Assessing HIV Infection in Primary Care Practice HARVEY J. MAKADON, MO I n r o u t i n e office practice, primary care physicians s e e both individuals at risk f o r HIV infection a n d t h o s e w h o a r e already infecte~ They m u s t be p r e p a r e d to a s s e s s risks

o f HIV infection in all patients, counsel patients with histories o f high-risk behavior a b o u t the m a s o n s to be t e s t e d f o r infection, and explain the m e a n i n g s o f both p o s i t i v e a n d negative test results. The initial medical evaluation o f a n infected individual should include a history and physical examination to detect early manifestations o f HIV infectton, basic diagnostic tests, including CD4 counts and a purified protein derivative tesg and ~i-,,unizaiion against potent/a//y preventab/e/nfect/ons. Key words: AIDS; HIV infection~ J GEN IN't-t~N MED 1991;6(suppl):S2-S7.

THE ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) was first described almost a decade ago; at that t i m e an e p i d e m i c of the present scale was unimaginable. In this c o u n t r y alone, almost 150,000 cases of AIDS as defined b y the Center for Disease Control (CDC) have b e e n reported; estimates are that a p p r o x i m a t e l y a million Americans are infected w i t h the h u m a n immunodeficiency virus (HIV) and will n e e d treatment for HIV-related conditions. 1 Available evidence suggests that app r o x i m a t e l y half of HIV-infected individuals will d e v e l o p AIDS b y an average o f ten years after their infection. 2 For most o f the past decade, a lack of effective treatment for HIV infection, c o u p l e d w i t h c o n c e r n about discrimination in a variety of settings against people k n o w n to be HIV-seropositive, led m a n y to choose not to be tested to d e t e r m i n e w h e t h e r they w e r e seropositive. Nevertheless, recent studies have d e m o n strated the effectiveness of b o t h antiretroviral therapy w i t h zidovudine in forestalling the progression of HIV infection 3 and p r o p h y l a c t i c therapies in decreasing the o c c u r r e n c e o f Pneumocystis p n e u m o n i a , w h i c h had b e e n a leading cause of m o r b i d i t y and mortality in people w i t h AIDS. 4 These studies have led to m o r e u n i f o r m s u p p o r t for r e c o m m e n d a t i o n s that individuals at risk for HIV infection d e t e r m i n e their serostatus so that they can receive a p p r o p r i a t e treatment as soon as indicated. 5 These r e c o m m e n d a t i o n s highlight the necessity for primary care physicians to discuss potential risks of HIV infection w i t h their patients and urge those at highest risk to be tested. This article considers these issues and addresses the initial evaluation of patients w h o are Hiv-positive. Received from the Division of General Medicine and Primary Care, The Department of Medicine, Beth Israel Hospital. Presented at the 13th annual meeting, Society of General Internal Medicine, precourse on incorporating HIV disease into primary care practice, Arlington, Virginia, May 2-4, 1990. Address correspondence and reprint requests to Dr. Makadon: Beth Israel Hospital, 330 Brookline Avenue, Boston, MA02215. SZ

