Complications
Acute (recent) infection will occur in 50% of those with HIV, with a viral illness resembling infectious mononucleosis characterised by: fever, malaise, myalgia, pharyngitis, gastrointestinal disturbance, headache, generalised lymphadenopathy, and hepatosplenomegaly. A rash and aphthous ulceration is also suggestive of the diagnosis. Nervous system involvement can occur (e.g., meningoencephalitis, Bell's palsy, and Guillain-Barre syndrome).
Viral load is extremely high due to the virus replicating before immune response has occurred. Management is largely supportive. Antiretroviral therapy (ART) should be initiated as soon as possible in the setting of acute seroconversion to reduce symptoms, decrease risk of transmission, preserve immune status, and potentially minimise the size of the latent HIV reservoir.[78]
Present with symptoms for more than 2 weeks, high viral loads and immune depletion may result in opportunistic infections (e.g., oesophageal thrush or Pneumocystis jirovecii infection), and a poorer overall prognosis.
Likely to be a rapid progressor and will require careful follow-up monitoring for immune depletion. Antiretroviral therapy (ART) should be initiated as soon as possible.
A small proportion of individuals develop AIDS within 1 to 2 years. This is associated with high levels of viral replication and a precipitous decline in CD4 numbers, probably due to impairment in the hosts' initial responses to infection.
Incidence is likely to decrease given the current recommendations to initiate antiretroviral therapy (ART) in all patients with HIV.
AIDS occurs as a result of HIV, and usually develops over 10-15 years in the absence of treatment, but sometimes longer.[2]
May present with an AIDS-defining illness such as oesophageal candida, extra-pulmonary tuberculosis, cryptococcal meningitis, or P jirovecii pneumonia.
CD4 count and viral load should be monitored closely and antiretroviral therapy (ART) initiated with timing depending on the presence of specific opportunistic infections.
People with HIV are twice as likely to develop cardiovascular disease (CVD). The global burden has tripled over the past two decades and is responsible for 2.6 million disability-adjusted life years.[175] The cumulative incidence is estimated to be 20.5% in men and 13.8% in women by the age of 60 years, compared with 12.8% (men) and 9.4% (women) in the US general population.[176]
HIV has also been associated with an increased risk of peripheral arterial disease; however, this risk appears to be highest in patients with a sustained CD4 count <200 cells/microlitre.[177]
May be related to HIV itself and/or to ART. Increased risk has been reported with cumulative use of protease inhibitors, integrase strand-transfer inhibitors, and the nucleoside reverse transcriptase inhibitor abacavir.[178][179][180]
Patients with HIV and hepatitis C coinfection have an increased risk of cardiovascular disease compared with patients who have HIV alone.[181]
Cardiomyopathy and congestive cardiac failure are common cardiovascular complications of untreated HIV. There is also an increased risk of ischaemic heart disease due to the chronic inflammation associated with HIV among those on long-term, suppressive ART. Certain ART drugs may worsen this risk by altering lipid metabolism and increasing hyperlipidaemia.
Adults with HIV have a two-fold higher risk of acute myocardial infarction compared to HIV-negative controls. Risk factors included hypertension, smoking, and dyslipidaemia.[182] The risk of ischaemic or haemorrhagic stroke is also significantly increased in people with HIV. Risk factors included male sex, black race, hypertension, diabetes, hyperlipidaemia, smoking.[183][184]
The American Heart Association has released guidance on the prevention and management of CVD in people living with HIV.[185]
Management of CVD in patients with HIV is similar to patients who are HIV negative.
This disorder is characterised by memory and cognitive difficulties, and is highly prevalent at 15% to 43% among individuals with HIV on ART, especially in sub-Saharan Africa and Latin America.[202][203]
Patients with HIV have substantially higher rates of depression compared with the general population. Antidepressant therapy may improve symptoms compared with placebo; however, the quality of evidence is low in people with HIV.[204]
Prevalence of diabetes in people with HIV ranges from 2% to 14% depending on type of study, ascertainment of diabetes, and risk factors. There is conflicting evidence on whether HIV is an independent risk factor for diabetes. Age-appropriate diabetes screening is important for this population.[205]
Risk factors for diabetes (or pre-diabetes) in patients with HIV includes family history of diabetes, older age, Black or Hispanic ethnicity, obesity, lipodystrophy/lipoatrophy, dyslipidaemia, metabolic syndrome, increased baseline fasting glycaemia, and certain ART regimens.[206]
Research is ongoing as to whether there is a causal association between diabetes in patients with HIV and antiretroviral therapy (ART).[207]
Up to 70% of men with HIV have testosterone deficiency and this problem persists despite successful antiretroviral therapy (ART). Hypogonadism is also expected to rise with the ageing HIV population. Testosterone replacement therapy is common in the setting of HIV and often done without proper evaluations or monitoring. Given studies suggesting testosterone replacement therapy may increase the risk of cardiovascular events, thrombosis, and death, caution is needed when initiating testosterone in the current ART era.[208]
A small proportion of individuals are able to control HIV viral load without assistance of antiretroviral therapy (ART). Many have low-to-undetectable viral loads and well-preserved CD4 counts for many years. This appears in part to be due to a robust immunity to HIV. However, even these individuals are likely to benefit from consistent and uninterrupted use of ART.[173]
The risk of venous thrombotic events is elevated in people with HIV. A retrospective cohort study found a crude incidence of 2.33 events per 1000 person-years, and an incidence of 2.50 events per 1000 person-years when standardised for age and sex. Factors associated with a higher risk of a venous thrombotic event included: CD4 count <200 cells/microlitre; high viral load; and a history of (or current) opportunistic infection. There was no association between any specific ART and the risk of a venous thrombotic event. Primary prophylaxis is not routinely recommended.[186]
Acute and chronic renal disease can be seen, including worsening of existing renal disease (diabetic, hypertensive), as well as HIV-related disease. Acute kidney injury has a pooled prevalence of 23% among people with HIV, and may be associated with antiretroviral therapy (ART) or the disease itself.[187] The most common cause of HIV-related chronic renal failure (GFR <60 mL/min) is HIV-associated nephropathy. Most commonly occurs at lower CD4 counts; affects older patients and people of African descent. Overall, end-stage renal disease is about 3 times higher among individuals with HIV compared with those without HIV.[188]
ART appears to reduce the risk of end-stage kidney disease or death in patients with HIV-associated nephropathy and HIV-immune complex kidney disease.[189] However, renal disease may also be related to certain ART. Renal toxicity can be minimised by using tenofovir alafenamide or abacavir instead of tenofovir disoproxil.
