Care Primary Care Issues in HIV David H. Spach, MD The International AIDS Society–USA DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June

Primary CareCare Issues in HIVPrimary CareCare Issues in HIV

David H. Spach, MD

The International AIDS Society–USADH Spach, MD.Presented at IAS–USA/RWCA Clinical Conference, June 2005.

Slide #2

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005.

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

Slide #3

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005.DHS/HIV/PP

Hepatitis A and B Vaccination

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Hepatitis A & B Vaccination Practices for Ambulatory Patients with HIV-Infection

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Screened Eligible for Vaccine Vaccinated (> 1 dose) Vaccinated (Series)

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

Study Design Results

From: Tedalid EM et al. Clin Infect Dis 2004;38:1478-84.

Slide #5


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

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.”

DHS/HIV/PP


Slide #7

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS//HIV/PP

ACIP: Hepatitis B Vaccine Recommendations

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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

Indications & Schedule HBV: anti-HBs Titers

*TWINRIX= HAVRIX 720 EL.U plus ENGERIX 20 ug

From: CDC National Immunization Program. 2004-2005 ACIP Recommendations.

Slide #8


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)

DHS/HIV/PP

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

Hepatitis B Core (Capsid)

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DHS/PP

HBV Vaccine: Naive & Anamnestic Responses

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HBV Vaccination Series

10 IU/L

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Isolated anti-HBc in HIV-Infected Persons

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anti-HBc(-) All anti-HBe(-) anti-HBe(+)

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

Study Design Patients with Anamnestic Response

From: Gandi RT, et al. J Infect Dis 2005;191:1435-41.

*Defined as anti-HBs titer > 10 IU/L within 4 weeks of vaccination

DHS/HIV//PP

anti-HBc+

Slide #11


Isolated HBcAb in HIV-Infected Persons Conclusions

• “After hepatitis B vaccination, the anamnestic response rate in HIV-1–positive 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.”

DHS/HIV/PP

From: Gandi RT, et al. J Infect Dis 2005;191:1435-41.

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HIV and Hepatitis B VaccineStandard Dose versus Double Dose

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Double-Dose

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

Study Design Seroconversion* Rate

From: Fonseca MO, et al. Vaccine 2005;23:2902-8. *Anti-HBsAB titer > 10 IU/L

Slide #13

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS/PP

ACIP: Hepatitis A Vaccine Recommendations

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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

Indications & Schedule Protective Titers Used In Studies

From: CDC National Immunization Program. 2004-2005 ACIP Recommendations.

Cut-Off, Range 20-33(Modified Enzyme Immunoassay)

*TWINRIX= HAVRIX 720 EL.U plus ENGERIX 20 ug

Cut-Off, Range 10-20 (Radioimmunoassay)

Slide #14

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS/HIV/PP

Hepatitis A Vaccine in HIV-Infected Adults

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Months After Vaccination

CD 4 Count <500 CD4 Count 200-500 CD4 Count < 200

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

Study Design HAV Seroconversion*

From: Kemper CA et al. JID 2003;187:1327-31.*Anti-HAV antibody titer > 33 mIU/mlVaccine had no effect on HIV RNA or CD4 count

Slide #15

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS/HIV/PP

Hepatitis A Vaccine in HIV-Infected Adults

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Week 28

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CD4 Count > 300

CD4 Count < 300

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

Study Design HAV Seroconversion Week 28*

From: Wallace MR, et al. CID 2004;39:1207-13.*Anti-HAV antibody titer > 10 mIU/mlVaccine had no effect on HIV RNA or CD4 count

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Screening for Cervical Abnormalities

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DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005.DHS/PP

HIV Classification HPV-Related Conditions

Category B Conditions- Cervical Dysplasia (Moderate or Severe)- Cervical Carcinoma in Situ

Category C Conditions- Invasive Cervical Cancer

From: CDC & Prevention. MMWR. 1992;41 (RR-17):1-19.

