Medical management of hiv infection

Go to a Chapter Table of Contents Natural History
and Classification Laboratory Tests Disease Prevention Antiretroviral Therapy
Management of Opportunistic Infections Drugs: Guide to Information Systems
Review HIV in Corrections

Medical Management of HIV Infection
by John G. Bartlett, M.D. and
Joel E. Gallant, M.D., M.P.H.

The 2001-2002 edition of Medical Management of HIV Infection serves as the standard of care
Hopkins AIDS Service and has been accepted as the standard of care for quality assurance by
Medicaid. The full text of the book is included here.

Throughout the chapter, red text indicates changes and updates made to the book for the 2001
Changes will stay highlighted in red for 3 months.

Chapter I: Natural History and Classification

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Management of HIV Infection:
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Chapter III: Disease Prevention: Prophylactic Antimicrobial Agents and V
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for shipping and handling. An invoice will be sent Chapter IV: Antiretroviral Therapy
with the book(s). Credit card payments not accepted.

Chapter V: Management of Opportunistic Infections and Miscellaneous C

Production of the 2001-2002 edition of Medical Chapter VI: Drugs: Guide to Information
Management of HIV Infection has been underwritten
by an unrestricted educational grant from
GlaxoSmithKline, Inc. Chapter VII: Systems Review

HIV in Corrections from the 2000-2001 edition

Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights reserved.

* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because no
or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical
specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other health care provid
any health related questions they may have.

Go to a Chapter Table of Contents Natural History and Classification
Tests Disease Prevention Antiretroviral Therapy Management of Opp
Infections Drugs: Guide to Information Systems Review HIV in Correc

Note: Throughout the chapter, red text indicates changes and updates made to the book for the 20
edition. Changes will stay highlighted in red for 3 months. Last updated 11/1/2001

I. Natural History and Classification

Stages
Table 1-1: Correlation of Complications with CD4 Cell Counts
Table 1-2: HIV Infection - Signs and Symptoms
Table 1-3: AIDS Surveillance Case Definition
Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) 1997

To order a copy of the 2001-2002
Medical Management of HIV Infection :
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the charge for shipping and handling.
An invoice will be sent with the book(s).
Credit card payments not accepted.

Production of the 2001-2002 edition of
has been underwritten by an
unrestricted educational grant from
GlaxoSmithKline, Inc.


* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in this site because n
reference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provi
advice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or othe
provider promptly with any health related questions they may have.



II. Laboratory Tests

HIV Types and Subtypes
HIV Serology
Alternative HIV Serologic Tests
Quantitative Plasma HIV RNA
CD4 Cell Count
Resistance Testing
Screening Battery
Complete Blood Count
Serum Chemistry Panel
Syphilis Serology
Chest X-Ray
PPD Skin Testing
PAP Smears
Serology for Hepatitis B Virus (HBV)
Testing for Hepatitis C Virus
To order a copy of the 2001-2002 Medical Toxoplasmosis Serology
Call 1-800-787-1254 Cytomegalovirus Serology
or order online. Glucose-6-Phosphate Dehydrogenase Levels
Adverse Drug Reaction Monitoring
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Tables
Table 2-1: Test for HIV-1
Table 2-2: Comparison Between Assay Methods for Viral Load
Table 2-3: Comparison of Genotypic and Phenotypic Assays
Production of the 2001-2002 edition of Medical
Management of HIV Infection has been underwritten by Table 2-4: Letter Designations for Amino Acids
an unrestricted educational grant from Table 2-5: Resistance Mutations
GlaxoSmithKline, Inc. Table 2-6: Routine Laboratory Test in Asymptomatic Patients
Table 2-7: Recommendations for Intervention Based on Results of PAP Smear
Table 2-8: Tests for HCV




IV. Antiretroviral Therapy

Recommendations for Antiretroviral Therapy

Goals of Therapy
Terms and Concepts
Antiretroviral Therapy for HIV Infected Patients
Recommendations for Antiretroviral Therapy in Pregnancy
Postexposure Prophylaxis for Health Care Workers
Postexposure Prophylaxis for Sexual Contact or Needle Sharing

Antiretroviral Agents

Nucleoside Analogs
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Protease Inhibitors
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Tables
shipping and handling. An invoice will be sent with the Table 4-16: Antiretroviral Drugs Approved by FDA for HIV
book(s). Credit card payments not accepted. Table 4-20: Drugs That Should Not be Used with Protease Inhibitors or NNRTIs*
Table 4-21: Drug Interactions Requiring Dose Modifications or Cautious Use
Table 4-22: Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhib
Drug on Levels (AUCs)/Dose
Table 4-27: HIV-Related Drugs with Overlapping Toxicities
Management of HIV Infection has been underwritten by Table 4-28: Dosing of Antiretroviral Agents in Renal and Hepatic Failure
an unrestricted educational grant from Table 4-29: Characteristics of Antiretrovirals During Dialysis


reference or service can take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provid
advice about any specific medical condition they may have or treatment they may need and they are encouraged to call or see their physician or other


highlighted in red for 3 months. Last updated 11/1/2001

V. Management of Opportunistic Infections and Other Complica

Opportunistic Infections

Table 5-1: Fungal Pneumocystis carinii, Aspergillosis, Candidiasis, Cryptococcal meningitis, Cryptoc
Coccidioidomycosis, Penicilliosis marneffei

Table 5-2: Parasitic Infections Toxoplasma gondii, Cryptosporidiosis, Isosporidiosis, Microsporidiosis

Table 5-3: Mycobacterial Infections M. tuberculosis, M. avium, M. kansasii, M. haemophilum, M.gor
malonoense, M. chelonei

Table 5-4: Viruses Herpes simplex, Herpes zoster, Cytomegalovirus retinitis, Progressive multifo

Table 5-5: Bacteria Streptococcus pneumoniae, Bartonella henselea/ quintana, Haemophilus
Pseudomonas aeruginosa, Rhodococcus equi, Salmonella, Staphylococcus aureus, Treponema pallid

To order a copy of the 2001-2002 Medical
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book(s). Credit card payments not accepted. Table 5-6I: Hepatobiliary
Table 5-6C: Renal Table 5-6J: Wasting
Table 5-6D: Neurologic Table 5-6K: Pain
Table 5-6E: Hematologic Table 5-6L: Psychiatric a
Table 5-6F: Tumors Table 5-6M: Terminal Illn
Production of the 2001-2002 edition of Medical Table 5-6G: Dermatologic
Management of HIV Infection has been underwritten by
an unrestricted educational grant from


medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical advice about any specific medi
need and they are encouraged to call or see their physician or other health care provider promptly with any health related questions they may have.



