C hapter 10:
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 77
A Guide to Primary Care of People with HIV/AIDS
Chapter 10: Abnormal Laboratory Values in HIV Disease
Table 10-1. Abnormalities Identified in symptoms, patients with therapeutic failure (persistent
Screening Tests clinical evidence of syphilis or a sustained 4-fold
increase in titer), and all patients with latent syphilis,
Test Implications of abnormal which includes latent syphilis of unknown duration.
findings Some experts have recommended performing lumbar
CBC Anemia – usually due to HIV or puncture for all HIV-infected persons with syphilis,
zidovudine regardless of the stage of syphilis. With respect to
Neutropenia – usually due to HIV followup, the nontreponemal test should be done at 3,
or drugs, especially ganciclovir and
zidovudine 6, 9, 12, and 24 months.
Thrombocytopenia – usually due to
HIV
Alanine
aminotransferase
Usual causes of elevated levels
are chronic hepatitis (HBV, HCV), HEMATOLOGIC
(ALT) alcoholic liver disease, or adverse
drug reactions.
COMPLICATIONS
Creatinine Usual causes of renal failure are
common medical conditions in this
What are the common causes of anemia?
population (hypertension, heroin Anemia, which is common in HIV disease, is usually
use, diabetes, IgA nepropathy, etc), caused by 1) late-stage HIV, presumably due to viral
adverse reactions to drugs (including
indinavir), or HIV nephropathy
infection of progenitor cells, 2) associated complications
that infiltrate the marrow, 3) nutritional deficiency,
Toxoplasma titer Positive results in 10% of adults in
US, higher in other countries. This
4) adverse drug reactions, or 5) iron deficiency. The
indicates latent disease with possible findings and management are summarized in
activation if CD4 count <100/mm3 Table 10-2.
VDRL or RPR If positive, need confirmatory
FTA-ABS What causes thrombocytopenia?
10
Screen for N. Positive results indicate high-risk Most cases are attributed to HIV infection of the multi-
gonorrhoeae and C. behavior and need for treatment
trachomatis
lineage hematopoietic progenitor cells in the marrow.
This HIV-associated thrombyocytopenia can occur in
PPD Induration ≥5mm indicates need
for evaluation for active TB and, if
relatively early HIV, but is more common with late-
negative, INH treatment stage disease. Although zidovudine (AZT) may cause
anemia or neutropenia, early studies showed that it
Chest x-ray Ghon complex, adenopathy, or
evidence of chronic lung disease reverses thrombocytopenia. For patients not receiving
ART, the preferred treatment for HIV-associated
CD4 count Barometer of immune function
thrombocytopenia is to promptly initiate ART. The
Viral load Indicates rate of progression of decision to intervene with intravenous immune globulin
untreated HIV and response to
HAART (IVIG) or corticosteroids is driven by signs or symptoms
of active bleeding, the need to do an invasive
Hepatitis panel
procedure, or a lack of response to ART.
Anti-HCV Positive results ± confirmatory HCV
RNA usually indicates chronic HCV
infection What causes neutropenia?
Anti-HBc or Positive results indicate prior Neutropenia is most commonly related to drug
antigenic experience with HBV therapy, especially with zidovudine (AZT), ganciclovir,
Anti-HBs
serology or valganciclovir, but it can also be caused by late-
stage HIV or marrow-infiltrate disease. With absolute
HBsAg Indicates HBV; if positive >6 months
indicates chronic HBV neutrophil counts of <500/mm3 it is important to
monitor for infection and intervene with empiric
Anti-HAV Positive test indicates prior antigenic
experience due to HAV infection or antibiotics rapidly when appropriate. Address
vaccination neutropenia by discontinuing the implicated agent or by
providing cytokine therapy using G-CSF or GM-CSF.
