Hiv infection Z21; B20-B24

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 23.04.2021

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Synonym(s)

HIV

Definition
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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.

Pathogen
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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 carrying the CD4 recept or and coreceptors (e.g. CCR5, CXCR4), e.g. T helper cells, monocytes, macrophages, dendritic cells, microglia.

Classification
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  • 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).

Occurrence/Epidemiology
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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.

Etiopathogenesis
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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 needle stick 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, before 1986: Haemophiliacs, 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 semen is ingested).

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

70% of infected persons develop flu-like symptoms such as fever, headache, vomiting, diarrhoea and arthralgia 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 in HIV RNA with dissemination of HIV into the lymphatic tissue. In 10% of cases, neurological complications appear as the first clinical manifestation (acute HIV meningoencephalitis). CD4 lymphocytes decrease for several weeks, while CD8 cells increase intermittently. HIV serology can 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 phase HIV antibodies are detectable. If left untreated, the HI viral load slowly increases. Clinically, a lymphadenopathy syndrome (LAS) and the AIDS-related complex (ARC) can occur. This stage is reached when at least two enlarged extrainguinal lymph nodes persist for more than 3 months, or when fever episodes of unclear origin persist for more than 4 weeks, or when diarrhoea refractory to therapy is observed without evidence of pathogens. Candidosis of the oral mucosa (oral thrush), oral hairy leukoplakia, bacterial infections (e.g. Streptococcus pneumoniae, Salmonella), zoster or severe herpes simplex virus disease may also 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), tumours or progressive multifocal leukoencephalopathy (Jacob-Creutzfeld virus). 30-60% of all HIV-infected persons develop neurological 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 on the decline; in contrast, the incidence of non-HIV-associated skin cancers has been on the rise (older age under HAART, thus higher relevance of the 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 to reach the AIDS stage or the duration of the AIDS stage is often greatly protracted or the progression of the disease is greatly slowed down.

Diagnosis
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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.

Therapy
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  • 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.

Tables
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The clinical categories of HIV infection in adults

Category A

(asymptomatic stage of infection)

Asymptomatic HIV infection

persistent generalized lymphadenopathy (LAS)

acute, symptomatic (primary) HIV infection (including history)

Category B

(symptomatic pat.

without AIDS)

bacillary angiomatosis

oropharyngeal Candida infections

vulvovaginal Candida infections

cervical dysplasia or carcinoma in situ

constitutional symptoms (fever > 38.5 °C, diarrhoea > 4 weeks)

oral hairy leukoplakia

herpes zoster with involvement of several dermatomes or after recurrence in one dermatome

idiopathic thrombocytopenic purpura

Listeriosis

pelvic inflammatory disease, especially with complications of tubal or ovarian abscesses

peripheral neuropathy

Category C

(symptomatic pat.

with AIDS)

Pneumocystis carinii pneumonia

Toxoplasma encephalitis

esophageal candida infection or infestation of bronchi, trachea or lungs

chronic herpes simplex ulcers or bronchitis, pneumonia, esophagitis

CMV retinitis

generalized CMV infection (not of liver or spleen)

recurrent salmonella septicaemia

recurrent pneumonia within one year

extrapulmonary cryptococcal infections

chronic intestinal cryptosporidium infection

chronic intestinal infection with Isospora belli

disseminated or extrapulmonary histoplasmosis

Tuberculosis

MAI infections

Kaposi's sarcoma

malignant lymphomas (Burkitt, immunoblastic, primary cerebral lymphoma)

invasive cervical carcinoma

HIV encephalopathy

progressive multifocal leukoencephalopathy

wasting syndrome

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

CD4 cells/μl

Clinical category

A (asymptomatic)

B (symptoms, no AIDS)

C (symptoms, AIDS)

≥ 500

A1

B1

C1

200-499

A2

B2

C2

< 200

A3

B3

C3

Clinical classification of HIV infection in children

Mild symptoms

Lymphadenopathy, hepatomegaly, splenomegaly

Dermatitis

Parotitis

Rec. Upper respiratory tract infections, incl. otitis media

Moderate symptoms

Lymphocytic interstitial pneumonitis (LIP)

Growth retardation

recurrent or persistent sinusitis

Hematological disorders (anemia, neutropenia, thrombocytopenia)

cardiomyopathy

hepatitis

Nephropathy

Severe symptoms

frequent or recent severe bacterial infections

recurrent or chronic Diarrhoea

Bronchiectasis

persistent fever of unknown origin

opportunistic infections

recent or persistent oral, esophageal or pulmonary candidiasis

recent or persistent herpes simplex (HSV) stomatitis

multidermatodermal or disseminated herpes zoster (VZV)

infections with Mycobacterium tuberculosis (extrapulmonary or disseminated)

disseminated infections with other mycobacteria

progressive multifocal leukoencephalopathy

opportunistic infections with onset after 1 month of life

Pneumocystis carinii pneumonia

cytomegalovirus (CMV) infections

Toxoplasmosis

HSV bronchitis, pneumonitis or esophagitis

Tumor diseases

primary CNS lymphoma

other non-Hodgkin lymphomas

Leiomyosarcoma

Kaposi's sarcoma

Encephalopathy with significant developmental delay

developmental arrest

restricted head circumference growth

brain atrophy

acquired symmetrical movement disorder (paresis, ataxia, pathological reflexes, gait disorder)

"wasting syndrome", i.e. without a competing disease sufficient to explain persistent weight loss

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

Age < 12 months

Age 1-5 years

Age 6-12 years

Immunological class

CD4 cells/μl (%)

CD4 cells/μl (%)

CD4 cells/μl (%)

1 = no to little immunosuppression

≥ 1500 (≥ 25)

≥ 1000 (≥ 25)

≥ 500 (≥ 25)

