HIV: WHERE DO WE STAND?
Educational Objectives
| The goal of this program is to improve the management of people with HIV infection, AIDS, and AIDS-related
psychiatric symptoms and comorbidities. After hearing and assimilating this program, the clinician will be better
able to:
|
 | 1. Describe current trends in diagnosis, prevention, and treatment of AIDS.
|
| 2. Explain the importance of the window period immediately following infection.
|
| 3. Review the diagnosis and treatment of opportunistic infections and other complications of AIDS.
|
| 4. Recognize the symptoms of AIDS dementia and other cognitive manifestations of the presence of the
AIDS virus in the brain.
|
| 5. Select appropriate psychopharmacologic agents for the management of AIDS dementia and other psychiatric
comorbidities in AIDS patients.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee 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 faculty and the
planning committee reported nothing to disclose.
Acknowledgements
Dr. Katz spoke at the 35th Annual UCLA Family Practice Refresher Course, held May 20-24, 2008, in Los Angeles, CA,
and sponsored by the David Geffen School of Medicine at the University of California, Los Angeles, and the UCLA
Department of Family Medicine. Dr. Smith was recorded at HIV and AIDS—Key Issues and Challenges, held June 2,
2007, in Sacramento, CA, and sponsored by the University of California, Davis, Health System. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
| HIV AND AIDS UPDATE —Mark H. Katz, MD, Regional HIV Physician Advisor for Kaiser Permanente of Southern California,
Los Angeles
|
| New developments: circumcision lessens risk; breast-feeding now advised in developing nations; risk for transmission
to health care worker, even from high-risk exposure such as needlestick from someone known to be infected, <1 in 200
(0.4%); track T cells and viral load (VL) together; screen HIV-positive patients for tuberculosis, syphilis and other sexually
transmitted diseases (STDs), hepatitis, and neoplasms
|
| Most common criterion for AIDS diagnosis today: T-cell count <200 mm3 in someone with HIV; Pneumocystis jirovecii
(carinii) pneumonia (PCP) commonest infectious criterion
|
| Treatment: 3 drugs usually effective; essential to render VL as low as possible if patient pregnant; prednisone recommended
to treat PCP
|
| Major opportunistic infections: less common than formerly; red flags include characteristic purplish lesions of Kaposi’s
sarcoma; dyspnea (PCP); dysphagia (esophageal candidiasis); visual disturbances (cytomegalovirus [CMV]); fever,
chills, sweating, and anemia (mycobacterium avium complex [MAC]); headaches (toxoplasmosis, cryptococcosis, or
lymphoma); diarrhea (cryptosporidiosis)
|
| Current trends: sub-Saharan Africa remains “epicenter” of epidemic; eastern Europe and central Asia have fastest-
growing documented rates of new infections; with advent of protease inhibitors (highly active antiretroviral therapy
[HAART; triple therapy]) in mid 1990s, death rate plummeted >80%
|
| Racial disparities: blacks and American Indians do worst once infected; Asian Pacific Islanders do best; probably due to
genetic as well as social factors, eg, access to health care
|
| Age: correlates with mortality risk (younger patients do better)
|
| Co-epidemics: syphilis—>50% of new cases occurring in people with known HIV infection; in New York City clinic
study, 97% of cases HIV-positive men who have sex with men (MSM); diagnosis often delayed; sore throat often first
symptom; most providers screen all HIV-positive patients for syphilis 2 to 4 times/yr; conversely, screen all patients
presenting with syphilis for HIV; methamphetamine (“crystal meth”) use—men who used crystal meth and erectile
dysfunction drugs together more likely to engage in high-risk sex and be HIV-positive
|
| Window period: VL highest within 2 wk of initial infection, then falls; if undiagnosed and untreated, after several years
VL rises again, T cells decrease, and patient develops AIDS symptoms; most people unaware of their infection so early;
in United States, average person with HIV transmits virus to 2.1 other people before diagnosis
|
| Risk factors: unprotected sex and injection drug use classic risky behaviors; lack of circumcision; substance abuse (alters
judgment)
|
| Vehicles of transmission: blood, semen, vaginal secretions, breast milk; requires “virtually immediate” contact with
break in skin or mucous membranes
|
| Circumcision: shown in 3 African studies to decrease risk for HIV acquisition by ≈50%; circumcised glans thought to be