RISK ASSESSMENT HIV infection has only three k n o w n routes of transmission: sexual transmission, either h o m o s e x u a l l y or heterosexually, b y an infected individual; transmission b y e x p o s u r e to c o n t a m i n a t e d b l o o d w h e n using intravenous drugs and sharing needles, or b y w a y of an occupational needlestick; and perinatal transmission during p r e g n a n c y or breastfeeding. For e p i d e m i o l o g i c purposes, cases have b e e n g r o u p e d into specific categories that focus o n "high-risk" behavior. The distribution of AIDS cases diagnosed a m o n g adults in the United States in 1989 is d e p i c t e d in Figure 1. G r o u p i n g o f cases in this w a y has led m a n y providers to discuss issues o f HIV infection only w i t h individuals w h o fit stereotypically into what have unfortunately b e e n labeled "high-risk" groups. Nevertheless, the potential for universal transmission of HIV infection should lead p r i m a r y care pror i d e r s to assume that all patients are at risk for HIV infection and to assess risk universally. The associations o f HIV infection w i t h homosexuality, bisexuality, and IV drug use and the awkwardness involved in conversations a b o u t these issues on the part of b o t h physicians and patients have historically k e p t m a n y patients f r o m discussing personal c o n c e r n s a b o u t potentially rislot behaviors w i t h their regular physicians. 6 Many patients have sought care specifically for concerns a b o u t these p r o b l e m s from other providers in sexually transmitted disease clinics or drug treatment programs. Given the implications of HIV, however, p r i m a r y care providers must frankly discuss the risk of HIV infection w i t h all patients. While this may b e particularly awkward w i t h patients of long standing, it m a y h e l p to introduce the discussion w i t h a frank statement of the p r o b l e m such as: " T h e spread o f HIV infection in the c o m m u n i t y coup l e d w i t h the possibility of treatment leads m e to rev i e w with all o f m y patients behavior that m a y p u t t h e m at risk and to discuss strategies to p r e v e n t infection." Such a statement gives the p r i m a r y p r o v i d e r an opportunity to elicit from the patient a history of potentially risky sexual b e h a v i o r or illicit substance use and to discuss p r e v e n t i o n strategies. In a p p r o a c h i n g risk assessment and the s u b s e q u e n t need for counseling of patients w i t h respect to risk reduction, it is important not to b e misled b y c o m m o n beliefs a b o u t transmission o f HIV infection. First, w h i l e there is a great deal o f debate about the potential for HIV infection to spread into the "heterosexual p o p u l a t i o n , " it is clear that AIDS is already a heterosexually transmitted disease. Statistics o n AIDS in w o m e n , particularly those f r o m the African-American

JOURNALOFGENERALINTERNALMEDICINE,Volume 6 (January/February Supplement), 1991

HIV EXPOSURE GROUP

[ ] 55.8% Homosexual/bisexual

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men

[ ] 22.6% IVDUs (women and heterosexual men) 1~1 6.1% IVDUs (homosexual/bisexual []

5.2% No identified risk

[]

4.4% Heterosexual contact

men)

17] 3.2% Hemophiliacs and transfusion []

1.6% Perinatal

[]

1.1% Other

FIGURE 1. Pa~erns of transmission among peoplediagnosedas havingAIDS in 1989 in the United States. Source: Update:AcquiredlmmunodeficiencySyndrome-- United States, 1989. MMWR. 1990;39:81-6.

and Hispanic communities, show that fully one-third of cases of AIDS in women are heterosexually transmitted. Cases of heterosexually transmitted AIDS increased more than 27% last year. 7 Recent dramatic increases in sexually transmitted diseases being reported among broad segments of the population, particularly among adolescents and young adults, certainly raise the specter of increased heterosexual transmission of HIV infection in the future. 8 Second, it is important to appreciate the extent of homosexual and bisexual transmission of HIV in patients of all ethnic groups. While men of color may not as readily identify themselves as "gay," almost half of the cases of HIV infection in African-American and Hispanic men occur in individuals who have histories of homosexual practices. 9 Failure to assess the risk of homosexually or bisexually transmitted HIV infection would overlook many at-risk individuals, Therefore, when taking a sexual history, it is important to inquire of all male patients whether they have had sex with other men. Finally, comprehensive programs developed largely by volunteer agencies in the gay community have led to early behavioral changes and a rapid decrease in the transmission of HIV infection, leading many to believe that there is no longer any ongoing transmission of HIV infection in the gay community. Nevertheless, recent evidence from the San Francisco cohort of gay men shows that in 1989 transmission of HIV infection in this cohort increased, after years of decline, lO Many studies suggest "slippage," and an increase in unsafe sexual practices. Analysis of some cases of new transmission have revealed both a lack of awareness of what truly constitutes safe sexual practices and a concomitant use of alcohol that led to unsafe conduct in spite of adequate knowledge. Primary care providers have an important role to play in reviewing patients' knowledge and conduct with respect to safe sexual practices and both working with patients and referring them for counseling when they have difficulty maintaining compliance.

