HIV Treatment: Delayed treatment due to lack of laboratory values

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HIV TreatmentDelayed treatment due to lack of
laboratory values?

• By
• Fernando Garcia, MD
• Valley AIDS council
• AIDS Education Training Center

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Objectives

• Review clinical syndromes associated with HIV
  based on CD4 counts
• Describe most common Opportunistic infections in
  HIV positive patients
• Review primary and secondary prophylaxis and
  treatment of clinical symptoms in HIV positive
  patients

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CD4 Count and Opportunistic Infection
Asymptomatic
Herpes zoster reactivation
400
Lymphoma
SymptomaticHIVInfection
Kaposis sarcoma
CD4 Count (/ml)
Thrush
300
Tuberculosis (reactivation)
Coccidioidomycosis, Histoplasmosis
200
Pneumocystis carinii pneumonia
Tuberculosis
AIDS - Early
Invasive candidiasis
100
Toxoplasmosis
50
AIDS - Late
CMV retinitisMAC disseminationCryptococcal
meningitisCNS lymphoma
0
Time
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Incidence rate ratio of development of an OI by
CD4-CD4 category
CD4 number vs percent as predictor of OIs
Incidence rate ratio
CD4
After adjustment for race, gender, HIV risk
factor and HAART usage

• Analysis of 15,736 CD4-CD4 pairs from an
  observational urban HIV cohort
• Absolute CD4 more predictive than CD4 percent

Gebo KA, et al. 10th CROI, Boston 2003, 792
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OPPORTUNISTIC INFECTIONS

• Risk based on level of immunosupression,
  exposures, geography
• Uncommon when CD4200 (adults)
• More frequent, severe typical infections (e.g..
  CAP)
• Early AIDS symptomsthrush, diarrhea, weight
  loss, sweats, VZV
• OIs are the most common cause of death in AIDS
• Effective ARV treatment reduces incidence

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Common Clinical Syndromes Associated with HIV

• Starting with CD4 500
• Peripheral generalized lymphadenopathy
• Herpes Zoster
• Severe herpes simplex
• Pneumococcal pneumonia (and other bacterial
  pneumonia)
• Recurrent candida vaginitis
• Molluscum contagiosum
• Severe condyloma accuminata
• Cervical intraepithelial neoplasia and carcinoma
• Syphilis (occasionally with multiple primary
  chancres)
• Severe aphthous ulcers
• Gingivitis
• Seborrheic dermatitis

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• 37 y/o M HIV positive since 2005 who came to the
  office first time visit.
• Pt appears healthy. Denies any weight loss or
  being ill.
• Has ulcers in mouth for 1 week and it hurts when
  he eats but not all the time
• VL and CD4 count are done.
• WBC6.2 Lymph 22

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Apthous Ulcer
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• What will we do next?
• Should we start him on meds immediately?
• What will the viral load and CD4 count be?

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• WBC X Lymph ALC 1.36
• Normal immune system CD4/CD8 2
• Immunosuppressed patient .5
• 1/3 CD4 453
• 2/3 CD8 906
• Patients severely ill .10
• Patients symptomatic .25
• Asymptomatic patients .33-.50

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• CD4 Count labs 398
• Viral Load 62,000

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Updated DHHS Guidelines Initiationof ART in
HIV-Infected Patient

• Clinical Category CD4 count Plasma
  Recommendation HIV RNA
• Symptomatic Any Any Treat(AIDS, severe symptoms)
• Asymptomatic
• Asymptomatic 200-350/mm3 Any Offer
  treatment controversy exists
• Asymptomatic 350 30,000 (bDNA) Experts
  recommendations 100,000 (RT-PCR) differ, many
  treat
• Asymptomatic 350 defer

www.aids-ed.org
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• 26 y/o HIV positive patients started on HAART 8
  weeks ago. (3TC,AZT,Kaletra)
• Initial CD422 and VL365,000
• Patient was seen at 4 weeks and he has gained 4
  lbs, diarrhea resolved and he was tolerating his
  meds well.
• Now he calls complaining of a painful rash in
  chest

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Herpes Zoster
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• What will we do next?
• Should we do labs today?
• Should we continue the same meds or change them?

