Understanding AIDS: From Early Symptoms to Advanced Diagnosis and Treatment

HIV infection and AIDS

 

ESSENTIALS OF DIAGNOSIS

Ø Risk factors: sexual contact with an infected person, parenteral exposure to infected blood by transfusion or needle sharing, perinatal exposure.

Ø Prominent systemic complaints such as sweats, diarrhea, weight loss, and wasting.

Ø Opportunistic infections due to diminished cellular immunity are often life-threatening.

Ø Aggressive cancers, particularly Kaposi sarcoma and extranodal lymphoma.

Ø Neurologic manifestations, including dementia, aseptic meningitis, and neuropathy.

 

 

General Considerations

The AIDS case definition established by the Centers for Disease Control and Prevention (CDC) encompasses opportunistic infections and malignancies that infrequently arise without severe immunodeficiency (for instance, Pneumocystis pneumonia and central nervous system lymphoma). Additionally, individuals are classified as having AIDS if they exhibit positive HIV serology along with specific infections and malignancies that, while they can occur in immunocompetent individuals, are more prevalent among those infected with HIV (such as pulmonary tuberculosis and invasive cervical cancer). Moreover, various nonspecific conditions, including dementia and documented weight loss (wasting) in conjunction with positive HIV serology, are recognized as indicators of AIDS [1].

The definition specifies criteria for definitive and presumptive diagnoses of particular infections and malignancies. In summary, individuals with positive HIV serology who have ever recorded a CD4 lymphocyte count below 200 cells/mcL or a CD4 lymphocyte percentage under 14% are regarded as having AIDS. The inclusion of individuals with low CD4 counts as AIDS cases illustrates the understanding that immunodeficiency is the essential feature of AIDS. The choice of a cutoff point at 200 cells/mcL is endorsed by several cohort studies, indicating that AIDS will occur within 3 years in more than 80% of individuals with counts below this threshold in the absence of effective antiretroviral therapy (ART). The prognosis for individuals living with HIV/AIDS has seen remarkable enhancement due to the progress made in effective antiretroviral therapy (ART). Consequently, a reduced number of individuals with HIV progress to develop infections or cancers, or maintain a CD4 count that qualifies them as having AIDS. This evolution suggests that the CDC's definition has become less relevant in measuring the impact of HIV/AIDS within the United States. Conversely, those who were diagnosed with AIDS based on severe opportunistic infections, cancers, or immunodeficiency may now enjoy significantly better health, with higher CD4 counts, owing to ART. Therefore, both the Social Security Administration and the majority of social service agencies emphasize functional assessments for eligibility determination for benefits, rather than simply the existence of an AIDS-defining illness [1].

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Epidemiology

The transmission modes of HIV closely resemble those of hepatitis B, especially in terms of sexual, parenteral, and vertical transmission. Although some sexual behaviors (like receptive anal intercourse) present a considerably higher risk than others (such as oral sex), it is challenging to measure the risks associated with each contact. This challenge stems from the fact that studies on HIV sexual transmission reveal that many individuals at risk participate in various sexual activities and have multiple partners, only some of whom may be HIV positive. Therefore, it is difficult to identify which specific practice with which partner resulted in the transmission of HIV[2].

However, the most reliable estimates suggest that the likelihood of HIV transmission through receptive anal intercourse ranges from 1:100 to 1:30, while for insertive anal intercourse it is 1:1000. The risk associated with receptive vaginal intercourse is also 1:1000. For insertive vaginal intercourse, it is 1:10,000. Additionally, receptive fellatio with ejaculation carries a risk of 1:1000. The per-contact risk of HIV transmission from other activities, such as receptive fellatio without ejaculation, insertive fellatio, and cunnilingus, remains unknown. Several cofactors are recognized to elevate the risk of HIV transmission during a specific encounter, including the presence of ulcerative or inflammatory sexually transmitted infections, trauma, menstruation, and the absence of male circumcision.

The risk of acquiring HIV infection from a needlestick with infected blood is approximately 1:300. Factors known to increase the risk of transmission include depth of penetration, hollow bore needles, visible blood on the needle, and advanced stage of disease in the source. The risk of HIV transmission from a mucosal splash with infected blood is unknown but is assumed to be significantly lower [1,2].

