Infectious Diseases

Evaluation and Management of the Newly Diagnosed HIV Patient

OVERVIEW: What every practitioner needs to know

Are you sure your patient has HIV infection? What should you expect to find?

Chronic HIV infection

  • Ideally, HIV infection should be diagnosed through routine testing before the patient becomes symptomatic. The Centers for Disease Control and Prevention (CDC) now recommends routine, voluntary HIV testing for all patients 13-64 years of age in all healthcare settings, regardless of perceived risk or health status. (The US Preventive Services Task Force recommends routine screening for all patients 15-65 years of age.)

  • HIV testing should also be performed in patients with symptoms suggestive of immunosuppression. These include unexplained weight loss, chronic diarrhea, fever, chills, sweats, dysphagia or odynophagia, oropharyngeal candidiasis (thrush), and more severe or frequent vaginal candidiasis.

  • Some skin conditions can be more severe or frequent in HIV-infected patients, including seborrheic dermatitis, psoriasis, dermatophyte infections, folliculitis, prurigo nodularis, anogenital or cutaneous herpes, anogenital warts or dysplasia, and herpes zoster (shingles).

  • Diagnoses that should prompt consideration of HIV testing include any infection associated with defective cellular immunity, lymphoma, Kaposi sarcoma, herpes zoster, tuberculosis, pneumonia, thrombocytopenia, or diseases that have similar risk factors, including sexually transmitted diseases, hepatitis B, and hepatitis C.

  • Physical findings that should prompt consideration of HIV testing include:

    • General: weight loss, wasting, cachexia, diffuse lymphadenopathy

    • Ocular: CMV retinitis (hemorrhagic retinal exudates), cotton wool spots

    • Oropharyngeal: candidiasis (thrush, palatal erythema, angular cheilosis), oral hairy leukoplakia, aphthous ulceration

    • Anogenital: evidence of sexually transmitted infections, HPV infection (warts, dysplasia), more severe or recurrent vaginal candidiasis

    • Dermatologic: herpes zoster, more severe or recurrent skin conditions

    • Neurologic: peripheral sensory neuropathy

Primary HIV infection (acute retroviral syndrome)

  • Typical signs/symptoms include fever, pharyngitis, lymphadenopathy, gastrointestinal (GI) symptoms, and rash. Therefore, primary HIV infection should be considered in any patient presenting with symptoms suggestive of infectious mononucleosis. Neurologic manifestations of primary HIV infection include aseptic meningitis, (less commonly) Guillain-Barre syndrome, mononeuritis multiplex, and facial nerve palsy.

  • Testing for primary HIV infection is different from testing for chronic HIV infection, since standard serologic tests may be negative. Typical testing procedure involves either simultaneous HIV serology and HIV RNA (viral load) or the use of fourth-generation assays that test for both antibody and p24 antigen. HIV RNA will be positive approximately 5 days before the fourth generation test.

How did the patient develop HIV Infection? What was the primary source from which the infection spread?

  • HIV is acquired from person-to-person through contact with infected bodily fluids, usually semen, vaginal secretions, or blood. Modes of transmission include:

    • Sexual: most common, with unprotected receptive anal or vaginal intercourse being the activities associated with the greatest risk

    • Injection drug use: blood contact with shared syringes or needles

    • Perinatal transmission: infants born to mothers with unsuppressed viremia; transmission through breast-feeding also occurs

    • Occupational transmission: most often from needle sticks (usually hollow-bore, blood-filled needles); extremely rarely from mucocutaneous splashes

    • Transfusion/blood products: extremely rare form of transmission today due to testing of blood supply

    • HIV is not transmitted through kissing, sharing eating/drinking utensils, or contact with skin or saliva.

    • With all modes of transmission, the viral load (quantity of viral particles in the infected person's blood) is strongly associated with the risk of transmission.

