HIV AND AIDS: WHAT DO WE KNOW?
| HIV UPDATE —Mark H. Katz, MD, Regional HIV Physician Advisor, Kaiser Permanente of Southern California, Los
Angeles
|
| Introduction: risk for infection in health care worker from highest-risk exposure (eg, needlestick from known HIV-positive
patient) 1 in 250 (nearly 0 with effective prophylaxis); window period 2 to 6 wk; screen HIV-positive patients for
other conditions (eg, tuberculosis [TB], syphilis); low T-cell count (<200/mm3 ) or Pneumocystis pneumonia most common
cause of AIDS diagnosis; therapy usually comprised of 3 drugs; treat pregnant HIV-positive women with lowest
dose possible; in patients with Pneumocystis, use steroids and antibiotics
|
| Epidemiology: ≈40 million people living with HIV worldwide (≈1 million in North America); estimated 30 to 40 million
deaths; ≈66% of population in sub-Saharan Africa living with HIV; fastest rate of new infections in former Soviet Union,
Indian subcontinent, and southeast Asia (eg, China); during 1996 to 1997, increased use of 3-drug regimen led to >80%
decrease in death rate within 2 yr; slight decrease in black non-Hispanic population, although it remains population in
which most new cases seen; slight increase in white non-Hispanic population; fairly level in Hispanic, Asian/Pacific Islander,
and American Indian/Native Alaskan populations (may be due to unidentified genetic barrier that prevents acquisition
of HIV); increasing number of cases in young adults (ages 20-24 yr); incidence in women increasing steadily; rate
of new infections in United States, 45,000 per year
|
| Factors in new infections: male-to-male sexual contact—in Los Angeles County in early 2001, incidence of new
syphilis cases in gay and bisexual men (many HIV-positive) increased; in Los Angeles, 90% of inpatient crystal methamphetamine
users in recovery HIV-positive (≈50% of chronic users in and out of treatment); unawareness of infection—
higher viral loads associated with greater chance (1 in 30 to 1 in 200) of infecting someone else; after becoming HIV-infected,
person may be unaware for weeks, months, or years; risk factors—unprotected sexual contact; injection drug
use; lack of circumcision; substance use; risk for transmission per 10,000 encounters (eg, sexual contact) when one person
HIV-positive and other HIV-negative usually <1%; in contrast, transmission rate from blood transfusion 90%
|
| Pregnancy and children: 66% decline in transmission in women given zidovudine (AZT) alone during second 2 mo
(calendar) of pregnancy; children—recent estimate in North America, only 500 new infections (in ages 11-15 yr, most
cases acquired through sexual activity); in United States, approximately 70 to 80 babies (or fewer) born with HIV per
year; in sub-Saharan Africa, 630,000 children born with HIV per year
|
| Postexposure prophylaxis: several studies showed 30-day course of anti-HIV medications (ideally commencing
within 3 days of event, eg, health care worker with needlestick or unprotected sex with known HIV-positive partner) led
to 0 seroconversions; HIV prophylaxis recommended only when source or sexual partner known to be positive; 5 sessions
of counseling about reducing risky behavior (compared to 2 sessions) resulted in greater decrease in risky sex acts,
need for repeat postexposure prophylaxis, and likelihood of acquiring HIV; no vaccine available; topical microbicides
undergoing clinical trials; cervical barriers; data emerging for preexposure prophylaxis; treating herpes simplex virus
(HSV) infection with acyclovir associated with decreased risk for HIV infection
|
| Testing: late testing—common; in >4000 people with AIDS, nearly 50% did not know they were HIV-positive until
within 1 yr of diagnosis; in people tested late, usually because of illness; HIV antibody testing—Abbott enzyme-linked
immunosorbent assay (ELISA) standard of care; mucosal swab; urine ELISA test; home HIV testing ($80); newer rapid
HIV antibody assay—available in many clinical settings; results available in 15 to 20 min; does not change window period
(ie, patient may not show antibody until 4 wk after infection, so result may be negative); if positive, must confirm
with Western blot test
|
| Diagnosing HIV: standard ELISA or enzyme immunoassay (EIA) repeatedly reactive, followed by confirmatory Western
blot test; do not give results until second ELISA and Western blot test complete; first ELISA positive and second
ELISA negative indicates negative result (ELISA must be repeatedly reactive to indicate HIV infection); negative Western
blot indicates no infection; positive Western blot read by certain bands; indeterminate Western blot may indicate
early HIV infection or other condition that immunologically resembles HIV; causes of false-negative results—testing
before seroconversion occurs; seroreversion (becoming HIV-negative; rare and not documented); other strains not common
