Complications

Complications table
ComplicationTimeframeLikelihood

acute seroconversion

short termmedium

Acute HIV infection will occur in 50% of those infected, with a viral illness resembling infectious mononucleosis characterized by: fever, malaise, myalgia, pharyngitis, gastrointestinal disturbance, headache, generalized lymphadenopathy, and hepatosplenomegaly. A rash and aphthous ulceration is also suggestive of the diagnosis.

Nervous system involvement can occur, for example, meningoencephalitis, Bell palsy, and Guillain-Barre syndrome.

Viral load is extremely high due to the virus replicating before immune response has occurred. Management is largely supportive. Potent combination antiretroviral therapy with the same regimens used for treating established chronic infection 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 minimize the size of the latent HIV reservoir.

severe acute syndrome

short termlow

Present with symptoms for more than 2 weeks, high viral loads and immune depletion may result in opportunistic infections, for example, esophageal 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 should be initiated as soon as possible.

rapid progressors

short termlow

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 HIV infection.

Incidence is likely to decrease given the current recommendations to initiate antiretroviral therapy in all HIV-infected patients.

AIDS

long termhigh

AIDS occurs as a result of HIV infection, and usually develops over 10-15 years (meidan 11 years).[1][2]

May present with an AIDS-defining illness such as esophageal candida, extrapulmonary tuberculosis, cryptococcal meningitis, or P jirovecii pneumonia.

CD4 count and viral load should be monitored closely and antiretroviral therapy initiated with timing depending on the presence of specific opportunistic infections.

HIV-associated hypotestosteronism

long termmedium

Up to 70% of HIV-infected men have testosterone deficiency and this problem persists despite successful ART. Hypogonadism is also expected to rise with the aging HIV population. Testosterone replacement therapy (TRT) is common in the setting of HIV and often done without proper evaluations or monitoring. Given studies suggesting TRT may increase the risk of cardiovascular events, thrombosis, and death, caution is needed when initiating TRT in the current ART era.[150]

long-term controllers

long termlow

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.[128]

HIV- or antiretroviral therapy (ART)-associated cardiovascular disease

long termlow

People with HIV are twice as likely to develop cardiovascular disease. The global burden has tripled over the past 2 decades and is responsible for 2.6 million disability-adjusted life years.[130] 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.[131]

HIV infection 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/microliter.[132]

May be related to HIV itself and/or to ART. Increased risk has been reported with cumulative use of protease inhibitors.[133] Patients with HIV and hepatitis C co-infection have an increased risk of cardiovascular disease compared with patients who have HIV infection alone.[134]

Cardiomyopathy, myositis, and congestive cardiac failure are common cardiovascular complications of untreated HIV infection. There is also an increased risk of ischemic heart disease due to the chronic inflammation associated with HIV infection among those on long-term, suppressive ART. Certain ART medications may worsen this risk by altering lipid metabolism and increasing hyperlipidemia.

The American Heart Association has released guidance on the prevention and management of cardiovascular disease in people living with HIV infection.[109]

HIV-associated venous thrombotic events

long termlow

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 standardized for age and sex. Factors associated with a higher risk of a venous thrombotic event included: CD4 count <200 cells/microliter; 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.[135]

HIV- or ART-associated renal disease

long termlow

Acute and chronic renal disease can be seen, including worsening of existing renal disease (diabetic, hypertensive), as well as HIV-related disease. The most common cause of HIV-related chronic renal failure (GFR <60ml/min) is HIV-associated nephropathy. Most commonly occurs at lower CD4 counts; affects older patients and people of African descent.

Renal disease may also be related to certain ART medications. Renal toxicity can be minimized by using tenofovir alafenamide or abacavir instead of tenofovir disoproxil fumarate. Overall, endstage renal disease is about 3 times higher among individuals with HIV infection compared with those without infection.[136]

HIV- or ART-associated bone disease

long termlow

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 ART medications such as tenofovir disoproxil fumarate. This toxicity can be minimized by using tenofovir alafenamide or abacavir instead of tenofovir disoproxil fumarate. Overall, HIV-infected individuals are at about a 4 times higher risk of osteoporosis compared with those without HIV.[137]

HIV-associated cancer

long termlow

AIDS-defining cancers (Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) are declining in the ART era, but continue to occur at rates several times higher than in the general population. Those infected with HIV are experiencing a rising burden of non-AIDS defining cancers in the ART era. These include anal cancer, Hodgkin 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.[138][139][140][141][142][143]

Long-term suppression of HIV with ART is associated with a lower risk of cancer compared with uncontrolled viremia; however, patients with long-term HIV suppression still have a higher risk for certain cancers, particularly those associated with viral co-infections, when compared with the general population.[144]

HIV-associated liver disease

long termlow

HIV-infected patients have high rates of end-stage liver disease (ESLD) mostly due to viral hepatitis co-infection. There has been little to no change in the rate of ESLD in the ART era, but this is expected to change with antiviral agents against hepatitis C virus. Appropriate liver cancer screening for those with viral hepatitis co-infection is important in this population.[145]

HIV-associated neurocognitive dysfunction

long termlow

This disorder is characterized by memory and cognitive difficulties, and is highly prevalent at 15% to 20% among HIV-infected individuals on ART.[146]

Patients with HIV infection 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 HIV-infected people.[147] 

HIV-associated diabetes

long termlow

Prevalence of diabetes in HIV-infected people ranges from 2% to 14% depending on type of study, ascertainment of diabetes, and risk factors. There is conflicting evidence on whether HIV infection is an independent risk factor for diabetes. Age-appropriate diabetes screening is important for this population.[148]

Research is ongoing as to whether there is a causal association between diabetes in HIV-infected patients and ART.[149]

HIV-associated lung disease

long termlow

COPD is the most common chronic lung condition diagnosed among those with HIV with a prevalence of approximately 20% in different cohorts. Whether HIV infection is an independent risk factor beyond associations with smoking or bacterial lung infection is unclear.[151]

hearing impairment

long termlow

Current evidence suggests a high prevalence of hearing impairment in people living with HIV compared with those without HIV; however, the etiology is not understood.[152]

immune suppression pre-AIDS

variablehigh

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 HIV-infected patients.

HIV-related opportunistic infections

variablehigh

Concomitant and opportunistic infections (OIs) are common in HIV-infected patients. 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 opportunistic infections, empiric, 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 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.[129]

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