  • The epidemiology of HIV infection varies, depending on geographical location. In the United States and other developed countries, men who have sex with men (MSM) and injection drug users are at higher risk than the general population. However, many infected individuals do not fall into traditional "high risk" categories, including heterosexual women who do not identify their male partner(s) as being at risk for HIV infection.

  • Traditional risk-based testing leads to under-diagnosis and has been replaced in the United States by routine voluntary testing regardless of risk. In many resource-limited settings, there is less of a gender difference in the prevalence of HIV infection, and heterosexual sex is the most common risk factor for infection.

Which individuals are of greater risk of developing HIV infection?

  • Risk factors for HIV infection are mostly epidemiologic and behavioral (see above) rather than biologic. However, some individuals are unlikely to be infected despite exposure This has been best characterized in individuals with the delta 32 deletion mutation resulting in a genetic absence of CCR5 co-receptors on the CD4+ cell surface. These co-receptors are required for entry of HIV into the cell.

Beware: there are other diseases that can mimic HIV infection:

  • Although there are other conditions that can cause cellular immunodeficiency with similar clinical manifestations, the sensitivity and specificity of the HIV serology make diagnostic confusion extremely unlikely. Patients who present with manifestations of cellular immunodeficiency should first be tested for HIV. Evaluation for other causes of immunodeficiency is indicated only if there is no laboratory evidence of HIV infection.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

  • Laboratory test results that should prompt consideration of HIV testing include unexplained anemia, lymphopenia, thrombocytopenia, elevated total protein, hypoalbuminemia, proteinuria (especially in black patients), evidence of active or prior sexually transmitted diseases, evidence of latent M. tuberculosis infection (positive tuberculin skin test or interferon gamma releasing assay), or any laboratory results diagnostic of an HIV-associated opportunistic condition.

Results that confirm the diagnosis

  • HIV serology: A positive fourth generation antigen/antibody test result (preferred) or positive enzyme immunoassay (EIA) with confirmatory Western blot establishes the diagnosis. (The exception is the rare false-positive result due to clerical or phlebotomist error. Repeat serology if viral load is very low or undetectable). Rapid HIV tests are highly sensitive, but positive results should be confirmed with standard serology or with a different rapid test. False-negative serologies can occur during the "window period": typically the first 2 weeks after infection. False-negatives are also more common with the OraSure In-Home rapid HIV test, when results are interpreted by the user. Some patients do not seroconvert for 3-4 weeks by conventional antibody tests; virtually all seroconvert within 6 months. The antigen/antibody tests have a shorter window period, decreasing the likelihood of false-negative results, including during acute or early infection.

  • HIV RNA (viral load): This is not typically used for diagnosis of chronic HIV infection, but should be ordered after diagnosis in all cases. Repeat and confirm HIV serology in patients with very low or undetectable viral loads. The use of either a combined antigen/antibody test or viral load testing is critical in cases of suspected primary HIV infection (acute retroviral syndrome), since standard serologies may be indeterminate or negative. It can also be useful when serology is indeterminate (positive EIA with presence of some bands on Western blot). Avoid using viral load in asymptomatic patients concerned about exposure, since serology is highly accurate and viral load can be false positive (low level result in HIV-uninfected patient) or false negative (undetectable viral load in infected elite controllers).

  • CD4+ cell count: The CD4+ cell count (CD4 count) neither confirms nor excludes the diagnosis of HIV infection but should always be ordered in patients diagnosed with HIV infection to determine immune status and to assess urgency of antiretroviral therapy and the need for opportunistic infection prophylaxis.

What imaging studies will be helpful in making or excluding the diagnosis of HIV infection?

  • Imaging studies are used to diagnose HIV-associated complications but are not helpful in diagnosing HIV infection itself. There are no imaging studies routinely recommended on the basis of a HIV diagnosis.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

  • HIV-infected patients should be managed, co-managed, or seen in consultation by an HIV expert, beginning as soon as possible after diagnosis.