VI: Drugs: Guide to Information
Understanding Drug Profiles
Antiretroviral Therapy for HIV-infected Patients
A B
Abacavir Bactrim
Acyclovir Benzodiazepines
Agenerase Biaxin
Albendazole Bupropion
Alprazolam Buspar
Amphotericin B Buspirone
Amprenavir
Ancobon
AndroGel
Ativan
Atorvastatin
Atovaquone
To order a copy of the 2001-2002 Medical Aventyl
Management of HIV Infection: Azithromycin
Call 1-800-787-1254 AZT
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D E
charge for shipping and handling. An invoice will
be sent with the book(s). Credit card payments
Dalmane Efavirenz
not accepted.
Dapsone Enoxacin
Daraprim Epivir
Daunorubicin Epogen
ddC Erythropoietin
Production of the 2001-2002 edition of Medical ddI Ethambutol
Management of HIV Infection has been Delavirdine
underwritten by an unrestricted educational
grant from GlaxoSmithKline, Inc. d4T
Desyrel
Didanosine
Diflucan
Doxycycline
Dronabinol

G H
Ganciclovir Halcion
G-CSF Humatin
Gemfibrozil Hydroxyurea
Growth Hormone

K L

Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights
reserved.

* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in
this site because no single reference or service can take the place of medical training, education, and experience. Consumers are
cautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatment
they may need and they are encouraged to call or see their physician or other health care provider promptly with any health related


VII. Systems Review

· Specific Psychiatric Problems
· Pulmonary Complications
· Nervous System Complications
· GI Complications
· Dermatologic Compilcations
· Wasting
· CMV Retinis
· Fever

To order a copy of the 2001-2002 Medical
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Management of HIV Infection has been underwritten by
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Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Diseases and AIDS Service. All rights
reserved.

* Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained in
this site because no single reference or service can take the place of medical training, education, and experience. Consumers are
cautioned that this site is not intended to provide medical advice about any specific medical condition they may have or treatment
they may need and they are encouraged to call or see their physician or other health care provider promptly with any health related
questions they may have.


Changes will stay highlighted in red for 3 months. Green text indicates material that no longer appe
of the book. Last updated 6/1/2001

HIV in Corrections from the 2000-2001 Edition

Testing Policies in Corrections
Prevalence of HIV in Corrections
Housing Issues for Inmates with HIV and AIDS
Challenges and Opportunites with Treating HIV in Corrections
Initial Medical Evaluation
HIV Case Management within the Correctional Environment
Medication Administration within the Prison System
Telementoring & Telemedicine in Corrections

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Medical Management of HIV Infection :
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Production of the 2001-2002 edition of
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take the place of medical training, education, and experience. Consumers are cautioned that this site is not intended to provide medical advice about
may have or treatment they may need and they are encouraged to call or see their physician or other health care provider promptly with any health re

Copyright © 1997-2001 The Johns Hopkins University on behalf of its Division of Infectious Disease
AIDS Service. All rights reserved.

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Joel E. Gallant, M.D., M.P.H.
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Trish M. Perl, M.D., MS.c.

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Chapter I: Natural History and Classification

Stages

Tables

Stages

Viral transmission Acute retroviral syndrome Recovery + serconversion
Asymptomatic chronic HIV infection Symptomatic HIV infection/AIDS Death
Figure 1-1: Natural History of HIV Infection in an Average Patient Without
Antiretroviral Therapy from the Time of HIV Transmission to Death at 10-11 Years

The initial event is the acute retroviral syndrome, which is accompanied by a precipitous decline in CD4 cell counts (closed squares), high plasma virem
circles), and high concentrations of HIV RNA in plasma (closed triangles). Clinical recovery is accompanied by a reduction in plasma viremia, reflecting
of cytotoxic T cell (CTL) response. The CD4 cell count gradually declines with a more accelerated decline 1.5 to 2 years before an AIDS-defining diagn
concentrations in plasma show an initial "burst" during acute infection and then decline to a "set point" as a result of seroconversion and development o
response. With continued infeciton, HIV RNA levels then gradually increase (J Infect Dis 1999;180:1018). Late-stage disease is characterized by a CD
<200/mm and the development of opportunistic infections, selected tumors, wasting, and neurologic complications. In an untreated patient, the median
3

the CD4 cell count has fallen to <200/mm3 is 3.7 years; the median CD4 cell count at the time of the first AIDS-defining complication is 60-70/mm 3; the
survival after an AIDS-defining complication is 1.3 years. (Figure reprinted with permission from Fauci AS, et al. Ann Intern Med, 1996;124:654).

Return to top

Top of Page | Next page -- Table 1-1: Correlation of Complications with CD4 Cell Counts




Chapter I: Natural History and Classification - Table 1-1

Stages

Tables

Table 1-1: Correlation of Complications With CD4 Cell Counts
(see Arch Intern Med 1995;155:1537)
CD4 Cell Count* Infectious Complications Noninfectious Complications

>500/mm 3 Acute retroviral syndrome Persistent generalized
lymphadenopathy (PGL)

Candidal vaginitis Guillain-Barré syndrome

Myopathy

Aseptic meningitis

200 - 500/mm 3 Pneumococcal and other Cervical intraepithelial neoplasia
bacterial pneumonia
Cervical cancer
Pulmonary tuberculosis
B-cell lymphoma
Herpes zoster
Anemia
Oropharyngeal candidiasis (thrush)
Mononeuronal multiplex
Cryptosporidiosis,
self-limited Idiopathic thrombocytopenic
purpura
Kaposi's sarcoma
Hodgkin's lymphoma
Oral hairy leukoplakia
Lymphocytic interstitial pneumonitis

<200/mm 3 Pneumocystis carinii pneumonia Wasting

Disseminated histoplasmosis and Peripheral neuropathy
coccidioidomycosis
HIV-associated dementia
Miliary/extrapulmonary TB
Cardiomyopathy
Progressive multifocal
leukoencephalopathy (PML) Vacuolar myelopathy

Progressive polyradiculopathy

HIV-associated dementia
Miliary/extrapulmonary TB
Cardiomyopathy
Progressive multifocal
leukoencephalopathy (PML) Vacuolar myelopathy

Progressive polyradiculopathy

<100/mm 3 Disseminated herpes simplex

Toxoplasmosis

Cryptococcosis

Cryptococcosis, chronic

Microsporidiosis

Candida esophagitis

<50/mm 3 Disseminated cytomegalorvirus (CMV) Central nervous system (CNS) lymphoma

Disseminated Mycobacterium avium complex

* Most complications occur with increasing frequency at lower CD4 cell counts.