Obviously, issues of discrimination against people at risk for HIV infection raise concern about the documentation of a risk assessment in the medical record. There have been numerous instances where records have been carefully screened when patients applied for health, disability, or life insurance and people have had difficulty getting insurance even when they were known to be HI-V-negative. It is important that patients understand that should they test positive, the information will ultimately be in their medical records and may be disclosed to insurance companies and other medical personnel. Some states require that positive results be reported to public health officials. 1 COUNSELING A N D T E S T I N G

After the completion of a risk assessment, individuals who have histories of behavior that put them at high risk for HIV infection should be tested for the presence of HW"antibodies in their blood. Before carrying out diagnostic testing, it is extremely important to discuss the testing process itself, ongoing risk reduction, and the consequences of a positive test, including its clinical implications, partner notification, and the potential for discrimination in insurance, housing, and employment. A psychological evaluation with particular attention to evidence for depression and the potential for suicide should be considered. The Massachusetts Department of Public Health has published guidelines on HW counseling for health care providers. 12 Table 1 summarizes the objectives of pretest and post-test counseling as suggested by these guidelines. In many parts of the country, alternative test sites established by the CDC provide HIV testing in association with skilled counseling. These can be of great assistance to busy clinicians. Testing should always be done voluntarily, and preferably in confidential or anonymous test sites that use standard laboratories where testing is routinely monitored for quality.13 Testing to detect HIV antibodies consists of two tests done in sequence. The first is an

Makadon, ASSESSING HIV INFECTIONIN PRIMARY CARE PRACTICE

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TABLE 1

Pretest and Posttest Counseling*

Physicians traditionally counsel patients on a variety of topics; HIV/AIDS counseling should be incorporated into the physician's established pattern.

Pretest Counseling Before testing, the physician should assessthe patient's understanding of the test and its implications, and his or her ability to deal with the results and the benefits of obtaining the information. If there are emotional contraindications to testing a patient, counseling should nevertheless be provided on how to reduce the risk of HIV transmission. It is important to note that prevention efforts are strengthened when an individual has exercised choiceand personal responsibility in seeking counseling and testing. Becausepatients who receive positive HIV test results often cannot fully comprehend new information at the time of receiving them, and because some patients may not return to get their test results, good counseling practice suggests covering the following information in the pretest session: 1. Explain the nature of AIDS and its related illnesses. 2. Explain the advantages of knowing one's antibody status in terms of medical management of HIV infection and other conditions. 3. Explain which behaviors put one at risk for HIV infection. 4. Ascertain the patient's understanding of how he or she can reduce the risk of infection, including the use of condoms, 5, Try to understand what, if anything, prevents the adoption of these risk-reduction practices. 6. Explain what an HIV antibody test result means. 7. Learn what the patient expects his or her test results to be, 8. Ask how the patient plans to change his or her behavior. 9. How will the patient cope with the psychosocialramifmations of a positive test result?. Does the patient have health insurance? Should he or she obtain health insurance before being tested? I O. If the test result is positive, how will the patient tell his or her partners? 1 I. Discussthe importance of partner notification and the availability of the Department of Public Health to help with this task.

12. Discussthe possibilities of discrimination that may result from disclosure of a patient's antibody status. 13. Finally, your patient should be encouraged to identify: a, one person who knows the patient is being tested. b. one person with whom he or she can discuss the test. c. what he or she plans to do in the 24 hours immediately following receipt of the test result.

Posttest Counseling Posttest counseling should always be provided, regardless of the test result. It is an opportunity for the physidan to emphasizethe importance of risk-reduction practices (such as the use of condoms) to both seroposilive and seronegative patients. For persons who test positive, posttest counseling offers the patient the opportunity to express his or her feelings and concerns, and permits the provider to clarify the implications for the patient's health and to plan medical follow-up and management. Posttest counseling for HIV+ individuals should cover: 1. Information on available medical treatment and counseling services. 2. Development of a comprehensive care plan for the patient. 3. Copingwith emotionalconsequencesof learningthe test results, including development of a social support plan. 4. Behavioral changeto preventtransmission, including howtouse condoms and, where appropriate, how to enter drug and alcohol abuse treatment programs. 5. Discrimination problems that could be causeclby disclosure ofthe patient's antibody status. (in general, patients should be encouraged to share positive test results only with their closest intimates and to wait before telling others. Discussing disclosure with professional or peer support group/systems is helpful in making such decisions.) 6. The need to notify sex partners.

*Excerpted with permission, from Guidelinesfor physiciansand health care providers on HIV counseling, testing, and early treatment. Massachusetts Department of Health, Boston, MA, February 1990. Publication no, 16202-52-20,000-2-90 CR.