Cancer

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PAP Smears in HIV-Infected PersonsRecommendations from IDSA OI Prophylaxis Guidelines

DHS/PP

Picture

Initial Evaluation: Twice in First Year after HIV Diagnosis

Manage According to NCI Consensus Panel Interim Guidelines for Abnormal Cervical Cytology

Annual Screening

From: 2001 USPHS/IDSA Prevention of OI Guidelines [www.aidsinfo.nih.org]

Normal Abnormal

Rescreen Annually

AbnormalNormal

Slide #19

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS/HIV//PP

Guidelines for Approach to Abnormal Cervical Cytology

Pap Smear Result Recommendation

ASCUS (with Severe Inflammation)Evaluate for infection; if found, treat and recheck PAP in 2-3 months

ASCUSFollow-up PAP q 4-6 months x 2 yrs (until 3 consecutive PAPs negative)

If another ASCUS, consider colposcopy

ASCUS (Neoplastic Process Suspected)Follow-up PAP q 4-6 months; ORColposcopy & biopsy if LSIL persists; OR Immediate colposcopy

Low-grade squamous intraepithelial lesion (LSIL)

Follow-up PAP q 4-6 months; ORColposcopy & biopsy if LSIL persists; OR Immediate colposcopy

High-grade squamous intraepithelial lesion (CIN 2 or 3, carcinoma in situ) OR

Squamous cell carcinomaColposcopy & biopsy of Abnormal Area;

From: 2001 USPHS/IDSA Prevention of OI Guidelines [www.aidsinfo.nih.org]

Slide #20

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS/HIV/Women/PP

HIV & Women: Frequency of Pap Smears

A Guide to the Clinical Care of Women with HIV/AIDS < http://hab.hrsa.gov/publications/womencare.htm>

ASCUS = atypical squamous cells of undetermined significanceLGSIL = low grade squamous intraepithelial lesion

Clinical Scenario Screening Frequency

Normal Pap 1 Year

Symptomatic InfectionCD4 < 200

6 Months

ASCUS/LGSIL (evaluated and followed without Rx)

4-6 Months

Following treatment of preinvasive lesions

3-4 Months for first year, then 6 Months

Slide #21

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005.DHS/HIV/Women/PP

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 Clinics*

<http://hab.hrsa.gov/tools/primarycareguide>

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HPV-16 Vaccine in Women

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Placebo 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

Study Design Persistent HPV-16 Infection

From: Koutsky L et al. N Engl J Med 2002;347:1645-51.

P < 0.001

*HPV virus-like particle vaccineCervical Intraepithelial Neoplasia- Placebo: 9 cases - Vaccine: 0 cases

Slide #23

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS/PP

HPV-16 & HPV-18 Vaccine in Women

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Placebo 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

Study Design Persistent HPV-16/18 Infection

From: Harper D et al. Lancet 2004;364:1757-65.

P < 0.001

*HPV virus-like particle vaccine

P < 0.001

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Evaluation & Management of Renal Disease

Recommendations from HIVMA-IDSA

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Screening for Renal Disease in HIV-Infected PersonsRecommendations from HIVMA-IDSA

DHS/PP

Picture

Screening Studies at Initial Evaluation - Urine analysis (for proteinuria) - Serum Creatinine (to estimate Ccl or GFR)

Abnormal Value- Grade > 1 proteinuria by dipstick- Ccl or GFR < 60 mL/min per 1.73m2

No Abnormal Value

From: Gupta SK, et al. Clin Infect Dis 2005;40:1559-85.

Risk Factors Present - Rescreen Annually

Risk Factors Absent - Follow Clinically

Further Evaluation- Spot Urine Prot/Creat Ratio- Renal Ultrasound - Consider Nephrology Referral

Slide #26


Screening for Renal Disease in HIV-Infected PersonsRecommendations from HIVMA-IDSA

DHS/PP

Picture

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 < 200 cells/mm3

- HIV RNA > 4,000 copies/ml- Diabetes mellitus- HTN- Chronic HCV Infection


Risk Factors* Present - Rescreen Annually

Risk Factors* Absent - Follow Clinically

Slide #27

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005.DHS/PP

1. Control BP < 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

Management of Nephropathy in HIV-Infected PersonsKey Recommendations from HIVMA-IDSA


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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 < 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 Cushing’s syndrome from fluticasone 3. Renal toxicity caused by tenofovir 4. Lopinavir-ritonavir hepatotoxicity

DHS/HIV/PP

Slide #30


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

DHS/HIV/PP

Slide #31

DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June 2005. DHS/ HIV/PP

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 patient’s 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

Documents

Care Primary Care Issues in HIV David H. Spach, MD The International AIDS Society–USA DH Spach, MD. Presented at IAS–USA/RWCA Clinical Conference, June