Hiv infection Z21; B20-B24

First cases occurred in Africa and Haiti.

1983: Luc Montagnier gave the virus the name LAV (lymphadenopathia-associated virus).

Robert Gallo named the virus HTLV-3 ("human T-lymphotropic virus") a little later.

Serious infectious disease caused by the human immunodeficiency virus (HIV 2 and HIV2 - see Retroviridae below), characterised by a progressive loss of cellular defence, characterised by an increasing incidence of opportunistic infections and certain tumours.

HIV 1 and HIV 2 (old names HTLV III and LAV), human pathogenic retroviruses from the subfamily of lentiviruses in the large family of Retroviridae.

They infect cells that carry the CD4 receptor and coreceptors (e.g. CCR5, CXCR4), e.g. T helper cells, monocytes, macrophages, dendritic cells, microglia.

• adults:
  • Clinical categories of HIV infection in adults (see table below).
  • Laboratory categories in adults:
    • Category 1: CD4 cells/μl ≥ 500
    • Category 2: CD4 cells/μl 200-499
    • Category 3: CD4 cells/μl < 200.
  • CDC Classification of 1993, (see below): The CDC classification allows important prognostic statements:
    • AIDS patients are classified in stage C.
    • All patients with > 500 CD4 cells/μl and asymptomatic patients with > 200 CD4 cells/μl are in stage A.
    • Exceptions: patients with > 500 CD4 cells/μl and a Kaposi sarcoma, non-Hodgkin lymphoma or tuberculosis = stage C.
    • All other patients are in stage B.
• children:
  • Clinical classification of HIV infection in children (see table below).
  • Immunological classification of HIV infection in children (see table below).

Prevalence (Germany, 2007): about 59 000 people with HIV/AIDS. Approximately 9000 people from high-prevalence regions (mainly migrants from sub-Saharan Africa) were affected.

New infections (Germany; 2007): n = approx. 2750. 1100 new AIDS cases were also reported to the RKI.

Increase in HIV infections among homosexual men in Germany since 2001 (due to increased promiscuity, dulled awareness of unsafe sex, easier sexual contacts through the Internet).

There is a high rate of co-infection with other sexually transmitted diseases (STI). Up to 60% of HIV positive participants in the KABASTI study report having had an STI in the last 12 months. The prevalence of HSV-2 antibodies is 30-50%. Up to 95% of all HIV-infected persons have undergone hepatitis B, about 10-15% have chronic hepatitis B. About 15% are coinfected with HCV/HIV. Up to 80% of those infected in Germany are TPHA-positive, up to 15% of those infected with syphilis have an HIV infection.

HIV infection through sexual intercourse, blood transfusions, contaminated cannulae, etc., organ transplants, during pregnancy (diaplacental, perinatal, via breast milk), artificial insemination. Here the so-called rule of three has been established. The risk of contracting HIV, hepatitis-C and hepatitis-B from a needlestick injury is, in ascending order, 0.3% (HIV), 3% (hepatitis-C), 30% (hepatitis-B).

Risk groups in Europe and USA: homosexuals, intravenous drug users, prostitutes, pre-1986: Hemophiliacs, recipients of blood transfusions.

Hierarchy of infection probabilities for HIV transmission (ordered by decreasing probability of infection, highest probability first:

• Sharing injection paraphernalia.
• Unprotected ingestive anal intercourse
• Unprotected receptive vaginal intercourse
• Unprotected penetrative vaginal intercourse
• Unprotected penetrative anal intercourse
• Receptive oral intercourse (when sperm is ingested).

Acute HIV infection (acute infection stage): In about 30% of patients, the infection stage is asymptomatic.

70% of infected individuals develop flu-like symptoms such as fever, headache, vomiting, diarrhea, and arthralgias due to viremia after 3-12 weeks. Lymph node swelling, morbilliform or maculopapular exanthema, and pharyngitis are also possible (see also acute retroviral syndrome). Not infrequently, the clinical picture resembles the course of infectious mononucleosis. There is a rapid rise and fall of HIV RNA with dissemination of HIV into the lymphatic tissue. In 10% of cases, neurological complications appear as the initial clinical manifestation (acute HIV meningoencephalitis). CD4 lymphocytes decrease for several weeks, whereas CD8 cells increase intermittently. HIV serology may be negative during this phase!

Clinically asymptomatic HIV infection (latency stage): The duration of this stage varies from a few weeks to several years, during which no symptoms occur. In this stage HIV antibodies are detectable. If untreated, there is a slow increase in the HI viral load. Clinically, lymphadenopathy syndrome (LAS) and AIDS-related complex (ARC) may occur. This stage is reached when at least two enlarged extrainguinal lymph nodes persist for a period of 3 months, or when episodes of fever of unclear etiology persist for more than 4 weeks, or when refractory diarrhea is observed without evidence of pathogens. Also, candidiasis of the oral mucosa (oral thrush), oral hairy leukoplakia, bacterial infections (e.g., Streptococcus pneumoniae, Salmonella), zoster, or severe herpes simplex virus disease may occur.

AIDS stage: If untreated, the AIDS stage is reached after 1-15 years. Due to progressive loss of cellular immunocompetence, occurrence of wasting, multiple opportunistic infections (e.g. Pneumocystis carinii pneumonia, toxoplasmosis, cytomegalovirus infections, atypical mycobacterioses or tuberculosis), tumors or progressive multifocal leukoencephalopathy (Jacob-Creutzfeld virus). 30-60% of all HIV-infected individuals develop neurologic complications.