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• CD4 88
• Viral Load

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Molluscum contagiosum
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Common Clinical Syndromes Associated with HIV

• Starting at CD4 200-500
• Fevers
• Night sweats
• Lymphoma (extranodal)
• Tuberculosis
• Dementia
• Oral hairy leukoplakia
• Thrush
• Kaposis Sarcoma

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• 22 y/o M w/ PMH of HIV for 2 years who came to
  the office and we found the following lesion.
• 6 months ago
• CD4 409
• VL 45,000

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(No Transcript)
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• Do we need biopsy or CD4 count Viral load?
• Biopsy showed dx of Kaposi Sarcoma
• Whats the next step?
• Does he needs HIV meds?
• Do we need labs?

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Kaposis Sarcoma
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CNS Lymphoma
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• 28 y/o F who came to the hospital due to cough w/
  green phlegm and blood
• She was diagnosed w/ TB.
• CD4 299 and VL 60,000

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Tuberculosis

• Abnormalities often seen in apical
• or posterior segments of upper
• lobe or superior segments of
• lower lobe
• May have unusual appearance
• in HIV-positive persons

Arrow points to cavity in patient's right upper
lobe.
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• What will we do?
• Which disease should we treat first?
• Should we start HIV and TB meds at same time?

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MAC Immune Reconstitution Syndrome

• Low CD4 (weight loss, leukocytosis, positive blood
  cultures (Race, Lancet, 1998)
• High CD4 ( 100-150) fewer systemic symptoms,
  more localized suppurative disease (Phillips,
  JAIDS, 1998)
• Treatment continue HAART and MAC therapy,
  NSAIDS, steroids (for severe symptoms), local
  surgery?

Slide From Bob Harrington, MD
DHS/ID/Cases/PP
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Case 2

• AIDS pt diagnosed 8 weeks ago with active TB. On
  INH/RIF/PZA/ETH. TB sx and CXR improved.
• CD4 90, VL 250,000. ARVs started 3 weeks ago.
• Presents to TB clinic with 2 days fever, SOB,
  malaise.

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Case 2 Cont.

• CXR shows slight worsening infiltrate
• 2 sputum smears negative AFB and bacterial and
  bronchoscopy negative for fungal
• Other evaluation for fever in advanced HIV
  patient negative

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Paradoxical Reactions Immune Reconstitution (
Restoration) Syndrome

• Clinically manifested by worsening of
  inflammatory
• effects of TB in the face of starting on HIV
  treatment
• Before HIV, commonly seen in extrapulmonary TB
• especially in lymph nodes
• Now reported in patients on TB therapy when
• new antiretroviral therapy started
• Sterile inflammatory responses at site of
  original
• TB

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Common Clinical Syndromes Associated with HIV

• Starting at CD4 100-200
• Wasting
• Toxoplasmosis
• PCP
• Cryptococcosis (can occur in normal hosts)
• Candida esophagitis

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Thrush
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PCP
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Wasting
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(No Transcript)
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Toxoplasmosis

• This is a disease obtained by eating raw meat.
  Feral cats are also carriers. HIV patients should
  use care in handling cat litter.
• Trimethoprim-sulfamethoxazole is prophylactic.
• The most common presentation is CNS
  toxoplasmosis.
• Patients can present with focal neurologic
  findings, seizures, or dementia.
• Diagnosis is made by CONTRASTED CT or MRI.
• Characteristic ring enhancing lesions are seen.
• Biopsy may be necessary to distinguish this
  entity from CNS lymphoma.