ELISA test, which, w h e n positive, is repeated and subsequently confirmed b y a Western blot analysis. W h e n this s e q u e n c e o f tests is used in individuals at high risk for HIV infection, the p r e d i c t i v e value o f a positive test e x c e e d s 9 9 % ) 3 Patients should not b e given positive test results prior to Western blot confirmation. Most HIV testing centers will not report e v e n negative ELISA test results within a time period shorter than it w o u l d take to do a Western blot analysis, eliminating attempts to predict results based on the t i m e w h e n they are available. Regardless of w h e t h e r test results are positive or negative, individuals tested n e e d post-test counseling. When patients test negative, it is important to w o r k w i t h t h e m to address ways to end to behavior that has put t h e m at high risk for infection and to make sure they do not v i e w themselves as " i m m u n e . " All patients

should understand that w h i l e the precise risks o f various sexual practices are u n k n o w n , anal or vaginal intercourse w i t h o u t latex c o n d o m s and a spermicidal jelly presents an e x t r e m e l y high risk for transmission o f HIV. Use o f these p r e c a u t i o n s makes intercourse safer b u t not w i t h o u t risk. While t h e r e have b e e n r e p o r t e d cases of transmission during o r a l - genital sex, the extent to w h i c h this occurs is unknown. 14 For individuals at risk because of high-risk sexual behavior, in m a n y urban areas there are n o w s u p p o r t g r o u p s to h e l p p e o p l e p r e v e n t " s l i p p a g e . " For individuals w h o use intravenous drugs, ongoing w o r k encouraging referral for t r e a t m e n t is necessary. Short o f this, there are resources available in m a n y c o m m u n i t i e s to h e l p individuals w h o use IV drugs learn h o w to do so w i t h o u t risking transmission of HIV. Such programs have b e e n e f f e c t i v e ) s In m a n y c o m m u n i t i e s there are

JOURNALOFGENERALINTERNALMEDICINE,Volume6 (January~FebruarySupplement), 1991

few resources to s u p p o r t w o m e n w h o are at risk b y virtue of the sexual practices or drug use of their partners. While in s o m e parts of the c o u n t r y there are e m p o w e r m e n t s u p p o r t groups for w o m e n to h e l p t h e m address issues of risk w i t h their sexual partners, these resources are often difficult to find. When individuals test positive for HIV, the p r i m a r y care provider must be p r e p a r e d to begin to manage a n u m b e r of medical and psychological issues. First, it is important to assess h o w a patient views b o t h the medical and the psychological c o n s e q u e n c e s of testing positive. Patients should understand the natural history of HIV infection, m e t h o d s used to m o n i t o r the progression of HIV, and strategies for early intervention. At the same time, it is i m p o r t a n t to r e v i e w again a patient's e m o t i o n a l state for e v i d e n c e o f depression a n d / o r suicidal behavior. Crisis intervention m a y be necessary in s o m e cases. In general, referral for counseling at this p o i n t will b e e x t r e m e l y helpful. It can h e l p establish a basis for future w o r k and b e the beginning o f a multidisciplinary process for care that will benefit most patients and providers. Given the sensitive nature of the HIV diagnosis, it is e x t r e m e l y important to discuss w i t h patients their concerns a b o u t disclosing this information to third parties before making any referrals or discussing a patient's care w i t h colleagues. Legal restrictions and the responsibility to notify partners o f p e o p l e w h o are HIV-posit i r e vary from state to state, x6 Physicians must w o r k with patients to ensure that they notify their sexual partners a b o u t their seropositivity. Many individuals will do this on their own. At times it m a y h e l p to offer to m e e t with a patient's sexual partner. Opinions vary regarding the ethical responsibility of the physician to warn an otherwise u n k n o w i n g partner. This t o p i c has b e e n debated and written about at length elsewhere. 17 Some states have d e v e l o p e d m e c h a n i s m s for p u b l i c health officials to assume this role.