  • There is currently no recognized medical subspecialty for HIV infection, and there are varying definitions of HIV expertise, which is generally defined by experience, patient load, and HIV-specific continuing medical education.

  • Some, but not all, HIV experts are infectious disease (ID) specialists; not all ID specialists are HIV experts.

  • Expert consultation is especially important in deciding when and how to initiate antiretroviral therapy (ART), in making changes to ART because of toxicity or failure, and in managing complications of HIV disease or ART.

  • Many HIV-infected patients benefit from referral for case management, mental health services, substance abuse treatment, risk reduction counseling, and/or adherence counseling. HIV-infected women should be referred to a gynecologist for cervical cancer screening and birth control or conception counseling.

  • HIV-infected patients frequently require referral to other specialists (preferably with HIV expertise), including, but not limited to, dermatologists, neurologists, nephrologists, endocrinologists, gastroenterologists, and psychiatrists.

If you decide the patient has HIV infection, what therapies should you initiate immediately?

  • ART is not an emergency, but it is urgent in the case of conditions that cannot be effectively treated without ART (e.g., HIV-associated dementia, HIV-associated nephropathy, PML, cryptosporidiosis, microsporidiosis, primary CNS lymphoma).

  • The benefit of ART for patients presenting with primary or recently acquired HIV infection remains uncertain, but some studies suggest benefit with very early therapy (preferably during symptomatic phase before seroconversion).

  • Current guidelines recommend ART for all HIV infected patients regardless of CD4 count, Need for immediate therapy depends mainly on CD4 count. OI prophylaxis can be started immediately, whereas ART can often be deferred briefly pending expert consultation.

    • CD4 greater than 500: ART should be initiated as soon as possible, but not urgent.

    • CD4 350-500: ART should be initiated as soon as possible, but not urgent.

    • CD4 200-350: ART should be initiated promptly.

    • CD4 100-200: Pneumocystis pneumonia (PCP) prophylaxis should be initiated immediately. ART is urgent.

    • CD4 50-100: PCP prophylaxis, plus Toxoplasma prophylaxis in patients with latent infection (IgG-positive). ART is urgent.

    • CD4 less than 50: PCP and Toxoplasma prophylaxis should be initiated immediately. ART is urgent. Prophylaxis against Mycobacterium avium complex (MAC) is controversial. U.S. opportunistic infection guidelines recommend MAC prophylaxis if there is no evidence of disseminated disease, but International AIDS Society-USA (IAS-USA) guidelines do not recommend it if ART is to be started immediately.

  • Initiate ART immediately regardless of CD4 count:

    • HIV-associated nephropathy (HIVAN)

    • HBV co-infection

    • Pregnancy

    • History of AIDS-defining illness

    • Most acute opportunistic infections

    • Risk of transmission

  • The goal of ART is to reduce the viral load to levels below the limit of detection (generally <20 copies/mL).

  • Virologic suppression leads to an increase in CD4 count, prevention of HIV-associated complications, reversal of many existing complications, decreased morbidity, hospitalization, healthcare cost, and mortality.

  • ART regimens should be chosen based on resistance test results. This is true for the initial regimen, as well as subsequent regimens. Baseline genotypic resistance testing should be performed at the time of diagnosis, regardless whether ART will be initiated immediately. Baseline integrase resistance testing not currently recommended because of low risk of transmitted integrase mutations.

  • Resistance occurs when the virus is allowed to replicate in the face of selective drug pressure. This can occur when patients are treated with antiretroviral agents to which their virus is resistant or when drug levels are inadequate because of drug interactions, failure to follow food restrictions, or non-adherence with therapy.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection what anti-infective should I order?

  • The choice of initial ART regimen is rarely empiric. It should be chosen after a review of baseline genotypic resistance test results and then individualized based on specific patient characteristics.

