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HIV Infection and AIDS

Practice Essentials

Human immunodeficiency virus (HIV) is a blood-borne virus typically transmitted via sexual intercourse, shared intravenous drug paraphernalia, and mother-to-child transmission (MTCT), which can occur during the birth process or during breastfeeding. HIV disease is caused by infection with HIV-1 or HIV-2, which are retroviruses in the Retroviridae family, Lentivirus genus. See the image below.

Electron microscopy of human immunodeficiency viru

Electron microscopy of human immunodeficiency virus (HIV)–1 virions. Courtesy of CDC (Dr Edwin P Ewing, Jr).

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Signs and symptoms

The patient with HIV may present with signs and symptoms of any of the stages of HIV infection. No physical findings are specific to HIV infection; the physical findings are those of the presenting infection or illness. Manifestations include the following:

Acute seroconversion manifests as a flulike illness, consisting of fever, malaise, and a generalized rash

The asymptomatic phase is generally benign

Generalized lymphadenopathy is common and may be a presenting symptom

AIDS manifests as recurrent, severe, and occasionally life-threatening infections or opportunistic malignancies

HIV infection can cause some sequelae, including AIDS-associated dementia/encephalopathy and HIV wasting syndrome (chronic diarrhea and weight loss with no identifiable cause)

The history should address risk factors for possible exposure to HIV, including the following:

Unprotected sexual intercourse, especially receptive anal intercourse

A large number of sexual partners

Previous or current sexually transmitted diseases (STDs)

Sharing of intravenous (IV) drug paraphernalia

Receipt of blood products (before 1985 in the United States)

Mucosal contact with infected blood or needle-stick injuries

Maternal HIV infection (for newborns, infants, and children)

See Clinical Presentation for more detail.

Diagnosis

HIV screening recommendations include the following:

The US Preventive Services Task Force (USPSTF) recommends that clinicians screen for HIV in all adolescents and adults at increased risk for HIV infection, and all pregnant women

The Centers for Disease Control and Prevention (CDC) recommends opt-out HIV screening for patients in all health-care settings; persons at high risk for HIV infection should be screened at least annually

The American College of Physicians (ACP) recommends that clinicians adopt routine screening for HIV and encourage all patients to be tested

Current CDC guidelines recommend testing for HIV infection with a US Food and Drug Administration (FDA)–approved antigen/antibody immunoassay that detects HIV-1 and HIV-2 antibodies and the HIV-1 p24 antigen, with supplemental testing following a reactive assay result to differentiate between HIV-1 and HIV-2 antibodies. If supplemental testing for HIV-1/HIV-2 antibodies shows nonreactive or indeterminant results (or if acute HIV infection or recent exposure is suspected or reported), an HIV-1 nucleic acid test is recommended to differentiate acute HIV-1 infection from a false-positive test result.

The World Health Organization (WHO) recommends an HIV testing strategy/algorithm whereby a combination of rapid diagnostic tests (RDTs) and/or enzyme immunoassays (EIAs) are used to achieve at least a 99% positive predictive value (ie, < 1 false-positive result per 100 people diagnosed with HIV infection).

The CD4 T-cell count reliably reflects the current risk of acquiring opportunistic infections, as follows:

Reference range, 500-2000 cells/μL

Because CD4 counts vary, serial counts are generally a better measure of significant changes

After seroconversion, CD4 counts tend to decrease (~700/μL) and continue to decline over time

For surveillance, a CD4 count below 200/μL is considered AIDS-defining in the United States

In children younger than 5 years, the CD4 T-cell percentage is considered more important than the absolute count (< 25% is considered to warrant therapy)

In adults with chronic hepatitis C and low absolute CD4 T-cells, the CD4 percentage may also be more useful

Viral load in peripheral blood is used as a surrogate marker of viral replication rate; however, quantitative viral-load assays should not be used as a diagnostic tool. Clinical relevance is as follows:

Rate of progression to AIDS and death is related to the viral load; patients with viral loads greater than 30,000/mL are 18.5 times more likely to die of AIDS than those with undetectable viral loads.

With therapy, viral loads can often be suppressed to an undetectable level (< 20-75 copies/mL; optimal viral suppression); complete inhibition of viral replication appears impossible and may be unnecessary

Successfully treated patients may demonstrate intermittent low-level viremia (eg, < 400 copies/mL), but this is not thought to represent viral replication or to predict virologic failure (defined as a confirmed viral load of > 200 copies/mL

In August 2013, the FDA approved Alere Determine HIV-1/2 Ag/Ab Combo test (Orgenics, Ltd) as the first rapid HIV test for the simultaneous detection of HIV-1 p24 antigen as well as antibodies to both HIV-1 and HIV-2 in human serum, plasma, and venous or fingerstick whole blood specimens.
The test does not distinguish between antibodies to HIV-1 and HIV-2, and is not intended to be used for screening of blood donors.

Baseline studies for other infections that are important in the initial workup of a patient with newly diagnosed HIV infection include the following:

Purified protein derivative (PPD) skin testing for tuberculosis

Cytomegalovirus (CMV) testing

Syphilis testing

Rapid amplification testing for gonococcal and chlamydial infection

Hepatitis A, B, and C serology

Anti-
Toxoplasma antibody

Ophthalmologic examination

The CDC classifies HIV infection into 3 categories, as follows
:

Category A: Asymptomatic HIV infection without a history of symptoms or AIDS-defining conditions

Category B: HIV infection with symptoms that are directly attributable to HIV infection (or a defect in T-cell–mediated immunity) or that are complicated by HIV infection

Category C: HIV infection with AIDS-defining opportunistic infections

These 3 categories are further subdivided on the basis of the CD4+ T-cell count, as follows:

> 500/µL: Categories A1, B1, C1

200-400/µL: Categories A2, B2, C2

< 200/µL: Categories A3, B3, C3

See Workup for more detail.