Some conditions listed as "Noninfectious" are probably associated with transmissible microbes: examples include lymphoma
(Epstein-Barr virus [EBV]) and cervical canver (human papillomavirus [HPV]).

Top of Page | Next page -- Table 1-2: Primary HIV Infection - Signs and Symptoms





Stages

Tables

Table 1-2: Primary HIV Infection - Signs and Symptoms
([Department of Health and Human ServicesGuidelines]
http://www.hivatis.org, April 2001)
Fever 96%

Adenopathy 74%

Pharyngitis 70%

Rash* 70%

Myalgias 54%

Diarrhea 32%

Headache 32%

Nausea and vomiting 27%

Hepatosplenomegaly 14%

Weight loss 13%

Thrush 12%

Neurologic symptom 12%

*Rash - Erythematous maculopapular rash on face and trunk, sometimes
extremities, including palms and soles. Some have mucocutaneous
ulceration involving mouth, esophagus, or genitals.

Aseptic meningitis, meningoencephalitis, peripheral neuropathy, facial
palsy, Guillain-Barré syndrome, brochial neuritis, cognitive impairment, or
psychosis.

Top of Page | Next page -- Table 1-3: AIDS Surveillance Case Definition for Adolescents and Adu





Stages

Tables

Table 1-3: AIDS Surveillance Case Definition for Adolescents and Adults 1993

CD4 Cell Clinical Categories
Categories
A B C*

Asymptomatic, Symptomatic AIDS Indicator
or PGL or Acute Condition
(not A or C)
HIV Infection (1987)

1) >500/mm 3 A1 B1 C1
(>29%)

2) 200 to 499/mm 3 A2 B2 C2
(14% to 28%)

3) <200/mm 3 A3 B3 C3
(<14%)

* All patients in categories A3, B3 and C1-3 defined as having AIDS, based on the presence of an AIDS-indicator condition (Table 1-4) and/or a CD4 ce
<200/mm 3.

Symptomatic conditions not included in Category C that are a) attributed to HIV infection or indicative of a defect in cell-mediated immunity, or b) consi
clinical course or management that is complicated by HIV infection. Examples of B conditions include but are not limited to bacillary angiomatosis; thrus
candidiasis which is persistent, frequent, or poorly responsive to therapy; cervical dysplasia (moderate or severe); cervical carcinoma in situ; constitution
such as fever (38.5º C) or diarrhea >1 month; oral hairy leukoplakia; herpes zoster involving two episodes or >1 dermatome; idiopathic thrombocytopen
(ITP); listeriosis; pelvic inflammatory disease (PID) (especially if complicated by a tubo-ovarian abscess); and peripheral neuropathy.

Top of Page | Next page -- Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults) -





Stages

Tables

Table 1-4: Indicator Conditions in Case Definition of AIDS (Adults)-1997*
Candidiasis of esophagus, trachea, bronchi, or lungs - 3846 (16%)

Cervical cancer, invasive - 144 (0.6%)

Coccidioidomycosis, extrapulmonary - 74 (0.3%)

Cryptococcosis, extrapulmonary - 1168 (5%)

Cryptosporidiosis with diarrhea >1 month - 314 (1.3%)

CMV of any organ other than liver, spleen, or lymph nodes; eye - 1638 (7%)

Herpes simplex with mucocutaneous ulcer >1 month or bronchitis, pneumonitis, esophagitis - 1250 (5%)

Histoplasmosis, extrapulmonary - 208 (0.9%)

HIV-associated dementia : Disabling cognitive and/or other dysfunction interfering with occupation or activities of daily living - 1196 (5%)

HIV-associated wasting : Involuntary weight loss >10% of baseline plus chronic diarrhea (>2 loose stools/day >30 days) or chronic weakness and doc
enigmatic fever >30 days - 4212 (18%)

Isoporosis with diarrhea >1 month - 22 (0.1%)

Kaposi's sarcoma in patient under 60 yrs (or over 60 yrs ) - 1500 (7%)

Lymphoma, Burkitt's - 162 (0.7%), immunoblastic - 518 (2.3%), primary CNS - 170 (0.7%)

Mycobacterium avium, disseminated - 1124 (5%)

Mycobacterium tuberculosis, pulmonary - 1621 (7%), extrapulmonary - 491 (2%)

Nocardiosis - <1%

Pneumocystis carinii pneumonia - 9145 (38%)

Pneumonia, recurrent-bacterial (>2 episodes in 12 months) - 1347 (5%)

Progressive multifocal leukoencephalopathy - 213 (1%)

Salmonella septicemia (nontyphoid), recurrent - 68 (0.3%)

Pneumocystis carinii pneumonia - 9145 (38%)

Pneumonia, recurrent-bacterial (>2 episodes in 12 months) - 1347 (5%)

Progressive multifocal leukoencephalopathy - 213 (1%)

Salmonella septicemia (nontyphoid), recurrent - 68 (0.3%)

Strongyloidosis, extraintestinal - <1%

Toxoplasmosis of internal organ - 1073 (4%)

Wasting syndrome due to HIV (as defined above - HIV-associated wasting)

* Indicates frequency as the AIDS-indicator condition among 42,350 reported cases in 1997. Numbers indicate sum of definitive and presumptive diag
condition. The number in parentheses is the percentage of all patients reported with an AIDS-defining diagnosis; these do not total 100%, since some h
diagnosis and many were reported based on the CD4 cell count criterion. See Viral Transmission.

Requires positive HIV serology.

Added in the revised case definition, 1993.

Top of Page | Next page -- Chapter II: Laboratory Tests




Chapter II: Laboratory Tests

Contents:
HIV Types and Subtypes Chest X-Ray
HIV Serology PPD Skin Testing
Alternative HIV Serologic Tests PAP Smears
Quantitative Plasma HIV RNA Serology for Hepatitis B Virus (HBV)
CD4 Cell Count Testing for Hepatitis C Virus
Resistance Testing Toxoplasmosis Serology
Screening Battery Cytomegalovirus Serology
Complete Blood Count Glucose-6-Phosphate Dehydrogenase Levels
Serum Chemistry Panel Adverse Drug Reaction Monitoring
Syphilis Serology

Tables
Table 2-4: Letter Designations for Amino Acids
Table 2-5: Resistance Mutations
Table 2-6: Routine Laboratory Test in Asymptomatic Patients

Laboratory tests recommended for initial evaluation and follow-up of all patients are summarized in
and 2-6.
HIV TYPES AND SUBTYPES

HIV infection is established by detecting antibodies to the virus, viral antigens, viral RNA/DNA, or by
(Lancet 1996;348:176). The standard test is for antibody detection. There are two types: HIV-1 and
which show 40% to 60% amino acid homology. HIV-1 accounts for nearly all cases except a minorit
strains that originate in West Africa. HIV-1 is divided into subtypes or clades designated "A to K" (co
referred to as "M subtypes") and "O." Subtype O shows 55% to 70% homology with the M subtypes
group of viruses labeled "N" for "new" have been reported (Nat Med 1998;4:1032; Science 2000;28
Over 98% of HIV-1 infections in the United States are caused by clade B; most non-B subtypes in th
States were acquired in other countries (J Infect Dis 2000;181:470).