Risk of osteoporosis and osteopenia is increased in HIV-positive patients, and vitamin D levels are often low. Bone disease may be related to certain antiretroviral therapy (ART) such as tenofovir disoproxil. This toxicity can be minimised by using tenofovir alafenamide or abacavir instead of tenofovir disoproxil. Overall, individuals with HIV are at about a four times higher risk of osteoporosis compared with those without HIV.[190] The prevalence of osteopenia/osteoporosis in people with HIV on ART was two times more compared to controls in one meta-analysis.[191]
People living with HIV have a lower bone mineral density and higher risk of fracture compared to the general population, partly due to the presence of osteoporosis, as well as the presence of other risk factors (e.g., smoking, hepatitis C coinfection, older age).[192][193]
AIDS-defining cancers (Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer) are declining in the antiretroviral therapy (ART) era, but continue to occur at rates several times higher than in the general population. People with HIV are experiencing a rising burden of non-AIDS defining cancers in the ART era. These include anal cancer, Hodgkin's lymphoma, oropharyngeal cancers, lung cancer, skin cancer, and liver cancer. Cancer as a cause of death has increased from 11% to 22% in a survey of French patients with HIV. Age-appropriate cancer screening is important for this population.[194][195][196][197][198][199]
Long-term suppression of HIV with ART is associated with a lower risk of cancer compared with uncontrolled viraemia; however, patients with long-term HIV suppression still have a higher risk for certain cancers, particularly those associated with viral coinfections, when compared with the general population.[200] Regular cancer screening and detection according to relevant guidelines is recommended (e.g., mammogram, digital anal rectal exam, Pap smear, ultrasound for hepatocellular carcinoma, colonoscopy, total body skin exam).[91]
Patients with HIV have high rates of end-stage liver disease (ESLD) mostly due to viral hepatitis coinfection. There has been little to no change in the rate of ESLD in the antiretroviral therapy (ART) era, but this is expected to change with antiviral agents against hepatitis C virus. Appropriate liver cancer screening for those with viral hepatitis coinfection is important in this population.[201]
COPD is the most common chronic lung condition diagnosed among those with HIV with a prevalence of approximately 20% in different cohorts. Whether HIV is an independent risk factor beyond associations with smoking or bacterial lung infection is unclear.[209]
Current evidence suggests a high prevalence of hearing impairment in people living with HIV compared with those without HIV; however, the aetiology is not understood.[210]
May present with signs of World Health Organization stage 2 or 3 symptoms, including shingles, oral thrush, loss of weight, or pulmonary tuberculosis.
CD4 count and viral load should be reviewed.
Incidence is likely to decrease given the current recommendations to initiate antiretroviral therapy in all patients with HIV.
Concomitant infections and OIs are common in patients with HIV. Primary prophylaxis is required in select patients. If an opportunistic infection occurs, rapid diagnosis is recommended so that treatment can be instituted as quickly as possible.
In early disease, the CD4 count may be transiently depressed at the time of concomitant infection if the patient is having it monitored regularly. Patients with advanced HIV deteriorate more easily, and infections should be diagnosed and contained as soon as possible.
In some OIs, empirical, best-guess treatment is warranted, especially in patients with compromised immunity. A broad-spectrum antibiotic is probably most commonly prescribed where an acute bacterial infection is suspected.
In patients with very advanced disease, monitoring the patient for immune reconstitution inflammatory syndrome (IRIS) for the first 3 to 6 months after starting antiretroviral therapy (ART) is very important, and will reduce morbidity and mortality if treatment is instituted early. IRIS is more common in patients with very advanced disease and extensive burden of OIs.[174]
In the pre-antiretroviral therapy (ART) era, wasting was associated with disease progression to AIDS and death. ART has effectively reduced the incidence of this form of wasting in patients with HIV, but some patients on ART who are virally suppressed continue to lose weight, particularly older people. HIV-associated weight loss is defined as sustained, unintentional weight loss in a person with HIV that: occurs in the absence of a concurrent illness or condition that could readily account for such weight loss; is characterised by >5% loss of premorbid body weight over 6 months, or >10% loss of pre-morbid body weight over 12 months (in the absence of objective weight loss); may be accompanied by reductions in physical functioning, in some cases. This definition does not apply to people living with HIV with prolonged non-suppressed viraemia. Rapid recognition and accurate diagnosis (e.g., serial weight measurements) are critical. Several non-pharmacological treatments (e.g., nutritional supplements, resistance training) and pharmacological treatments (e.g., appetite stimulants, testosterone, anabolic steroids, human growth hormone, cytokine production modulators) have been used to mitigate unintentional weight loss.[211]
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