  • The exception is the patient being treated during primary infection for whom resistance test results are not available. While waiting for resistance test results, a boosted protease inhibitor (PI)-based regimen or an integrase inhibitor-based regimen can be started, since transmitted resistance to these regimens is less likely. Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens should be avoided because of the possibility of transmitted NNRTI resistance.

For the Recommended and alternative antiretroviral regimens (DHHS July 14 2016) see Table I. For the Recommended Antiretroviral Regimens (IAS-USA Guidelines, July 2016) see Table II

Table I.

Recommended and Alternative Antiretroviral Regimens (DHHS Guidelines, April 14, 2015)

Table II.

Recommended Antiretroviral Regimens (IAS-USA Guidelines, July 2016). For advantages and disadvantages, see Table I.

2. Next list other key therapeutic modalities.

  • Opportunistic Infection Prophylaxis

    • Pneumocystis pneumonia (PCP)

      • Indication: CD4 less than 200, CD4% less than 14, history of AIDS-defining illness, oropharyngeal candidiasis, prior PCP

      • Preferred: TMP/SMX 1 single strength (SS) or double strength (DS) tablet daily

      • Alternative: TMP/SMX 1 DS tablet 3 times weekly

      • Alternative: dapsone 100 mg daily or 50 mg twice daily (avoid if G6PD deficient)

      • Alternative: dapsone 50 mg daily + (pyrimethamine 50 mg + leucovorin 25 mg) weekly

      • Alternative: (dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25 mg) weekly

      • Alternative: aerosolized pentamidine 300 mg monthly

      • Alternative: atovaquone 1500 mg daily

      • Alternative: (atovaquone 1500 mg + pyrimethamine 25 mg + leucovorin 10 mg) daily

    • Toxoplasma encephalitis

      • Indication: Toxoplasma IgG-positive patients with CD4 count less than 100

      • Preferred: TMP/SMX 1 DS tab daily

      • Alternative: TMP/SMX 1 DS tab 3 times weekly or 1 SS tab daily

      • Alternative: dapsone 50 mg daily + (pyrimethamine 50 mg + leucovorin 25 mg) weekly

      • Alternative: (dapsone 200 mg + pyrimethamine 25 mg + leucovorin 25 mg) weekly

      • Alternative: atovaquone 1500 mg +/- pyrimethamine 25 mg + leucovorin 10 mg daily

    • Tuberculosis

      • Indications (in patients without evidence of active tuberculosis (TB) or prior treatment for TB or latent M. tuberculosis infection (LTBI):

        • LTBI based on tuberculin skin test (TST) or interferon gamma releasing assay (IGRA)

        • Close contact with person with infections TB, regardless of screening test result

        • Preferred: isoniazid 300 mg daily or 900 mg twice weekly + pyridoxine 50 mg daily x 9 months

        • Alternative: rifampin 600 mg daily x 4 months

        • Alternative: rifabutin (dose based on concomitant ART) x 4 months

    • Disseminated Mycobacterium avium complex (MAC)

      • Indications: CD4 less than 50 (with no active MAC infection), but IAS-USA guidelines do not recommend MAC prophylaxis if ART to be started immediately

      • Preferred: azithromycin 1200 mg once weekly or 600 mg twice weekly

      • Preferred: clarithromycin 500 mg twice daily (more drug interactions with ART)

      • Alternative: rifabutin 300 mg daily (with adjustment based on concomitant ART); avoid if active TB suspected

  • Vaccinations (greater likelihood of immune response with higher CD4 count and undetectable viral load; vaccines may sometimes be deferred until CD4 greater than 200 on ART, or repeated after response to ART)

    • Streptococcus pneumoniae (pneumococcus)

      • Indications: All HIV+ patients

      • Pneumococcal vaccine-naïve persons. One dose of 13-valent pneumococcal vaccine (PCV13, Prevnar 13) followed by a dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23, Pneumovax) at least 8 weeks later and second dose of PPSV23 5 years later.