Return to top

HIV-2

HIV-2 is another human retrovirus that causes immune deficiency due to depletion of CD4 cells. It is
found in West Africa*. Compared to HIV-1, HIV-2 is less transmissible (5- to 8-fold less efficient than
early-stage disease and rarely the cause of vertical transmission), is associated with a lower viral lo
associated with a slower rate of both CD4 cell decline and clinical progression (Lancet 1994;344:13
1994;8[suppl 1]:585; J Infect Dis 1999;180:1116; J AIDS 2000;24:257; Arch Intern Med 2000;160:3
patients with HIV-2 infections with CD4 cell counts have no detectable virus with viral load testing a
relatively low viral loads with CD4 cell counts <500/mm3; some feel low viral replication may accoun
lower rate of transmission and longer period of clinical latency with HIV-2 infections (J AIDS 2000;2
HIV-2 shows reduced homology with HIV-1 compared to HIV-1 subtypes (Nat Med 1987;328:543). A
to 30% of patients with HIV-2 infection have negative antibody tests depending on the enzyme
immunosorbent assay (EIA) tests used; Western blots (WBs) are weakly cross-reactive. WB for HIV
neither well standardized nor FDA approved (Ann Intern Med 1993;118:211; JAMA 1992;267:2775)
EIA was licensed by the FDA in 1990 and became mandatory for screening blood donors in 1992. S
commercial labs now use combination EIA screening assays to detect HIV-1 and HIV-2 simultaneou
although this is not recommended for routine testing by the Centers for Disease Control and Preven
(CDC) (MMWR 1992;41[RR-12]:1). Viral load tests are not generally available for HIV-2 (Arch Intern
2000;160:3286). There were 78 persons diagnosed with HIV-2 infection in the United States betwee
and January 1998: 52 were born in West Africa, and most of the rest had traveled there, had a sexu
from that region, or had incomplete data (MMWR 1995;44:603; JAMA 1992;267:2775). The CDC
recommends that HIV-2 serology be included in serologic testing of: 1) natives of endemic areas,* 2
needle-sharing and sex partners of persons from an endemic area,* 3) sex partners or needle-shari
partners of persons with HIV-2 infection, 4) persons who received transfusions or nonsterile injectio
endemic areas,* and 5) children of women with HIV-2 infection. Contact CDC for HIV-2 serologic tes

*Endemic areas in West Africa - Benin, Burkina Faso, Cape Verde, Cote d'Ivoire, Gambia, Ghana, Guinea Guinea-Bis
Mali, Mauritania, Niger, Nigeria, São Tome, Senegal, Sierra Leone, and Togo; other African countries - Angola and Mo
(MMWR 1992;4[RR-12]:1).

Return to top

HIV SEROLOGY

Standard Test: The standard serologic test consists of a screening EIA followed by a confirmatory
EIA uses antigens prepared by lysis of whole virus, recombinant and/or synthetic peptides. The sen
specificity of the tests are dictated by these preparations. Currently used EIA reagents are generally
recombinant antigens that improve specificity and reduce the window period compared with earlier
preparations, but about 30% of infections with HIV-2 are falsely negative. The EIA screening test re
"repeatedly reactive" test, which is the criterion for WB testing. WB detects antibodies to HIV-1 prot
including core (p17, p24, p55), polymerase (p31, p51, p66), and envelope (gp41, gp120, gp160). W
should always be coupled with EIA screening; WB alone has a 2% rate of false positives. Results (
2000;109:568) of WB are interpreted as:

Negative: No bands
Positive: Reactivity to gp41 + gp120/160 or p24 + gp120/160
Indeterminate: Prescence of any band pattern that does not meet criteria for positive results

Accuracy: Standard serologic assays (EIA and WB or immunofluorescent assay [IFA]) show sensit
specificity rates of >98% (JAMA 1991;266:2861; Am J Med 2000;109:568). Positive tests should be
confirmed with repeat tests or with corroborating clinical or laboratory data.

False-negative results: False-negative results are usually due to testing in the "window period." Fo
population with high rates of seroconversion, such as injection drug users in Baltimore, who have
seroconversion rates of 3% to 4%/year, false-negative serology results occur in 0.3% (J Infect Dis
1993;168:327). For a low seroprevalence group such as blood donors, false-negative results are mu
common (0.001%) (N Engl J Med 1991;325:1; N Engl J Med 1991;325:593). Causes of false-negati
include:

The window period: The time delay from infection to positive EIA averages 10 to 14 days with
test reagents (Clin Infect Dis 1997;25:101; Am J Med 2000;109:568). Some do not seroconve
4 weeks, but virtually all patients seroconvert within 6 months (Am J Med 2000;109:568). Prop
with antiretroviral agents and acute hepatitis C infection may prolong the time from transmissio
seroconversion.
Seroreversion: Some patients serorevert in late-stage disease (JAMA 1993;269:2786; Ann Int
1988;108:785). Seroreversion may also occur in patients who achieve prolonged immune reco
due to highly active antiretroviral therapy (HAART) (N Engl J Med 1999;340:1683).
"Atypical host response" accounts for rare cases and is largely unexplained (AIDS 1995;9:95;
1996;45:181; Clin Infect Dis 1997;25:98).
Agammaglobulinemia
Type N or O strains or HIV-2: EIA screening tests may fail to detect the O subtype (Lancet
1994;343:1393; Lancet 1994;344:1333; MMWR 1996;45:561). This strain is rare; only one pa
strain O HIV infection was detected in the United States through July 1996 (MMWR 1996;45:5
Emerg Infect Dis 1996;2:209). The N group is another variant that causes false-negative EIA s
tests, but may be positive by WB (Nat Med 1998;4:1032). There have been no recognized infe
with the N strain in the United States through March 2000 (J Infect Dis 2000;181:470). Standa
screening tests are falsely negative in 20% to 30% of patients infected with HIV-2. Detection m
require tests specifically for HIV-2. Risks for HIV-2 are summarized above.
Technical or clerical error

False-positive results: The frequency of false-positive HIV serology in a low-prevalence population
military recruits from rural United States) was 1/135,000 (0.0007%) (N Engl J Med 1988;319:961); f
donors in Minnesota it was 6/million (0.0006%) (Ann Intern Med 1989;110:617). A survey of 5 millio
donor samples obtained from 1991 to 1995 found that the prevalence of false positives was 0.0004%

Technical or clerical error

False-positive results: The frequency of false-positive HIV serology in a low-prevalence population
military recruits from rural United States) was 1/135,000 (0.0007%) (N Engl J Med 1988;319:961); f
donors in Minnesota it was 6/million (0.0006%) (Ann Intern Med 1989;110:617). A survey of 5 millio
donor samples obtained from 1991 to 1995 found that the prevalence of false positives was 0.0004%
251,000. The greatest source of error was a p31 band on WB, a band that has subsequently been d
from the interpretive criteria (JAMA 1998;280:1080).

