Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

HIV-associated conditions

Last updated: September 24, 2021

Summarytoggle arrow icon

As HIV infection progresses, immune function declines. Patients become increasingly vulnerable to opportunistic infections and certain malignancies. Some of these conditions are typically seen when CD4 counts are less than 200 cells/μL and are known as AIDS-defining conditions. With early detection of HIV infection and widespread use of antiretroviral therapy (ART), many of these conditions have become less common and treatable. Patients with HIV are now more likely to develop non-HIV-associated conditions or complications of starting ART such as immune reconstitution inflammatory syndrome (IRIS), hepatotoxicity, or nephrotoxicity. However, even patients with well-controlled HIV remain at increased risk of some communicable and noncommunicable diseases, and the presentation of these conditions may be atypical. This article provides a system-based overview of HIV-associated conditions and their management.

See also “Kaposi sarcoma,” “Progressive multifocal leukoencephalopathy,” “Bacillary angiomatosis,” and “Mycobacterium avium complex infections.”

Overview [1]

AIDS-defining conditions [1][3]
CD4 count (in cells/μL) Conditions
Variable
< 250
< 200
< 150
< 100
< 50

Some AIDS-defining conditions are opportunistic infections, but the terms are not interchangeable!

Management [3]

Adequate HIV treatment (ART) is key to minimizing the risk of opportunistic infections.

The most common causes of focal neurological deficits in patients with advanced HIV or AIDS are cerebral toxoplasmosis, primary CNS lymphoma, and progressive multifocal leukoencephalopathy. [3]

Overview

Differential diagnosis of CNS lesions in HIV-positive patients with CD4 count < 200
Condition Description Clinical features Diagnostics Treatment
Cerebral toxoplasmosis [3][12]

Primary CNS lymphoma (PCNSL) [14][15]

Cerebral abscess (bacterial) [17][18][19][20]

Progressive multifocal leukoencephalopathy (PML) [3][22]

  • Rapidly progressive focal-neurologic deficits (e.g., visual field defects, hemiparesis)
  • Cognitive impairment
  • Impaired vigilance
  • ART (if not already started)
  • Supportive therapy

Cryptococcal meningitis [3]

HIV-associated neurocognitive disorder (HAND)

HAND is typically a diagnosis of exclusion.

Avoid efavirenz in patients with suspected or confirmed HIV-associated neurocognitive disorder as it may worsen cognitive impairment.

Other [18][28]

General principles [3][28]

Patients with HIV can present with neurologic problems at any stage of infection.

Diagnostics

The following is applicable to patients with suspected opportunistic infections or AIDS-related CNS tumors. [3]

Management

Avoid administering corticosteroids before diagnostic confirmation, as corticosteroids alter neuroimaging and biopsy findings and may delay a diagnosis of PCNSL. [15]

Ocular complications in HIV are important to recognize because of the potential risk of vision loss. Consult ophthalmology in all patients with HIV who have ocular symptoms or abnormal findings on examination.

Differential diagnosis of ophthalmologic presentations in HIV-positive patients
Clinical presentation Painless Painful
Vision loss
No vision loss
Ophthalmologic complications of HIV [33][34]
CD4 count (in cells/μL) Condition Clinical features Treatment
Variable HIV retinopathy [35]
  • Typically resolves spontaneously without progression
Herpes simplex keratitis [36]

Herpes zoster ophthalmicus

[3][37][38]

Varicella-zoster retinitis (acute retinal necrosis and progressive outer retinal necrosis. [3][37][40]
< 100 Toxoplasmosis retinochoroiditis [41][42][43]
  • Visual impairment, floaters
  • Pain (can also be painless)
  • Fundoscopy findings [44]
    • Raised yellow-white fluffy cotton lesions on the retina
    • Severe vitritis may cause an overlying "headlight in the fog” appearance while trying to look at the lesions.
< 50 Cytomegalovirus retinitis [3][45]
  • Urgent ophthalmology consult.
  • Treatment depends on severity and location of lesions, level of immunosuppression, and individual factors (e.g., medication adherence). [3]
    • Oral antiviral therapy with valganciclovir is indicated for all patients.
    • In addition, intravitreal antiviral therapy (e.g., ganciclovir, foscarnet) is required for sight-threatening lesions.
    • Continue treatment for 3–6 months, until ART has restored immune function.
  • In patients who are not on ART, consider delaying the initiation of ART for 2 weeks.

General principles

  • Cardiovascular abnormalities in patients with HIV include:
  • The clinical presentation of and diagnostic approach to cardiovascular conditions are the same as in patients without HIV.

