c.Significant change in HIV RNA assay  is defined by at least a 2-fold (0. .3 log) change in viral RNA (accounts for normal variation in clinically stable patients), or a 3-fold (0. .5 log) change in response to new antiretroviral therapy (accounts for intra-laboratory and patient variability). . For example, if a HIV RNA result = 50,000 copies/mL, then the range of possible actual values = 25,000–100,000 copies/ mL, and the value needed to demonstrate antiretroviral activity is ≤ 17,000 copies/ mL..

4.Indications for HIV RNA Testing.  Usually performed in conjunction with CD4 cell counts. . Indicated for the diagnosis of acute HIV infection, and for initial evaluation of newly diagnosed HIV. . Also recommended 2–8 weeks after initiation of antiretroviral therapy and every 3–4 months in all HIV patients..

5.When to Avoid HIV RNA Testing

a.During acute illnesses and immunizations.  Patients with acute infections (opportunistic infection, bacterial pneumonia, even HSV recurrences) may

experience significant (> 5-fold) rises in HIV RNA, which return to baseline 1–2 months after recovery.. Although data are conflicting, many studies show at least a transient increase in HIV RNA levels following influenza and other immunizations, which return to baseline after 1–2 months..

b.When results of test would not influence therapy.  Frequent scenario in patients with advanced disease who have no antiretroviral options or cannot tolerate therapy..

c. As a screening test for HIV infection,  except if acute (primary) HIV disease is suspected during the HIV antibody window (i. .e. ., first 3–6 weeks after viral transmission)..

INITIAL ASSESSMENT OF HIV INFECTION

A.Clinical Evaluation.  History and physical exam should focus on diagnoses associated with HIV infection. . Compared to patients without HIV, the severity, frequency, and duration of these conditions are usually increased in HIV disease..

1.Dermatologic:  Severe herpes simplex (oral/anogenital); herpes zoster (especially recurrent, cranial nerve, or disseminated); molluscum contagiosum; staphylococcal abscesses; tinea nail infections; Kaposi’s sarcoma (from HHV-8 infection); petechiae (from ITP); seborrheic dermatitis; new or worsening psoriasis; eosinophilic pustular folliculitis; severe cutaneous drug eruptions (especially sulfonamides)..

2.Oropharyngeal:  Oral candidiasis; oral hairy leukoplakia (from EBV); Kaposi’s sarcoma (most commonly on palate or gums); gingivitis/periodontitis; warts; aphthous ulcers (especially esophageal/perianal)..

3.Constitutional symptoms:  Fatigue, fevers, chronic diarrhea, weight loss..

4.Lymphatic:  Persistent, generalized lymphadenopathy..

5.Others:  Active TB (especially extrapulmonary); non-Hodgkin’s lymphoma (especially CNS); unexplained leukopenia, anemia, thrombocytopenia (especially ITP); myopathy; miscellaneous neurologic conditions (cranial/peripheral neuropathies, Guillain-Barre syndrome, mononeuritis multiplex, aseptic meningitis, cognitive impairment)..

B.Baseline Laboratory Testing (Table 5.1)

C.CD4 Cell Count (lymphocyte subset analysis)

1.Overview.  Acute HIV infection is characterized by a decline in CD4 cell count, followed by a gradual rise associated with clinical recovery. . Chronic HIV infection shows

progressive declines (~ 50–80 cells/year) in CD4 cell count without treatment, followed by more rapid decline 1–2 years prior to opportunistic infection (AIDS-defining diagnosis).. Cell counts remain stable over 5–10 years in 5% of patients, while others may show rapid declines (> 300 cells/year).. Since variability exists within individual patients and between laboratories, it is useful to repeat any value before making management decisions.

2.Uses of CD4 Cell Count

a.Gives context of degree of immunosuppression  for interpretation of symptoms/signs (Table 5..2)..

b.Used to guide therapy.  Guidelines support CD4 < 500/mm3 as the threshold for initiating treatment, regardless of HIV RNA or symptoms.. For prophylaxis against PCP, toxoplasmosis, and MAI/CMV infection, CD4 cell counts of 200/mm3, < 100/mm3, and

<50/mm3 are used as threshold levels, respectively..

c.Provides estimate of risk of opportunistic infection or death.  CD4 cell counts

<50/mm3 are associated with a markedly increased risk of death (median survival 1 year), although some patients with low counts survive > 3 years even without antiretroviral therapy.. Prognosis is heavily influenced by HIV RNA, presence/history of opportunistic infections or neoplasms, performance status, and the immune reconstitution response to antiretroviral therapy..

D.  HIV RNA Assay (HIV RNA PCR) (p. 307)

Table 5.1. Baseline Laboratory Testing for HIV-Infected Patients

Table 5.1. Baseline Laboratory Testing for HIV-Infected Patients (cont’d)

Table 5.1. Baseline Laboratory Testing for HIV-Infected Patients (cont’d)

Table 5.2. Use of CD4 Cell Count for Interpretation of Patient Signs/Symptoms

>500 Most illnesses are similar to those in HIV-negative patients. . Some increased risk of bacterial infections (pneumococcal pneumonia, sinusitis), herpes zoster, tuberculosis, skin conditions..

200–500* Bacterial infections (especially pneumococcal pneumonia, sinusitis), cutaneous Kaposi’s sarcoma, vaginal candidiasis, ITP..

50–200* Thrush, oral hairy leukoplakia, classic HIV-associated opportunistic infections (e..g.., P.. [carinii] jiroveci pneumonia, cryptococcal meningitis, toxoplasmosis).. For patients receiving prophylaxis, most opportunistic infection do not occur until CD4 cell counts fall significantly below 100/mm3..

< 50* “Final common pathway” opportunistic infections (disseminated M. . aviumintracellulare, CMV retinitis), HIV-associated wasting, neurologic disease (neuropathy, encephalopathy)..

*Patients remain at risk for all processes noted in earlier stages..