Autoantibodies: A single case has been reported and was ascribed to autoantibodies in a patie
lupus erythematosus and end-stage renal disease (N Engl J Med 1993;328:1281). A subsequ
indicated that this patient did have HIV infection as verified by positive cultures (N Engl J Med
1994;331:881). Another patient with two positive tests and two indeterminate WB tests was fo
uninfected with a negative HIV culture and PCR (Clin Infect Dis 1992;15:707).
HIV vaccines: This is the most common cause of false-positive HIV serology. In an analysis of
healthy volunteers in HIV vaccine studies, 68% had positive EIA tests and 0% to 44% had pos
depending on the antigen in the vaccine (Ann Intern Med 1994;121:584).
Factitious HIV infection: This refers to patients who report a history of a positive test that is err
either due to misunderstanding or to intent to deceive (Ann Intern Med 1994;121:763). It is imp
confirm anonymous tests and laboratory reports that cannot be obtained, using either repeat s
viral load testing. [Note that 2% to 9% of viral load tests are falsely positive, usually with low v
(Ann Intern Med 1999;130:37)].
Technical or Clerical Error

Indeterminate results: Indeterminate test results account for 4% to 20% of WB assays with positiv
for HIV-1 proteins. Causes of indeterminate results include:

Serologic tests in the process of seroconversion; anti-p24 is usually the first antibody to appea
Late-stage HIV infection, usually with loss of core antibody
Cross-reacting nonspecific antibodies, as seen with collagen-vascular disease, autoimmune d
lymphoma, liver disease, injection drug use, multiple sclerosis, parity, or recent immunization
Infection with O strain or HIV-2
HIV vaccine recipients (see above)
Technical or Clerical error

The most important factor in evaluating indeterminate results is risk assessment. Patients in low-risk
categories with indeterminate tests are almost never infected with either HIV-1 or HIV-2; repeat test
continues to show indeterminate results, and the cause of this pattern is infrequently established (N
Med 1990;322:217). For this reason, such patients should be reassured that HIV infection is extrem
unlikely, although follow-up serology at 3 months is recommended to provide absolute assurance. P
with indeterminate tests who are in the process of seroconversion usually have positive WBs within
repeat tests at 1, 2, and 6 months are generally advocated with appropriate precautions to prevent v
transmission in the interim (J Gen Intern Med 1992;7:640; J Infect Dis 1991;164:656; Arch Intern M
2000;160:2386; J AIDS 1998;17:376).

Frequency of testing: Periodic tests are recommended for patients who practice high-risk behavio
frequency is arbitrary, but most suggest 6- to 12-month intervals. Annual seroconversion rates are e
as follows: general population - 0.02%, military recruits - 0.04%, gay men - 0.5% to 2% (higher for y
men), and injection drug users in areas with high seroprevalence - 0.7% to 6% (Am J Epidemiol
1991;134:1175; J AIDS 1993;6:1049; Arch Intern Med 1995;155:1305; Am J Public Health 1996;86
Public Health 2000;90:352).

Top of Page | Next page -- Alternative HIV Serologic Tests





Contents:
Syphilis Serology

Tables

Alternative HIV Serologic Tests (Table 2-1)

IFA: This is another method to detect HIV antibodies using patient serum reacted with HIV-infected
using a fluorochrome as the indicator method.

Home Kits: Johnson & Johnson has withdrawn the Confide HIV Test, making Home Access Express
(Home Access Health Corp., Hoffman Estates, III; 800-HIV-TEST) the only available home kit. This
sold in retail and on-line pharmacies at approximately $39.99 for routine mailing with results in 7 day
$49.99 for Federal Express transport with results in 3 days. Blood is obtained by lancet, and a filter
blotted blood is mailed in a protected envelope using an anonymous code. Home Access tests use
EIA with a confirmatory IFA. Sensitivity and specificity approach 100%. Callers learn of a negative te
through a prerecorded message, but the patient can access a representative to discuss results if de
Callers with positive results receive counseling and health care referral from a counselor. In a study
174,316 HIV home sample collection tests in 1996 to 1997, 0.9% were positive, and 97% of users c
their results. Nearly 60% of all users and 49% of HIV-positive persons had never previously been te
(JAMA 1998;280:1699). Merits of this type of home testing are debated (N Engl J Med 1995;332:12

Rapid Tests: SUDS (Abbott Diagnostics) is the only FDA-approved rapid test for HIV (On October 17
Abbott Diagnostics notified customers that the SUDS test was not available due to "manufacturing p
and time of availability is not known). SUDS must be performed by a trained laboratory technician a
are available in 10 to 15 minutes. Studies with 6200 specimens demonstrated that the sensitivity is
the specificity is 99.6% (J AIDS 1993;6:115; Am J Emerg Med 1991;9:416; Ann Intern Med 1996;12
Based on these studies of sensitivity and specificity, it is recommended that negative results be repo
definitive, but that positive results be confirmed with standard serology. The cost is $9/test, but two
must be included, so the true cost is $27 for one test and $36 for two. This test is recommended for
determining the serologic status of the source in healthcare worker exposures, for pregnant women
present in labor and have not been tested, and for patients who are unlikely to return for test results
patients seen in sexually transmitted disease (STD) clinics, emergency rooms, etc. (MMWR 1998;4

Based on these studies of sensitivity and specificity, it is recommended that negative results be repo
definitive, but that positive results be confirmed with standard serology. The cost is $9/test, but two
must be included, so the true cost is $27 for one test and $36 for two. This test is recommended for
determining the serologic status of the source in healthcare worker exposures, for pregnant women
present in labor and have not been tested, and for patients who are unlikely to return for test results
patients seen in sexually transmitted disease (STD) clinics, emergency rooms, etc. (MMWR 1998;4
Newer and better rapid tests are anticipated in 2001. These newer tests have the following advanta
detect HIV-1 and HIV-2, they appear to be as accurate as standard serologic tests, they can be perf
using saliva as well as blood, results are available in 10 minutes, and they can be read by the provid
Intern Med 1999;131:4810; J Clin Microbiol 1999;37:3698; ASM News 2000;66:451). Initial results w
OraQuick, a rapid test using saliva, in 219 seropositive persons and 779 seronegative persons show
sensitivity of 100% and specificity of 99.9% compared with standard serology (8th CROI, Chicago, I
February 2001, Abstract 232).