more lichenified and less porous
|
| Risk for HIV acquisition: highest through blood transfusion; 90% of people transfused with HIV-positive blood become
HIV-positive; risk associated with every other risk factor <1%
|
| Prophylaxis: for infected pregnant women, zidovudine (AZT) during last 2 trimesters decreases risk of transmission to
fetus from 30% to 8%; postexposure prophylaxis—now standard of care; treatment for 1 mo with 2 or 3 antiviral drugs as
soon as possible after unprotected sex with HIV-positive partner, plus patient education, recommended; breast-feeding—
exclusive breast-feeding recommended in developing nations, unless acceptable replacement feeding available; not recommended
in United States; other prophylactic measures—topical microbicides, cervical barriers, preexposure prophylaxis,
treatments to reduce infectivity, and prevention of herpes simplex virus 2 infection with acyclovir
|
| Testing: clinician should encourage people to test early; tests have not changed for many years; blood test most common;
others include buccal mucosal swabs and urine tests; home blood tests now available; rapid antibody test—now available
in United States; enzyme-linked immunosorbent assay (ELISA) test must be positive twice, followed by positive
Western blot test, for diagnosis of HIV infection; window period single biggest cause of false-negative tests (takes 10-
14 days before infected person tests positive; may be as long as 3 mo); negative test 3 mo after exposure confirms lack
of HIV infection; indeterminate results—seen in ≤20% of Western blot tests; most common causes seroconversion in
progress (retest 1-2 wk later), or cross-reacting nonspecific antibodies (from, eg, autoimmune illness, pregnancy, syphilis);
take risk history into account when counseling patient; either way, another test necessary; consistently indeterminate
results suggest cross-reacting antibodies
|
| Testing guidelines from Centers for Disease Control and Prevention (CDC): routine screening recommended for all persons
aged 13 to 64 yr in health care settings, not based on risk; repeat annually for people with known ongoing risks;
opt-out screening no longer recommended; one-third of Americans with HIV still unaware of it
|
| Sentinel symptoms: new infection—similar to flu or mononucleosis (fever, fatigue, lymphadenopathy, pharyngitis,
rash, malaise, arthralgia); more established infection—symptoms include any skin condition, vaginal or oral candidiasis,
nonspecific diarrhea, lymphadenopathy, periodontal disease, and sinusitis; if HIV suspected, take thorough risk
history; suggest HIV antibody test only; counsel about safe sex; arrange prompt follow-up; if acute infection suspected,
take risk history and perform antibody test; also measure quantitative VL
|
| Work-up of newly positive patient: includes testing for STDs and hepatitis; immunizations; monitoring T cells and VL
|
| VL tests: qualitative—polymerase chain reaction (PCR; determines whether virus present; used rarely and only for diagnosis);
quantitative—extremely sensitive (lower limit 50-75 copies/mL; warn patient that result reading “undetectable”
or “below level of quantification” [BLQ] does not mean zero)
|
| AIDS: defined as HIV infection plus ≥1 of 25 conditions identified by CDC; T-cell count <200 mm3 most common; PCP
second most common, followed by Kaposi’s sarcoma, wasting syndrome, and tuberculosis
|
| Therapy: goal to achieve and maintain undetectable VL; only ≈60% of HIV-positive people in United States currently on
treatment; widespread consensus that pregnant women, people with AIDS, or those with symptoms such as lymphadenopathy,
candidiasis, or shingles should be treated; for people without symptoms, treatment initiated at T-cell count
<350/mm3 ; therapy preceded by resistance testing to determine which of 25 antivirals effective; triple therapy cornerstone
of treatment, with most common regimen being 2 nucleoside analogue reverse transcriptase inhibitors (NARTIs;
“nukes”; family includes zidovudine) plus one “non-nuke,” eg, efavirenz (Sustiva) or protease inhibitors, eg, lopinavir
plus ritonavir (Kaletra); change regimen if patient intolerant or if virus not suppressed to undetectable level; maximize
adherence; consider resistance testing if regimen fails; do not interrupt treatment unless patient needs psychologic
“break” or is intolerant; nadir in VL occurs within few weeks to months of starting therapy; symptoms also diminish;
monitor stable patients every 3 to 4 mo
|