MEDICAL EVALUATION The care of p e o p l e w h o are HIV-positive often involves balancing h o p e for long-term life and n e w treatments w i t h the reality of the treatments that are available and the c o m p l i c a t i o n s that arise. Clearly patients' responses to their diagnoses vary greatly, and b o t h medical and psychological supports must b e d e t e r m i n e d o n that basis. The basic medical evaluation of HIV-positive individuals is straightforward. There are a n u m b e r of comm o n clinical syndromes that o c c u r as patients' i m m u nologic function begins to deteriorate, and the history and physical e x a m i n a t i o n should be tailored to detect them. Constitutional s y m p t o m s s u c h as night sweats, fever, and weight loss are c o m m o n . While evaluation to rule out a treatable infection is necessary, often no specific cause is f o u n d and s y m p t o m s may b e attributable

SS

to HIV itself. Generalized l y m p h a d e n o p a t h y is an early manifestation of HIV infection in u p to 70% of infected individuals. W h e n nodes are small and scattered, no i m m e d i a t e w o r k - u p is generally indicated. W h e n a node or a g r o u p of nodes is dominant c o m p a r e d w i t h those elsewhere, or is rapidly growing, or w h e n constitutional s y m p t o m s suggest systemic disease, b i o p s y is indicated.18, x9 Dermatologic manifestations including seborrheic dermatitis, folliculitis, psoriasis, extensive fungal infections, herpes zoster, and h e r p e s s i m p l e x are legion in individuals w i t h HIV. Initially, treatments can be standard, but high doses o f acyclovir are recomm e n d e d to p r e v e n t disseminated zoster. Oral manifestations include candida infection and hairy leukoplakia. Candida can present in four forms. P s e u d o m e m b r a n o u s candidiasis or thrush presents as r e m o v a b l e curd-like exudates; e r y t h e m a t o u s (atrop h i c ) candidiasis presents as sensitive patches on the palate or tongue; hyperplastic candidiasis is characterized by hyperkeratosis of the tongue; angular cheilitis presents as an inflammation in the corner of the mouth. 2° T r e a t m e n t is generally w i t h clotrimazole troches initially, but recurrent cases may require ketoconazole or fluconazole. Many r e c o m m e n d chronic prophylaxis. 2° C o m m o n respiratory manifestations inc l u d e r e c u r r e n t sinusitis or allergic rhinitis. Conventional therapeutic strategies are a p p r o p r i a t e initially, but r e c u r r e n c e m a y indicate a n e e d for m o r e extensive evaluation. Neuropsychiatric manifestations should b e considered. Cognitive defects are rare in early HIV infection b u t should b e evaluated w h e n they do occur. Many patients have psychological issues that n e e d to b e e x p l o r e d at the t i m e of diagnosis. Further evaluation and m a n a g e m e n t o f patients dep e n d on clinical findings. Many o f the findings discussed above are associated w i t h a l o w CD4 ceil c o u n t and i m m u n e dysfunction significant e n o u g h to warrant therapy w i t h antiretroviral agents in addition to specific therapy. AIDS-defining o p p o r t u n i s t i c infections m u s t always be in the differential, particularly w h e n CD4 counts are k n o w n to b e b e l o w 2 5 0 - 3 0 0 . Diagnostic tests r e c o m m e n d e d for n e w l y seroposirive patients are listed in Table 2. A c o m p l e t e b l o o d c o u n t and liver function tests are i n c l u d e d to d e t e r m i n e

TABLE Z RecommendedDiagnosticEvaluation 1. 2. 3. 4. 5. 6. 7.

Completeblood count with differential BUN, creatinine, glucose,liver function tests Rapidplasmareagin test Hepatitis screen Purified protein derivative test and control CD4 count, CD4: CD8 ToxoplasmosisIgG antibody titer

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Makadon, ASSESSINGHIV INFECTIONIN PRIMARYCAREPRACTICE TABLE 3 RecommendedImmunizations for HIV-positive Persons

Diphtheria/tetanus Inactivatedpolio Measles Pneumococcal Influenzavirus Hepatitis

