History and exam

Key diagnostic 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.

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.[65]

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).[65] Loss of weight may result from malnutrition, tuberculosis infection, and HIV wasting syndrome.[65]

Rashes may occur throughout HIV disease 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).[65]

The mouth should always be thoroughly examined. Both thrush and oral hairy leukoplakia indicate WHO stage 3.

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).[65]com.bmj.content.model.Caption@14eccb48[Figure caption and citation for the preceding image starts]: Oral candidiasis in a patient with HIVPublic Health Image Library (PHIL) [Citation ends].

Unexplained diarrhoea of more than 1 month in duration (with no pathogen diagnosed) indicates WHO stage 3 disease.[65]

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).[65]

Depression and anxiety are common in HIV-positive individuals. 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.[65]

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][65]

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 2 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][65]

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 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 medicines should be given.

HIV is largely spread through sexual intercourse in all parts of the world. Because of this, ongoing assessments of sexual activity and risk for STIs should be done routinely for all patients with HIV.

Painless enlarged nodes, in 2 or more non-contiguous sites of >1 cm for more than 3 months.[65]

Kaposi's sarcoma may present as a pink or violaceous patch on the skin or in the mouth. It is an AIDS-defining condition.[65]

Chronic herpes infection, that is, progressive painful genital or anal ulceration for >1 month, is an AIDS-defining illness.[65] Other STIs associated with HIV infection include syphilis, chlamydia, and gonorrhoea.

Occurs in WHO stage 3 disease.[65] Rates of vaginal Candida colonisation are higher in women with HIV infection.[71]

Occurs in WHO stage 2 disease.[65] Only an AIDS-defining illness if multidermatomal.

Headaches may be indicative of central nervous system (CNS) disease. Headaches with focal CNS signs and symptoms may indicate toxoplasmosis infection (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).[65] 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.

Poor oral hygiene with loosening of teeth, bleeding of gums, and bad odour indicates gingivitis or periodontitis, a WHO stage 3 condition.[65]

Medical emergency and requires immediate referral for sight-saving intervention if cytomegalovirus retinitis.

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

Needle-sharing injection drug use with an infected source is a risk factor for HIV infection, and an obstacle to HIV treatment adherence.

May be related to HIV or some other medicine or toxin. Important to try to find aetiology since some antiretroviral therapy also causes peripheral neuropathy.

Occurs in WHO stage 4 disease.[65]

May indicate acute HIV syndrome, opportunistic infection, or malignancy such as lymphoma.

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

67 infections/10,000 exposures to an infected source who has a detectable viral load.[22]

50 infections/10,000 exposures to an infected source who has a detectable viral load.[23][24]

10 infections/10,000 exposures to an infected source who has a detectable viral load.[23][24]

30 infections/10,000 exposures to an infected source who has a detectable viral load.[25]

The level of HIV RNA at delivery is independently associated with risk of transmission.[26]

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.[27]

The US Centers for Disease Control and Prevention (CDC) recommends that implants, progestin-only pills, and combined hormonal contraceptives can be used without restriction in women at high risk for HIV infection.[28] The CDC believes the benefits of depot medroxyprogesterone outweigh any theoretical or possible risks, and that women at a high risk for HIV should not be denied this treatment.[28]

The World Health Organization 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.[29]

Evidence suggests that HSV-2 infection may increase the risk of HIV acquisition.[30][31]

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