/SMX he receives IV pentamidine 4 mg/kg/d.
  He is on no ARV therapy.
• On the 6th day after admission, the patients
  respiratory status has improved, but he complains
  of sudden onset of headache and blurred vision.
  The nurse notes he is acutely confused and
  minimally responsive. You are immediately
  called. What is likely to be the most effective
  diagnostic measure you could take? 1. Emergent
  contrast brain CT scan2. Stat cryptococcal
  antigen3. Finger stick for glucose level4. Stat
  sodium level

DHS/ HIV/PP