Saliva Test: OraSure (Epitope Co., Beaverton, Ore.), is an FDA-approved device for collecting saliva
concentrating IgG for application of EIA tests for HIV antibody. The OraSure test system consists of
specimen collection device, the Organon Teknika Vironostika HIV-1 antibody screen, and the WB
confirmatory assay, at a cost of $24.15/test. It is available for testing in public health departments, p
offices, community-based service organizations and AIDS Service organizations. OraSure testing is
available by calling 800-Ora-Sure (800-672-7872). The test may be anonymous or confidential. Res
available by phone or fax within 3 days. The test uses a specially treated pad which is placed betwe
lower cheek and gum for 2 minutes. The pad is then placed in a vial that is submitted to a lab. The a
IgG obtained from saliva is far higher than in plasma and is well above the 0.5mg/L level necessary
detection of HIV antibodies. Specimens saved from 3570 subjects gave correct results compared w
standard serology in 672 of 673 (99.9%) positives and 2893 of 2897 (99%) negatives (JAMA 1997;2
Potential advantages over standard serologic testing are the ease of collecting specimens, reduced
better patient acceptance.

Urine Test: Calypte HIV-1 Urine EIA is an FDA-approved screening EIA available through Seradyn In
800-428-4007. This test can be administered only by a physician, and positive results require confirm
a standard serologic test. Reported sensitivity is 99% (88/89), specificity is 94% (49/52) (Lancet
1991;337:183; Clin Chem 1999;45:1602). The supplier has included a pretest counseling form, whic
be read to and initialed by the patient prior to administration. The assay is sold as a 192-test kit at $
480-test kit at $1920; these costs equal $4/test.

Vaginal secretions: HIV antibodies can be detected in vaginal secretions with IgG EIA (Wellcozym
HIV-1&2, Gracelisa Murex Diagnostics Ltd., Darford, UK). This test is recommended by the CDC for
rape, since HIV IgG antibodies are in semen (MMWR 1985;34:75S; J Clin Microbiol 1994;32:1249).

Viral Detection: Other methods to establish HIV infection include techniques to detect HIV antigen, D
RNA (Table 2-1). HIV-1 DNA PCR is the most sensitive and can detect 1-10 copies of HIV proviral D
None of these tests is considered superior to routine serology in terms of accuracy, but some may b
patients with confusing serologic test results, when there is a need to clarify indeterminate test resu
virologic monitoring in therapeutic trials, and for HIV detection when routine serologic tests are likely
misleading such as in patients with agammaglobulinemia, acute retroviral infection, neonatal HIV inf
and patients in the window following viral exposure. In most cases, confirmation of positive serology
accomplished simply by repeat serology. The sensitivity of tests for detection of HIV varies with the
disease and test technique, but is usually reported at >99% for DNA-PCR, 90% to 95% for quantitat
HIV-RNA, 95% to 100% for viral culture of peripheral blood mononuclear cells (PBMC), and 8% to 3
p24 antigen detection (J Clin Microbiol 1993;31:2557; N Engl J Med 1989;321:1621; J AIDS 1990;3
Infect Dis 1994;170:553; Ann Intern Med 1996;124:803). None of these tests should replace serolog
circumvent the informed consent process.

Table 2-1: Tests for HIV-1
Assay Sensitivity Comments
Routine 99.7% Readily available and inexpensive. Sensitivity and specificity >99.9% (MMWR 1990;39:
serology Engl J Med 1988;319:961; JAMA 1991;266:2861).

Routine 99.7% Readily available and inexpensive. Sensitivity and specificity >99.9% (MMWR 1990;39:
serology Engl J Med 1988;319:961; JAMA 1991;266:2861).
Rapid test 99.9% Results are available in <10 minutes but test must be performed by a lab technician. Sp
SUDS [Murex 99.6%; positive tests should be confirmed. Highly sensitive; negative tests do not usuall
Diagnostics, confirmation. Other rapid tests are available but are not FDA approved (Int J STD AIDS
Norcross, Ga.] 1997;8:192; Vox Sang 1997;72:11).
Salivary test 99.9% Salivary collection device to collect IgG for EIA and WB. Advantage is avoidance of phle
(OraSure Test Sensitivity and specificity are comparable to standard serology (JAMA 1997;227:254).
System)
Urine test >99.9% Used for EIA test only, so positive results must be verified by serology. Must be adminis
(Calypte 1) physician. Cost is low - about $4/test.
PBMC culture 95% to Viral isolation by co-cultivation of patient's PBMC with phytohemagglutinin (PHA)-stimul
100% PBMC with IL-2 over 28 days. Expensive and labor-intensive. May be qualitative or qua
Main use of qualitative technique is viral isolation for further analysis and for HIV detect
infants. Quantitative results correlate with stage: Mean titer is 20/10 6 cells in asymptoma
patients and 2200/106 cells in patients with AIDS (N Engl J Med 1989;321:1621).
DNA PCR >99%
assay Qualitative DNA PCR is used to detect cell-associated proviral DNA; primers are comme
available from Roche Laboratories. Sensitivity is >99% and and specificity is 98%. This
considered sufficiently accurate for diagnosis without confimation and is not FDA-appro
Intern Med 1996;124:803). Main use is for viral detection in the case of neonatal HIVand
or indeterminate serologic tests.