      • Previous vaccination with PPSV23: One dose of PCV13 ≥1 year after last PPSV23 dose. If second dose of PPSV23 required, should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23.

    • Influenza A and B virus

      • Indications: All HIV+ patients

      • Dose: Inactivated influenza vaccine 0.5 mL IM annually

    • Hepatitis A virus (HAV)

      • Indications: Non-immune patients with chronic liver disease, injection drug users, men who have sex with men, travelers to endemic areas (or consider in all non-immune patients); consider deferral of vaccination until CD4 greater than 200

      • Dose: HAV vaccine 1 mL IM 2 doses (at 0 and 6-12 months); revaccinate non-responders (HAV IgG-negative), or as component of combined HAV/HBV vaccine

    • Hepatitis B virus (HBV)

      • Indication: All non-immune patients without active HBV infection; vaccinate patients with isolated HBcAb if HBV DNA negative

      • Dose: HBV vaccine IM at 0, 1, and 6 months (or as component of combined HAV/HBV vaccine); revaccinate those with negative HBsAb after vaccination

    • Varicella zoster virus (VZV)

      • Indication: Patients without prior varicella or VZV who are seronegative for VZV IgG and have CD4 greater than 200

      • Dose: Primary varicella vaccine (Varivax) 0.5 mL SQ at 0 and 3 months (then wait at least 5 months before varicella vaccination)

      • Post-exposure prevention:

        • Non-immune patients would receive varicella zoster immune globulin (VariZIG) 125 IU/10kg (max 625 IU) IM as soon as possible and within 10 days of exposure.

        • Alternative: acyclovir 800 mg 5 times daily for 5-7 days

        • Alternative: valacyclovir 1 gm TID for 5-7 days

    • Human papilloma virus (HPV)

      • Indications: Men and women 13-26 years of age

      • Dose in females: HPV quadrivalent or bivalent vaccine 0.5 mL IM at 0, 1-2 and 6 months

      • Dose in males: HPV quadrivalent vaccine 0.5 mL IM at 0, 1-2, and 6 months

    • Travel vaccines

      • Avoid yellow fever vaccine in patients with low CD4 counts

      • Use inactivated typhoid vaccine

      • No indication for use of cholera vaccine, which is ineffective

      • Consult travel medicine specialist

What complications could arise as a consequence of HIV infection?

Loss of cell-mediated immunity results in opportunistic conditions, including but not limited to:

  • Malignancies: non-Hodgkins lymphoma, Kaposi's sarcoma, primary CNS lymphoma

  • Viral Infections: cytomegalovirus, Epstein-Barr virus, herpes simplex virus, herpes zoster virus

  • Bacterial Infections: tuberculosis, infection with Mycobacterium avium complex and other non-tuberculous bacteria, nocardiosis, listeriosis

  • Fungal Infections: Pneumocystis pneumonia, cryptococcal meningitis, histoplasmosis, coccidioidomycosis, dermatophytic infections, penicilliosis

  • Parasitic infections: toxoplasmosis, leishmaniasis, cryptosporidiosis, microsporidiosis, isosporiasis

Other conditions associated with HIV infection include:

  • Hematologic: thrombocytopenia, anemia, leukopenia, thrombotic thrombocytopenic purpura (TTP), hypercoagulable states

  • Cardiac: cardiomyopathy, pulmonary hypertension

  • Neurologic: HIV-associated dementia and less severe cognitive dysfunction, peripheral sensory neuropathy, autonomic neuropathy

  • Gastrointestinal: HIV enteropathy, cholangiopathy, wasting (chronic diarrhea with weight loss)

  • Renal: HIV-associated nephropathy

  • Endocrine: hypogonadism, adrenal insufficiency, aldosterone deficiency

  • Musculoskeletal: osteopenia/osteoporosis, osteonecrosis with avascular necrosis

  • Dermatologic: psoriasis, seborrheic dermatitis, folliculitis, prurigo nodularis

  • Psychiatric: depression, mania

In addition to causing disease resulting from decreased cell-mediated immunity, HIV infection increases levels of inflammation and immune activation. This may result in potential long-term complications that include increased risk of coronary heart disease, cerebrovascular disease, liver disease, decreased bone density, and non-AIDS defining malignancies.