Haemophilusinfluenzae

a patient's baseline, given the frequent toxicities o f m a n y drugs that are used to treat c o m p l i c a t i o n s o f HIV, in addition to detecting e v i d e n c e of anemia or c o n c o m Rant hepatitis. A purified protein derivative (PPD) test and control are e x t r e m e l y important, because the incidence of tuberculosis in HIV-positive p e o p l e is high. In evaluating skin tests in HIV-positive patients, it is recomm e n d e d that -> 5 m m of induration be considered a positive test, in contrast to the -> 1 O - 15 m m of induration considered positive in o t h e r populations. 2t All individuals w h o test positive should b e treated for at least o n e year w i t h isoniazid (INH). Some r e c o m m e n d lifet i m e treatment. A toxoplasmosis IgG antibody titer is being increasingly r e c o m m e n d e d to identify patients at risk for cerebral toxoplasmosis and aid in making a p r o m p t diagnosis of that condition. Some authorities argue that prior e x p o s u r e to toxoplasmosis, d e m o n strated serologically, should lead the physician to consider use of t r i m e t h o p r i m - s u l f a m e t h o x a z o l e (TMPSMX) rather than aerosolized p e n t a m i d i n e w h e n P n e u m o c y s t i s carinii p n e u m o n i a (PCP) prophylaxis is undertaken. TMP-SMX has the potential advantage, as yet unproven, of providing simultaneous p r o p h y l a x i s against systemic toxoplasmosis. A n u m b e r of tests have b e e n evaluated w i t h r e s p e c t to h o w w e l l they predict progression to the AIDS-related c o m p l e x (ARC) or AIDS in seropositive patients. These tests include: absolute CD4 counts and CD4 : CD8 ratio, beta-2-microglobulin, neopterin, p 2 4 antibody, and p 2 4 antigen. While they can all b e helpful in following an individual's progression through the stages of HIV infection, studies s h o w that the clinical effectiveness o f zidovudine therapy and prophylaxis against PCP have correlated best w i t h absolute CD4 counts. R e c o m m e n d a t i o n s regarding the use o f CD4 testing in a s y m p t o m a t i c individuals have recently b e e n made b y the National Institute of Allergy and Infectious Disease. 5 CD4 testing should b e d o n e no m o r e freq u e n t l y than every six m o n t h s until the patient's c o u n t is less than 600, at w h i c h p o i n t they should be r e p e a t e d every four months, w i t h consideration given to beginning zidovudine t h e r a p y w h e n the c o u n t is b e l o w 500. These r e c o m m e n d a t i o n s are discussed further in subseq u e n t sections o f this s u p p l e m e n t . It is important to k e e p in m i n d that despite these r e c o m m e n d a t i o n s ,

there is great variability in CD4 counts in a given individual during the day, as w e l l as variability f r o m laboratory to laboratory. To the greatest extent possible, measurements should be m a d e at a p p r o x i m a t e l y the same time e a c h day b y the same laboratory. A s c h e d u l e for r e c o m m e n d e d immunizations of individuals w h o are HIV-positive is s h o w n in Table 3. These r e c o m m e n d a t i o n s have recently b e e n reviewed.22, 23 It is clear f r o m the literature that p e o p l e w h o have HIV infection are at risk for p n e u m o c o c c a l p n e u m o n i a , H e m o p h i l u s influenza, influenza, and hepatitis B. Despite the fact that d e v e l o p m e n t of protective antibody titers to these appears to be variable, given the l o w risk, vaccination against these organisms is r e c o m m e n d e d as early in the course o f HIV infection as possible. CONCLUSION

The natural history o f HIV infection in adults suggests that at the current t i m e o n l y 50% of infected individuals progress to AIDS after ten years. Recent studies have s h o w n prolongation o f life e x p e c t a n c y attributable to earlier recognition o f HIV positivity and treatm e n t w i t h b o t h zidovudine and prophylaxis against Pneumocystis p n e u m o n i a . N e w strategies to e n h a n c e these treatments and prophylaxis against the developm e n t of opportunistic infections hold forth the p r o m i s e that life e x p e c t a n c y will c o n t i n u e to increase and that HIV infection will b e c o m e m o r e of a chronic manageable illness over the next decade. The implications for p r i m a r y care physicians and those with w h o m w e w o r k are great. Primary care physicians m u s t assess all patients for risk o f HIV infection and w o r k w i t h t h e m to p r e v e n t the further spread o f HIV. Individuals w h o are HIV-infected will require close evaluation and follow-up. In addition to understanding m o r e a b o u t medical m a n a g e m e n t , w e must carefully consider h o w w e can d e v e l o p the multidisciplinary supports necessary to care for this g r o u p of patients. REFERENCES