| Side effects or toxicity: most common reason for discontinuing regimen; new medication combines efavirenz, emtricitabine,
and tenofovir in one pill (Atripla) that can be taken once daily; however, all HIV drugs have plethora of side effects,
including hepatotoxicity and renal insufficiency; metabolic complications—dyslipidemias, glucose intolerance,
osteopenia, avascular necrosis of hip, body fat redistribution (lipoatrophy, abnormal fat deposition), and lactic acidosis;
increasingly complex regimens associated with rise in serum lipids; diabetes 4 times more common in people on
treatment for HIV than in uninfected people; however, even HIV-positive people not on drugs have slightly increased
risk for diabetes; findings from Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study of >24,000 patients
showed 26% increase in risk for myocardial infarction associated with HAART; risk now thought to be declining
|
| Risk for malignancy: Kaposi’s sarcoma, cervical carcinoma, and central nervous system lymphoma each considered
diagnostic of AIDS in HIV-positive person; with patients living longer, incidence of anal cancer, Hodgkin’s lymphoma,
liver cancer, testicular cancer, melanoma, head and neck cancer, and lung cancer also rising; guidelines now being considered
for increased surveillance for cancer and cardiovascular disease in this population
|
| AIDS complications: extremely rare today, especially in office practice; PCP prophylaxis with cotrimoxazole (eg,
Bactrim) standard of care whenever T cells <200/mm3 ; MAC prophylaxis when T cells <50/mm3; any positivity for
purified protein derivative (tuberculin; PPD) indication for prophylaxis with isoniazid for 9 mo; toxoplasmosis indicates
prophylaxis with Bactrim if patient’s T cells <100/mm3
|
| Kaposi’s sarcoma: pathogenesis may involve infection with human herpesvirus-8; HAART reduces lesion size and
spread; treatments effective (topical treatment now available); metastases to liver and lungs rare today
|
| PCP: consider in any patient presenting with fever, cough, and dyspnea, plus bilateral interstitial infiltrates on x-ray, even
if HIV status unknown; rarely occurs if T-cell count >200/mm3 or in patients on PCP prophylaxis; associated with pneumothorax;
diagnose through induced sputum and silver stain; most patients require intravenous (IV) cotrimoxazole,
plus 60 mg/day prednisone for 3 wk
|
| Cytomegalovirus retinitis: usually associated with T-cell count <50/mm3 ; may also affect gastrointestinal (GI) tract,
lungs, and nervous system; treat with valganciclovir or IV ganciclovir
|
| MAC infection: usually associated with low T cells; characterized by flu-like symptoms; treat empirically
|
| Tuberculosis: causes one-third of AIDS-related deaths
|
| Cryptococcal meningitis: usually diagnosed through lumbar puncture; symptoms include headache and fever, especially
if T cells low; stiff neck unlikely; amphotericin drug of choice; fluconazole used for maintenance
|
| Toxoplasmosis encephalitis: symptoms include fever, headache, and seizures; “signet ring lesion” on brain computed tomography;
focal neurologic signs
|
| GI manifestations of HIV: thrush, oral hairy leukoplakia; esophageal dysphagia (difficulty swallowing) may signal candidiasis;
painful swallowing suggests CMV or herpes
|
| HIV-hepatitis coinfection: HIV hastens progression of hepatitis C infection
|
| Surgery: study shows people with HIV can endure any surgical procedure, including coronary bypass, hip replacement,
and liver transplantation
|
| Postexposure prophylaxis: immediate antiretroviral therapy for 4 wk, regardless of test results
|
| NEUROLOGIC AND PSYCHIATRIC COMORBIDITIES IN HIV PATIENTS —David W. Smith, MD, Associate Clinical
Professor of Psychiatry and Behavioral Sciences, University of California, Davis, School of Medicine, Sacramento
|
| Suicide risk: highest early in disease course, usually soon after diagnosis made
|
| Dementia and other effects of virus on brain: patients with low T-cell counts and high VLs most likely to exhibit
frank dementia
|
| Most common symptoms of HIV dementia: personality change with increased emotional lability; praxis; dementia subcortical
(resembles Parkinson’s dementia more than Alzheimer’s dementia); psychosis and mania infrequent but possible
|
| Cognitive manifestations: impaired short-term memory; diminished concentration and attention; confusion; disorientation;
overall intellectual capacity persists until late in disease; visuospatial deficits; apathy; problems with judgment;
social withdrawal; rigidity of thought; patient’s partner usually best source of information; history best screen and also
