History and exam
Key diagnostic factors
common
no antiretroviral treatment (ART) or failure of ART
Patients who are not receiving suppressive ART are more likely to develop opportunistic infections.[52]
fever
In people living with HIV (PLWH) with fever of undetermined cause, diagnostic studies for extrapulmonary tuberculosis should be considered.[144]
In the US, disseminated Mycobacterium avium complex is the leading cause of HIV-associated fever of unknown origin and usually presents with fever, night sweats, weight loss, anaemia, and elevated serum levels of alkaline phosphatase.[145][146]
In patients with Pneumocystis jirovecii pneumonia, fever is usually accompanied by dry cough and dyspnoea.[147]
Cytomegalovirus accounts for approximately 5% to 11% of cases of prolonged, undifferentiated fever in PLWH.[145][148]
Toxoplasmic encephalitis can present with fever that is usually accompanied by headache and altered mental status.[149]
headache and altered mental status
In cryptococcal chronic or sub-acute meningoencephalitis, these symptoms may be present for several weeks and can be accompanied by fever and malaise.[150]
Tuberculous meningitis may present with fever, lassitude, weight loss, behaviour changes, headache, and vomiting. A delay in diagnosis may lead to neurological deficits, loss of consciousness, or convulsions.[151]
In toxoplasmosis, focal encephalitis with headache and confusion is common.[149][150]
Cytomegalovirus encephalitis may also present with confusion and focal neurological abnormalities.[152]
dyspnoea or cough
Mainly suggestive of tuberculosis or Pneumocystis jirovecii pneumonia (PCP) infection, particularly if exertional.
Less commonly, toxoplasmosis may cause pneumonitis, which can be difficult to distinguish from PCP.[110]
abdominal pain, diarrhoea, weight loss
Weight loss and diarrhoea are common symptoms of disseminated Mycobacterium avium complex and may precede the onset of fever.[146]
In cytomegalovirus disease, diarrhoea is the most common gastrointestinal tissue-invasive symptom.[122] Cholangitis and gastritis are less common manifestations.
Diarrhoea in a patient with AIDS may also be due to parasitic infections caused by organisms such as cryptosporidia, microsporidia, and cystoisosporiasis.
dysphagia
Oropharyngeal candidiasis (OPC) may present with burning pain, altered taste sensation, and difficulty swallowing liquids and solids.
Oesophageal candidiasis usually causes is dysphagia and odynophagia, yet 40% of patients may be asymptomatic. Oesophageal disease can present without concomitant OPC.
lymphadenopathy
Focal lymphadenopathy and/or lymphadenitis due to Mycobacterium avium complex can be seen shortly after the initiation of antiretroviral treatment as a result of restoration of immune function (immune reconstitution inflammatory syndrome).
Cervical, intra-abdominal, and mediastinal lymph nodes are most commonly involved.[153]
Lymphadenopathy in patients with AIDS may also be due to tuberculosis, Bartonella henselae, and various endemic mycoses, such as coccidioidomycosis and histoplasmosis.
visual floaters, eye pain, and blindness
Cytomegalovirus (CMV) chorioretinitis is the most common manifestation of CMV disease in people living with HIV and generally causes visual floaters and visual impairment.[154]
Toxoplasmic chorioretinitis typically presents with eye pain and impaired visual acuity.[155]
Visual loss can also occur as a results of cryptococcal meningitis.[156]
Endophthalmitis is rarely caused by disseminated Mycobacterium avium complex.[94]
ocular haemorrhage
Ocular hemorrhages are associated with CMV retinitis and with advanced toxoplasmic chorioretinitis.[157]
mucosal changes
White plaques on the buccal mucosa, gums, or tongue are typical of oral pseudomembranous candidiasis (thrush). Acute atrophic candidiasis (erythematous mucosa) or chronic hyperplastic candidiasis (leukoplakia) are less common.[138]
Vaginal erythema with adherent white discharge, marked itching, watery to curd-like discharge, dyspareunia, and swelling of labia and vulva with discrete pustulopapular peripheral lesions are seen in vaginal candidiasis.