Neoplasms include basal cell carcinoma, squamous cell carcinoma, cervical CA, anal intraepithelial neoplasia, anal carcinoma, Kaposi's sarcoma, and NHL lymphoma. In recent years, HIV-typical malignancies such as Kaposi's sarcoma have been declining; in contrast, the incidence of non-HIV-associated skin cancers has been increasing (older age on HAART, thus higher relevance of usual risk factors).

Condylomata acuminata are frequently diagnosed. Latent HPV infections exist in 90% of cases.

Notice. In treated patients, due to HAART and multiple prophylactic measures, the time courses until reaching the AIDS stage or the duration of the AIDS stage are often strongly protracted or the progression of the disease is strongly slowed down.

Detection of infection: Antibody detection (anti p24, anti gp 120/160) in ELISA and Western blot. Seroconversion usually 2-6 weeks after infection, but also possible after months. Antigen detection with polymerase chain reaction (HIV-spec. DNA) possible after 7 days. P24 in serum (core protein).

Detection of cellular immunodeficiency: Most important criterion is the reduction of the CD4 cell count below 500/μl. Furthermore: Decrease of the CD4/CD8-quotient below 1,2 and the total lymphocyte count.

Additional immunological diagnostics (parameters correlating with the disease activity): circulating immune complexes, CRP, beta-2-microglobulin, neopterin, gamma-globulins, lymphokines, interferon gamma, interleukin-2-receptors.

Since 2004, several infectious diseases caused by opportunistic pathogens have been detected in adults without immunodeficiency. They were not infected with HIV but, similar to AIDS, showed clinical manifestations due to extremely low immunity. The term"adult-onset immunodeficiency syndrome" was proposed to describe this new type of disease, as the main patient group consists of adults. To date, a few studies on AOID have been conducted and published. The cumulative reports confirmed the crucial role of anti-IFN-γ autoantibodies in the pathogenesis of AOID (Chen LF et al. 2021).

• S.a.u. HAART. S.a.u. HIV infection, post-exposure prophylaxis.
• Based on recent study results, the therapy of HIV infection has been fundamentally reconsidered in recent years. Whereas in the past therapy was only started for symptomatic HIV patients or for patients with < 500 CD4 cells/μl or later, today the indication for therapy is no longer based on the CD4 cell number/μl or the occurrence of HIV-associated diseases alone, but mainly on the viral load (HIV-RNA copies/ml) and the course of the CD4 cells in the blood, since it is known that patients with a high viral load fall ill with AIDS much faster.
• More than 20 preparations and combinations of preparations are now available for therapy, and more are in clinical approval studies. The aim of the therapy must be to reduce the viral load by at least 2 log10 levels or to bring it below the detection limit (control of the viral load before initiation of therapy, after 4 weeks and subsequently at intervals of 1-3 months). As a rule, antiretroviral combination therapy is started. An additional problem is the possible development of resistance of the reverse transcriptase or the viral protease, which can lead to the ineffectiveness of individual preparations in the therapy. For the above-mentioned reasons, the indication for regular determination of the viral load arises (e.g. initially for 3 months 4-weekly, then 3-monthly). If therapy failure is suspected, genotypic ("genotyping") and, if necessary, phenotypic ("phenotyping") resistance testing should be carried out before therapy is implemented. The occurrence of resistance can be expected at different points in time for the various substances: if the viral load increases again, the antiretroviral therapy should be changed, taking the resistance situation into account.
• In addition to adequate antiretroviral therapy, primary prophylaxis against opportunistic infections plays an important role in advanced immunodeficiency.
• The efficacy of the therapy is largely dependent on the patient's compliance. It is also discussed whether a single dose of antiretroviral therapy is superior to multiple doses. However, due to the small number of cases, the data situation is not clear. Further studies are needed to clarify this issue.
• Treatment of HIV-discordant couples who wish to have children: The counselling and care of HIV-discordant couples who wish to have children is an interdisciplinary task based on comprehensive diagnostics. If the husband or wife is infected with HIV, assisted reproduction techniques can be used to achieve the desire for children with at best a hypothetical residual risk of infection for the healthy partner. If the woman is HIV-infected, the fertile couple should be informed about the possibilities of self-insemination. In view of the current state of knowledge, especially because of the risk of material-fetal transmission and the liability considerations mentioned above, decisions on active reproductive medical therapy can only be made in individual cases. Of course, these assessments must be adapted to future developments.

The clinical categories of HIV infection in adults

CDC classification of HIV infection for adults (CDC, 1993).

Clinical classification of HIV infection in children

Immunologic staging of HIV infection in children (CDC, 1994).

Dermatologic manifestations of HIV infection.

Median survival of HIV patients with < 500 CD4 cells/μl as a function of viral load.

Primary prophylaxis against opportunistic infections

In recent years, the life expectancy of HIV-infected patients has increased significantly. Despite all the progress made, concomitant diseases are gaining in importance and consume part of the increase in years and quality of life. With the availability of antiretroviral therapy, non-AIDS-associated events now account for 42% of all deaths in the USA, with cardiovascular diseases in first place, followed by liver and lung diseases, even before tumours. According to a survey of HIV-specialized hospitals in France, already in 2000 (4 years after the introduction of highly active antiretroviral therapy) 28% of all deaths were due to tumor diseases, 45% of which were non-AIDS-defining. In addition to lymphomas, Kaposi's sarcoma and cervical carcinomas, bronchial carcinomas, hepatocellular carcinomas and anal carcinomas were the most common.

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