Hiv infection Z21; B20-B24

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

HIV

Definition
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Severe infectious disease caused by the human immunodeficiency virus (HIV), characterized by an increasing loss of cellular defense, characterized by an increasing incidence of opportunistic infections and certain tumors.

Pathogen
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HIV-1 and HIV-2 (old designations HTLV III and LAV), human pathogenic retroviruses from the lentivirus subfamily They infect cells that carry the CD4 receptor 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 cannulas etc., organ transplants, during pregnancy (diaplacental, perinatal, through breast milk), artificial insemination.

Risk groups in Europe and the USA: homosexuals, intravenous drug users, prostitutes, before 1986: haemophiliacs, recipients of blood transfusions.

Hierarchy of infection probabilities for HIV transmission (order according to decreasing probability of infection, highest probability first:

  • Common use of injection equipment
  • Unprotected recording anal intercourse
  • Unprotected ingestive vaginal intercourse
  • Unprotected invasive vaginal intercourse
  • Unprotected invasive anal sex
  • Engaging in ingestive oral sex (when sperm is ingested).

Clinical features
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  • Acute HIV infection (acute stage of infection): In about 30% of patients the stage of infection is asymptomatic.
  • 70% of infected persons develop flu-like symptoms such as fever, headache, vomiting, diarrhoea and arthralgia after 3-12 weeks due to viremia. Lymph node swelling, morbilliform or maculopapular exanthema and pharyngitis are also possible (see also acute retroviral syndrome). The clinical picture is often similar to 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 a clinical first manifestation (acute HIV meningoencephalitis). The CD4 lymphocytes decrease for a few weeks, while the CD8 cells temporarily increase. The HIV serology can be negative during this phase!
  • Clinically asymptomatic HIV infection (latency stage): The duration of this stage varies between a few weeks and several years, during which no symptoms occur. HIV antibodies are detectable in this phase. Untreated, there is a slow increase in the HIV viral load. Clinically, a lymphadenopathy syndrome (LAS) and the AIDS-Related-Complex (ARC) can occur. This stage is reached when there are at least two enlarged extrainguinal lymph nodes over a period of 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 the pathogen. Candidosis of the oral mucosa (oral thrush), oral hair leukoplakia, bacterial infections (e.g. Streptococcus pneumoniae, Salmonella), zoster or severe herpes simplex virus diseases can also occur.
  • AIDS stage: Untreated, the AIDS stage is reached after 1-15 years. Due to the increasing loss of cellular immunocompetence, wasting, multiple opportunistic infections (e.g. Pneumocystis carinii pneumonia, toxoplasmosis, cytomegalovirus infections, atypical mycobacterioses or tuberculosis), tumors or progressive multifocal leukoencephalopathy (Jacob's disease) occur. 30-60% of all HIV-infected persons develop neurological complications.
  • The neoplasms are basal cell carcinomas, squamous cell carcinomas, cervical CA, anal intraepithelial neoplasias, anal carcinomas, Kaposi's sarcoma and NHL lymphomas. In recent years, the incidence of HIV-typical malignancies such as Kaposi's sarcoma has been declining; in contrast, the incidence of non-HIV-associated skin cancers has been increasing (higher 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 until reaching the AIDS stage or the duration of the AIDS stage is often strongly protracted or the progression of the disease is strongly 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 (also in the medical 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 hair leukoplakia

Herpes zoster with infestation of several dermatomes or after recurrences in one dermatome

idiopathic thrombocytopenic purpura

Listeriosis

Inflammation of the pelvis, especially in the case of complications of a tubal or ovarian abscess

peripheral neuropathy

Category C

(symptomatic Pat.

with AIDS)

pneumocystis carinii pneumonia

Toxoplasma encephalitis

esophageal candida infection or infestation of the bronchi, trachea or lungs

chronic herpes simplex ulcers or bronchitis, pneumonia, esophagitis

CMV retinitis

generalized CMV infection (not of liver or spleen)

recurrent salmonella septicemias

recurrent pneumonia within one year

extrapulmonary cryptococcal infections

chronic intestinal cryptosporidia infection

chronic intestinal infection with Isospora belli

disseminated or extrapulmonary histoplasmosis

Tuberculosis

MAI Infections

Kaposi's Sarcoma

malignant lymphomas (Burkitt's, 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

Slight symptoms

lymphadenopathy, hepatomegaly, splenomegaly

Dermatitis

Parotitis

rez. Infections of the upper airways, incl. otitis media

Moderately severe symptoms

Lymphocytic interstitial pneumonitis (LIP)

Growth arrest

recurrent or persistent sinusitis

haematological disorders (anaemia, neutropenia, thrombopenia)

