Table of Contents
Definition and Overview
HIV (Human Immunodeficiency Virus) is a blood borne virus transmitted through unprotected sexual contact, infected intravenous injections or transfusion and mother to child during birth process and breastfeeding. It causes an acquired immune deficiency and has different latency periods from individual to individual. Immune deficiency depends primarily on the progressive destruction of CD-4 Helper T cells.
Acquired Immune Deficiency Syndrome (AIDS) describes the late stages of HIV infection and is characterized by opportunistic diseases (AIDS-defining diseases). To date, there is no causal therapy for the disease.
The antiretroviral therapy HAART has presented at the world AIDS congress in Vancouver in 1996, 15 years after the first report about AIDS in the “Morbidity and Mortality Weekly Report”. Due to further development and increased availability of the treatment, the worldwide morbidity rate was able to be massively reduced. There were 1.5 million deaths due to the disease in 2013, whereas in the middle of the previous decade, that figure was still 2.2 million.
Epidemiology of AIDS
Strong prevalence of AIDS in West Africa
According to UNAIDS, the last major wave of infection in the USA occurred in the 1980s. Large scale campaigns promoting “Safer Sex” helped to reduce the number of new cases by 1990. An estimate in 2010 suggested there were 33 million infected people worldwide, and 2.6 million new cases each year (UNAIDS).
Worldwide: The most affected area in the world is sub-Saharan Africa approxiamately 5.2% of the population. HIV-1 is pandemic and is primarily found in West Africa. In Eastern Europe, the number of new cases has dramatically increased by 21 % in the last few years. Swaziland has the highest overall prevalence of HIV infection.
USA: Although more females are infected worldwide, bisexual males are primarily affected in the USA. Each year there are approximately 50,000 new cases diagnosed in the United States alone.
Germany: Men are the most affected with about 65,000 infected (Germany, 2013), women 15,000. About 3,000 women are newly diagnosed each year.
Age-sex race related differences in incidence
HIV infection is observed highest among the Hispanic persons probably due to socioeconomic factors rather than genetic causes.
Males are more likely to acquire HIV infection in United States. In developing countries, males has more predilection towards HIV infection.
Young adults are at highest risk of the disease exposure as they are highly involved in unprotected sexual intercourse. Children acquire infection through mother by trans parental transmission and breastfeeding.
Etiology and Pathogenesis of AIDS
HIV-1 and HIV-2 are retroviruses belonging to the lentivirus genus. They are cuboid, enveloped viruses with linear (single strand) RNA. Genetic information is stored in the RNA: reverse transcriptase from the human host is used to transcribe the RNA into protein-coding DNA.
The target cells are all CD4 receptor-carrying cells:
- T-Helper Cells
- CD4 positive monocyte cells: Monocytes, macrophages, and dendritic cells.
HIV enters the Langerhans cells through mucous membrane defects and is then further transported to the lymph nodes. The virus penetrates the T-Lymphocytes through their CD4 receptors and destroys them. The virus spreads through the rest of the body through lymphatic vessels. This results in severe immune deficiency with the risk of contracting major opportunistic infections.
Transmission of HIV
All bodily fluids contain the Human Immunodeficiency Virus in varying quantities. The most significant amounts are found in blood, sperm, vaginal secretions and breast milk. The likelihood of transmission depends upon the virus load.
The most common route of infection is homosexual intercourse in males followed by infection via heterosexual intercourse. In these cases, the risk of infection depends on the size of the virus load in the secretions exchanged.
The third most common method of transmission is from intravenous drug abuse (7,800) with the practice of sharing needles. Transmission within medical professions may occasionally occur through accidental needle puncture with an infected needle.
Trans-placental mother-child transmissions are infrequent (1 in 1 million). It occurs during pregnancy or birth.
Incubation period for HIV
The incubation period is between three and six months and is usually not apparent during the first two months. In 6 % of infections, the disease becomes AIDS after around two years.