HIV RNA PCR 95% to False-positive tests in 2% to 9%; usually at low titer. Sensitivity depends on viral load th
98% assay and assumes no antiretroviral therapy.
Top of Page | Next page -- Quantitative Plasma HIV RNA





Contents:
Syphilis Serology

Tables

Quantitative Plasma HIV RNA (Viral Burden)
Techniques: see Table 2-2 and Table 2-3

1. HIV RNA PCR (Amplicor HIV-1 Monitor versions 1.0, and 1.5, Roche Labs; 800-526-1247). Ve
is FDA approved; version 1.5 is available commercially and detects non-B subtypes. Both the
1.5 versions are available in the "standard" assay and the "ultrasensitive" assay (J Clin Microb
1999;37:110).
2. Branched chain DNA or bDNA (Quantiplex HIV RNA 3.0 assay, Bayer, 800-434-2447, formerl
Version 2.0 is being phased out.
3. Nucleic acid sequence-based amplification or Nuclisens HIV-1 QT (Organon Teknika), 800-68
x152

Reproducibility: Commercially available assays vary based on the lower level of detection and dynam
(J Clin Microbiol 1996;34:3016; J Med Virol 1996;50:293; J Clin Microbiol 1996;34:1058; J Clin Micr
1998;36:3392). Two standard deviations (95% confidence limits) with this assay are 0.3 to 0.5 log (2
3-fold) (J Infect Dis 1997;175:247; AIDS 1999;13:2269). This means that the 95% confidence limit f
of 10,000 c/mL ranges from 3100 to 32,000 c/mL. Recent studies indicate that the viral load in asym
women is 2-fold lower than seen in men at the same CD4 cell counts for early stage disease (Lance
1998;352:1510; N Engl J Med 2001;344:270). This difference disappears with disease progression
Dis 1999;180:666). Quantitative results with the Amplicor (Roche) assay are about one-half (0.3 log
those of Quantiplex version 3.0; comparitive data for the Nuclisens assay are not available (J Clin M
2000;38:2837).

Cost: $100 to $150 per assay (Medicare reimbursement $111 to $130)

Indications: Quantitative HIV RNA is useful for diagnosing acute HIV infection, for predicting progres
chronically infected patients, and for therapeutic monitoring (Ann Intern Med 1995;122:573; N Engl

Cost: $100 to $150 per assay (Medicare reimbursement $111 to $130)

Indications: Quantitative HIV RNA is useful for diagnosing acute HIV infection, for predicting progres
chronically infected patients, and for therapeutic monitoring (Ann Intern Med 1995;122:573; N Engl
1996;334:426; J Infect Dis 1997;175:247).

Acute HIV infection: Plasma HIV RNA levels are commonly determined to detect the acute re
syndrome prior to seroconversion. Most studies show high levels of virus (10 5 to 106 c/mL). No
2% to 9% of persons without HIV infection have false-positive results, virtually always with low
titers (<10,000 cells/mm3) (Ann Intern Med 1999;130:37; J Clin Microbiol 2000;38:2837; Ann I
2001;134:25). The alternative is the HIV p24 antigen assay, which is less expensive ($20 vs $
highly specific, but only 89% sensitive (Ann Intern Med 2001;134:25).
Prognosis: The most comprehensive study to assess the association between viral load and
history is the analysis of stored sera from the Multicenter AIDS Cohort Study (MACS), which s
strong association between "set point" and rate of progression that was independent of the ba
CD4 cell count (Ann Intern Med 1995;122:573; Science 1996;272:1167; J Infect Dis 1996;174
Infect Dis 1996;174:704; AIDS 1999;13:1305).
Probability of transmission: The probability of HIV transmission with nearly any type of expo
directly correlated with viral load (N Engl J Med 2000;342:921; J AIDS 1996;12:427; J AIDS 1
J AIDS 1999;21:120).
Therapeutic Monitoring: Following initiation of therapy there is a rapid initial decline in HIV R
(alpha slope), reflecting activity against free plasma HIV virions and HIV in acutely infected CD
This is followed by a second decline (beta slope) that is longer in duration (months) and more
degree. The latter reflects activity against HIV infected macrophages, and HIV released from o
compartments, especially those trapped in follicular dendritic cells of lymph follicles. The maxim
antiviral effect is expected by 4 to 6 months. Most authorities now believe that HIV RNA levels
most important barometer of therapeutic response (N Engl J Med 1996;335:1091; Ann Intern M
1996;124:984).
Unexpectedly low viral load: The Roche assay (RT-PCR) Version 1.0 uses primers designe
for detection of clade B strains of HIV, since this is the predominant clade in the United States
Europe, where HAART is used. Patients with non-clade B strains may show deceptively low p
RNA levels. The bDNA assay, the Roche 1.5 version test, or the Nuclisens HIV-1QT assay wi
more accurate quantitation of non-clade B strains, since these assays amplify subtypes A-G. N
accurate for the non-M subtypes (N or O) or HIV-2 strains.

Recommendations: Adapted from the International AIDS Society-USA (Nat Med 1996;2:625) and DHH
Guidelines (MMWR 1998;47[RR-3]:38).

Quality assurance: Assays on individual patients should be obtained at times of clinical stabi
least 4 weeks after immunizations or intercurrent infections, and with use of the same lab and
technology.
Frequency: Tests should be performed at baseline (x2) followed by routine testing at 3- to 4-m
intervals. With new therapy and changes in therapy, assays should be obtained at 2 to 4 week
slope), 12 to 16 weeks, and at 16 to 24 weeks. An optimal response to therapy should be asso
with a 1.5 to 2 log10 decrease at 4 weeks, <500 c/mL at 12 to 16 weeks, and <50 c/mL at 16 to
weeks. (Author's comment: Time to viral load nadir is dependent on pretreatment viral load as
potency of the regimen, compliance, pharmacology, and resistance. Patients with high baselin
loads take longer to achieve suppression than those with low viral loads.)
Interpretation: Changes of >50% (0.3 log10) are considered significant.
Factors not measured by viral load tests: immune function, CD4 regenerative reserve, sus
to antivirals, infectivity, syncytial vs nonsyncytial inducing forms and viral load in compartment
than blood (eg, lymph nodes, CNS, genital secretions).
Factors that increase viral load:
1. Progressive disease
2. Failing antiretroviral therapy due to inadequate potency, inadequate drug levels, nonadhere

Factors not measured by viral load tests: immune function, CD4 regenerative reserve, sus
to antivirals, infectivity, syncytial vs nonsyncytial inducing forms and viral load in compartment
than blood (eg, lymph nodes, CNS, genital secretions).
Factors that increase viral load:
1. Progressive disease
2. Failing antiretroviral therapy due to inadequate potency, inadequate drug levels, nonadhere
resistance, and/or drug interactions.
3. Active infections: active TB increases viral load 5- to 160-fold (J Immunol 1996;157:1271);
pneumococcal pneumonia increases viral load 3- to 5-fold.
4. Immunizations such as influenza and Pneumovax (Blood 1995;86:1082; N Engl J Med
1996;335:817; N Engl J Med 1996;334:1222).
False low viral loads: 1) non-B subtypes using the Amplicor (Roche) Version 1.0; 2) HIV-2 in
dual HIV-1 and HIV-2 infection.
Relative merit of tests:

The Quantiplex version 3.0 assay has good reproducibility for viral load levels of 100 to
500,000 c/mL. The linear range for Amplicor is 50 to 75,000 c/mL for the ultrasensitive test
requiring a different test for specimens with higher viral loads (J Clin Microbiol 2000;38:283
Amplicor version 1.0 is FDA approved. The Nuclisens assay has a broad dynamic range (5
3,000,000 c/mL) and can be used for HIV quantitation in non blood or on various body fluid
tissue such as seminal fluid, CSF, breast milk, saliva, and vaginal fluid. (J Clin Microbiol
2000;38:1414).