78 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to Primary Care of People with HIV/AIDS
Chapter 10: Abnormal Laboratory Values in HIV Disease
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 79
A Guide to Primary Care of People with HIV/AIDS
Chapter 10: Abnormal Laboratory Values in HIV Disease
80 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to Primary Care of People with HIV/AIDS
Chapter 10: Abnormal Laboratory Values in HIV Disease
recommend pegylated interferon with subcutaneous With regard to treatment of HCV, the goal is for cure,
injections once a week, although there are few published something that cannot be achieved with HIV or, to a
studies with this formulation for treatment of HBV. The large extent, with HBV. All patients with HCV should be
second form of therapy is nucleosides and nucleotides evaluated for HCV therapy. Standard indications in the
with activity against HBV. This gets tricky because many absence of HIV infection are chronic HCV, detectable
of these agents are active against HIV as well, and HCV-RNA, and a liver biopsy showing bridging or portal
there are variable rates of HBV resistance. Lamivudine fibrosis. The ALT levels may be elevated, but this finding
(3TC) is highly active against HBV but is associated with is variable and does not indicate the severity of HCV-
high rates of HBV resistance, up to 90% at 4 years. associated liver disease and is considered nonspecific.
The same applies to emtricitabine (FTC). Alternatives The liver biopsy is important for HCV therapeutic
are adefovir dipivoxil (trade name Hepsera), which decisionmaking, but it is indicated only if the patient is
is used in a dose that is probably not active against considered a candidate for treatment based on multiple
HIV but is highly active against HBV, has good activity variables including the severity and stability of HIV,
against lamivudine-resistant strains, and has low rates other comorbidities, probability of adherence, and
of resistance by HBV during treatment. Tenofovir (TDF) contraindications for interferon. The standard treatment
has the same attributes as adefovir but is also highly is pegylated interferon plus ribavirin for 48 weeks,
active against HIV. It should be emphasized that the regardless of the genotype. There is limited long-term
rationale for treating HBV is to reduce viral replication experience with this treatment in patients with HIV
and hepatic disease progression but that cure is rarely coinfection, but it appears that the rate of a sustained
achieved. Other standard components of therapy in virologic response as indicated by negative HCV DNA
patients coinfected with HBV are 1) advising them to levels at 6 months post-therapy are significantly lower
avoid or limit alcohol consumption, 2) teaching them compared to those who are seronegative for HIV. This
appropriate precautions to prevent transmission of both particularly applies to genotype 1, which accounts for
viruses, and 3) administering hepatitis A vaccine if they the majority of cases. It also appears that the optimal
are susceptible. response occurs when patients have relatively high CD4
cell counts, so this treatment is often preferred for those
Who should receive HBV vaccine? in early stage disease and for those who have responded 10
to ART.
All HIV-infected persons with no evidence of HBV
infection should receive this vaccine, although the
response rates are related to age (decreased with What HCV therapy should you use for persons
increasing age) and with CD4 cell counts (responses coinfected with HIV and HCV?
decrease with lower counts). The standard is 3 doses Currently, there are limited published data regarding
followed by a measurement of HBs antibody levels various HCV treatment regimens for persons coinfected
about 1 month after the third dose. If the level is <10 with HIV. Trials have generally shown relatively poor
IU/mL the 3-dose series should be repeated. If the responses to interferon monotherapy. Based on rapidly
patient does not respond to the second series, no further accumulating data from trials that have not included
vaccinations are currently recommended and the patient HIV-infected persons, pegylated interferon (pegylated
is considered a “non-responder.” interferon-alpha-2a or pegylated interferon-alpha-2b)
plus ribavirin is now the standard of care. (For treatment
How do you treat patients with HCV guidelines, refer to Suggested Resources.) In addition,
coinfection? several series involving persons coinfected with HIV
and HCV have suggested better sustained viral response
Patients coinfected with HIV and HCV should be
rates with pegylated interferon plus ribavirin than with
1) advised to avoid or limit alcohol consumption,
older regimens. For persons not infected with HIV,
2) counseled to use appropriate precautions to
recent guidelines have recommended that those with
prevent transmission of both viruses, and 3) given
genotypes 2 or 3 receive 24 weeks of therapy and those
hepatitis A and B vaccine if they are susceptible. The
with genotypes 1 and 4 receive 48 weeks of therapy. The
prevention message should emphasize that the major
optimal duration of therapy for persons coinfected with
route of transmission is by shared needles; the risk of
HIV and HCV remains unknown, but most trials have
transmission of HCV perinatally or with sexual contact is
used 48 weeks, regardless of genotype.
substantially less than that for HIV or HBV.