What should you tell the patient about his/her prognosis?

  • The prognosis of HIV infection is excellent in adherent patients without significant comorbid conditions.

  • Some modeling studies have estimated that life expectancy is the same as that of the general population in patients who achieve and maintain virologic suppression with good CD4 response to ART (e.g., CD4 > 500).

  • Negative prognostic factors: HCV co-infection, non-adherence, substance abuse, mental illness, delayed initiation of ART (at low CD4 count), poor CD4 response to ART, prolonged or high viremia before initiating ART

  • HIV infection is associated with elevated levels of immune activation and inflammation, which may have long-term consequences independent of CD4 count. These may include increased risk of coronary heart disease, malignancies, cognitive dysfunction, decreased bone density and fractures, and liver disease. Early initiation of ART lowers inflammation and immune activation and presumably decreases the risk of these complications, but possibly not to the same levels as in HIV-negative individuals.

How do you contract HIV infection and how frequent is this disease?

Epidemiology

  • United States

    • There are approximately 50,000 new cases of HIV infection each year. Approximately 1.1 million people were living with HIV infection by the end of 2010, 16% of whom do not know they are infected.

    • As of 2010, 63% of new cases were men who have sex with men, 25% were acquired through heterosexual contact, and 8% through injection drug use (IDU).

  • Global

    • It is estimated that there are 35 million people living with HIV worldwide, including 3.3 million children.

    • An estimated 2.3 million new infections occurred in 2012. Ninety-five percent of new infections occur in low- and middle-income countries, especially in sub-Saharan Africa.

    • There were 1.6 million AIDS deaths in 2012, and it is estimated that 36 million people have died since the beginning of the AIDS epidemic.

HIV infection is transmitted from person-to-person.

What pathogens are responsible for this disease?

  • HIV-1 is the most common cause of HIV/AIDS worldwide and in the United States. It is a lentivirus (member of retrovirus family) that infects human CD4 cells, macrophages, dendritic cells, and other human cells, establishing both latent and productive infection.

  • HIV-2 causes similar manifestations as HIV-1, but with slower progression and lower severity. It is seen primarily in West Africa or in people with West African exposures.

How do these pathogens cause HIV infection?

HIV infects CD4+ T-cells (helper T-cells), macrophages, dendritic cells, and other human cells. Patients with untreated HIV infection develop cellular immunodeficiency as a result of loss of CD4 cells, a result of direct viral killing of infected cells, increased rates of apoptosis in infected cells, and killing of infected CD4 cells by CD8 cytotoxic lymphocytes. Some long-term complications of HIV infection appear to be associated with elevated levels of inflammation and immune activation, which are reduced but not to normal levels by ART.

When should this disease be tested for?

  • Routine, voluntary HIV testing is recommended by the CDC for all patients 13-64 years of age and by the USPSTF for all patients 15-65 years of age, regardless of perceived risk or health status.

  • HIV testing should be performed in patients with symptoms suggestive of immunosuppression, including unexplained weight loss, chronic diarrhea, fever, chills, sweats, dysphagia or odynophagia, oropharyngeal candidiasis (thrush), and more severe or frequent vaginal candidiasis.

  • HIV testing should always be performed in patients with a history of tuberculosis, shingles, sexually transmitted infections, lymphoma, thrombocytopenia, hepatitis B, or hepatitis C, as well as in patients with AIDS-defining opportunistic infections or malignancies.

  • Consider testing for primary HIV infection (acute retroviral syndrome) with HIV serology and viral load in patients presenting with an unexplained mononucleosis-like illness, aseptic meningitis, Guillain-Barre syndrome, mononeuritis multiplex, or facial nerve palsy.