I. HIV prevalence, projected AIDScase estimates: workshop, Oct 31-Nov 1, 1989. MMWR. 1990;39:110-9. 2. Moss AR, Bacchetti P. Natural history of HIV infections. AIDS. 1989;3:55-61. 3. Volberding PA, Lagakos SW, Koch MA, et al. Zidovudine in asymptomatic human immunodeficiency virus infection; a controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N EnglJ Med. 1990;332:941-9. 4. Kovacs JA, Masur H. AIDS commentary: Pneomocystis c~3rinH pneumonia: therapy" and prophylaxis. J Infect Dis. 1988: 158:254-9. 5. AZTtherapy for early intervention, State-of:the-ArtConference, National Institute of Allergy and Infectious Diseases, Washington, DC, March 3-4, 1990. 6. Lewis CE, Freeman HE, Corey CR. AiDS-related competence of California's primary care physicians. AJPH. 1987;77:795-9. 7. Update: reducing HIVtransmission in intravenous drug users not

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in drug treatment--United States. MMWR. 1990;39:529-38. 8. Department of Health and Human Services.Annual report 1989. Division of STD/HW Prevention. MMWR. 1989;38:69-78. 9. Table 4, AIDScases by age group, exposure category, and race/ ethnicity through July 1990, CDC HIV/AIDSSurveillance, U.S. AIDS Program, Centers for Infectious Diseases, Centers for Disease Control, August 1990. 10. San Francisco Department of Public Health. Continued seroconversion for HIV antibody among homosexual and bisexual men. San Francisco Epidemiol Bull. 1989(5);35-7. 11. HIV reporting in the states. Intergovernmental AIDS reports. George Washington University, Washington, DC, 1989;2,5. 12. Guidelines for physicians and health care providers on HIV counseling, testing, and early treatment. Massachusetts Department of Health, Boston, MA, February 1990. 13. Lo B, Steinbrook RL, Cooke M, Coates TJ, Waiters EJ, Hulley SB. Voluntary screening for human immunodeficiencyvirus (HD0 infection. Ann Intern Med. 1989;110:727-33. 14. Safer sex guidelines: a resource document for educators and counsellors. Report from: The Canadian AIDSSociety Consultation on Safer Sex, Ottawa, Quebec, Canada, March 1988. 15. Reducing HIV transmission in intravenous drug users not in drug treatment. MMWR. 1990;39:529.

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16. Partner notification for preventing human immunodeficiency virus infectionJColorado, Idaho, South Carolina, Virginia. MMWR. 1988;37:613-615. 17. Guide to public health practice: HIV partner notification strategies. Association of State and Territorial Health Officials, September 1988. 18. LangW, Anderson RE, Perkins H, et al: Clinical immunologyand serologic findings in men at risk for acquired immune deficiency syndrome. JAMA, 1987;257:326. 19. Cooney T. Clinical management of the complications of HIV infection: incorporating HW infection into primary care practice. J Gen Intern Med. Supplement t991;6(suppl):S12-8. 20. PudborgJ. Oral candidiasis in HIV infection. In: Robertson PB, Greenspan JS, eds. Oral manifestations of AIDS. Littleton, MA: PSG Publishing, 1988;28-37. 21. Screening for tuberculosis and tuberculosis infection in high risk populations: recommendations of the Advisory Committee for Eliminationof Tuberculosis. MMWR. 1990;39:8. 22. Centers for Disease Control. General recommendations for immunization. Ann Intern Med. 1989;111:133-42. 23. Poland GA, Love KR, Hughes CE. Routine immunization of the HIV-positive asymptomatic patient. J Gen Intern Med. 1990;5:147-52.

Recent Advances in the Medical Management of Early HIV Disease PAUL A. VOLBERDING, MD The management o f patients who have HIV disease, partic. ularly those in early, asymptomatic disease stages, has re. cently in~rotmd. Clinical trials with zidovudine have dem. onstrated efficacy and greatly reduced toxicity when the drug is used f o r asymptomatic HIV-infected persons who h a v e f e w e r than 500 CD4+ ceils/ram ~. Also, the optimum dose o f zidovudine is lower than previously believed, probably in the range o f 300-500 mg daily in oral divided doses. The use o f antibiotics to prevent Pfleumocystis carinii pneumonia (PCP) is also o f clear value f o r HIV-infected asymptomatic or symptomatic persons withf e w e r than 200 CD4+ cells/mm 3. While aerosolized pentantidine is the only regimen approved f o r PCP prophylaxis, oral drugs, such as trimethoprim/sulfamethoxazole or dapsone, also appear effective. Together, these and similar advances argue f o r the widespread use o f voluntary HIV testing to enable optimum medical monitoring and appropriate interventiom These i s s u e s and recommendations f o r laboratory and clinical monitoring are provided in this review. Key words: HIV disease; zidovudinc; Pneumocystis carinii lmetm~nia; aerosolized pentamidinc; trimethoprim/ sulfamethoxazole; dapsone, J GEN INTERN MED 1991;6(suppl):S7- $12.

WE HAVERECENTLYSEENa series of a d v a n c e s i n t h e m e d i cal m a n a g e m e n t o f p a t i e n t s w h o are i n f e c t e d w i t h HIV. Received from the Department of Medicine, University of California at San Francisco, San Francisco, CA 94110. Presented at the 13th annual meeting, Society of General Internal Medicine, precourse on incorporating HIV disease into primary care practice, Arlington, Virginia, May 2-4, 1990. Address correspondence and reprint requests to Dr. Volberding.

More a n d m o r e , w e a p p r e c i a t e t h a t o u r p r i o r classificat i o n o f p a t i e n t s b y c l i n i c a l m a n i f e s t a t i o n a l o n e is n o l o n g e r a d e q u a t e . Instead, all t h o s e w i t h HIV i n f e c t i o n are c o n s i d e r e d to have HIV disease t a n d this disease is t h e n staged, p r i m a r i l y b y a v a r i e t y o f l a b o r a t o r y markers. At t h e s a m e t i m e that this c o n c e p t u a l c h a n g e i n o u r d e f i n i t i o n a n d s t a g i n g is o c c u r r i n g , r e s u l t s f r o m c l i n i c a l trials c o n d u c t e d w i t h p a t i e n t s w h o have e a r l i e r stages o f HIV disease are b e c o m i n g a v a i l a b l e a n d are b e i n g u s e d to d e f i n e n e w s t a n d a r d s for m e d i c a l care. T h e p u r p o s e o f this r e v i e w is to briefly h i g h l i g h t s o m e o f this n e w i n f o r m a t i o n , f o c u s i n g o n t h o s e r e s u l t s that c u r r e n t l y a p p e a r to b e o f m o s t d i r e c t i m p l i c a t i o n for the practice of medicine. T h e p r e c i s e n u m b e r o f cases o f a s y m p t o m a t i c HIV i n f e c t i o n is u n k n o w n b u t is c e r t a i n to b e large. To s o m e d e g r e e , this figure c a n b e e s t i m a t e d f r o m n u m e r o u s e p i d e m i o l o g i c s t u d i e s that i d e n t i f i e d t h e r a p i d s p r e a d o f HIV t h r o u g h i n f e c t e d p o p u l a t i o n s i n t h e U n i t e d States i n t h e late 1 9 7 0 s a n d e a r l y 1980s. I n San Francisco, for e x a m p l e , t h e v i r u s was first d e t e c t e d i n s e r u m o b t a i n e d d u r i n g t h e p e r i o d o f 1 9 7 8 to 1 9 7 9 . Estimates o f n e w HIV i n f e c t i o n cases h a d c l i m b e d r a p i d l y u n t i l 1 9 8 3 to 1 9 8 4 , w h e n rates of n e w i n f e c t i o n s fell e v e n more dramatically than they had previously increased. This has r e s u l t e d in a large g r o u p o f i n d i v i d u a l s ( a n e s t i m a t e d 3 0 , 0 0 0 i n San F r a n c i s c o a l o n e a n d u p to 1.5 m i l l i o n i n t h e U n i t e d States) w h o have b e e n i n f e c t e d o v e r a v e r y b r i e f t i m e s p a n , G i v e n this, w e m u s t t h e n

Assessing HIV infection in primary care practice.

In routine office practice, primary care physicians see both individuals at risk for HIV infection and those who are already infected. They must be pr...
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