in United States; technical error; causes of false-positive results—receipt of HIV vaccines as part of clinical trial;
factitious infection; autoantibodies (rare); indeterminate results—4% to 20% of all Western blot tests; early seroconversion
most common cause; can occur in pregnancy; new guidelines for testing—Centers for Disease Control and Prevention
(CDC) recommends that all health care settings in United States screen all people 13 to 64 yr of age; opt-out
screening (ie, “we test everyone for HIV, unless you tell us we can’t test you”) shown to increase testing
|
| Signs of infection: acute infection—resembles influenza; fever; fatigue; lymphadenopathy; pharyngitis; rash; malaise;
arthralgias; thorough risk history important; presence of cough helps rule out acute retroviral infection; established
infection—skin condition (eg, folliculitis); nonspecific diarrhea; lymphadenopathy; periodontal disease; sinusitis; if
chronic established infection suspected—take thorough risk history; suggest HIV antibody testing (repeat in 3-6 mo);
measurement of viral load not recommended for initial evaluation; counseling and appropriate follow-up; if acute retroviral
infection suspected—take thorough risk history; order HIV antibody testing and quantitative HIV viral load; acute
retroviral syndrome defined as negative or indeterminate HIV antibody test with positive viral load (>10,000 copies/mL)
|
| Work-up of newly HIV-positive patient: check T cells and viral load; hepatitis panel; sexually transmitted disease
(STD) screening; hepatitis and pneumococcal vaccines (Pneumovax 23); assess for cardiac and osteoporotic risk factors;
viral load sensitivity may be low; viral load <50 (or <75) copies/mL “undetectable” (“does not mean zero”)
|
| Definition of AIDS: HIV infection with ≥1 of 25 conditions defined by CDC (eg, T-cell count <200/mm3 , Pneumocystis
, Kaposi’s sarcoma, wasting syndrome, TB)
|
| HIV and having children: reasonable option; studies show HIV-positive men may be treated with sperm washing and
HIV-positive women may be treated with intracytoplasmic sperm injection; treatments allow normal pregnancies with no
HIV in infants; refer to tertiary care center
|
| Therapy: goal to achieve and maintain undetectable viral load; wide consensus that everyone with AIDS diagnosis, HIV-
positive pregnant women, and HIV-positive symptomatic patients should be treated; patients who are not pregnant, or not
symptomatic, or not diagnosed with AIDS need treatment if T cells <350/mm3 or viral load >100,000 copies/mL; higher
T-cell count at time of initiation of highly active antiretroviral therapy (HAART) improves chance for survival; starting
treatment involves patient’s perceptions; “the earlier we start treatment, the better”
|
| Most commonly used treatment regimens: 2 nucleoside analogue reverse transcriptase inhibitors (NARTIs or
“nukes”) plus protease inhibitor (“non-nuke”); switch regimen if patient intolerant or virus not suppressed; maximize patient
adherence; use resistance testing when regimen appears to be failing; treatment interruption no longer recommended,
except when patient intolerant or requires psychologic break; issues involve patient adherence, safety, and tolerance; most
drugs work by inhibiting reverse transcriptase or protease; medications that inhibit integrase to be approved by Food and
Drug Administration (FDA); one medication blocks HIV binding; with antiviral therapy, viral load drops promptly (within
2 wk) to undetectable level and remains over time (recheck T-cell count and viral load in few weeks; when patient stable,
recheck 3-4 times per year)
|
| Highly active antiretroviral therapy: reasons for failure—poor adherence; pharmacokinetic conundrums; disease
too advanced; insufficient efficacy of drug; more patients stop medications because of side effects than because of virologic
failure; single HIV medication available (efavirenz, emtricitabine, and tenofovir combined [Atripla]; 1 pill taken
once daily); metabolic complications—HIV clearly associated with increased risk for diabetes, prediabetes, hyperlipidemia,
body fat redistribution, and bone complications; ≈50% of patients on HIV treatment for >2 yr have morphologic
changes (eg, fat atrophy or accumulation); as complexity of regimen increases, chance for rise in triglycerides, total cholesterol,
and low-density lipoprotein (LDL) increases; no effect on high-density lipoprotein (HDL); screen routinely; diabetes
4.3 times more likely in patients on HAART, compared to HIV-negative people; in HIV-positive patients not on
HAART, incidence of diabetes greater but not as great as on treatment; heart disease—HAART risk factor for acute coronary
syndrome; counsel patients about minimizing risk factors (eg, tobacco smoking); treat hypertension and hyperlipidemia;
