CLINICAL STAGES AND MANIFESTATIONS OF HIV AND AIDS

Following transmission of the virus, the individual will typically progress through three stages of illness.

  • Stage 1: Acute infection is the earliest stage, when seroconversion takes place and the person is very contagious.
  • Stage 2: Clinical latency or chronic HIV. During this stage, the virus is still active and continues to reproduce. This stage can last for 10–15 years, and immunosuppression gradually develops. The person may be asymptomatic and can transmit the virus to others. People who receive HIV treatment as prescribed may never move into the next stage (AIDS).
  • Stage 3: Acquired immunodeficiency syndrome (AIDS) is the final, severe stage of HIV infection, at which point the immune system is severely damaged and opportunistic infections or cancers begin to appear. The person with AIDS can have a high viral load and may easily transmit HIV to others.
    (CDC, 2022b)

Acute Infection

About 10%–60% of people with early HIV infection will not experience any symptoms. In those that do, the usual time from HIV exposure to development of symptoms is 2–4 weeks. This incubation period, however, has been known to last as long as 10 months.

Acute signs and symptoms during this stage can include:

  • Constitutional signs (most common):
    • Fever in the range of 100.4–104 °F
    • Fatigue
    • Myalgia
  • Adenopathy: Nontender lymphadenopathy, most commonly in axillary, cervical, and occipital nodes, often presents during the second week along with the emergence of a specific immune response. The nodes do not decrease in size after the acute phase but tend to persist to a small degree. Mild hepatosplenomegaly can also occur.
  • Oropharyngeal: Sore throat is a frequent manifestation of acute HIV. The physical exam reveals pharyngeal edema and hyperemia, usually without tonsillar enlargement or exudate. Tonsilitis has also been described.
  • Mucocutaneous ulceration: A very common and very painful feature of acute HIV infection, these ulcers may be found on the oral mucosa, anus, penis, or esophagus.
  • Rash: A generalized rash is also a common finding, typically developing 48–72 hours following onset of fever and persisting for up to 5–8 days. The upper thorax, collar region, and face are most often involved, although the scalp and extremities, including palms and soles, may be affected.
  • Gastrointestinal symptoms: The GI tract is a primary target during acute infection, and patients often complain of nausea, diarrhea, anorexia, and weight loss. Pancreatitis, hepatitis, and other serious GI manifestations are rare.
  • Neurological findings: These can include headache and retroorbital pain exacerbated by eye movements. More serious neurological findings may include:
    • Aseptic meningitis with severe headache, meningismus, photophobia, and lymphocytic pleocytosis; also meningoencephalitis
    • A rare, self-limited encephalopathy with fever, pronounced personality changes, confusion, and tonic-clonic seizures
    • Encephalopathy and myelopathy including extremity spasticity, bilateral extensor plantar reflexes, and urinary retention
    • Peripherally, facial nerve and brachial palsies or Guillain-Barré
  • Respiratory: Dry cough and rare reports of pneumonitis with cough, dyspnea, and hypoxia have occurred.
  • Opportunistic infections may include:
    • Oral and esophageal candidiasis
    • Pneumocystis jirovecii pneumonia
    • Prolonged severe cryptosporidiosis
    (Sax, 2022; Wood, 2023)

Clinical Latency or Chronic HIV

Following acute infection when the body loses the battle with HIV, the symptoms disappear and the person moves into the second stage, referred to as the chronic infection or clinical latency phase. During this period, the virus continues to multiply at very low levels, there is a steady decline in the CD4 cell count, and immunosuppression gradually develops.

People in this stage may not feel sick or have any symptoms. Without antiretroviral therapy, people can remain in this stage for 10–15 years, but some will move through it more quickly. Most people have few to no symptoms prior to the development of severe immunosuppression. During this stage, however, the person can still transmit the virus to others (HIV.gov, 2023b).