Cardiomyopathy

Hepatitis

Nephropathy

Severe symptoms

severe bacterial infections or recurrent severe bacterial infections

rez. or chronic. Diarrhea

Bronchiectasis

persistent fever of unknown origin

opportunistic infections

recurrent or persistent oral, esophageal or pulmonary candidiasis

recurrent 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 starting after the 1st month of life

pneumocystis carinii pneumonia

Cytomegaly (CMV) infections

Toxoplasmosis

HSV bronchitis, pneumonitis or esophagitis

Tumour diseases

primary CNS lymphoma

Other non-Hodgkin lymphomas

Leiomyosarcoma

Kaposi's Sarcoma

Encephalopathy with significant developmental delay

Development standstill

limited circumferential head growth

Brain atrophy

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

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


Immunological stages 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 low 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)


Dermatological manifestations of HIV infection

Pathogen

Disease / Manifestation

Fungal infections

Candida spp.

oral candidiasis, candidavulvovaginitis, candidabalanitis

oval pityrosporon

Pityriasis versicolor, pityrosporon folliculitis

Dermatophytes

Tinea corporis and tinea profunda, onychomycosis

cryptococcus neoformans

cutaneous cryptococcosis

histoplasm capsulatum

cutaneous histoplasmosis

Aspergillus fumigatus

cutaneous aspergillosis

Bacterial infections

Staphylococci

large vesicles of impetigo contagiosa, varioliform pyoderma, folliculitis, furunculosis

Streptococci

Erysipelas, Ecthymata

Bartonella spp.

bacillary angiomatosis

mycobacterium tuberculosis

Tuberculosis cutis luposa

M. avium intracellular

cutaneous atypical mycobacteriosis

treponema pallidum

Syphilis

Viral infections

herpes simplex virus

rez. 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 hair leukoplakia

poxvirus mollusci

contagious mollusc

Cytomegalovirus

mainly perianal ulcers (see below cytomegaly)

human papillomaviruses

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

Infections by protozoa

toxoplasma gondii

cutaneous toxoplasmosis

mite infestation

Sarcoptes scabiei

Skabies

Demodex folliculorum

Demodex folliculitis

Tumours

Human herpes virus 8

Kaposi's Sarcoma

Other

seborrheic eczema

Desiccation eczema

habituated aphthae

Carbamazepine hypersensitivity syndrome

Purpura in autoimmune thrombocytopenia

sterile eosinophilic pustulose

psoriasis vulgaris

Zidovudine-associated melanoonychia and cutaneous hyperpigmentation

Drug exanthema up to the Lyell syndrome, especially under HAART, Cotrimoxazol, and penicillin therapy


Median survival time of HIV patients with < 500 CD4 cells/μl depending on 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 at < 200 CD4 cells/µl

Cotrimoxazole

960 mg 3 times/week p.o.

Eusaprim forte, Cotrim forte

Alternatively:

Dapson

2 times/week 100 mg p.o.

Dapsone Fatol

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

Alternatively:

Pentamidine

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

Pentacarinate

cerebral toxoplasmosis

Indicated at < 150 CD4 cells/µl

Cotrimoxazole

960 mg 3 times/week p.o.

eusaprim forte

Alternative: Combination Dapsone + Pyrimethamine

Dapson

200 mg/week

Dapsone Fatol

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

in combination with

Pyrimethamine

75 mg/week

Daraprim

Atypical mycobacteriosis

For CD4 cells < 50 consider

Azithromycin

1 time 1200 mg/week

Ultreon

Alternatively:

Clarithromycin

2 times/day 500 mg

Mavid

discontinuation in case of a persistent increase > 100 CD4 cells/µl (for 3 months) under antiretroviral therapy


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

Factor by which the risk of transmission increases

Presence of a bacterial venereal disease (I/E) (e.g. gonorrhoea, syphilis, trichomonads, chlamydia)

2-5

Genital herpes simplex (I/E)

5-10

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

Initial exposure to HIV (E)

not known

Vaginal intercourse during menstruation (I/E)

not known


Type of contact/partner

Probability of infection/contact

Unprotected receptive anal sex with known HIV positive partner

approx. 0.82% approx.

Unprotected receptive anal sex with partner of unknown HIV sero status

approx. 0.27% approx.

Unprotected advertised anal sex with partner of unknown HIV sero status

approx. 0.06% approx.

Unprotected receptive vaginal intercourse

approx. 0.1 per cent

Unprotected insertive vaginal intercourse

approx. 0.035.6% (depending on source)

oral sex

no probability is known, but individual cases have been described, especially when sperm is taken into the mouth.


Type of exposure to HIV

Exposure risk in relation to the average risk of HIV transmission

Very deep stab or cut injuries

16:1

Visible fresh traces of blood on the injured instrument

5:1

Injuring cannula or needle was 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 changed skin areas

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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Last updated on: 29.10.2020