Management

Current Department of Health and Human Services (DHHS) guidelines on the timing of initiation of antiretroviral therapy are as follows:

Antiretroviral therapy (ART) is recommended in all persons with HIV infection to reduce morbidity and mortality and to prevent HIV transmission to others.

The Panel on Antiretroviral Guidance for Adults and Adolescents recommends initiating ART immediately (or as soon as possible) after diagnosis to increase the uptake of ART linkage to care and to hasten and improve the rate of viral suppression.

When initiating ART, it is important to educate patients regarding the benefits of ART and to deploy strategies to optimize care engagement and treatment adherence.

Initiating ART is particularly important in patients with AIDS-defining conditions, patients with acute or recent HIV infection, and pregnant patients. Delaying therapy in these subpopulations has been associated with high risks of morbidity and mortality and HIV transmission.

Durable viral suppression improves immune function and overall quality of life, lowers the risk of both AIDS-defining and non–AIDS-defining complications, and allows persons with HIV infection to live a lifespan approaching that of persons without HIV infection. Two large randomized controlled trials, ART-START and TEMPRANO, demonstrated reductions in morbidity and mortality among individuals with HIV infection who had CD4 T-lymphocyte (CD4) cell counts of greater than 500 cells/uL and who were randomized to receive ART immediately compared with individuals in whom ART initiation was delayed.

All persons with HIV infection should be informed that maintaining a plasma HIV RNA (viral load) of less than 200 copies/mL with ART prevents sexual transmission of HIV to their partners. Patients may recognize this concept as “Undetectable = Untransmittable (U=U).” For persons with HIV infection who intend to rely on treatment as prevention (TasP), providers should make an individual assessment of the person’s risk tolerance, personal health, history of maintaining viral suppression with treatment, and access to healthcare services and ART, as well as other factors that may affect their ability to maintain a high level of adherence to ART.

Highly active antiretroviral therapy (HAART) is the principal method for preventing immune deterioration. Classes of antiretroviral agents include the following:

Nucleoside reverse transcriptase inhibitors (NRTIs)

Protease inhibitors (PIs)

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Fusion inhibitors

CCR5 co-receptor antagonists (entry inhibitors)

HIV integrase strand transfer inhibitors

Entry inhibitors (CD4-directed post-attachment inhibitors)

Current DHHS guidelines list the below regimens as preferred in most treatment-naive patients.

INSTI-based regimens are as follows:

Bictegravir/tenofovir alafenamide/emtricitabine (single-tablet regimen)

Dolutegravir/abacavir/lamivudine (single-tablet regimen) – Only for patients who are HLA-B*5701–negative and without chronic hepatitis B virus (HBV) coinfection (In women of childbearing age, discuss the risks and benefits of prescribing dolutegravir around the time of conception, including the low risk of neural tube defects [NTDs] and the relative lack of information regarding the safety of using other commonly prescribed antiretrovirals [ARVs].)

Dolutegravir plus (emtricitabine or lamivudine) plus (tenofovir alafenamide or tenofovir disoproxil fumarate)

Raltegravir plus (emtricitabine or lamivudine) plus (tenofovir alafenamide or tenofovir disoproxil fumarate)

Dolutegravir plus lamivudine – Except in individuals with HIV RNA of more than 500,000 copies/mL, persons with HBV coinfection, or patients in whom ART is to be started before the results of HIV genotypic resistance for reverse transcriptase or HBV testing are available

The PI/r–based regimen is darunavir/ritonavir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine).

HIV-2 is intrinsically resistant to NNRTIs and enfuvirtide.

To address individual patient characteristics and needs, the Panel also provides a list of Recommended Initial Regimens in Certain Clinical Situations.

Regimen selection is individualized based on the following:

Virologic efficacy

Toxicity

Pill burden

Dosing frequency

Drug-drug interaction potential

Drug resistance testing results

Comorbid conditions

Pregnancy

In particular cases, prophylaxis is indicated for specific opportunistic infections, including the following:

Pneumocystis jiroveci

Toxoplasma

Mycobacterium avium complex

Fungal and viral infections: Although prophylaxis for these infections is not routinely necessary, some recommend fluconazole in patients with CD4
+ T-cell counts under 50/µL to protect against cryptococcosis and endemic fungal infections. Oral fluconazole is not recommended for routine primary prophylaxis against
Candida infection. Administration of ART and immune restoration are effective for preventing disease. Oral valganciclovir primary prophylaxis for CMV infection is not recommended in patients who will be receiving or are not receiving ART.

Additional treatment measures include the following:

Treatment of opportunistic infections (directed at the specific pathogen)

Treatment of
HIV lipodystrophy (tesamorelin)

Suppressive therapy for herpes simplex virus 2 (HSV-2) infection (acyclovir)

Treatment of HIV-associated diarrhea (crofelemer

)

The CDC has recommended HIV postexposure prophylaxis (PEP) and HIV pre-exposure prophylaxis (PrEP) regimens.

PEP drug regimens are as follows:

Preferred option 1: Dolutegravir plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (Truvada)

Preferred option 2: Raltegravir plus Truvada (TDF/FTC)

Alternative: Truvada (TDF/FTC ) plus darunavir (Prezista) plus ritonavir daily

PrEP drug regiments are as follows:

Preferred PrEP drug regimen: Truvada (TDF/FTC)

Alternative: Descovy (TAF/FTC)

See HIV Infection and AIDS Treatment & Management for more detail.

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