Acquired Immunodeficiency Syndrome (AIDS)

Without HIV treatment and when the CD4 cell count drops below 200 cells per milliliter, the person will then progress to acquired immunodeficiency syndrome (AIDS). This is the last stage of the illness, at which point the immune system is severely damaged and opportunistic infections or cancers begin to appear. The person can have a high viral load and may easily transmit HIV to others. Without HIV medications, people with AIDS typically survive for about three years. Once someone has a dangerous opportunistic infection, life expectancy without treatment falls to about one year.

SIGNS AND SYMPTOMS

Clinical signs and symptoms of AIDS can include:

  • Rapid weight loss
  • Recurring fever or profuse night sweats
  • Extreme and unexplained tiredness
  • Prolonged swelling of the lymph glands in the axillae, groin, or neck
  • Diarrhea that persists for more than one week
  • Sores of the mouth, anus, or genitals
  • Pneumonia
  • Red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids
  • Memory loss, depression, and other neurologic disorders

OPPORTUNISTIC INFECTIONS (OIs)

Many of the severe symptoms of HIV disease at this stage result from common opportunistic infections and include:

  • Candidiasis affecting the skin, nails, and mucous membranes, especially in the mouth, vagina, and esophagus.
  • Invasive cervical cancer.
  • Coccidiomycosis, also known as valley fever, desert fever, or San Joaquin Valley fever, is caused by breathing in fungal spores. It is common in hot, dry regions of the southwestern United States, Central America, and South America.
  • Cryptococcosis, a fungal infection that affects the lungs or central nervous system as well as other parts of the body.
  • Cryptosporidiosis, which is caused by a parasite that enters through contaminated food or water. Symptoms include abdominal cramps and severe, chronic watery diarrhea.
  • Cystoisosporiasis from a parasite in contaminated food or water, which causes diarrhea, fever, headache, abdominal pain, vomiting, and weight loss.
  • Cytomegalovirus (CMV) affecting multiple parts of the body, causing pneumonia, gastroenteritis, encephalitis, and retinitis that can lead to blindness.
  • HIV encephalopathy, whose exact cause is unknown but thought to be related to infection of the brain and resulting inflammation.
  • Herpes simplex virus (HSV), which is usually acquired sexually or passed from mother to child during birth. HSV normally is latent in those with healthy immune systems, but HIV can reactivate the latent virus, and symptoms can return. HSV causes painful cold sores in or around the mouth or painful ulcers on or around the genitals or anus. It can also cause infection of the bronchus, pneumonia, and esophagitis.
  • Histoplasmosis, a fungal infection that develops mostly in the lungs and causes symptoms similar to flu or pneumonia. Those with severely damaged immune systems can develop progressive disseminated histoplasmosis that can spread to other parts of the body.
  • Kaposi’s sarcoma (KS) is a viral illness that causes small blood vessels to grow abnormally anywhere in the body. It appears as firm pink or purple raised or flat spots on the skin. It can be life-threatening when it affects organs such as the lungs, lymph nodes, or intestines.
  • Lymphoma refers to cancer of the lymph nodes and other lymphoid tissues. Some types of lymphomas associated with HIV are non-Hodgkin lymphoma and Hodgkin lymphoma. Generalized lymphadenopathy is found on physical exam. The nodes are mostly symmetrical, moderately enlarged, mobile, painless, rubbery, and located in the cervical, submandibular, occipital, and axillary chains.
  • Tuberculosis is caused by breathing in a bacterium that usually attacks the lungs, but it can affect any part of the body, such as the kidneys, spine, and brain. Symptoms include cough, tiredness, weight loss, fever, and night sweats.
  • Mycobacterial avium complex (MAC) are bacteria that live in the environment, including in soil and dust particles, and which cause lung disease that can be life threatening.
  • Pneumocystis pneumonia (PCP) is a fungal lung disease that causes difficulty breathing, high fever, and dry cough.
  • Pneumonia can be caused by many agents, including bacteria, viruses, and fungi. The most common and life-threatening cause in those with HIV is Streptococcus pneumoniae.
  • Progressive multifocal leukoencephalopathy is a rare viral brain and spinal cord disease causing loss of muscle control, paralysis, blindness, speech problems, and altered mental state; it can progress rapidly and may be fatal.
  • Salmonella septicemia is a severe form of infection that exceeds the immune system’s ability to control it.
  • Toxoplasmosis is caused by a parasite carried by warm-blooded animals and released in their feces. Infection can occur in the lungs, retina of the eye, heart, pancreas, liver, colon, testes, and brain.
  • Wasting syndrome is the involuntary loss of more than 10% of body-weight due to HIV-related diarrhea or weakness and fever for more than 30 days.
    (CDC, 2021a; HIV.gov, 2023b)