Disseminated Mycobacterium avium complex rarely results in palatal and gingival ulceration.[92]
Other diagnostic factors
common
hepatosplenomegaly
Suggestive of disseminated Mycobacterium avium complex.
exercise-induced oxygen desaturation
Oxygen desaturation occurring with exercise is highly suggestive of Pneumocystis jirovecii pneumonia.[158]
uncommon
blurred vision and photophobia
papilloedema
In cryptococcal meningitis, papilloedema may be present on fundoscopic examination.[150]
meningismus, focal neurological findings
In cryptococcal meningitis, signs are often absent but may include depressed level of consciousness, cranial nerve palsies, and other focal neurological findings.
Manifestations of toxoplasmic encephalitis include seizures, cranial nerve abnormalities, visual field defects, sensory disturbances, cerebellar dysfunction, meningismus, movement disorders, and neuropsychiatric disturbance.[149]
pain and weakness
May indicate the presence of toxoplasmic encephalitis, or cytomegalovirus polyradiculopathy.[123]
bone or joint pain
Unusual presentation of disseminated Mycobacterium avium complex.[93]
skin lesions
Erythema nodosum (painful raised erythematous nodules over pre-tibial region) is an uncommon manifestation of tuberculosis.[161][162]
Papular umbilicated skin lesions may rarely be seen in disseminated Cryptococcus infection.[163]
Erythema nodosum and erythema multiforme are relatively manifestations of coccidioidomycosis.[164]
Risk factors
strong
post-HIV seroconversion with any CD4 count
Tuberculosis (TB) can occur after HIV seroconversion and throughout the course of HIV disease, including after antiretroviral treatment initiation. TB incidence doubles in the first year after HIV seroconversion.[41][42] The annual risk of reactivation of latent TB is 3% to 16% per year for people with untreated HIV infection, which is approximately the lifetime risk of reactivation in those without HIV infection.[1]
TB risk further increases as CD4 count decreases.[43]
CD4 count below 250 cells/microlitre
Individuals with a CD4 count less than 250 cells/microlitre living in or visiting areas in which Coccidioides species are endemic are at increased risk for coccidioidomycosis.[40]
CD4 count below 200 cells/microlitre
Patients with a CD4 count less than 200 cells/microlitre are at increased risk for Pneumocystis jirovecii pneumonia (PCP) infection or candidiasis. The development of thrush or fever significantly and independently increases the risk of PCP in these patients.[44]
CD4 count below 100 cells/microlitre
Toxoplasmic encephalitis usually occurs in people living with HIV (PLWH) with CD4 counts below 100 cells/microlitre (particularly when CD4 counts are below 50 cells/microlitre), and it is almost always caused by reactivation of a chronic infection.[45] Seroprevalence ranges geographically, from approximately 10% among PLWH in the US to 50% to 80% among PLWH who live in certain countries in Europe, Latin America, and Africa.[46][47][48]
CD4 count below 50 cells/microlitre
More than three-quarters of cryptococcal infections associated with AIDS develop when the CD4 count falls below 50 cells/microlitre.[49] The incidence is higher among patients with AIDS in Africa and South-east Asia than in the US; it appears less frequently in Europe than in the US.[50]
Patients with AIDS who have a CD4 count below 50 cells/microlitre are at highest risk of developing organ-invasive cytomegalovirus disease.
The risk of developing disseminated Mycobacterium avium complex infection inversely correlates with absolute CD4 count values.[51]
no antiretroviral treatment (ART) or failure of ART
All opportunistic infections are more likely in patients not receiving ART; in the period after initiating ART, resulting from an inflammatory immune response that was previously absent; or in patients in whom ART fails because of viral resistance.[52]
men who have sex with men (MSM)
Cytomegalovirus is common among nearly all populations around the world, and it is generally acquired during childhood, although sexual activity is an important mode of transmission, and higher rates of infection have been noted to be higher among MSM living with HIV compared with MSM without HIV (98% vs. 80%).[53]
black or Hispanic race
intravenous drug use
social factors (poverty, over-crowding, homelessness, poor nutrition)
dust inhalation in areas endemic for Coccidioides
Coccidioidomycosis is acquired when airborne fungal arthroconidia are inhaled; therefore, occupational (e.g., construction, digging) or recreational activities that increase the likelihood of dust inhalation in endemic areas also increase the likelihood of infection.
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