History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors for contracting HIV infection include HIV-infected blood transfusion, intravenous drug use, homo- and heterosexual unprotected sexual intercourse, and percutaneous needle prick injury.
fevers and night sweats
Unexplained fever and night sweats for more than 1 month (with no response to antibiotics) comprise a WHO stage 3 illness. These symptoms may indicate tuberculosis, which should be excluded. Malaria should be excluded in endemic areas.[89]
weight loss
Unexplained involuntary weight loss of less than 10% of body weight is a WHO stage 2 symptom. If more than 10% of body weight is lost or the BMI reduces to 18.5 this indicates more severe immunocompromise (WHO stage 3).[89] Loss of weight may result from malnutrition, tuberculosis, and HIV wasting syndrome.[89]
skin rashes and post-inflammatory scars
Rashes may occur throughout HIV and close attention should be paid to the skin. Rashes are the most common sign of WHO stage 2 disease: including herpes zoster (shingles), seborrhoeic dermatitis, pruritic papular eruptions, and fungal skin and nail infections (tinea corporis or unguium).[89]
oral ulcers, angular cheilitis, oral thrush, or oral hairy leukoplakia
The mouth should always be thoroughly examined. Both thrush and oral hairy leukoplakia indicate WHO stage 3 disease.
Recurrent painful oral aphthous ulcers indicate WHO stage 2, as does angular cheilitis (cracking at the corners of the mouth due to a fungal infection).[89][Figure caption and citation for the preceding image starts]: Oral candidiasis in a patient with HIVPublic Health Image Library (PHIL) [Citation ends].
diarrhoea
Unexplained diarrhoea of more than 1 month in duration (with no pathogen diagnosed) indicates WHO stage 3 disease.[89]
changes in mental status or neuropsychiatric function
Depression and anxiety are common in HIV-positive individuals. Screening for depression and anxiety using a validated screening tool is recommended.[91] Change in mental status or cognition could be due to organic disease in late-stage HIV (WHO stage 4). Toxoplasmosis and cryptococcal disease should be excluded. In the absence of another condition to explain a drop-off in cognition or motor function, HIV encephalopathy may be diagnosed.[89]
recent hospital admissions
Recent admission for management of an infectious disease including bacterial infections (such as pneumonia, meningitis, bone or joint infection, severe pelvic inflammatory disease, septicaemia), tuberculosis (TB), or fungal or viral infections should be elicited in the history.
Bacterial infections and pulmonary TB are WHO stage 3-defining illnesses. Recurrent bacterial pneumonia is indicative of WHO stage 4 disease, as is a diagnosis of other pneumonias such as Pneumocystis jirovecii pneumonia and extrapulmonary TB.
Fungal infections such as oesophageal candidiasis and cryptococcal meningitis are WHO stage 4 illnesses, as are viral infections such as cytomegalovirus retinitis.[4][89]
tuberculosis (TB)
The risk of TB increases with worsening immunosuppression. If a patient with HIV presents with symptoms of TB (e.g., cough, loss of weight, fever and night sweats) and/or a history of a TB contact, TB should be excluded by sending two sputum samples for smear and direct microscopy and/or culture and examining a CXR (for infiltrates, cavitation, or effusion). In severe immunosuppression, TB may be present without a positive sputum (smear-negative TB).[4][89]
medical comorbidities
Patients should be assessed for any other medical comorbidities that may impact on both disease progression and treatment decisions. For example, a patient with renal disease will require adjustment of antiretroviral doses. A patient with tuberculosis (TB) should have the TB treatment initiated as soon as possible, and those patients presenting with other opportunistic infections (OIs) should receive OI treatment along with antiretroviral therapy (ART). The timing of ART in the setting of OIs depends on the particular OI. Those with other chronic disease such as diabetes or heart disease will need to be managed in consultation with other specialty physicians. Consideration of drug interactions with ART and all other drugs should be given.
generalised lymphadenopathy
Painless enlarged nodes, in two or more non-contiguous sites of >1 cm for more than 3 months.[89]
genital sexually transmitted infections (STIs)
Chronic herpes infection - that is, progressive painful genital or anal ulceration for >1 month - is an AIDS-defining illness.[89] Other STIs associated with HIV include syphilis, chlamydia, and gonorrhoea.
chronic vaginal candidiasis
Occurs in WHO stage 3 disease.[89]
shingles
Occurs in WHO stage 2 disease.[89] Only an AIDS-defining illness if multidermatomal.
uncommon
wasting syndrome
Unexplained weight loss (>10% of body weight) or wasting together with either unexplained fever (lasting >1 month) or unexplained chronic diarrhoea (for >1 month) comprise HIV wasting syndrome, an AIDS-defining illness (WHO stage 4).[89]
headaches
Headaches may be indicative of central nervous system (CNS) disease. Headaches with focal CNS signs and symptoms may indicate toxoplasmosis (WHO stage 4). When accompanied by acute symptoms of meningism, headaches may indicate bacterial meningitis (WHO stage 3). Those with more low-grade chronic symptoms of meningism may indicate cryptococcal meningitis (WHO stage 4).[89] May also be associated with lymphoma.
However, most cases of HIV-associated meningitis will be associated with headache without neck stiffness and with or without fever.