OTHER COMPLICATIONS

Other complications resulting from HIV infection can include:

  • AIDS dementia complex (ADC), also known as HIV encephalopathy or HIV-associated neurocognitive disorders (HAND), can range from mild symptoms of behavioral changes and reduced mental functioning to severe dementia causing weakness and inability to function. Not all patients with HAND progress to HIV-associated dementia.
  • HIV-associated dementia (HAD) patients demonstrate deficits in memory, abstraction, verbal ability, decision-making, and attention. Rare features include sleep disturbances, psychosis (with mania), and seizures. Motor problems include imbalance, clumsiness, and weakness. In some extreme cases, vegetative state and mutism are also seen.
  • HIV-associated progressive encephalopathy (HPE) can occur in infants with HIV. Features may include decline in intellectual and motor milestones. In young children, the rate of acquiring new skills decreases, and fine motor ability and dexterity may become impaired. In older children and adolescents, the presentation is like that of AIDS dementia complex (ADC).
  • HIV-associated nephropathy (HIVAN) causes progressive acute renal failure due to direct HIV infection of renal epithelial cells and is closely associated with individuals of African descent (96%–100%).
  • Liver diseases are also a major complication, especially in those who also have hepatitis B or hepatitis C infection.
    (Reilly, 2020; Mayo Clinic, 2022; Wyatt & Fisher, 2023)

Less commonly, people with HIV/AIDS may develop the following cancers:

  • Angiosarcoma, which begins in the lining of the blood vessels
  • Anal cancer
  • Liver cancer
  • Mouth and throat cancers
  • Lung cancer
  • Testicular cancer
  • Penile cancer
  • Colorectal cancer
  • Skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma
    (ASCO, 2021)

HIV/AIDS INFECTION AMONG CHILDREN

Signs and symptoms of HIV/AIDS among the pediatric population include:

  • Unusually frequent occurrences of common childhood bacterial infections, such as otitis media, sinusitis, and pneumonia, which can be more severe than they are in immunologically healthy children
  • Recurrent fungal infections, such as candidiasis, that do not respond to standard antifungal agents, suggesting lymphocytic dysfunction
  • Recurrent or unusually severe viral infections, such as disseminated herpes simplex, zoster infection, or cytomegalovirus retinitis, seen with moderate-to-severe cellular immune deficiency
  • Growth failure, failure to thrive, or wasting, which may indicate HIV infection when other common metabolic and endocrine disorders do not appear to be the etiologies and may signify disease progression or underlying malnutrition
  • Failure to attain typical milestones, suggesting developmental delay, particularly impairment in the development of expressive language, which may indicate HIV encephalopathy
  • Loss of previously attained milestones, which may signify a CNS insult due to progressive HIV encephalopathy or opportunistic infection
  • In older children, behavioral abnormalities (e.g., loss of concentration and memory), which may indicate HIV encephalopathy
  • Recurrent bacterial infections (especially invasive infections), such as bacteremia, meningitis, and pneumonia, or unusual infections such as those caused by the Mycobacterium avium–intracellulare complex

Older children and young teenagers can have HIV infection or AIDS without a history of immunodeficiency or severe illness. Fever of unknown origin, recurrent infection, growth failure, or developmental regression without obvious etiology should raise suspicion of HIV infection (Rivera, 2020).