HIV is a virus that gradually attacks the immune system, which is our body’s natural defence against illness. If a person becomes infected with HIV, they will find it harder to fight off infections and diseases. The virus destroys a type of white blood cell called a T-helper cell and makes copies of itself inside them. T-helper cells are also referred to as CD4 cells.1
There are many different strains of HIV – someone who is infected may carry various different strains in their body. These are classified into types, with lots of groups and subtypes. The two main types are:
AIDS is a syndrome caused by the HIV virus.4 It is when a person’s immune system is too weak to fight off many infections, and develops when the HIV infection is very advanced. This is the last stage of HIV infection where the body can no longer defend itself and may develop various diseases, infections and if left untreated, death.
There is currently no cure for HIV or AIDS. However, with the right treatment and support, people can live long and healthy lives with HIV. To do this, it is especially important to take treatment correctly and deal with any possible side-effects.
Retroviruses are enveloped RNA viruses defined by their mechanism of replication via reverse transcription to produce DNA copies that integrate in the host cell genome. Several retroviruses, including 2 types of HIV and 2 types of human T-lymphotropic virus (HTLV—see HTLV Infections), cause serious disorders in people.
HIV-1 causes most HIV infections worldwide, but HIV-2 causes a substantial proportion of infections in parts of West Africa. In some areas of West Africa, both viruses are prevalent and may coinfect patients. HIV-2 appears to be less virulent than HIV-1.
HIV-1 originated in Central Africa in the first half of the 20th century, when a closely related chimpanzee virus first infected humans. Epidemic global spread began in the late 1970s, and AIDS was recognized in 1981.
In 2015, about 36.9 million people, including 2.6 million children, were living with HIV worldwide, according to the World Health Organization (WHO [ 1]). Almost half do not know they are infected. In 2014, 1.2 million died, and 2 million were newly infected. Most new infections (95%) occur in the developing world, > 1/2 are in women, and 1/7 are in children <15 yr. In many sub-Saharan African countries, incidence is declining markedly from the very high rates of a decade before.
In the US in 2012, 1.2 million people aged ? 13 yr were estimated to be living with HIV infection; HIV was undiagnosed in about 12.8% of them. About 50,000 new cases are estimated to occur each year in the US. In 2010 (the most recent year for these data), there were 47,500 new cases. Almost two thirds of new infections occurred in gay and bisexual men, and 8 times as many cases occurred in black/African Americans as in whites
Initially, primary HIV infection may be asymptomatic or cause transient nonspecific symptoms (acute retroviral syndrome).
Acute retroviral syndrome usually begins within 1 to 4 wk of infection and usually lasts 3 to 14 days. Symptoms and signs are often mistaken for infectious mononucleosis or benign, nonspecific viral syndromes and may include fever, malaise, fatigue, several types of dermatitis, sore throat, arthralgias, generalized lymphadenopathy, and septic meningitis.
After the first symptoms disappear, most patients, even without treatment, have no symptoms or only a few mild, intermittent, nonspecific symptoms for a highly variable time period (2 to 15 yr).
Symptoms during this relatively asymptomatic period may result from HIV directly or from opportunistic infections. The following are most common:
White plaques due to oral candidiasis
Fever with intermittent sweats
Asymptomatic, mild-to-moderate cytopenias (eg, leukopenia, anemia, thrombocytopenia) are also common. Some patients experience progressive wasting (which may be related to anorexia and increased catabolism due to infections) and low-grade fevers or diarrhea.
When the CD4 count drops to < 200/?L, nonspecific symptoms may worsen and a succession of AIDS-defining illnesses develop (see AIDS-Defining Illnesses).
Evaluation may detect infections that do not typically occur in the general population, such as Mycobacterium sp, P. jirovecii, Cryptococcus neoformans, or other fungal infections.
Infections that also occur in the general population but suggest AIDS if they are unusually severe or frequently recur include herpes zoster, herpes simplex, vaginal candidiasis, and Salmonella septicemia.
In patients with HIV infection, certain syndromes are common and may require different considerations (see Table: Common Manifestations of HIV Infection by Organ System). Some patients present with cancers (eg, Kaposi sarcoma, B-cell lymphomas) that occur more frequently, are unusually severe, or have unique features in patients with HIV infection (see Cancers Common in HIV-Infected Patients). In other patients, neurologic dysfunction may occur.
HIV antibody testing
Nucleic acid amplification assays to determine HIV RNA level (viral load)
HIV infection is suspected in patients with persistent, unexplained, generalized adenopathy or any of the AIDS-defining illnesses (see AIDS-Defining Illnesses). It may also be suspected in high-risk patients with symptoms that could represent acute primary HIV infection.
Detection of antibodies to HIV is sensitive and specific except during the first few weeks after infection. Enzyme-linked immunosorbent assay (ELISA) to detect HIV antibodies is highly sensitive, but rarely, results are false-positive. Positive ELISA results are therefore confirmed with a more specific test such as Western blot. However, these tests have drawbacks:
ELISA requires complex equipment.
Western blot requires well-trained technicians and is expensive.
The full testing sequence takes at least a day.