Kaposi's sarcoma
Kaposi's sarcoma may present as a pink or violaceous patch on the skin or in the mouth. It is an AIDS-defining condition.[89]
periodontal disease
Poor oral hygiene with loosening of teeth, bleeding of gums, and bad odour indicates gingivitis or periodontitis, a WHO stage 3 condition.[89]
retinal lesions on fundoscopy
Medical emergency and requires immediate referral for sight-saving intervention if cytomegalovirus retinitis.
shortness of breath on exertion, cyanosis on exertion, dry cough, silent chest on auscultation
These are clinical features of Pneumocystis jirovecii pneumonia. This rarely occurs in patients with CD4 counts >200 cells/microlitre. It presents with shortness of breath, with few clinical signs. Post-treatment will require on-going secondary prophylaxis, or all patients with CD4 counts <200 cells/microlitre or stage 3 or 4 illness should be offered prophylaxis with trimethoprim/sulfamethoxazole (co-trimoxazole) or dapsone.
Other diagnostic factors
common
uncommon
hepatomegaly or splenomegaly
May indicate acute HIV syndrome, opportunistic infection, or malignancy such as lymphoma.
meningeal signs (bacterial or viral meningitis)
Vomiting, neck stiffness, and photophobia may indicate bacterial or viral meningitis; however, the finding of meningeal signs (meningism) is less likely in fungal meningitis. Most cases of HIV-associated meningitis will be associated with headache without neck stiffness and with or without fever.
Risk factors
strong
unprotected anal intercourse
unprotected penile-vaginal sexual intercourse
gay men and other men who have sex with men (MSM)
MSM are at increased risk of HIV and are disproportionately affected by HIV. MSM have a 23 times higher relative risk of acquiring HIV than in the wider population globally.[10]
transgender people
Transgender people are at increased risk of HIV and are disproportionately affected by HIV. Transgender women have a 20 times higher relative risk of acquiring HIV than for people in the wider population globally. Transgender men who have sex with men may also be at increased risk; however, there are few data available for this population.[10]
Low income, homelessness, and food insecurity are common among the transgender population and associated with a lower likelihood of receiving HIV prevention and care.[25]
commercial sex worker
Male and female sex workers are at increased risk of HIV and are disproportionately affected by HIV. Commercial sex workers have a 9 times higher relative risk of acquiring HIV than the wider population globally.[10]
The median incidence of HIV among women who engage in sex work in sub-Saharan Africa was 4.3 per 100 person years; this is disproportionately high compared with the total female population.[26]
people who inject drugs
People who inject drugs are at increased risk of HIV and are disproportionately affected by HIV. People who inject drugs have a 14 times higher relative risk of acquiring HIV than for people in the wider population globally.[10]
People who inject drugs account for 67 infections/10,000 exposures to a person with HIV who has a detectable viral load.[27] The pooled incidence of HIV in people who inject drugs was 1.7 per 100 person years between 1987 and 2021, and the risk of acquisition was higher in younger people and women compared to older people and men.[28]
This population tends to be diagnosed later when CD4 count is <350 cells/microlitre.[29]
Unstable housing and homelessness are associated with an increased risk of HIV acquisition in people who inject drugs.[30]
coinfection with other sexually transmitted infections (STIs)
Coinfection with another STI increases the risk of HIV.[31]
Gay men and other men who have sex with men (MSM) with bacterial sexually transmitted infections are at particularly higher increased risk of HIV acquisition.[32] Evidence suggests that herpes simplex virus type 2 (HSV-2) infection may increase the risk of HIV acquisition.[33][34]
people living in prisons
People living in prisons (and other closed settings) are at increased risk of HIV and are disproportionately affected by HIV. Prevalence in these settings was two times higher than among adults aged 15-49 years in the general population.[10] Lack of access to treatment and prevention services is a significant barrier in these populations.
percutaneous needle stick injury
The rate of HIV among people who have a percutaneous needlestick injury is approximately 30 infections/10,000 exposures to a person with HIV who has a detectable viral load.[35]
racial and ethnic minorities
Racial and ethnic minorities (particularly women) often experience HIV-related inequalities. Declines in new diagnoses have been smaller among black people in the UK, and black people and Hispanic/Latino people in the US compared with white people. HIV acquisition rates are higher in indigenous communities in some countries.[10]
weak
use of progestin-only injectable contraceptives
Evidence from studies evaluating the association between HIV acquisition and progestin-only injectable contraceptives, including depot medroxyprogesterone, suggests a possible increased risk of HIV acquisition in patients using these types of contraceptives, possibly due to hormonally-mediated changes in the vaginal epithelium. However, findings are inconsistent across studies.[36]
However, the World Health Organization (WHO) still recommends that women at a high risk of HIV can use all methods of contraception without restriction, including depot medroxyprogesterone. This recommendation is based on high-quality evidence from one randomised clinical trial that showed no statistically significant differences in HIV acquisition among women using intramuscular depot medroxyprogesterone acetate, copper IUDs, or levonorgestrel implants.[37]
cosmetic injection procedures
Transmission of HIV via non-sterile cosmetic injection services via blood is theoretically possible, but no known cases have been previously documented. However, a cluster of HIV cases among people with no known HIV risk factors who received platelet-rich plasma microneedling facials at an unlicensed spa in New Mexico has been reported. The source of contamination remains unknown.[38]
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