HIV-associated atherosclerotic cardiovascular disease (ASCVD) [46][47]

People living with HIV are at an increased risk of ASCVD compared to uninfected individuals. [46]

HIV-associated cardiomyopathy [49]

Miscellaneous [48][50]

Reactivation tuberculosis [3]

Diagnosing TB in patients with HIV [3]
Indications for testing Recommended studies
Latent TB infection (LTBI)
  • All patients at the time of HIV diagnosis
  • Yearly for patients with ongoing exposure to risk factors for TB
  • Negative test for LTBI in patients with CD4 count < 200 at the time of testing: Repeat testing after initiation of ART and when CD4 count is > 200.
  • IGRA (preferred)
  • TST may be used: TST ≥ 5 mm is positive in patients with HIV.
Active TB disease
  • Symptoms suggestive of active TB
  • Asymptomatic patients with a positive test for LTBI

All patients should be screened for latent TB at the time of HIV diagnosis and at regular intervals thereafter based on individual risk factors.

In asymptomatic patients with a positive IGRA or TST, a normal chest x-ray is sufficient to rule out active TB in nonendemic areas like the US. [3]

In patients with advanced HIV, start immediate empiric treatment if suspicion for TB is high!

Pneumocystis jirovecii pneumonia (PCP) [3]

Pneumocystis jirovecii is a ubiquitous fungus that can cause pneumonia in patients with AIDS, especially those with CD4 counts < 200. The incidence has declined since the introduction of ART and the use of prophylaxis.

Community-acquired pneumonia [3]

Miscellaneous

General principles

Dyspepsia, dysphagia, and odynophagia [58][59]

Inadequate response to empiric treatment should prompt further evaluation for other causes (e.g., HSV esophagitis).

Diarrhea [59]

Diarrhea is the most common GI complaint in patients with HIV and may occur at any CD4 count.

CMV colitis manifests as abdominal pain, bloody diarrhea. CMV esophagitis can manifest as odynophagia. Linear ulcers on endoscopy and intracellular inclusions (“owl's eye” appearance on histology are characteristic diagnostic findings of CMV infection. [63]

HIV wasting syndrome [64][65]

Protozoal infections

Cystoisosporiasis (isosporiasis) [3]

Cryptosporidiosis [3]

AIDS cholangiopathy [66]

Miscellaneous [67]

HIV-associated nephropathy [70][71]

Miscellaneous [71][74][75]

Anemia [77]

HIV-associated thrombocytopenia [77]

Unexplained thrombocytopenia may be the first manifestation of HIV and should prompt screening! [78]

Neutropenia [77]

Miscellaneous [77]

Overview [79]

Patients with HIV also develop incidental cancers (e.g., bowel, breast); encourage patients to attend all age-appropriate screening!

Early diagnosis and treatment of HIV with ART is the most important step in preventing HIV-associated malignancies.

AIDS-defining malignancies[1][79]

Include cancers that are associated with profound immunosuppression and are categorized as AIDS-defining illnesses

Non-AIDS-defining malignancies [79]

Include cancers that are found at higher rates among individuals with HIV but which are not classified as AIDS-defining conditions

Castleman disease [82]

A rare lymphoproliferative disorder that may affect one (unicentric) or multiple lymph nodes (multicentric).

Rituximab can exacerbate Kaposi sarcoma.

Primary effusion lymphoma (PEL) [3][83]

PEL is a rare subtype of non-Hodgkin B-cell lymphoma most commonly seen in HIV-positive patients coinfected with HHV-8. Patients are also frequently coinfected with EBV.

Differential diagnosis [85]

Acute HIV infection can manifest with myalgias, arthralgias, and symmetrical viral polyarthritis.

HIV-specific rheumatological conditions [85]

HIV-specific rheumatological presentations [85][86]
Clinical features Diagnosis Management

HIV-associated arthritis

Painful articular syndrome [87]

  • Primarily a clinical diagnosis
  • Analgesics
  • Reassurance
  • Symptoms typically resolve within 2–24 hours.

Diffuse infiltrative lymphocytosis syndrome

  • ART-naive patients: Initiate ART.
  • Persistent symptoms on ART: Consider steroids or DMARDs in consultation with specialists.
Rheumatological manifestations of IRIS
  • Paradoxical worsening of preexisting autoimmune conditions after starting ART
  • Can occur days to months after starting treatment
  • Clinical diagnosis; further workup typically not required
  • Continue ART; the condition is typically self-limiting.
  • Treat associated autoimmune disease symptoms as for HIV-negative patients.