Newer point-of-care tests using blood or saliva (eg, particle agglutination, immunoconcentration, immunochromatography) can be done quickly (in 15 min) and simply, allowing testing in a variety of settings and immediate reporting to patients. Positive results of these rapid tests should be confirmed by standard blood tests (eg, ELISA with or without Western blot) in developed countries and repetition with one or more other rapid tests in developing countries. Negative tests need not be confirmed.
If HIV infection is suspected despite negative antibody test results (eg, during the first few weeks after infection), the plasma HIV RNA level may be measured. The nucleic acid amplification assays used are highly sensitive and specific. HIV RNA assays require advanced technology, such as reverse transcription–PCR (RT-PCR), which is sensitive to extremely low HIV RNA levels. Measuring p24 HIV antigen (p24 is a core protein of the virus) by ELISA is less sensitive and less specific than directly detecting HIV RNA in blood.
When HIV is diagnosed, the following should be determined:
Plasma HIV RNA level
Both are useful for determining prognosis and monitoring treatment.
The CD4 count is calculated as the product of the following:
WBC count (eg, 4000 cells/mL)
Percentage of WBCs that are lymphocytes (eg, 30%)
Percentage of lymphocytes that are CD4+ (eg, 20%)
Using the numbers above, the CD4 count (4000 x 0.3 x 0.2) is 240 cells/mL, or about 1/3 of the normal CD4 count in adults, which is about 750 ±250/?L.
Plasma HIV RNA level (viral load) reflects HIV replication rates. The higher the set point (the relatively stable virus levels that occur after primary infection), the more quickly the CD4 count decreases and the greater the risk of opportunistic infection, even in patients without symptoms.
HIV infection can be staged based on the CD4 count. In patients ? 6 yr, stages are as follows:
Stage 1: ? 500 cells/?L
Stage 2: 200 to 499 cells/?L
Stage 3: < 200 cells/?L
The CD4 count after 1 to 2 yr of treatment provides an indication of ultimate immune recovery; CD4 counts may not return to the normal range despite prolonged suppression of HIV.
Diagnosis of the various opportunistic infections, cancers, and other syndromes that occur in HIV-infected patients is discussed elsewhere in TheManual. Many have aspects unique to HIV infection.
Hematologic disorders (eg, cytopenias, lymphomas, cancers) are common and may be usefully evaluated with bone marrow aspiration and biopsy. This procedure can also help diagnose disseminated infections with MAC, M. tuberculosis, Cryptococcus, Histoplasma, human parvovirus B19, P. jirovecii, and Leishmania. Most patients have normocellular or hypercellular marrow despite peripheral cytopenia, reflecting peripheral destruction. Iron stores are usually normal or increased, reflecting anemia of chronic disease (an iron-reutilization defect). Mild to moderate plasmacytosis, lymphoid aggregates, increased numbers of histiocytes, and dysplastic changes in hematopoietic cells are common.
HIV-associated neurologic syndromes can be differentiated via lumbar puncture with CSF analysis and contrast-enhanced CT or MRI (see Table:Common Manifestations of HIV Infection by Organ System and elsewhere in The Manual).
Screening antibody tests should be offered routinely to adults and adolescents, particularly pregnant women, regardless of their perceived risk. For people at highest risk, especially sexually active people who have multiple partners and who do not practice safe sex, testing should be repeated every 6 to 12 mo. Such testing is confidential and available, often free of charge, in many public and private facilities throughout the world.
CD4 count in the short term
Plasma HIV RNA level in the longer term
For every 3-fold (0.5 log10) increase in viral load, mortality over the next 2 to 3 yr increases about 50%. HIV-associated morbidity and mortality vary by the CD4 count, with the most deaths from HIV-related causes occurring at counts of < 50/?L. However, with effective treatment, the HIV RNA level decreases to undetectable levels, CD4 counts often increase dramatically, and risk of illness and death falls but remains higher than that for age-matched populations not infected with HIV.
Another, less well-understood prognostic factor is the level of immune activation as determined by evaluating the expression of activation markers on CD4 and CD8 lymphocytes. Activation, which may be caused by leakage of bacteria across the HIV-damaged colonic mucosa, is a strong prognostic predictor but is not used clinically because this test is not widely available and antiretroviral therapy changes the prognosis, making this test less important.
A subgroup of HIV-infected people (termed long-term nonprogressors) remains asymptomatic with high CD4 counts and low HIV levels in the blood without antiretroviral treatment. These people usually have vigorous cellular and humoral immune responses to their infecting HIV strain as measured by assays in vitro. The specificity of this effective response is shown by the following: When these people acquire a superinfection with a second strain of HIV to which their immune response is not as effective, they convert to a more typical pattern of progression. Thus, their unusually effective response to the first strain does not apply to the second strain. These cases provide a rationale for counseling HIV-infected people that they still need to avoid exposure to possible HIV superinfection through unsafe sex or needle sharing.
Cure of HIV infection has not been thought possible, and thus lifelong drug treatment is considered necessary. However, several recent cases of HIV-infected infants who were treated briefly with antiretroviral therapy after diagnosis and who have remained HIV-negative for many months after stopping treatment suggests that cure is possible in this setting.