cardiovascular screening important; increased risk for malignancies—AIDS-defining malignancies (eg, non-
Hodgkin’s lymphoma, cervical cancer, Kaposi’s sarcoma) and Hodgkin’s lymphoma, head and neck cancer, and lung
cancer; cancer screening important
|
| Opportunistic conditions: cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections occur at
lower T-cell counts than Pneumocystis or Kaposi’s sarcoma; patients with T-cell count <200/mm3 should receive prophylaxis
for Pneumocystis with co-trimoxazole; patients with T-cell counts <50/mm3 effectively prophylaxed for MAC
infection with azithromycin (1200 mg once weekly); Kaposi’s sarcoma—purplish lesions resemble blood blisters; many
treatments available; caused by human herpesvirus 8 (HHV-8); treated according to oncologic model; use doxorubicin
(Doxil) or daunorubicin (DaunoXome); paclitaxel (eg, Taxol) for failure; topical alitretinoin (Panretin) approved by FDA
|
| Pneumocystis jiroveci pneumonia: classic triad—fever, dyspnea, and nonproductive cough; chest x-ray shows bilateral
interstitial infiltrates; may require bronchoscopy; obtain induced sputum; treatment—oral or intravenous (IV) co-
trimoxazole treatment of choice; prednisone (60 mg/day) shown to decrease morbidity and mortality
|
| Cytomegalovirus: presentation of vision disturbance; whitish exudates on retina; usually occurs with low T-cell count;
multiple organ manifestations; drug of choice valganciclovir or IV ganciclovir
|
| Mycobacterium infection: classic symptoms—fever; chills; sweating; fatigue; myalgias; ethambutol and clarithromycin
or azithromycin effective
|
| Others: TB—all HIV-positive patients must be screened; any positive purified protein derivative (PPD; 2-5 mm) in HIV
patient sufficient for prophylaxis; in high-risk cases, TB prophylaxis recommended de novo; cryptococcal meningitis—
classic sign, positive India ink stain; successfully treated with amphotericin and lifelong maintenance with oral fluconazole
(Diflucan); toxoplasmosis—ring lesion seen on computed tomography (CT), with fever, headache, and neurologic
symptoms; treatable with pyrimethamine and sulfadiazine; gastrointestinal (GI) manifestations—thrush; esophageal
candidiasis; cholecystitis; CMV can present as acute abdomen; colitis; diarrhea; hepatitis C virus (HCV) coinfection—
rate may be as high as 20% to 30%; HCV currently believed not to accelerate HIV; in presence of HIV, hepatitis C may
progress more quickly; coinfected patients often given hepatitis C treatment first
|
| Surgical outcomes of HIV-positive patients: study saw no statistically significant difference in length of stay,
morbidity, mortality, or complications between HIV-positive patients and HIV-negative patients who underwent procedures
(eg, bypass surgery, transplantation)
|
| Summary: successes—decreased vertical transmission (mother-to-child) in United States; effective antiretroviral therapy;
potent regimens; effective prophylaxis; less hospitalization; increased survival; lack of success—increased transmission
rate; low access to treatment in inner cities; no effective immune-boosting drug; no vaccine
|
| ADDITIONAL THOUGHTS ON HIV—Jeffrey T. Kirchner, DO, Associate Professor of Family Medicine, Temple University
School of Medicine, and Associate Director of Family and Community Medicine, Lancaster General Hospital, Lancaster,
PA
|
| Epidemiology: incidence increasing in former Soviet Union and eastern Europe due to IV drug use; low prevalence in
Canada and Australia due to aggressive prevention programs; in parts of India and South America access to treatment increasing;
circumcision reduces risk for HIV acquisition by 50%; vaginal microbicides associated with increased risk for
HIV; US data—first cases in 1981; >500,000 deaths; ≈60% decline in deaths between 1995 and 1997; case reports from
33 states show ≈50% of cases in blacks
|
| Transmission: in women, predominantly heterosexually transmitted; IV drug use (higher incidence of infection in
women than in men); can be transmitted heterosexually from women to men (condom use essential); 1.2 million people
in United States living with HIV (25%-33% unaware of infection and may not perceive themselves as at risk)
|
| Testing for HIV infection: HIV ELISA available since 1985; nucleic acid (viral load) testing—polymerase chain
reaction (PCR); branched-chain DNA testing; highly sensitive, but not as specific; rate of false-positive results 20%;
specificity of PCR 75% to 80%; not recommended for screening or diagnostic purposes, unless acute HIV infection suspected
(eg, patients who present 7-21 days after infection; HIV ELISA nonreactive in most cases); used to follow patients
on therapy; rapid testing—6 tests approved by FDA; OraQuick Advance rapid HIV-1/2 antibody test waived by Clinical