CDC Stages of HIV Infection
The CDC (Center for Disease Control) stages allow for classification of the progression of the disease in combination with the Helper T-Cell count. The normal value for helper T-lymphocytes is 650 – 1250/μl.
|A1, B1, C1||Helper T Lymphocytes > 500/μl|
|A2, B2, C2||Helper T Lymphocytes 200 – 499/μl|
|A3, B3, C3||Helper T Lymphocytes < 200/μl|
There are three stages. Stage A can be accompanied by an influenza-like symptom complex (50—90 % also suffer from acute retroviral syndrome – fever, angina, lymphadenopathy, exanthema, muscle and joint pain), however, even completely asymptomatic patients (latent phase) suffer from reduced performance, symptoms of exhaustion such as tiredness and lethargy.
Lymphadenopathy syndrome is defined as generalized lymph node swelling for longer than three months.
This stage is asymptomatic and chronic in nature. Patient does not exhibit any symptom. HIV is still active and reproduced in very low level. The disease is still transmeable in this stage. Those patient who are on ART can remain in this stage for decades and are not contagious.
Stage C: AIDS-defining diseases
AIDS is most severe phase of HIV infection with deteriorated immune system and severe illness. Patients having AIDS can exhibit high viral load and can be highly infectious. The pathogen spectrum of opportunistic infections that do not cause infection in immunocompetent people is far reaching.
- Wasting Syndrome with significant cognitive and vigilance impairment, depression and ataxia
- Encephalopathy associated with HIV: slowly progressing dementia with deficits in emotion, cognition and motor skills due to progressive CNS inflammation
Amongst the known AIDS-defining diseases are :
- Herpes Zoster
- Oral hairy leukoplakia
- Chronic diarrhea
- Changes in the blood count with anemia, thrombocytopenia, and neutropenia
- Infections with molluscumcontagiosum
- Tubo-ovarian abscesses
- Cerebral Toxoplasmosis (most common neurological AIDS Manifestation)
- Salmonella septicemia
Mycotic and parasitic infections
- Pneumocystis jirovecii pneumonia
- Cryptococcal meningitis
- Coccidioidomycosis (extrapulmonary/disseminated)
- Cytomegalic manifestations
- Herpes Simplex encephalitis
- Progressive multifocal Leukoencephalopathy (triggered by the JC virus, John Cunningham virus, a type of human polyomavirus (formerly known as papovavirus) )
Non-Hodgkin’s Lymphoma of the B Cell type
- Cervical carcinoma
- Kaposi sarcoma (associated HHV8)
- Invasive cervical carcinoma and anal carcinoma
Diagnosis of AIDS
Anamnesis and clinical examination of AIDS
The anamnesis should focus in particular on health complaints, medication, travel, and sexual history. The clinical examination should particularly focus on weight, lymph node status and opportunistic infections.
Pathogen identification and CD4 cell count
Indirect viral screening
- Screening test: Antibody screening with HIV ELISA. ELISA has a high sensitivity but not 100 % specificity. A positive test result requires further testing to confirm the findings.
- Confirmatory test: Western blot. The western blot test has a very high specificity but despite that, a second positive confirmatory test should be performed before giving the results back to the patients.
Direct virus identification
Direct identification of HIV can be done by electron microscopy, virus isolation, and PCR testing.
Virus quantification via PCR serves as a therapeutic device and also for monitoring purposes. The detection limit is 20—50 copies/ml.
Determination of the CD4 Helper T Lymphocyte count
The amount of CD4 Helper T Lymphocytes can be determined via flow cytometry. The CD4 count is a component of CDC classification.
|Stage||Possible differential diagnosis||Landmark studies|
|Acute retroviral syndrome||
Source: Genzwürker et al. (2014): AllEX – Alles fürs Examen. Thieme Verlag, p. 533.