2 = moderate immunosuppression

750-1499 (15-24)

500-999 (15-24)

200-499 (15-24)

3 = severe immunosuppression

< 750 (< 15)

< 500 (< 15)

< 200 (< 15)

Dermatologic manifestations of HIV infection

Pathogen

Disease / manifestation

Fungal infections

Candida spp.

oral candidosis, candidavulvovaginitis, candidabalanitis

Pityrosporon ovale

Pityriasis versicolor, Pityrosporon folliculitis

Dermatophytes

Tinea corporis and Tinea profunda, Onychomycosis

Cryptococcus neoformans

cutaneous cryptococcosis

Histoplasma capsulatum

cutaneous histoplasmosis

Aspergillus fumigatus

cutaneous aspergillosis

Bacterial infections

Staphylococci

large blistered impetigo contagiosa, varioliform pyoderma, folliculitides, furunculosis

Streptococci

erysipelas, ecthyma

Bartonella spp.

bacillary angiomatosis

Mycobacterium tuberculosis

Tuberculosis cutis luposa

M. avium intracellulare

cutaneous atypical mycobacteriosis

Treponema pallidum

Syphilis

Viral infections

Herpes simplex virus

rec. Herpes labialis or genitalis, ulcerative genital herpes, herpes simplex generalisatus

Varicella zoster virus

Varicella, herpes zoster over several dermatomes, herpes zoster generalisatus

Epstein-Barr virus

oral hairy leukoplakia

Poxvirus mollusci

Mollusca contagiosa

Cytomegalovirus

especially perianal ulcers (see below cytomegaly)

human papillomaviruses

Condylomata acuminata, AIN, PIN, VIN, KIN, Verrucae vulgares

Infections by protozoa

Toxoplasma gondii

cutaneous toxoplasmosis

Infestation by mites

Sarcoptes scabiei

Scabies

Demodex folliculorum

Demodex folliculitis

Tumors

Human herpes virus 8

Kaposi's sarcoma

Other

seborrheic eczema

Exsiccation eczema

Habitual aphthae

hypersensitivity syndrome after carbamazepine

purpura in autoimmune thrombocytopenia

sterile eosinophilic pustulosis

psoriasis vulgaris

zidovudine-associated melanoonychia and cutaneous hyperpigmentation

drug exanthema up to Lyell syndrome, especially under HAART, cotrimoxazole, and penicillin therapy

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

HIV RNA [copies/ml]

Median time to AIDS [years]

< 500

> 10

500-3.000

> 10

3.000-10.000

8,3

10.000-30.000

5,5

> 30.000

2,8

Primary prophylaxis against opportunistic infections

Opportunistic infection

Indication/ discontinuation of primary prophylaxis

Substance

Dosage

Preparation

Pneumocystis carinii pneumonia

Indicated for < 200 CD4 cells/µl

Cotrimoxazole

960 mg 3 times/week p.o.

Eusaprim forte, Cotrim forte

Alternative:

Dapsone

2 times/week 100 mg p.o.

Dapson-Fatol

Discontinue if increase > 200 CD4 cells/µl persists (for 3-6 months) on antiretroviral therapy.

Alternative:

Pentamidine

1 time 300 mg/month per inhalationem (e.g. with Respigard II or Fisoneb nebulizer)

Pentacarinate

Cerebral toxoplasmosis

Indicated for < 150 CD4 cells/µl

Cotrimoxazole

960 mg 3 times/week p.o.

Eusaprim forte

Alternative: combination dapsone + pyrimethamine

Dapsone

200 mg/week

Dapsone-Fatol

Discontinuation in case of persistent increase > 200 CD4 cells/µl (for 3-6 months) under antiretroviral therapy

in combination with

Pyrimethamine

75 mg/week

Daraprim

Atypical mycobacteriosis

Consider with CD4 cells < 50

Azithromycin

1 time 1200 mg/week

Ultreon

Alternative:

Clarithromycin

2 times/day 500 mg

Mavid

Discontinue if increase > 100 CD4 cells/µl persists (for 3 months) on antiretroviral therapy.

Factors that may increase the risk of transmission in infected (I) or exposed (E) individuals.

Factor by which the risk of transmission is increased

Presence of a bacterial sexually transmitted disease (I/E) (e.g. gonorrhoea, lues, trichomonads, chlamydia)

2-5

Genital herpes simplex (I/E)

5-10

Intact foreskin compared to circumcised men during insertive vaginal (anal?) sexual intercourse

2-3

High plasma viral load (I) (reference value: viral load > 2500 copies/ml)

10- > 30

Fresh HIV infection (I), seroconversion syndrome

10-100

First exposure to HIV (E)

not known

Vaginal intercourse during menstruation (I/E)

not known

Type of contact/partner

Likelihood of infection/contact

Unprotected receptive anal intercourse with known HIV-positive partner

approx. 0.82%

Unprotected receptive anal intercourse with partner of unknown HIV serostatus

approx. 0,27%

Unprotected insertive anal intercourse with partner of unknown HIV serostatus

approx. 0,06%

Unprotected receptive vaginal intercourse

about 0,1%

Unprotected insertive vaginal intercourse

approx. 0.035.6% (depending on source)

Oral sex

No probability known, but individual cases have been described, especially when semen is ingested in the mouth.

Type of HIV exposure

Exposure risk in relation to the mean risk of HIV transmission

Very deep stab or cut injuries

16:1

Visible, fresh traces of blood on the injuring instrument

5:1

Injuring needle or cannula previously placed in a vein or artery

5:1

Index person has high viral load (acute HIV infection, AIDS without ART)

6:1

Exposure of mucosa

1:10

Exposure of inflammatory skin lesions

1:10

Note(s)
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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.

Literature
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Authors

Last updated on: 23.04.2021