helps to assess psychomotor speed
|
| Pathogenesis: infection of non-neuronal cells activates CNS macrophages, which produce toxins that affect brain; HIV
produces reversible and irreversible effects; affects mood as well as cognition
|
| Treatment: most commonly used drugs include stimulants, such as methylphenidate (eg, Ritalin), donepezil (Aricept), or
memantine (Namenda)
|
| Effects of stress: antidepressants and psychotherapy effective; antianxiety medications also help; sleep disturbances common;
“life stress definitely affects the progress of the disease”; relapse to substance abuse also exacerbates disease (patients
then fail to take medications regularly)
|
| Drug interactions that affect mental health: paroxetine (eg, Paxil) and fluoxetine (eg, Prozac) inhibit cytochrome
P450 (CYP450 ) system; prevent conversion of codeine to morphine, neutralizing previously positive response and inducing
withdrawal; fluoxetine also associated with rise in other drug levels, with possible legal consequences; amitriptyline (Elavil)
and ritonavir (Norvir) also inhibit CYP450 system, causing amitriptyline levels to rise; St. John’s wort potent inducer of
CYP450 system, with subsequent decrease in drug levels; phenytoin (Dilantin) speeds methadone metabolism, inducing opiate
withdrawal; alprazolam (eg, Xanax; benzodiazepine) associated with withdrawal seizures (opiate withdrawal does not
cause seizures); CYP450 inducers sometimes associated with decreased blood levels of oral contraceptives and subsequent
pregnancy
|
| Psychiatric comorbidities
|
| Bipolar disorder (BPD): speaker treats with simple medications that require minimal monitoring and blood testing, have
minimal risk for end organ damage, and have high compliance rates due to once-daily dosing; these include lamotrigine
(Lamictal), divalproex (Depakote), and atypical antipsychotic agents; lithium effective but high maintenance, eg,
tests for kidney and thyroid toxicity
|
| Attention-deficit/hyperactivity disorder (ADHD): do not rule out stimulants for patients formerly addicted to methamphetamines;
new nonstimulant medications available
|
| Major depressive disorder: serotonin reuptake inhibitors—also modulate behavior and relieve anxiety; norepinephrine-
dopaminergic antidepressant—bupropion (eg, Wellbutrin); improves activation, initiation, focus, and concentration;
dual-action drugs—raise norepinephrine and serotonin levels; duloxetine (Cymbalta) newest (also treats peripheral
neuropathy); venlafaxine (Effexor) also good choice
|
| Insomnia: contributes to stress; exacerbates dementia; triazolam (Halcion) contraindicated with protease inhibitors; virtually
any other sleep agent acceptable; also consider sleep study
|
Suggested Reading
Brown P et al: Repeatedly false-negative rapid HIV test results in a patient with undiagnosed advanced AIDS. Ann Intern
Med 149:71, 2008; Buchacz K et al: HIV incidence among men diagnosed with early syphilis in Atlanta, San Francisco,
and Los Angeles, 2004 to 2005. J Acquir Immun Defic Syndr 47:234, 2008; Fournier PO et al: A shift in referral
patterns of HIV/AIDS patients. J Fam Pract 57:E1, 2008; Friis-Moller N et al: Cardiovascular disease risk factors in
HIV patients—association with antiretroviral therapy. Results from the DAD study. AIDS 17:1179, 2003; Jenny-Avital
ER et al: Cerebrospinal fluid HIV load in diverse clinical circumstances. Clin Infect Dis 46:1938, 2008; Letendre S et
al: Neurologic complications of HIV disease and their treatment. Top HIV Med 15:32, 2007; Martin JN et al: Use of
postexposure prophylaxis against HIV infection following sexual exposure does not lead to increases in high-risk behavior.
AIDS 18:787, 2004; Montaño DE et al: STD/HIV prevention practices among primary care clinicians: risk assessment,
prevention counseling, and testing. Sex Transm Dis 35:154, 2008; Pinkerton SD et al: Cost-effectiveness of HIV postexposure
prophylaxis following sexual or injection drug exposure in 96 metropolitan areas in the United States. AIDS
18:2065, 2004; Vranceanu AM et al: The relationship of post-traumatic stress disorder and depression to antiretroviral
medication adherence in persons with HIV. AIDS Patient Care STDs 22:313, 2008; Weaver MR et al: Utilization of
mental health and substance abuse care for people living with HIV/AIDS, chronic mental illness, and substance abuse disorders.
J Acquir Immun Defic Syndr 47:449, 2008; Wojna V, Nath A: Challenges to the diagnosis and management of
HIV dementia. AIDS Read 16:615, 2006.
|