Therapy of AIDS
Antiretroviral Treatment for AIDS prevention
The current recommendation for initiation of HAART is a lower limit for Helper T Cell value of 200/µl. It has been argued that it should begin as early as 200—350/µl.
Currently, HAART (highly active antiretroviral therapy) consists of at least three antiretroviral drugs used to treat HIV infection: two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). The term HAART is presently being replaced by cART (combined anti-retroviral therapy) as this term better describes the combination of drugs used.
- 2 Nucleoside reverse transcriptase inhibitors (NRTI): Zidovudine (AZT), Lamivudine, Abacavir
- 1 Non-nucleoside reverse transcriptase inhibitor (NNRTI): Nevirapine, Efavirenz
- 1 Protease Inhibitor (PI): Indinavir, Ritonavir, Nelfinavir, Lopinavir
- 1 Integrase Inhibitor: Raltegravir
Chemoprophylaxis: In order to avoid an outbreak of opportunistic infections, chemoprophylaxis is carried out consisting of co-trimoxazole (for pneumocystis jirovecii pneumonia and toxoplasmosis) and isoniazid (for tuberculosis)
A detailed overview of antiretroviral therapy can be found in “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents”.
Among the undesirable side effects of antiretroviral therapy are:
- Bone marrow depression
- Headaches, nausea
- Hypersensitivity reactions
Metabolic changes are most commonly observed during treatment with cART/HAART: Lipoatrophy, lipodystrophy, impaired glucose tolerance (IGT), diabetes mellitus and hyper- or dyslipidemia. These changes are associated with an increased cardiovascular risk.
How AIDS can be avoided
- “Safer sex“ (Using condoms)
- Education for the general public
- Avoiding sexual intercourse with unknown and promiscuous partners
- Use of sterile instruments for drug abuse
- In medical professions: protective gloves, face masks, and protective glasses
Post-Exposure prophylaxis (PEP)
In the case of accidental contact with exposure to the mucous membranes or parenteral contact with potentially HIV containing materials, PEP can be considered within 72 hours of exposure to HIV. The risk of infection due to a percutaneous injury: 1 in 300. Immediate PEP with antiretroviral drugs has been proven to be effective in case-control studies. PEP does not only play an important role in medical professionals, but it has also been successfully used after unprotected sexual intercourse (i.e. following a rape) or after patients have shared needles during drug abuse.
Prognosis of AIDS
The mortality rate of untreated HIV is poor up to more than 90 %. The average survival time from infection to death is 8-10 years in untreated cases. Once it has advance to AIDS, the survival time reduces to less than 2 years. Mortality is higher in intravenous drug users.
Access to drugs determines the progression of AIDS
Since the introduction of antiretroviral therapy, the life expectancy of HIV patients has drastically changed.
However, this is only the case if two main points are observed in patients:
- Access to drugs
The Swiss Cohort Study, initiated in 1988 was able to determine that only 9 % of HIV patients died from AIDS, while 24 % died from AIDS-defining cancers. The Swiss Cohort Study (SHCS) is a longitudinal study within Swiss university hospitals, Canton hospitals and practicing doctors who treat HIV patients. Its primary aim is to “provide optimal patient care, reduce HIV transmission and to conduct research”. This progress is naturally not in line with the global situation, where the majority of patients still have no access to the necessary drugs.
Answers can be found below the references.
1. Which of the following groups of drugs does not belong to the antiretroviral AIDS treatments?
- Nucleoside Reverse Transcriptase Inhibitors
- Non-Nucleoside Reverse Transcriptase Inhibitors
- Transferase Inhibitors
- Protease Inhibitors
- Integrase Inhibitor
2. Which of these diseases is typical for stage C in the CDC stage classification system for HIV infection?
- Oral hairy leukoplakia
- Chronic diarrhea
- Tubo-ovarian abscesses
- Cryptococcal Meningitis
3. HIV is a retrovirus. Which group do retroviruses belong to?