Laboratory Improvement Amendments (CLIA); can be used in office; low complexity; detects HIV antibody in saliva;
results available in 20 min; sensitivity and specificity 99% to 100%; well-received by patients; may be available
over-the-counter in 1 to 2 yr; CDC guidelines—routine screening in areas with HIV prevalence ≥1%; targeted testing
based on risk emphasized; however, may miss significant number of HIV-positive people due to perception that patient
not at risk or unwillingness to address sexual history; many people unaware of infection or risk and do not request testing
until symptomatic; routine screening cost-effective; revised guidelines—routine voluntary HIV screening; opt-out
screening (present option in nonjudgmental, nonbiased manner); annual screening for high-risk patients; screening of
pregnant women during third trimester in high-prevalence areas or in high-risk settings; 15 states require written informed
consent; with opt-out testing, acceptance ≈90%; prevention counseling not required (no good evidence showing
efficacy in patients who tested negative); HIV testing should be done in private physician practices and inpatient settings;
in low-prevalence settings, consider “sunset” provision (if positive rate <1 in 1000 after testing for 1 yr, reverting to old
guidelines of risk-based assessment for more selective testing reasonable)
|
| Immunizations: annual influenza vaccine recommended in patients with HIV diagnosis, regardless of age; pneumococcal
vaccine every 5 yr; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap) vaccine (eg,
Adacel); hepatitis A and B—perform baseline serologies and vaccinate appropriately if surface antibody to hepatitis A
(IgG) negative; combination hepatitis A (inactivated) and hepatitis B (recombinant) vaccine (Twinrix)
|
Suggested Reading
Jayasuriya A et al: Twenty-five years of HIV management. J R So Med 100:363, 2007; Jespers V et al: Safety trial
of the vaginal microbicide cellulose sulfate gel in HIV-positive men. Sex Transm Dis 34:519, 2007; Kong BN et al: Opportunistic
infections and HIV clinical disease stage among patients presenting for care in Phnom Penh, Cambodia. Southeast
Asian J Trop Med Public Health 38:62, 2007; Majumdar D: An overview of the recent trends in HIV/AIDS in the
United States. Indian J Public Health 50:28, 2006; Millett GA et al: The known hidden epidemic HIV/AIDS among
black men who have sex with men in the United States. Am J Prev Med 32:S31, 2007; Nesheim SR et al: Trends in opportunistic
infections in the pre- and post-highly active antiretroviral therapy eras among HIV-infected children in the Perinatal
AIDS Collaborative Transmission Study, 1986-2004. Pediatrics 120:100, 2007; Nishiura H: Lessons from
previous predictions of HIV/AIDS in the United States and Japan: epidemiologic models and policy formulation. Epidemiol
Perspect Innov 4:3, 2007; Poynten I et al: The public health impact of widespread availability of nonoccupational
postexposure prophylaxis against HIV. HIV Med 8:374, 2007; Smith R et al: Beyond the end of exceptionalism: integrating
HIV testing into routine medical care and HIV prevention. Expert Rev Anti Infect Ther 5:581, 2007; Stekler J et
al: Negative rapid HIV antibody testing during early HIV infection. Ann Intern Med 147:147, 2007; Tarantola D et al:
New guidance on recommended HIV testing and counseling. Lancet 370:202, 2007.
Educational Objectives
| The goals of this program are to improve the management and to reduce the incidence of HIV infection and AIDS.
After hearing and assimilating this program, the participant will be better able to:
|
 | 1. Stratify risk for infection based on exposure routes and patient history.
|
| 2. Use appropriate screening methods to diagnose HIV.
|
| 3. Recognize occurrence of opportunistic infections, such as Pneumocystis jiroveci pneumonia.
|
| 4. Discuss adverse effects of HIV treatment, such as metabolic complications and cardiovascular risks.
|
| 5. Review Centers for Disease Control and Prevention guidelines for HIV screening.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant
financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts
were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial
interest. For this program, the following has been disclosed: Dr. Kirchner is on the Speakers’ Bureau for Bristol-Myers
Squibb.
Acknowledgements
Dr. Katz spoke in Los Angeles, CA, at the 34th Annual UCLA Family Practice Refresher Course, presented May 29 to
June 2, 2007, by the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Kirchner was recorded
in Lancaster, PA, at the 31st Semi-Annual Family Practice Review, presented March 25-30, 2007, by the Temple
University School of Medicine and Lancaster General Hospital. The Audio-Digest Foundation thanks the speakers and the
sponsors for their cooperation in the production of this program.
|