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 81
A Guide to Primary Care of People with HIV/AIDS
Chapter 10: Abnormal Laboratory Values in HIV Disease
82 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to Primary Care of People with HIV/AIDS
Chapter 10: Abnormal Laboratory Values in HIV Disease
KEY POINTS
Laboratory tests are frequently abnormal SUGGESTED RESOURCES
in HIV disease because 1) HIV is a (CONTINUED)
multi-system disease, 2) HIV causes
Management of Hepatitis C: 2002. NIH
immune suppression that may result in
opportunistic infections and tumors, 3) Consensus and State-of-the-Science
treatment has many potential adverse Statements. 2002 Jun 10-12;19:1-46.
reactions affecting multiple systems, and Available at: http://www.consensus.nih.gov.
4) patients with HIV are often at high risk Accessed 12/03.
for other medical conditions.
Ogedegbe AO, Sulkowski MS.
Hematologic complications
include anemia, neutropenia, and Antiretroviral-associated liver injury. Clin
thrombocytopenia. The most common Liver Dis. 2003;7:475-499.
causes of anemia and neutropenia are
either drug toxicity or the direct effect Orenstein R. Presenting syndromes of
of HIV on progenitor cells; the cause of human immunodeficiency virus. Mayo Clin
thrombocytopenia is most commonly a Proc. 2002; 77:1093-1102.
direct effect of HIV.
Liver disease is common because of Rockstroh JK. Management of hepatitis B
high rates of concurrent viral hepatitis, and C in HIV co-infected patients. J Acquir
especially HCV, and because all Immune Defic Syndr. 2003;34 Suppl 1:S59-65.
antiretrovirals are potentially hepatotoxic.
Sulkowski MS, Thomas DL. Hepatitis C in
Abnormal renal function is usually
the HIV-infected person. Ann Intern Med 10
a direct effect of HIV infection of the
kidneys resulting in a rapid progression 2003;138:197-207.
with nephrosis and end-stage renal
disease; abnormal renal function from Volberding P. Consensus statement:
any cause is important to know about anemia in HIV infection--current trends,
because it requires altering dose regimens treatment options, and practice strategies.
for nucleosides. Anemia in HIV Working Group. Clin Ther.
2000;22:1004-1020.
WEBSITES
SUGGESTED RESOURCES CDC National Center for Infectious
Kimmel PL, Barisoni L, Kopp JB. Diseases: http://www.cdc.gov/ncidod/
Pathogenesis and treatment of HIV- diseases/hepatitis/ Accessed 2/04.
associated renal diseases. Ann Intern Med.
2003;139:214-226. Hepatitis B Foundation: http://
www.hepb.org Accessed 2/04.
Lok ASF, McMahon BJ. AASLD Practice
Guidelines Hepatology 2001;34:1225- HIV and Hepatitis: http://
1241. Available at http://www.cdc.gov/ www.hivandhepatitis.com Accessed 2/04.
ncidod/diseases/hepatitis/b/hepatitis_b_
guidelines.pdf Accessed 1/04.
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 83
A Guide to Primary Care of People with HIV/AIDS
Chapter 10: Abnormal Laboratory Values in HIV Disease
REFERENCES
Ragni MV, Belle SH, Im K, et al. Survival of
human immunodeficiency virus-infected
liver transplant recipients. J Infect Dis.
2003;188:1412-20.
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84 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau