Preventive Counseling, Screening, and Therapy for the Patient with Newly Diagnosed HIV Infection



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Am Fam Physician. 2006 Jan 15;73(2):271-280.

  Related Editorial

The epidemic of human immunodeficiency virus (HIV) continues, and the infection is converting into a treatable chronic disease; therefore, it is increasingly important for family physicians to be current with and comfortable in providing basic care to patients infected with HIV. Important aspects of counseling and patient education include stabilization of psychosocial issues and prevention of HIV transmission through behavior change counseling. Reporting HIV and acquired immunodeficiency syndrome (AIDS) is mandatory in most states, whereas partner notification laws vary from state to state. Baseline evaluation includes screening for comorbid conditions such as viral hepatitis, syphilis, and tuberculosis, as well as common HIV-related manifestations such as recurrent candidal infections and thrombocytopenia. Baseline testing includes CD4+ T-lymphocyte cell counts and HIV viral RNA levels to assess HIV disease stage, and numerous studies to screen for opportunistic infections. Initial preventive interventions include patient education to reduce exposure to infections, treatment of comorbid conditions such as human papillomavirus-related dysplasia, and vaccinations such as for pneumococcus and hepatitis B. Prophylaxis against opportunistic pathogens is recommended when CD4+ cell counts fall below 200 cells per mm3. Lastly, the indications for antiretroviral therapy include symptomatic patients or those with AIDS, and pre-AIDS patients with CD4+ cell counts of 200 to 350 cells per mm3 or HIV RNA above 55,000 to 100,000 copies per mL.

As the prevalence of human immunodeficiency virus (HIV) continues to increase,1,2 family physicians are encountering more patients at risk for this disease. It is imperative to diagnose patients as early as possible because advances in antiretroviral therapy are resulting in impressive extensions of life span and increased quality of life,13 and because of the need to break the cycle of ongoing infections through preventive behavior changes.4,5 Family physicians need to be current and comfortable in their approach to patients at risk for and those infected with HIV. The management of advanced acquired immunodeficiency syndrome (AIDS), opportunistic infections, and antiretroviral therapy is complex and requires additional training and expertise. However, the initial evaluation and preventive care of patients with HIV is straightforward6,7 and within the scope of family physicians.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence Rating References

Patients with HIV should be monitored for CD4+ lymphocyte and HIV RNA levels every three to six months.

C

7,8,26,28

Patients who are hepatitis A or B nonimmune at baseline should be vaccinated.

B

7,8,25

Tuberculosis prophylaxis should be given to patients with any of the following: history or symptoms of tuberculosis, a PPD of at least 5 mm, or a possible false-negative PPD.

C

7,8,25

Pneumocystis jiroveci prophylaxis with trimethoprim/sulfamethoxazole (Bactrim, Septra) should be initiated at CD4+ counts of less than 200 cells per mm3.

A

7,8,25

Women with HIV should have Pap smears every six months for the first year and, if normal, annual Pap smears thereafter.

C

7,8,25

High-risk patients with ongoing exposure should be checked annually for gonorrhea, chlamydia, syphilis, and hepatitis C.

C

7,8,25

[corrected] Antibiotic prophylaxis should be used to prevent toxoplasmosis and Mycobacterium avium-intracellulare complex infection at CD4+ cell counts below 100 and below 50 cells per mm3, respectively.

B

7,8,25


HIV = human immunodeficiency virus; PPD = purified protein derivative.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 196 or http://www.aafp.org/afpsort.xml.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

View Table

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence Rating References

Patients with HIV should be monitored for CD4+ lymphocyte and HIV RNA levels every three to six months.

C

7,8,26,28

Patients who are hepatitis A or B nonimmune at baseline should be vaccinated.

B

7,8,25

Tuberculosis prophylaxis should be given to patients with any of the following: history or symptoms of tuberculosis, a PPD of at least 5 mm, or a possible false-negative PPD.

C

7,8,25

Pneumocystis jiroveci prophylaxis with trimethoprim/sulfamethoxazole (Bactrim, Septra) should be initiated at CD4+ counts of less than 200 cells per mm3.

A

7,8,25

Women with HIV should have Pap smears every six months for the first year and, if normal, annual Pap smears thereafter.

C

7,8,25

High-risk patients with ongoing exposure should be checked annually for gonorrhea, chlamydia, syphilis, and hepatitis C.

C

7,8,25

[corrected] Antibiotic prophylaxis should be used to prevent toxoplasmosis and Mycobacterium avium-intracellulare complex infection at CD4+ cell counts below 100 and below 50 cells per mm3, respectively.

B

7,8,25


HIV = human immunodeficiency virus; PPD = purified protein derivative.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 196 or http://www.aafp.org/afpsort.xml.

Issues For Patients Newly Diagnosed with HIV

PSYCHOSOCIAL STABILIZATION

As with any potentially life-threatening illness (especially HIV, which can be associated with social stigma), coping should be the first issue addressed.4,8,9 Family physicians are trained in psychosocial and community medicine, and therefore are able to address patients’ safety; support systems; potential depression and suicide risk; family reactions such as blame and domestic violence; and potential impact on employment, finances, and health insurance resources. Knowledge of local legal regulations and community resources is important, and physicians should be prepared to provide appropriate referrals to counselors; social workers; financial and insurance assistance programs; and housing, drug treatment, and legal resources.

TRANSMISSION PREVENTION

Diagnosing a new case of HIV infection presents a unique opportunity to interrupt the cycle of HIV spread.4,5 Despite physicians’ knowledge and education about HIV transmission, the annual number of new HIV infections has not declined over the past decade.1,2,4,10 In 2002, there were more than 40,000 new HIV infections in the United States, one half of them occurring in people younger than 25 years. Among women, the majority of cases are attributable to heterosexual contact. Thus, enhanced effort in preventing HIV transmission, among infected and uninfected persons, is crucial.

The most important prevention approach is education and behavior modification. The Centers for Disease Control and Prevention’s (CDC’s) revised guidelines4,11,12 on the prevention of HIV emphasize behavioral intervention strategies that focus on interpersonal prevention skills rather than just patient knowledge. Key points include screening patients with HIV for ongoing or recurring risk behaviors, discussing sexual activities and drug use, positively reinforcing incremental changes toward safer behavior, and addressing how to disclose HIV-seropositive status to a sex or drug partner.12

The safest sexual practices are abstinence followed by monogamy. For patients who are neither abstinent nor monogamous, the physician should convey the following infection prevention messages: consistent and correct condom use; sex only while sober; reduced numbers of sex partners; and less mucosal trauma. For patients who use intravenous drugs, physicians should recommend cessation of illicit drug use or, if this is unlikely, using bleached or new needles and not sharing needles.

Other approaches to the prevention of HIV transmission include interruption of maternal-child transmission through prenatal HIV testing and antiretroviral therapy for mother and newborn,5,13 reduction of HIV sexual transmission through antiretroviral therapy to reduce viral concentration in genital secretions,14 and treatment of other sexually transmitted diseases (STDs) to mitigate the enhancement of HIV transmission that otherwise occurs in this context.15 Numerous studies1317 have reported decreased rates of sexual and perinatal transmission among persons with lower levels of plasma viremia, including those undergoing antiretroviral therapy.14 However, other studies1820 have documented an imperfect correlation between serum viremia and viral levels in sexual secretions, finding that an undetectable serum viral load does not guarantee the safety of unprotected sex.

The increased risk of HIV transmission due to elevated HIV viral concentrations in genital tract secretions during acute HIV infection21 and episodes of STDs underscores the importance of early HIV detection and screening and counseling for all STDs in the context of sexually transmitted infections or risk factors.22

Prevention approaches that are highly attractive from a pandemic perspective are topical microbicides and HIV vaccination. Unfortunately, research to date has produced no viable candidates, relegating these modalities to future hopes. Lastly, although HIV is not casually transmitted, patients in the household setting should be advised to clean visible blood spills or soiled garments with a bleach solution and not to share toothbrushes or razors with anyone. No other specific precautions are necessary.

PARTNER NOTIFICATION AND CASE REPORTING

The goals of partner notification and HIV testing are to interrupt the cycle of repeated HIV exposure and to detect other cases of HIV infection to facilitate entry into medical care. Providers need to be familiar with local public health statutes concerning partner notification and patient confidentiality, because these vary among states. When providing testing of contacts, attention must be paid to the likely timing of potential exposures because seroconversion typically occurs subsequent (and consequent) to the initial period of acute infection viremia. Thus, during the first three months after HIV exposure, early detection may require testing of HIV RNA levels confirmed by repeat serologic testing.4,6,7,9,23

The reporting of cases of HIV or AIDS is an important public health requirement, especially because in most states these figures determine the distribution of federal Ryan White AIDS CARE Act funds or Medicaid funds for the care of uninsured patients.9,24 Information regarding requirements and procedures for reporting cases of HIV or AIDS can be obtained through local public health departments.

Baseline Medical Evaluations

The main goals of baseline evaluation are to: (1) assess the risk of HIV disease progression to determine the need for antiretroviral therapy; (2) assess the risk for opportunistic complications, to guide prevention education and prophylaxis; (3) evaluate current symptoms based on HIV stage; (4) screen for common infectious and noninfectious comorbidities related to HIV infection; and (5) target appropriate health maintenance interventions.

HISTORY AND PHYSICAL EXAMINATION

High-risk sexual activity and drug use increases the risk of HIV transmission and may have direct health risks for patients infected with HIV. It is recommended that physicians regularly ask their patients about such behaviors; published guidelines and questionnaires are available to guide physicians in having these discussions.7,8,12 Physicians also should evaluate patients for the signs and symptoms of high-risk activities, such as manifestations of genital and systemic STDs.22

Other important evaluations concern detection of HIV-related disease manifestations.7,8  Common early manifestations include fever and sweats, weight loss, generalized lymphadenopathy, recurrent vaginal candidiasis, recurrent oral ulcers, onychomycosis, seborrhea, and shingles (Table 16,7,25). There are also many comorbid conditions common to patients with HIV that should be evaluated, such as tuberculosis and hepatitis B and C.

TABLE 1

Disease Conditions Associated with Stages of Immunodeficiency

Stage of immunodeficiency Type of condition Conditions AIDS defining?

Symptomatic HIV (CD4+ cell count less than 500 cells per mm3 [500 × 109 per L])

Superficial fungal infections

Thrush, recurrent vaginal candidiasis, onychomycosis, seborrhea

No

Superficial viral infections

Shingles, oral hairy leukoplakia, recurrent oral ulcers

No

Laboratory abnormalities

Thrombocytopenia, neutropenia, hypergammaglobulinemia

No

Constitutional symptoms

Night sweats, fever, fatigue, generalized lymphadenopathy

No

AIDS (CD4+ cell count less than 200 cells per mm3 [200 × 109 per L])

Opportunistic infections

Pneumocystis jiroveci pneumonia, candida esophagitis, cryptococcal infections, Isospora belli diarrhea, prolonged herpes simplex ulcers

Yes

Opportunistic malignancies

Lymphoma, Kaposi’s sarcoma

Yes

Advanced AIDS (CD4+ cell count less than 50 cells per mm3 [50 × 109 per L])

Opportunistic infections

Disseminated Mycobacterium aviumintracellulare complex, cytomegalovirus infections, toxoplasmosis

Yes

Other advanced AIDS conditions

AIDS wasting syndrome, AIDS dementia complex

Yes


AIDS = acquired immunodeficiency syndrome; HIV = human immunodeficiency virus.

Information from references 6,7, and 25.

TABLE 1   Disease Conditions Associated with Stages of Immunodeficiency

View Table

TABLE 1

Disease Conditions Associated with Stages of Immunodeficiency

Stage of immunodeficiency Type of condition Conditions AIDS defining?

Symptomatic HIV (CD4+ cell count less than 500 cells per mm3 [500 × 109 per L])

Superficial fungal infections

Thrush, recurrent vaginal candidiasis, onychomycosis, seborrhea

No

Superficial viral infections

Shingles, oral hairy leukoplakia, recurrent oral ulcers

No

Laboratory abnormalities

Thrombocytopenia, neutropenia, hypergammaglobulinemia

No

Constitutional symptoms

Night sweats, fever, fatigue, generalized lymphadenopathy

No

AIDS (CD4+ cell count less than 200 cells per mm3 [200 × 109 per L])

Opportunistic infections

Pneumocystis jiroveci pneumonia, candida esophagitis, cryptococcal infections, Isospora belli diarrhea, prolonged herpes simplex ulcers

Yes

Opportunistic malignancies

Lymphoma, Kaposi’s sarcoma

Yes

Advanced AIDS (CD4+ cell count less than 50 cells per mm3 [50 × 109 per L])

Opportunistic infections

Disseminated Mycobacterium aviumintracellulare complex, cytomegalovirus infections, toxoplasmosis

Yes

Other advanced AIDS conditions

AIDS wasting syndrome, AIDS dementia complex

Yes


AIDS = acquired immunodeficiency syndrome; HIV = human immunodeficiency virus.

Information from references 6,7, and 25.

A more detailed review of HIV-related manifestations (including those that occur at more advanced stages of HIV disease) and the implications of antiretroviral therapy (e.g., drug interactions and effects on non-HIV-related conditions such as diabetes and hyperlipidemia) and other therapies (e.g., methadone, herbal remedies) is provided in the following sections and in referenced resources.7,8,2628

LABORATORY TESTS

When patients are first identified as HIV seropositive, there are numerous baseline laboratory evaluations that should be performed. As listed in Table 2,7,8,25,26 the first category of tests is to assess patients’ risk for HIV disease progression and opportunistic complications as determined by CD4+ T-lymphocyte cell counts, which decline at a rate that is affected by plasma HIV RNA levels (viral load).25,29 In addition, baseline is the best time to perform an HIV-1 genotype test to determine whether the patient is infected with a drug-resistant virus.26

TABLE 2

Baseline and Periodic Testing in Patients with HIV

Indication Condition Test Purpose

All patients (every three to six months)

HIV

CD4+ T-lymphocyte count

HIV disease staging and opportunistic infection risk assessment

HIV

HIV RNA level

HIV disease activity

Baseline (before antiretroviral treatment)

HIV

HIV-1 genotype

Antiretroviral treatment resistance

Baseline (before vaccination)

HBV

HBsAg and core antibody, or surface antibody titer if previously vaccinated

Vaccination if negative or nonimmune

HBV e-antigen and HBV DNA if HBsAg- positive

HBV treatment if active infection

HAV

HAV total antibodies

Vaccination, especially if infected with HCV or HBV

Annually (if ongoing exposure risk)

Syphilis

Rapid plasma reagin or VDRL

Treatment of primary, secondary, or tertiary disease

Gonorrhea and chlamydia

Gonorrhea and chlamydia culture*; immunofluorescence; DNA amplification

Treatment of sexually transmitted diseases

HCV

Anti-HCV enzyme immunoassay (BIII), confirm with RIBA or HCV RNA (CIII); HCV RNA if antibody negative but transaminases elevated

HCV preventive education and treatment; also for HAV and HBV vaccination

Annually

Tuberculosis

PPD skin test by administration of intermediate strength (5-TU) [AI]

Tuberculosis prophylaxis or treatment

Chest radiograph [AII]

If positive PPD, possible false-negative PPD, history of tuberculosis, or symptomatic

Human papillomavirus-associated dysplasia

Pap smear†

Screening/treatment

Baseline (depending upon patient history)

Toxoplasmosis

Toxoplasma IgG‡ [BIII]

Preventive education if negative [BIII]; prophylaxis if toxoplasma IgG+ and CD4+ less than 100 cells per mm3 (100 × 109 per L) [AII]

CMV

CMV IgG

If low-risk group (neither men who have sex with men nor injection drug use); for preventive education; before blood transfusion (white blood cell–depleted blood if CMV-negative)

VZV

VZV IgG

For prophylaxis if potential VZV exposure and negative IgG [AIII]

Only if advanced AIDS (CD4+ less than 50 to 100 cells per mm3 [50 to 100 × 109 per L])

Mycobacterium avium-intracellulare complex

Acid fast bacteria blood culture

Before initiation of prophylaxis if symptomatic and CD4+ less than 100 cells per mm3

CMV

Dilated funduscopic examination (every three to six months)

Screening for CMV retinitis (usually at CD4+ counts less than 100 cells per mm3)

Baseline and periodically

Noninfectious comorbidities

Complete metabolic panel

Liver and kidney disease, malnutrition, hypergammaglobulinemia

Complete blood count

Cytopenias

Urinalysis

Nephropathy


note: Not all test recommendations were rated. See Table 3 for definitions of the Centers for Disease Control and Prevention’s evidence ratings system.

HIV = human immunodeficiency virus; HBV = hepatitis B virus; HBsAg = hepatitis B surface antigen; HAV = hepatitis A virus; HCV = hepatitis C virus;

VDRL = Venereal Disease Research Laboratory; RIBA = recombinant immunoblot assay; PPD = purified protein derivative; IgG = immunoglobulin G;

CMV = cytomegalovirus; VZV = varicella zoster virus.

*—Gonorrhea and chlamydia tests should be performed on specimens from all body areas involved in sexual activities (e.g. cervical, anal, oral, urethral [urine]).

†—Following diagnosis and treatment of dysplasia, repeat Pap every four to six months for the first two years in women, annually thereafter if normal; consider anal Pap smear in women with any genital human papillomavirus disease (regardless of history of anal sex) and in men who have sex with men (history of receptive anal sex).

‡—Repeat IgG levels when CD4+declines below 100 cells per mm3 if baseline results negative.

Information from references 7,8,25, and 26.

TABLE 2   Baseline and Periodic Testing in Patients with HIV

View Table

TABLE 2

Baseline and Periodic Testing in Patients with HIV

Indication Condition Test Purpose

All patients (every three to six months)

HIV

CD4+ T-lymphocyte count

HIV disease staging and opportunistic infection risk assessment

HIV

HIV RNA level

HIV disease activity

Baseline (before antiretroviral treatment)

HIV

HIV-1 genotype

Antiretroviral treatment resistance

Baseline (before vaccination)

HBV

HBsAg and core antibody, or surface antibody titer if previously vaccinated

Vaccination if negative or nonimmune

HBV e-antigen and HBV DNA if HBsAg- positive

HBV treatment if active infection

HAV

HAV total antibodies

Vaccination, especially if infected with HCV or HBV

Annually (if ongoing exposure risk)

Syphilis

Rapid plasma reagin or VDRL

Treatment of primary, secondary, or tertiary disease

Gonorrhea and chlamydia

Gonorrhea and chlamydia culture*; immunofluorescence; DNA amplification

Treatment of sexually transmitted diseases

HCV

Anti-HCV enzyme immunoassay (BIII), confirm with RIBA or HCV RNA (CIII); HCV RNA if antibody negative but transaminases elevated

HCV preventive education and treatment; also for HAV and HBV vaccination

Annually

Tuberculosis

PPD skin test by administration of intermediate strength (5-TU) [AI]

Tuberculosis prophylaxis or treatment

Chest radiograph [AII]

If positive PPD, possible false-negative PPD, history of tuberculosis, or symptomatic

Human papillomavirus-associated dysplasia

Pap smear†

Screening/treatment

Baseline (depending upon patient history)

Toxoplasmosis

Toxoplasma IgG‡ [BIII]

Preventive education if negative [BIII]; prophylaxis if toxoplasma IgG+ and CD4+ less than 100 cells per mm3 (100 × 109 per L) [AII]

CMV

CMV IgG

If low-risk group (neither men who have sex with men nor injection drug use); for preventive education; before blood transfusion (white blood cell–depleted blood if CMV-negative)

VZV

VZV IgG

For prophylaxis if potential VZV exposure and negative IgG [AIII]

Only if advanced AIDS (CD4+ less than 50 to 100 cells per mm3 [50 to 100 × 109 per L])

Mycobacterium avium-intracellulare complex

Acid fast bacteria blood culture

Before initiation of prophylaxis if symptomatic and CD4+ less than 100 cells per mm3

CMV

Dilated funduscopic examination (every three to six months)

Screening for CMV retinitis (usually at CD4+ counts less than 100 cells per mm3)

Baseline and periodically

Noninfectious comorbidities

Complete metabolic panel

Liver and kidney disease, malnutrition, hypergammaglobulinemia

Complete blood count

Cytopenias

Urinalysis

Nephropathy


note: Not all test recommendations were rated. See Table 3 for definitions of the Centers for Disease Control and Prevention’s evidence ratings system.

HIV = human immunodeficiency virus; HBV = hepatitis B virus; HBsAg = hepatitis B surface antigen; HAV = hepatitis A virus; HCV = hepatitis C virus;

VDRL = Venereal Disease Research Laboratory; RIBA = recombinant immunoblot assay; PPD = purified protein derivative; IgG = immunoglobulin G;

CMV = cytomegalovirus; VZV = varicella zoster virus.

*—Gonorrhea and chlamydia tests should be performed on specimens from all body areas involved in sexual activities (e.g. cervical, anal, oral, urethral [urine]).

†—Following diagnosis and treatment of dysplasia, repeat Pap every four to six months for the first two years in women, annually thereafter if normal; consider anal Pap smear in women with any genital human papillomavirus disease (regardless of history of anal sex) and in men who have sex with men (history of receptive anal sex).

‡—Repeat IgG levels when CD4+declines below 100 cells per mm3 if baseline results negative.

Information from references 7,8,25, and 26.

CD4+ T-lymphocyte cell counts are obtained by ordering a complete blood count, along with a CD4 and CD8 lymphocyte subset analysis. Table 16,7,25 lists the correlations between HIV disease stages, CD4+ cell counts, and common clinical manifestations associated with each stage.25,30 Knowledge of a patient’s CD4+ T-lymphocyte levels can help focus the clinical evaluation of presenting symptoms. For example, a dry cough at high-normal CD4+ T-lymphocyte levels would be less consistent with AIDS-related Pneumocystis jiroveci pneumonia (formerly known as Pneumocystis carinii pneumonia) than if the same presentation were to occur at CD4+ T-lymphocyte cell count levels of less than 200 cells per mm3 (200 × 109 per L).

A normal CD4+ cell count is roughly 1,000 cells per mm3 (1,000 × 109 per L). Early symptoms may begin when CD4+ T-lymphocyte cell count levels drop below 500 cells per mm3 (500 × 109 per L). AIDS-related opportunistic manifestations usually do not occur until CD4+ counts are below 200 cells per mm3, with a subset of more serious complications at CD4+ cell counts below 50 cells per mm3 (50 × 109 per L). However, it is common for patients to remain asymptomatic (or unaware of mild symptoms) even with CD4+ cell counts below 200 cells per mm3. In addition, although CD4+ cell counts typically decline at a rate of 50 to 100 cells per year following infection, as many as 30 percent of patients may progress at faster or slower rates. Thus, whereas an initial CD4+ cell count of 700 to 800 cells per mm3 (700 to 800 × 109 per L) might be reassuring of early or mild disease, T-lymphocyte cell counts should be reassessed every three to six months to monitor disease progression.

Tests approved by the U.S. Food and Drug Administration for HIV RNA include: the Amplicor HIV-1 Monitor test by Roche Diagnostics (PCR), the Versant branched-DNA (bDNA) assay distributed by Chiron Corp., and the NucliSens HIV-1 RNA nucleic acid amplification test by Organon Teknika. A repeat viral load test conducted one to two weeks after the initial test generally is recommended (unless waiting for the repeat test would delay intervention in a patient with advanced HIV) because of normal test variability (up to threefold differences) and to detect false elevations caused by recent illness or vaccination. Thereafter, serum viral load tests typically are monitored every four to six months.26

The interpretations of plasma viral load and CD4+ tests are based on numerous studies7,8,2629 of the natural history of disease progression and the effectiveness of antiretroviral agents. In general, the higher the viral load, the more active and aggressive the HIV infection, resulting in a more rapid decline in CD4+ cell counts and quicker progression to AIDS or death. Regardless of viral load, the CD4+ level is the determining factor for a patient’s risk of opportunistic complications, although both are independent predictors of risk of AIDS.29 Thus, low viral load levels (i.e., below 10,000 copies per mL or, ideally, undetectable at the ultra-sensitive level) or high CD4+ cell counts (i.e., above 200 cells per mm3 and, ideally, above 500 cells per mm3) are associated with a better prognosis and are the basis for and outcome goals of antiretroviral therapy.

INFECTION SCREENING TESTS

Patients infected with HIV often are coinfected with other pathogens related to the route of transmission or to psychosocial circumstances. Thus, broad-spectrum screening for these pathogens at baseline and periodically is an integral part of the care of patients with HIV.7,8,22,25  Table 27,8,25,26  lists the relevant screening tests to consider. Table 325 lists the definitions of the CDC’s evidence ratings system.

TABLE 3

Definitions of the Centers for Disease Control and Prevention’s Evidence Ratings System

Rating Strength of recommendation

A

Both strong evidence for efficacy and substantial clinical benefit support recommendation for use; should always be offered.

B

Moderate evidence for efficacy or strong evidence for efficacy, but only limited clinical benefit, supports recommendation for use; should usually be offered.

C

Evidence for efficacy is insufficient to support arecommendation for or against use, or evidence for efficacy might not outweigh adverse consequences (e.g., drug toxicity, drug interactions) or cost of the chemoprophylaxis or alternative approaches; use is optional.

D

Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use; should usually not be offered.

E

Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use; should never be offered.

Rating Quality of evidence supporting the recommendation

I

Evidence from at least one correctly randomized, controlled trial

II

Evidence from at least one well-designed clinical trial without randomization, from cohort or case-control analytic study (preferably from more than one center), or from multiple time-series studies, or dramatic results from uncontrolled experiments

III

Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of consulting committees


Adapted from Kaplan JE, Masur H, Holmes KK; USPHS; Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons—2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep 2002;51(RR-8):35.

TABLE 3   Definitions of the Centers for Disease Control and Prevention’s Evidence Ratings System

View Table

TABLE 3

Definitions of the Centers for Disease Control and Prevention’s Evidence Ratings System

Rating Strength of recommendation

A

Both strong evidence for efficacy and substantial clinical benefit support recommendation for use; should always be offered.

B

Moderate evidence for efficacy or strong evidence for efficacy, but only limited clinical benefit, supports recommendation for use; should usually be offered.

C

Evidence for efficacy is insufficient to support arecommendation for or against use, or evidence for efficacy might not outweigh adverse consequences (e.g., drug toxicity, drug interactions) or cost of the chemoprophylaxis or alternative approaches; use is optional.

D

Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use; should usually not be offered.

E

Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use; should never be offered.

Rating Quality of evidence supporting the recommendation

I

Evidence from at least one correctly randomized, controlled trial

II

Evidence from at least one well-designed clinical trial without randomization, from cohort or case-control analytic study (preferably from more than one center), or from multiple time-series studies, or dramatic results from uncontrolled experiments

III

Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of consulting committees


Adapted from Kaplan JE, Masur H, Holmes KK; USPHS; Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons—2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep 2002;51(RR-8):35.

The first screening category is for pathogens that are preventable through vaccination, namely hepatitis A and B. The second category is for infections to which patients may have repeated exposure through unsafe sexual practices or illicit drug use. These include syphilis, chlamydia, gonorrhea, and hepatitis C. Note that management of hepatitis B and C in patients with HIV is critically important because it can affect patient longevity (directly, by counteracting progressive liver disease; or indirectly, by protecting a patient’s liver against the side effects of antiretroviral medications).31 In patients who are immunodeficient, it is not uncommon for hepatitis C infections to be seronegative; therefore, it is important to check serum HCV RNA levels if serum alanine transaminase levels are elevated.

The third category is screening for recurrence of previous or newly acquired infections, such as Mycobacterium tuberculosis and human papillomavirus (HPV). Tuberculosis is intertwined with the AIDS epidemic, with each infection exacerbating and commonly coexisting with the other. The standard public health approach is to screen for coinfection whenever either infection is detected.

When screening for tuberculosis in patients with HIV, the tuberculin skin test generally is considered positive at an induration of at least 5 mm. In addition, routine chest radiograph examination often is needed for patients with a negative tuberculin skin test given the increased possibility of anergy, particularly at lower CD4+ cell counts (although anergy skin testing is not recommended by the CDC because of a lack of effectiveness).25,32 Lastly, even in patients with HIV whose skin test and chest radiograph screening results are negative, prophylaxis may be indicated based solely on a history of high exposure risk.

HPV is more aggressive in patients with HIV and tends to be more prevalent, persistent, and recurrent, and progresses more rapidly to HPV-related dysplasia. Thus, increased vigilance in screening is indicated in patients with HIV, including cervical Papanicolaou (Pap) smears performed every six months for the first year and annually thereafter, if normal.

The fourth category of screening is for opportunistic infections unique to patients who are immunodeficient.25 Infections in this category include cytomegalovirus, toxoplasmosis, and varicella zoster virus. For opportunistic infections, there are two relevant timing considerations in patients with HIV. First, baseline evaluations are needed for all patients, regardless of CD4+ cell count level, with education on how to limit pathogen exposure and thereby reduce the risk for subsequent reactivation of such infections. Second, all patients whose immunodeficiency is in the AIDS range (i.e., CD4+ cell count less than 200 cells per mm3) should be screened for previous pathogen exposure (e.g., toxoplasmosis), or current symptoms (e.g., fever and anemia of Mycobacterium avium intracellulare) because these will affect initiation of prophylaxis. In addition, baseline knowledge about previous occurrence of chickenpox or activities with high risk for cytomegalovirus exposure (e.g., men who have sex with men) also guide preventive interventions.

The outcome goal of screening for coinfections is not only to direct the provision of prophylactic therapies but to guide patients in ways of minimizing exposure to potential opportunistic pathogens. Table 425 lists the basic areas of patient education relevant to preventing infections associated with HIV.

TABLE 4

Patient Education to Prevent Infections Associated with HIV

Type of exposure Potential pathogens Patient education

Sexual

Drug-resistant HIV; CMV; Kaposi’s sarcoma; herpes virus (human herpes virus-8); cryptosporidium; enteric pathogens; others

Use barriers with penetrative sex (male condoms [AII]; female condoms [BIII]).

Avoid oral-to-anal sexual contact [BIII].

Blood

Hepatitis B and C viruses

Use blood-borne precautions with injection drug use, drug snorting, tattooing, and body piercing.

Enteric

Hepatitis A; salmonella; cryptosporidium; others

Use standard food-borne illness precautions (e.g., no raw eggs or fish, use pasteurized juices and dairy products, avoid contaminated water, use standard travel food precautions).

Environmental, occupational, and pet-related

Tuberculosis; CMV; varicella; cryptococcus; Toxoplasma gondii; cryptosporidium; campylobacter; salmonella; bartonella; others

Use caution with occupational activities (e.g., working in prisons, day care facilities, and homeless shelters).

Avoid exposure to bat droppings and dust storms.

Avoid exposure to ill animals and to cat excrement.

Travel

All of the above, plus regional endemic infections (e.g., polio)

Precautions above, plus CDC guidelines for travelers with attention to differences for immunodeficient persons (e.g., those in whom live vaccines are contraindicated)


note:Only general recommendations and typical pathogens and prevention guidelines are listed. See Table 3 for definitions of the CDC’s evidence ratings system.

HIV= human immunodeficiency virus; CMV = cytomegalovirus; CDC= Centers for Disease Control and Prevention.

Information from reference 25.

TABLE 4   Patient Education to Prevent Infections Associated with HIV

View Table

TABLE 4

Patient Education to Prevent Infections Associated with HIV

Type of exposure Potential pathogens Patient education

Sexual

Drug-resistant HIV; CMV; Kaposi’s sarcoma; herpes virus (human herpes virus-8); cryptosporidium; enteric pathogens; others

Use barriers with penetrative sex (male condoms [AII]; female condoms [BIII]).

Avoid oral-to-anal sexual contact [BIII].

Blood

Hepatitis B and C viruses

Use blood-borne precautions with injection drug use, drug snorting, tattooing, and body piercing.

Enteric

Hepatitis A; salmonella; cryptosporidium; others

Use standard food-borne illness precautions (e.g., no raw eggs or fish, use pasteurized juices and dairy products, avoid contaminated water, use standard travel food precautions).

Environmental, occupational, and pet-related

Tuberculosis; CMV; varicella; cryptococcus; Toxoplasma gondii; cryptosporidium; campylobacter; salmonella; bartonella; others

Use caution with occupational activities (e.g., working in prisons, day care facilities, and homeless shelters).

Avoid exposure to bat droppings and dust storms.

Avoid exposure to ill animals and to cat excrement.

Travel

All of the above, plus regional endemic infections (e.g., polio)

Precautions above, plus CDC guidelines for travelers with attention to differences for immunodeficient persons (e.g., those in whom live vaccines are contraindicated)


note:Only general recommendations and typical pathogens and prevention guidelines are listed. See Table 3 for definitions of the CDC’s evidence ratings system.

HIV= human immunodeficiency virus; CMV = cytomegalovirus; CDC= Centers for Disease Control and Prevention.

Information from reference 25.

TESTS FOR NONINFECTIOUS COMORBIDITIES

There are many laboratory abnormalities commonly seen in patients with HIV,7,8 including: anemia (caused by chronic disease, malnutrition, or quiescent mycobacterium infection); thrombocytopenia (related to untreated HIV or to chronic liver disease); leukopenia and lymphopenia (reflective of immunosuppression); hypergammaglobulinemia (caused by overall dysregulation of the immune system); hypoalbuminemia (caused by malnutrition or liver disease); transaminitis (caused by viral hepatitis); and proteinuria (caused by HIV-associated nephropathy, most often in blacks). Patients who are diagnosed later in the course of their infection may also have complications related to HIV that may be initially detected through routine chemistry evaluations (e.g., lymphoma with an elevated lactate dehydrogenase, M. avium intracellulare complex with an elevated serum alkaline phosphatase).

Patients with HIV also have typical health care needs beyond conditions related to HIV.7,8 These include the need for routine, age-appropriate health-maintenance screening for cardiovascular health and for cancer (e.g., breast, prostate, colorectal). In addition, as patients with HIV age they may become afflicted with obesity, hypertension, insulin resistance, diabetes, hyperlipidemia, or atherosclerotic disease. Any of these may be a consequence of the antiretroviral therapies or of aging itself. Thus, extra preventive focus at baseline is increasingly important for these patients.

Baseline Therapies

Initial therapy in patients newly diagnosed with HIV follows from the goals and results of baseline evaluation: (1) health maintenance interventions, (2) opportunistic infection prophylaxis, and (3) antiretroviral therapy.

HEALTH MAINTENANCE

One component of health maintenance in patients with HIV is routine vaccinations such as for tetanus and diphtheria.7,8,25 However, there are several special considerations pertinent to these patients. First, live viral vaccinations (e.g., smallpox, oral polio vaccine) pose an actual risk of infection consequent to the vaccines and are therefore contraindicated in patients with HIV and their household contacts. Second, because of immunodeficiency, patients with HIV are in the high-risk group targeted to receive immunization against pneumococcus and influenza. However, patients initially vaccinated at low CD4+ cell count levels often have a blunted immune response to the pneumococcal vaccine and thus generally should be revaccinated when their CD4+ cell counts rise above 200 cells per mm3. In addition, vaccination against hepatitis A and B also is important for patients with HIV, with post-vaccination serology to assess immune response.

INSTITUTION OF OPPORTUNISTIC INFECTION PREVENTION

Table 52,6,7,25,27 lists the CDC’s recommended prophylaxis guidelines and their indications. The most important prophylaxis is for P. jiroveci pneumonia, because the incidence rate approaches 80 percent in the absence of prophylaxis at CD4+ cell count levels below 200 cells per mm3, and its preventability is above 90 percent. Even pending the results of baseline T-lymphocyte cell counts and viral load, the presence of oral thrush or herpes ulcers for more than four weeks indicates sufficient immunodeficiency to warrant P. jiroveci pneumonia prophylaxis, which may save the patient an unnecessary bout with the most common opportunistic infection related to HIV.

TABLE 5

Prophylaxis of Infections Associated with HIV

Infection Intervention Indication

Hepatitis B virus (HBV)

HBV vaccination [BII]

Hepatitis B negative

Hepatitis A virus (HAV)

HAV vaccination [BII]

Coinfected with HBV or hepatitis C virus, or high-risk exposures

Streptococcus pneumoniae

Pneumococcal vaccination (23-valent polysaccharide)

CD4+ cell count greater than 200 cells per mm3(200 × 109 per L) [BII]

CD4+ cell count less than 200 cells per mm3 [CIII]

Influenza

Inactivated vaccine

Annually

Pneumocystis jiroveci pneumonia

Trimethoprim/sulfamethoxazole (TMP-SMX; Bactrim, Septra) [AI]

CD4+ cell count less than 200 cells per mm3 [AI], or CD4+ cell count less than 14 percent or history of AIDS diagnosis [BII], or history of oral thrush [AII]

Toxoplasmosis

TMP-SMX [AII]

CD4+ cell count less than 100 cells per mm3 (100 × 109 per L) and toxoplasma IgG+ [AII]

Mycobacterium avium intracellulare complex

Azithromycin (Zithromax) [AI] or clarithromycin (Biaxin) [AI]

CD4+ cell count less than 50 cells per mm3 (50 × 109 per L) [AI]

Tuberculosis

Isoniazid (INH) [AII]

As per text.


note: Only first-line regimens are listed. See published guidelines for details. See Table 3 for definitions of Centers for Disease Control and Prevention’s evidence ratings system.

HIV = human immunodeficiency virus; AIDS = acquired immunodeficiency syndrome; IgG = immunoglobulin G.

Information from references 2,6,7,25, and 27.

TABLE 5   Prophylaxis of Infections Associated with HIV

View Table

TABLE 5

Prophylaxis of Infections Associated with HIV

Infection Intervention Indication

Hepatitis B virus (HBV)

HBV vaccination [BII]

Hepatitis B negative

Hepatitis A virus (HAV)

HAV vaccination [BII]

Coinfected with HBV or hepatitis C virus, or high-risk exposures

Streptococcus pneumoniae

Pneumococcal vaccination (23-valent polysaccharide)

CD4+ cell count greater than 200 cells per mm3(200 × 109 per L) [BII]

CD4+ cell count less than 200 cells per mm3 [CIII]

Influenza

Inactivated vaccine

Annually

Pneumocystis jiroveci pneumonia

Trimethoprim/sulfamethoxazole (TMP-SMX; Bactrim, Septra) [AI]

CD4+ cell count less than 200 cells per mm3 [AI], or CD4+ cell count less than 14 percent or history of AIDS diagnosis [BII], or history of oral thrush [AII]

Toxoplasmosis

TMP-SMX [AII]

CD4+ cell count less than 100 cells per mm3 (100 × 109 per L) and toxoplasma IgG+ [AII]

Mycobacterium avium intracellulare complex

Azithromycin (Zithromax) [AI] or clarithromycin (Biaxin) [AI]

CD4+ cell count less than 50 cells per mm3 (50 × 109 per L) [AI]

Tuberculosis

Isoniazid (INH) [AII]

As per text.


note: Only first-line regimens are listed. See published guidelines for details. See Table 3 for definitions of Centers for Disease Control and Prevention’s evidence ratings system.

HIV = human immunodeficiency virus; AIDS = acquired immunodeficiency syndrome; IgG = immunoglobulin G.

Information from references 2,6,7,25, and 27.

ANTIRETROVIRAL THERAPY

Even if patients are referred to an outside consultant, it is important for family physicians to be aware of the indications for initiation of antiretroviral therapy. The overall goal of antiretroviral therapy is to convert HIV infection into a chronic disease by suppressing viral replication to arrest or revert immunodeficiency progression and prevent opportunistic complications. With this goal in mind, therapy is desirable for patients who have or are near to having AIDS, based on symptomatology or CD4+ cell counts. In addition, there are some proponents of antiretroviral treatment during acute (primary) HIV infection for the purpose of limiting viral dissemination and disease progression23; however, more recent studies33 have shown that these benefits are lost after discontinuation of therapy, thus necessitating lifelong therapy after such early initiation.

Several guidelines2628 for antiretroviral therapy concur that treatment is indicated for patients who are symptomatic (e.g., have thrush, fevers, thrombocytopenia, or wasting); have AIDS (CD4+ cell counts of less than 200 cells per mm3 or AIDS-defining conditions); or who are pregnant (to prevent perinatal transmission). The controversy among the guidelines revolves around the appropriate CD4+ cell count or HIV RNA levels at which to initiate therapy in asymptomatic pre-AIDS patients. Depending upon the amount of “pre-AIDS buffer zone” desired, antiretroviral therapy can be initiated later, when CD4+ cell counts are nearing the AIDS level of 200 cells per mm3; or sooner, when CD4+ cell counts are below 350 cells per mm3 (350 × 109 per L). The later therapy is initiated, the greater the risks of opportunistic complications, potential suboptimal immune restoration, and medication toxicity. Conversely, the earlier antiretroviral therapy is initiated, the longer the duration of therapy and the greater the risk of medication-related long-term side effects (e.g., lipodystrophy, hyperlipidemia, and insulin resistance)34 and the development of viral-resistant mutations through imperfect medication adherence. Regardless of the disease stage or need for therapy, a patient’s readiness, willingness, and ability to adhere to therapy are key prerequisites for treatment success.26

Antiretroviral therapy requires expertise to deal with these complex issues and to keep up with the changing treatment guidelines and new research data. Accordingly, treatment by “HIV experts” is the national standard. Although some family physicians have the additional training and experience necessary to become HIV experts, referral to HIV subspecialists often is necessary. Verification of provider expertise can be assessed in reference to national HIV-expert criteria.35,36 General family physicians, however, still have an important role in the care of patients with HIV. Early diagnosis and counseling, ongoing prevention emphasis, screening and provision of continuity health maintenance, and reinforcement of the importance of medication adherence are all important contributions that family physicians can provide.

The Author

ANN M. KHALSA, M.D., M.S.ED., is associate medical director for the La Fe C.A.R.E. HIV/AIDS Center and the director of human immunodeficiency virus (HIV) training under the federal AIDS Education and Training Center at the La Fe Center in El Paso, Tex. She also is a clinical faculty member at the Texas Tech University Health Sciences Center School of Medicine, El Paso. Dr. Khalsa received her medical degree and master of medical education degree from the University of Southern California, Los Angeles.

Address correspondence to Ann M. Khalsa, M.D., M.S.Ed., La Fe C.A.R.E. HIV/AIDS Center, 1505 Mescalero Dr., El Paso, TX 79925-2019. Reprints are not available from the author.

Author disclosure: nothing to disclose.

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8. New York State Department of Health AIDS Institute. Primary Care Approach to the HIV-Infected Patient. March 2004. Accessed online July 15, 2005, at: http://www.hivguidelines.org./public_html/a-primca/a-primca.htm.

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13. Bryson YJ. Perinatal HIV-1 transmission: recent advances and therapeutic interventions. AIDS. 1996;10(suppl 3):S33–42.

14. Cohen MS. Conference report: HAART and prevention of HIV transmission. Atlanta, June 6–7, 2002. Medscape. Accessed online July 15, 2005, at: http://www.medscape.com/viewarticle/437545.

15. Pilcher CD. Acute HIV in STD clinics: detection of co-transmission of pathogens. Presented at the 42nd annual meeting of the Infectious Diseases Society of America, Boston, September 30–October 3, 2004. Accessed online July 15, 2005, at: http://www.idsociety.org/Template.cfm?Section=Program&CONTENTID=10150&TEMPLATE=/Content-Management/ContentDisplay.cfm.

16. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342:921–9.

17. Pedraza MA, del Romero J, Roldan F, Garcia S, Ayerbe MC, Noreiga AR, et al. Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner. J Acquir Immune Defic Syndr. 1999;21:120–5.

18. Taylor S, Sadiq T, Sabin C, White D, Cane P, Drake S, et al Seminal super shedding of HIV: implications for sexual transmission. Presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10–14, 2003. Accessed online July 15, 2005, at: http://www.retroconference.org/2003/cd/Abstract/454.htm.

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21. Pilcher CD, Tien HC, Eron JJ Jr, Vernazza PL, Leu SY, Stewart PW, et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004;189:1785–92.

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24. The Ryan White Comprehensive AIDS Resources Emergency (care) act. Accessed online July 15, 2005, at: http://www.hhs.gov/news/press/1998pres/981218d.html.

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27. Yeni PG, Hammer SM, Carpenter CC, Cooper DA, Fischl MA, Gatell JM, et al. Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2002;288:222–35.

28. New York State Department of Health AIDS Institute. Criteria for the medical care of adults with HIV infection. Antiretroviral therapy. Revised June 2005. Accessed online July 15, 2005, at: http://www.hivguidelines.org/public_html/a-arv/a-arv.pdf.

29. Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. 1997;126:946–54.

30. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992;41(RR-17):1–19.

31. Chung RT, McGovern BH. Hepatitis primer, including the HIV-infected patient. Accessed online July 15, 2005, at: http://www.idsociety.org/Template.cfm?Section=Program&CONTENTID=10150&TEMPLATE=/ContentManagement/ContentDisplay.cfm.

32. Targeted tuberculin testing and treatment of latent tuberculosis. American Thoracic Society MMWR Recomm Rep 2000;49(RR-6):1–51. Accessed online July 15, 2005, at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm.

33. Kaufmann D, Lichterfeld M, Altfeld M, Allen T, Johnston M, Lee P, et al. Limited durability of immune control following treated acute HIV infection. 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, February 8–11, 2004. Accessed online July 15, 2005, at: http://www.retroconference.org/2004/cd/abstract/24.htm.

34. Lesho EP, Gey DC. Managing issues related to antiretroviral therapy. Am Fam Physician. 2003;68:675–86.

35. The American Academy of HIV Medicine. Accessed online July 15, 2005, at: http://www.aahivm.org.

36. HIV Medicine Association. Accessed online July 15, 2005, at: http://www.hivma.org.

Members of various family medicine departments develop articles for “Problem-Oriented Diagnosis.” This is one in a series from the Department of Family Medicine at the University of Southern California, Los Angeles, Calif. Coordinator of the series is Ricardo G. Hahn, M.D.


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