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TOXOPLASMOSIS

• Toxo IGM and IGG is helpful
• Can cause pneumonitis
• Treatment clindamycin or sulfadiazine plus
  pyrimethamine (with leucovorin) for life

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Cryptococcal MeningitisFeatures of High ( 350
mm H2O) CSF Pressure

• Clinical Features - More frequent headache
  meningismus - More frequent papilledema
  abnormal reflexes
• Lab Features - Higher CSF Cryptococcal
  antigen - More frequent positive India ink
• Outcome Features - Reduced short-term survival
  if CSF pressure 250

From Graybill JR et al. Clin Infect Dis
20003047-54.
DHS/OIs/HIV
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Common Clinical Syndromes Associate with HIV

• CD4
• Mycobacterium avium complex (disseminated)
• Cryptosporidial diarrhea (self limited form at
  higher CD4)
• Cytomegalovirus (retinitis, colitis, and other
  end organ damage)
• CNS lymphoma
• Disseminated histoplasmosis

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CMV
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Case Study

• Joan, G8P3, HIV for 3 years, admitted with
  ruptured membranes (4hrs). No prenatal care. Lost
  2 children to HIV. Urine for cocaine, GB strep
  (urine, cervix), other STDs negative. Unknown CD4
  and Viral load.
• What are the recommendations for this mother and
  infant?
• What alternative therapies can she choose to
  decrease perinatal transmission?
• What should follow-up care include?

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Results of ACTG 076
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This represents a 66 reduction in risk for
transmission (P in all subgroups
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22.6
Transmission Rate ()
10
7.6
ZDV Group
Placebo
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Comparison of ART Prophylaxis Trials
Red 67 51 24 30 50 37 --- 47
Pregnancy (weeks)
Labor
Perinatal (weeks)
0
1
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6
14
ACTG 076
Notbreast fed
Bangkok
Retro-CI
DITRAME
PETRA-A
Breast fed
PETRA-B
PETRA-C
HIVNET 012
AZT AZT3TC NVP
Gray G. XIII IAC, Durban 2000. Session Lb5
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HIV Resistance in Treatment Naïve Pregnant Women

• Retrospective review of HIV pregnant women in St
  Louis, MO, 20002001 n72
• Mean age 25 years
• ARV therapy naïve
• 75 African-American
• Mean CD4 448 cells/mm3
• Mean VL 3310 c/mL

Juethner SN, et al. XIV Int AIDS Conference,
Barcelona 2002, 5950
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Current Perinatal Prevention Recommendations(Mate
rnal Regimens)

• Oral ZDV 300mg BID
• (or 200mg TID)
• may defer ART in 1st trimester
• ZDV other ART for HIV-1 RNA 1000

PRENATAL

• Intravenous ZDV
• 2mg/kg bolus, then 1 mg/kg/hr
• NVP 200mg PO at onset of labor
• 3TC 150mg PO Q12 until delivery

INTRA- PARTUM
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Antibiotic Prophylaxis in HIV positive patients
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Summary of OIs for Which Prevention Is Recommended

• Primary Prophylaxis
• P. carinii
• Tuberculosis
• T. gondii
• M. avium
• Varicella zoster
• S. pneumoniae
• Hepatitis A B
• Influenza

• Secondary Prophylaxis
• P. carinii
• T. gondii
• M. avium
• Cryptococcosis
• Histoplasmosis
• Coccidioidomycosis
• Cytomegalovirus
• Salmonella bacteremia

Standard of care
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OIs for Which Prevention Is Not Routinely
Indicated

• Primary Prophylaxis
• Bacteria (Neutropenia)
• Cryptococcosis
• Histoplasmosis
• Cytomegalovirus

• Secondary Prophylaxis
• Herpes simplex virus
• Candida

Recommended only if subsequent episodes are
frequent or severe
Evidence for Efficacy but Not Routinely
Indicated
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Prophylaxis for Opportunistic Infections

• 1999 USPHS/IDSA Guidelines, evidence-based
• Strongly recommended, standard of care, primary
  prevention
• PCP CD4common
• Not recommended prophylaxis for fungus infections
• Toxo CD4
• MAC CD4
• VZV significant exposure VZIG
• Generally recommended pneumococcal vaccine, Hep
  B vaccine (if antibody -), influenza vaccine, Hep
  A vaccine (if Hep C )

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Conclusion

• HIV remains a complicated medical management
  problem requiring an interdisciplinary approach
• Lab Values are important in the care of our
  patients but the clinical evaluation is what is
  most important.
• It is important for all health care providers to
  know enough about HIV to know when they need to
  get help.

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Thank you!!!

• Questions?