The risk of acquiring HIV infection from illicit drug use with sharing of needles from an HIV-infected source is estimated to be 1:150. Use of clean needles markedly decreases the chance of HIV transmission but does not eliminate it if other drugs are shared (eg, cookers).

When a blood transfusion is conducted from a donor infected with HIV, the likelihood of transmission stands at 95%. Fortunately, since 1985, the United States has implemented universal blood donor screening utilizing the HIV enzyme-linked immunosorbent assay (ELISA). Additionally, individuals who have recently participated in high-risk behaviors (such as sexual relations with someone at risk for HIV or injection drug use) are prohibited from donating. This effectively removes donations from individuals who are HIV positive but have not yet produced antibodies (i.e., those in the 'window' period). To further reduce the risk of HIV transmission, testing for HIV antigens and viral load has been incorporated into the blood screening process. By implementing these precautions, the likelihood of HIV transmission through blood transfusion in the United States is approximately 1 in 1,000,000. Between 13% and 40% of children born to mothers infected with HIV acquire the virus if the mother has not undergone treatment or if the child has not received perinatal HIV prophylaxis. The risk is elevated with vaginal deliveries compared to cesarean deliveries, is greater among mothers with high viral loads, and is increased for those who breast-feed their infants. The integration of prenatal HIV testing and counseling, antiretroviral therapy for infected mothers during pregnancy and for the newborn immediately after birth, planned cesarean delivery when the mother has a viral load exceeding 1000 copies/ml, and the avoidance of breastfeeding has successfully decreased the rate of perinatal HIV transmission to below 2% in both the United States and Europe. It has not been demonstrated that HIV can be transmitted through respiratory droplets, by vectors such as mosquitoes, or through casual nonsexual interactions. [2].

An estimated 1,201,100 Americans aged 13 and older are living with HIV infection, with approximately 50,000 new infections occurring annually. It is estimated that 494,602 individuals in the United States are living with AIDS. Among these, 76% are men, with 64% having been exposed through male-to-male sexual contact, 15% through injection drug use, 11% through heterosexual contact, and 8% through both male-to-male sexual contact and injection drug use. Women represent 24% of those living with AIDS, with 69% infected through heterosexual contact and 28% through injection drug use. Children under 13 years old account for less than 0.1% of the total living cases. The epidemic has disproportionately affected African Americans. The estimated rate of new HIV diagnoses in the United States per 100,000 individuals is 58.3 for African Americans, 18.5 for Latinos, 17.3 for individuals of multiple races, 15.1 for native Hawaiians and Pacific Islanders, 9.9 for Native Americans and native Alaskans, 6.7 for whites, and 6.1 for Asians [3].

Overall, the progression of HIV-related diseases is comparable between men and women. Nevertheless, there are significant distinctions. Women face risks of gynecological complications associated with HIV, such as recurrent candidal vaginitis, pelvic inflammatory disease, and cervical dysplasia. Factors such as violence against women, pregnancy, and the frequent occurrence of drug use and poverty further complicate the treatment of women infected with HIV.

While "safer sex" initiatives significantly reduced the rates of seroconversions among men who have sex with men (MSM) in urban areas of the United States by the mid-1980s, there has been a resurgence of unsafe sexual behaviors among MSM in several major cities in the United States and Western Europe. The increased rates of unsafe sexual practices seem to correlate with a diminished concern about contracting HIV, attributed to the availability of effective antiretroviral therapy (ART). Additionally, the rising use of crystal methamphetamine among specific risk groups appears to contribute to the heightened rates of unsafe sex. [1, 3].

Worldwide, there are an estimated 35 million persons infected with HIV, with heterosexual spread being the most common mode of transmission for men and women. In Central and East Africa, in some urban areas, as many as one-third of sexually active adults are infected. The reason for the greater risk for transmission with heterosexual intercourse in Africa and Asia than in the United States may relate to cofactors such as general health status, the presence of genital ulcers, relative lack of male circumcision, the number of sexual partners, and different HIV serotypes.

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B. Laboratory Findings

Specific tests for HIV encompass the detection of antibodies and antigens. Traditional HIV antibody testing is performed using ELISA. Positive samples are subsequently verified through an alternative method (for instance, Western blot). The sensitivity of screening serologic tests exceeds 99.9%.