Impact of HIV and ART on other rheumatological disorders [85][86][87]

Impact of HIV and ART on rheumatological and musculoskeletal disorders
Systemic lupus erythematosus [86]
  • Low CD4 counts may improve the disease activity of lupus or induce remission.
  • Initiation of ART may worsen symptoms due to IRIS.
Rheumatoid arthritis (RA) [86]
  • Low CD4 counts may improve the disease activity of RA or induce remission.
  • Initiation of ART may worsen symptoms when CD4 count > 200 with a controlled viral load
Psoriatic arthritis [87]
  • Severe and rapidly progressive skin lesions and erosive and deforming arthropathy (especially at low CD4 counts)
  • May be refractory to treatment.
Reactive arthritis [87]
  • Higher prevalence in HIV-positive patients
  • Typically manifests with seronegative oligoarthritis affecting peripheral joints of the lower extremities
  • Frequently accompanied by enthesitis and mucocutaneous and skin involvement
Osteoporosis [85]
Avascular necrosis [86]
  • More common in HIV-positive individuals

Management [85][86]

All HIV patients on immunosuppressive or immunomodulatory therapy like DMARD or glucocorticoids are at a high risk of developing opportunistic infections and should always receive prophylactic treatment (see “Primary prevention of opportunistic infections in HIV”)!

Overview [88]

Dematological complications in patients who are HIV-positive are extremely common and may be infectious, inflammatory, neoplastic, or related to HIV treatment. These conditions may be atypical, severe, and refractory in patients with HIV.

Mucosal and mucocutaneous manifestations

Mucosal and mucocutaneous complications in HIV infection [3][88][89]
Condition Clinical features Diagnostics Treatment

Kaposi sarcoma

[3][90][91]

Bacillary angiomatosis [3]

Oral hairy leukoplakia
Mucocutaneous candidiasis [3]
  • Clinical diagnosis
  • Can be confirmed via microscopic examination of scrapings/biopsy
Herpes simplex infections [3][89]

Human papilloma virus [3][89]

  • Typically clinical
  • Consider biopsy of the lesion in the following situations:
    • Uncertain clinical diagnosis
    • Inadequate response to empirical therapy
    • Features concerning for malignant transformation

Syphilis [3][88][92]

  • HIV-positive patients may present with multiple chancres or a combination of primary and secondary syphilis.
  • Neurological manifestations occur earlier.
  • Syphilis is associated with a higher risk of HIV transmission and acquisition.
Recurrent aphthous ulcers [93]
  • Solitary or multiple painful ulcers on the buccal mucosa
  • Ulcers are round, well-circumscribed, tender, and have an erythematous halo.
  • Occur more often, are more painful, and last for a longer period of time in patients with HIV
  • Clinical diagnosis
  • Consider biopsy for large recurrent ulcers (1–2 cm in diameter) or nonhealing ulcers to rule out other causes (e.g., malignancy, infection).

Kaposi sarcoma lesions resemble those of bacillary angiomatosis and histology is required to differentiate between the conditions.

Cutaneous manifestations

Cutaneous complications in HIV infection
Condition Clinical features Diagnosis Treatment

Varicella-zoster virus [3][89]

  • Clinical diagnosis
  • Atypical presentation: Tzanck smear and viral culture of vesicular fluid, direct fluorescent antigen testing, or PCR
Molluscum contagiosum [89][94]
  • Pearly papular rash with central umbilication
  • Infection is typically severe and prolonged with large lesions (> 10 mm).
  • The face and upper trunk are more commonly affected.
Scabies [88][89][95]
  • Microscopic examination of skin scraping: mites, eggs, or feces visible
  • Mild to moderate disease: treatment same as for immunocompetent patients with permethrin cream or a single dose of ivermectin
  • Severe or crusted scabies: ivermectin or repeated permethrin until clinical signs of infection have resolved
  • Decontamination of clothing, bedding, and towels
  • Treatment of household and close contacts is recommended.

Seborrheic dermatitis [89]

Psoriasis [96]
Eosinophilic folliculitis [89][97]

Miscellaneous [89]

This section provides a brief overview of the management of common systemic fungal infections in patients with HIV. See “Systemic fungal infections” and “Yeasts” for further information on diagnostics and clinical features.

Overview of systemic fungal infections in patients with HIV [3]
Condition CD4 count (in cells/μL) Clinical and diagnostic features Management
Coccidioidomycosis
  • < 250
Histoplasmosis
  • < 150

Candidiasis

  • < 100