Roche Bayer (formerly Chiron) Organon

Contact 800-526-1247 800-434-2447 800-682-2666 x152

Technique RT-PCR bDNA Nuclisens HIV-1 QT

Comparison of Results with the RT-PCR assay Results with bDNA are 50% of results Comparative results with PT-PCR
results are about 2x results with bDNA with RT-PCR for the version 2.0 or
using version 2.0 or 3.0. 3.0.

Advantages Amplicor Version 1.0 is FDA Technician time demands are less May be used with tissue or body f
approved such as genital secretions

Amplifies subtypes A-G Amplifies subtypes A-G
Fewer false positives compared
with Chiron
Greatest dynamic range
Version 1.5 amplifies subtypes A-G

Dynamic range Standard: (Amplicor 1.0 and 1.5) bDNA Quantiplex Version 3.0: 100 to Nuclisens HIV-1 QT: 40 to 10,000
400 to 750,000 c/mL 500,000 c/mL c/mL (depending on volume)

Ultrasensitive (Ultra-Direct 1.0 and
1.5):
50 to 75,000 c/mL

Subtype Version 1.0: B only A-G A-G
amplified Version 1.5: A-G

Specimen Amplicor - 0.2 mL 1 mL 10 µL to 2 mL
volume Ultrasensitive - 0.5 mL

Tubes EDTA EDTA EDTA, heparin, whole blood, any
(lavender top) (lavender top) fluid, PMBC, semen, tissue etc.

Requirement Separate plasma <6 hrs and freeze Separate plasma <4 hrs and freeze Separate serum or plasma <4 hrs
prior to shipping at -20 oC or -70 oC prior to shipping at -20 oC or -70 oC freeze prior to shipping at -20oC o
-70 oC

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Top of Page | Next page -- CD4 Cell Count





Contents:
Syphilis Serology

Tables

CD4 Cell Count

This is a standard test to stage the disease, formulate the differential diagnosis of patient complaints
1-2), and to make therapeutic decisions regarding antiviral treatment and prophylaxis for opportunis
pathogens. It is also a relatively reliable indicator of prognosis that complements the viral load assay
two assays independently predict clinical progression and survival (Ann Intern Med 1997;126:946).
counts have not been found to predict outcome (N Engl J Med 1990;322:166).

Return to top

Technique

The standard method for determining CD4 cell count uses flow cytometers and hematology analyze
expensive and require fresh blood (<18 hours old). The cost of the test ranges from $50 to $150. An
alternative system that uses EIA technology is the TRAX CD4 Test Kit (J AIDS 1995;10:522). This m
attractive in resource-limited areas.

Normal values for most laboratories are a mean of 800 to 1050/mm 3 with a range representing two
deviations of approximately 500 to 1400/mm3 (Ann Intern Med 1993;119:55).

Frequency of testing: CD4 cell count <350/mm3 - every 3 to 4 months; CD4 cell count >350/mm 3
6 months (Clin Infect Dis 2000;30:5); <50 cells/mm 3 optional. Frequency will vary with individual
circumstances.

Factors that influence CD4 cell counts include analytical variation, seasonal and diurnal variation
intercurrent illnesses, and corticosteroids. Substantial analytical variations, which account for the wi
in normal values (usually about 500 to 1400/mm 3), reflect the fact that the CD4 cell count is the prod
three variables: the white blood cell count, % cells, and the % CD4 cells (cells that bear the CD4 rec
There are also seasonal changes (Clin Exp Immunol 1991;86:349) and diurnal changes with lowest
12:30 PM and peak values at 8:30 PM (J AIDS 1990;3:144), these variations do not clearly corresp
circadian rhythm of corticosteroids. Modest decreases in the CD4 cell count have been noted with s
acute infections and with major surgery. Corticosteroid administration may have a profound effect w
decreases from 900/mm 3 to less than 300/mm3 with acute administration; chronic administration has
pronounced effect. (Clin Immunol Immunopathol 1983;28:101). Acute changes are probably due to
redistribution of leukocytes between the peripheral circulation and the marrow, spleen, and lymph no
Exp Immunol 1990;80:460). Co-infection with HTLV-1 may be responsible for a deceptively high CD
count in the presence of immune suppression from HIV-1. Splenectomy may also cause deceptively
levels. The following have minimal effect on the CD4 cell count: gender, age in adults, risk category
psychological stress, physical stress, and pregnancy (Ann Intern Med 1993;119:55).

The CD4 cell percentage is sometimes used in preference to the absolute number, since this reduce
variation to one measurement (J AIDS 1989;2:114). In the AIDS Clinical Trial Group (ACTG) labora
within-subject coefficient of variation for % CD4 was 18% compared with 25% for the CD4 cell coun
Dis 1994;169:28). Corresponding CD4 cell counts are:

CD4 Cell Count % CD4
>500/mm3 >29%
3
200 to 500/mm 14% to 28%
<200/mm3 <14%

Precautions in the use and interpretation of CD4 cell counts include the need for both clinicians
patients to be aware of the fluctuations described above. Test results that represent "milestones" fo
therapeutic decisions be repeated, especially if they show values that do not correlate well with prio
Prior studies show the 95% confidence ranges for a true count of 500/mm3 were 297 to 841/mm3 an
337/mm3 for a count of 200/mm3 (J AIDS 1993;6:537). Deceptively high CD4 cell counts are noted i
with concurrent human T-cell leukemia virus (HTLV)-1 infection and in patients with a splenectomy,
the agent of adult T cell leukemia and tropical spastic paraparesis. HTLV-1 is closely related to HTL
most serologic assays show cross reactivity, but only HTLV-1 causes deceptively high CD4 cell cou
Serologic studies in the United States show HTLV-1/2 infection rates of 7% to 12% in injection drug
2% to 10% in commercial sex workers (N Engl J Med 1990;326:375; JAMA 1990;263:60); 80% to 9
these are HTLV-2 in both populations. High rates of concurrent HIV and HTLV-1 have been reporte

Medical management of hiv infection

Medical management of hiv infection

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