What other additional laboratory studies may be ordered?

  • HIV RNA (viral load) to confirm infection (repeat HIV serology if undetectable), to help determine need for ART, to help determine rate of progression

  • CD4 cell count to determine stage of disease, urgency of ART, and need for opportunistic infection prophylaxis

  • HIV genotype to determine whether patient was infected with a drug-resistant strain

  • Comprehensive chemistry panel to assess baseline renal and liver function, nutritional status

  • Fasting lipid panel to diagnose hyperlipidemia and assess baseline lipid status before starting ART

  • Fasting glucose to diagnose diabetes or insulin resistance

  • Hepatitis B serologies (HBsAb and HBcAb) to determine immunity and need for vaccination; HBsAg to diagnose active HBV infection; HBV DNA if HBsAg positive or in patients with isolated HBcAb+

  • HAV antibody (total or IgG) to determine HAV immunity and need for vaccination

  • HCV antibody to diagnose chronic HCV infection; confirm positive tests with HCV RNA; order HCV RNA in seronegative patients with unexplained transaminase elevation or risk for HCV (e.g., injection drug use)

  • Syphilis serology to diagnosed syphilis or follow previously treated syphilis

  • Testing for gonorrhea and Chlamydia: urine probes in all patients; anal and/or pharyngeal swabs in patients with history of receptive anal and/or oral sex

  • Cervical Pap smears in all women; repeat in 6 months; assess abnormal cytology with colposcopy

  • Anal Pap smears are recommended by HIVMA/IDSA HIV primary care guidelines in MSM or women with a history of anal sex; assess abnormal cytology with high resolution anoscopy

  • Toxoplasma IgG: If positive, give anti- Toxoplasma prophylaxis if CD4 is less than 100; if negative, counsel on prevention of infection (proper cooking of meat, avoidance of exposure to cat feces)

  • CMV IgG: Order in patients at low risk for CMV infection (assume latent infection in MSM and IDUs). If negative, counsel on prevention of infection (safe sex) and use CMV-negative blood products for transfusion

  • Glucose-6-phosphate dehydrogenase (G6PD) level: consider in patients at genetic risk (African or Mediterranean descent) to prevent use of oxidant drugs (e.g., sulfonamides, dapsone, primaquine) in deficient patients

  • HLA B*5701 assay if use of abacavir being considered

  • HIV tropism assay if use of maraviroc being considered

  • Testosterone level, free and total (AM) to diagnose hypogonadism in men with weight loss, depression, loss of libido, or erectile dysfunction

  • Cryptococcal antigen (serum) to diagnose cryptococcosis in patients with CD4 less than 100 who have fever, headache, or neurologic symptoms; sometimes recommended in all asymptomatic patients with CD4<100 to rule out subclinical cryptococcosis

  • Blood cultures for AFB to diagnose disseminated MAC in febrile patients with CD4 < 50; sometimes recommended in all asymptomatic patients with CD4 <50

How can HIV infection be prevented?

  • Behavioral methods: abstinence, monogamy, condom use, avoidance of higher risk sexual activities (e.g., insertive intercourse by HIV+ partner), use of clean needles and syringes for injection drug use

  • Biomedical methods:

    • ART for HIV+ partner is probably most effective form of prevention if viral load suppressed.

    • Circumcision shown to decrease transmission to heterosexual African men.

    • Pre-exposure prophylaxis (PrEP): daily use of TDF/FTC by HIV-negative individuals reduces transmission when taken regularly.

    • Microbicides: vaginal tenofovir gel shown to reduce transmission in women when used before and after intercourse. It is not yet commercially available. Rectal microbicides are also being studied.

    • Post-exposure prophylaxis (PEP): The benefit is demonstrated for occupational exposure, and it is assumed effective after sexual exposure if administered quickly.

WHAT'S THE EVIDENCE for specific management and treatment recommendations?

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