The specificity of positive outcomes from two distinct techniques nears 100%, even among low-risk populations. False-positive results in screening tests may arise due to normal biological variations or in connection with recent influenza vaccinations or other medical conditions, such as connective tissue diseases.

These instances are typically identified through negative confirmatory tests. Molecular biology methods (PCR) reveal a minor occurrence of individuals (less than 1%) who are HIV-positive for up to 36 months without producing an antibody response.

Nevertheless, antibodies that can be detected by screening serologic tests will manifest in 95% of individuals within 6 weeks following infection.

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Rapid HIV antibody tests of blood or oral fluid provide results within 10-20 minutes and can be performed in clinicians' offices, including by personnel without laboratory training and without a Clinical Laboratory Improvement Amendment (CLIA)-approved laboratory. Persons who test positive on a rapid test should be told that they may be HIV-infected or their test may be falsely reactive. Standard testing (ELISA with Western blot confirmation) should be performed to distinguish these two possibilities. Rapid testing is particularly helpful in settings where a result is needed immediately (eg, a woman in labor who has not recently been tested for HIV) or when the patient is unlikely to return for a result. Rapid HIV home tests that allow the testers to learn their status privately by simply swabbing along their gum lines are also available (www.oraquick.com).

Nonspecific laboratory findings with HIV infection may include anemia, leukopenia (particularly lymphopenia), and thrombocytopenia in any combination, elevation of the erythrocyte sedimentation rate, polyclonal hyper-gammaglobulinemia, and hypocholesterolemia. Cutaneous anergy is common [1,2,3].

The absolute CD4 lymphocyte count is the most commonly utilized marker for providing prognostic information and guiding therapy decisions. As the counts decline, the likelihood of serious opportunistic infections over the next 3-5 years rises. There are several limitations associated with the use of the CD4 count, such as diurnal variation, depression due to intercurrent illness, and variability both within and between laboratories. Consequently, the trend in counts is more significant than any single measurement. The frequency of count performance is contingent upon the patient's health status and whether they are undergoing antiretroviral treatment. All patients, irrespective of their CD4 count, should be offered ART; CD4 counts should be monitored every 3-6 months for those on stable ART. It is advisable to initiate Pneumocystis jirovecii prophylactic therapy when the CD4 count falls below 200 cells/mcL, and to start Mycobacterium avium prophylaxis when the CD4 count drops below 75-100 cells/mcL.

Some studies suggest that the percentage of CD4 lymphocytes is a more reliable indicator of prognosis than the absolute counts because the percentage does not depend on calculating a manual differential. While the CD4 count measures immune dysfunction, it does not provide a measure of how actively HIV is replicating in the body. HIV viral load tests (discussed below) assess the level of viral replication and provide useful prognostic information that is independent of the information provided by CD4 counts [3].

Differential Diagnosis:

HIV infection may mimic a variety of other medical illnesses. Specific differential diagnosis depends on the mode of presentation. In patients presenting with constitutional symptoms such as weight loss and fevers, differential considerations include cancer, chronic infections such as tuberculosis and endocarditis, and endocrinologic diseases such as hyperthyroidism. When pulmonary processes dominate the presentation, acute and chronic lung infections must be considered, as well as other causes of diffuse interstitial pulmonary infiltrates. When neurologic disease is the mode of presentation, conditions that cause mental status changes or neuropathy, e.g, alcoholism, liver disease, kidney dysfunction, thyroid disease, and vitamin deficiency-should be considered. If a patient presents with a headache and a cerebrospinal fluid pleocytosis, other causes of chronic meningitis enter the differential. When diarrhea is a prominent complaint, infectious enterocolitis, antibiotic-associated colitis, inflammatory bowel disease, and malabsorptive symptoms must be considered [3].

References:

1.     Centers for Disease Control and Prevention. Diagnoses of HIV Infection in the United States and Dependent Areas, 2012. HIV Surveillance Report. 2014;24. http://www.cdc.gov/hiv/library/reports/surveillance

 

2.     Panel on treatment of HIV-infected pregnant women and prevention of perinatal transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. July 31, 2012 Guideline. http://aidsinfo.nih.gov/contentfiles/lvguidelines/Perinatalil. pdf

 

3.       World Health Organization. HIV/AIDS. Fact sheet No. 360. November 2014. http://www.who.int/mediacentre/factsheets/1s360/en/

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