Symptoms
Stage 1
Some HIV-infected patients develop a flu-like clinical picture 2-3 weeks after infection. The patients develop u.a. Fever, acute swelling of the lymph nodes, discrete exanthema of the trunk, and painful dysphagia.
Stage 2
This acute phase of the disease is usually followed by a symptom-free or asymptomatic period, which can last from months to years. Symptoms of chronic HIV infection are usually nonspecific and include, for example, disturbances of the general condition, indolent lymph node swellings and gastrointestinal complaints. Diseases may occur as a sign of intermittent immunodeficiency, for example external candidiasis or herpes zoster.
Stage 3 – AIDS
The severe, usually life-threatening, manifestation of the disease leads to the full-blown Acquired Immune Deficiency Syndrome (AIDS). Opportunistic infections may occur at this stage. Important examples of these infections are:
– Pneumonias caused by Pneucystis jirovecii (formerly Pneumocystis carinii) – Esophagitides caused by Candida albicans – Cerebral abscesses caused by toxoplasmosis – Reactivations of cytomegalovirus infections.
Malignant neoplasms such as Kaposi's sarcoma also occur at this stage.
Diagnostics
The mainstay of HIV diagnostics is the detection of specific antibodies in combination with the detection of viral antigen or viral nucleic acids. As a rule, specific antibodies can be detected 2-10 weeks after infection with HIV.
Reliable HIV detection is possible with the use of modern screening tests of the 4. Generation usually possible after a maximum of 6 weeks.
Two-stage diagnostics
As a rule, a two-step diagnostic procedure is performed. In the first step of this diagnostic procedure, antibodies against viral antigens and/or viral antigen p24 are detected by ELISA or a comparable test, if available. This is followed by a second highly specific test, the so-called immunoblot, which checks the specificity of the binding of the antibodies to the viral antigens. If the immunoblot result is inconclusive, an HIV nucleic acid amplification test (NAT) can be performed. If this is also inconclusive, the test must be repeated from a second blood sample after 1-3 weeks.
In addition, the number or. the proportion of CD4 helper cells can be determined. In addition to this, the viral load in the blood (viral copies/ml of plasma) and the extent of activation of the immune system are important prognostic markers.
When HIV infection is first diagnosed, other infections should also be ruled out. the serostatus of certain diseases must be clarified. These include, for example, tuberculosis, hepatitides A, B and C, and other sexually transmitted diseases such as z.B. Syphilis or also chlamydia or gonorrhea.
Therapy
General
Antiretroviral therapy, via inhibition of HIV replication, aims to suppress infection-related symptoms and reduce disease progression to achieve reconstitution of cellular immunity. Since the introduction of antiretroviral therapy, the prognosis of HIV patients has improved and the infectiousness or. reduce the risk of transmission.
Reliable use of the drugs is essential for the success of therapy. The therapy must be administered for the rest of the patient's life. In addition, only high antiviral activity and a permanent reduction of the viral load to below 50 RNA copies/ml can prevent the development of resistance with consecutive treatment failure.
Genotypic resistance testing should be performed prior to initiation of therapy, as approximately 10-12% resistant HIV variants are expected in Germany. If resistance is present, the guideline recommends the use of three drugs interpreted as sensitive.
Indications for therapy
Symptomatic HIV-1 infection (CDC stages B and C) is an indication for antiretroviral treatment. HIV nephropathy and symptomatic HIV-associated neurological deficit are also included, according to the guideline.
In asymptomatic patients, an individual risk assessment must be used to decide whether or not patients should receive therapy.
Antiretroviral therapy should also be given if the CD4 cell count is between 200-350/μl, as a significantly reduced risk of progression has also been shown in these patients.
Therapy should be initiated in patients with a CD4 cell count between 350-500/μl. In patients with a CD4 cell count>500/μl, therapy can be given according to the guidelines, as the study situation regarding the benefit of therapy is contradictory.
Pregnancy is an indication for therapy because of the goal of materno-fetal transmission prophylaxis.
Additional criteria for a therapy indication are u.a. a high plasma viremia (>100.000 RNA copies/ml), the patient's desire to reduce infectivity, and chronic hepatitis C (HCV) or B (HBV) co-infection. Older age is also associated with a higher progression rate. Thus represents a therapy indication.
Furthermore, therapy should be initiated if there is a rapid decline in CD4 cell count. A high cardiovascular risk also argues for an earlier start of therapy.
Drugs
Three antiretroviral drugs are usually used in combination, which is referred to as cART (combined Anti-Retroviral Therapy). The use of drugs from different substance classes is intended to prevent the development of resistance through their different mechanisms of action. The use of fixed combinations can improve patient compliance. This is urgently required to prevent the development of resistance, since only a permanent reduction of the viral load to For antiretroviral therapy, various drugs are available:
– Nucleoside/nucleotide analogues (NRTI resp. NtRTI) Examples: Abacavir, tenofovir-DF, lamivudine – Non-nucleoside reverse transcriptase inhibitors (NNRTI) Examples: Efavirenz, nevirapine, rilpivirine, or cobicistat boosted protease inhibitors (PI/r) Examples: Atazanavir, darunavir, saquinavir, lopinavir – Integrase inhibitors (INI) Examples: Raltegravir, Dolutegravir, Elvitegravir – CCR5 inhibitors (caveat: not recommended for initial therapy due to lack of approval for first-line therapy) Example: Maraviroc.
Combinations of 2 NRTIs with an NNRTI, an INI, or boosted PI have been shown to be effective and safe in initial therapy. In routine therapy, it may be necessary to u.a. to change the substance in order to improve individual tolerability or concomitant risks.
If the therapy is successful, the patient's condition improves and the CD4+ T-lymphocytes increase again. The goal is a decrease in plasma viremia
Prognosis
HIV infection is currently not curable. However, modern HIV drugs have been able to significantly increase the life expectancy of HIV sufferers in recent years/decades. With timely therapy, full-blown AIDS can usually be prevented. Late diagnosis worsens the prognosis of patients. In addition to the number/proportion of CD4 helper cells, the viral load in the blood (viral copies/ml plasma) and the extent of activation of the immune system are also important prognostic markers.
In many regions with a high HIV prevalence, antiretroviral drugs are still not available in sufficient quantities. If the therapy does not take place, half of the patients are in the AIDS stage from 10 years post infection.
Prophylaxis
The most effective HIV prophylaxis is the prevention of the infection. Risky behavior such as unprotected sexual contact should be avoided. In addition, effective antiretroviral therapy reduces the risk of infection.
To reduce the risk of infection to others, HIV patients should be screened especially before invasive procedures such as z.B. at the dentist inform the practitioner about their infection.
The risk of transmission during intravenous drug use can be reduced by using sterile disposable syringes and needles.
If the viral load of a pregnant HIV-infected person is detectable before birth, a sectio should be sought, since perinatal transmission is the most common vertical route of infection. In addition, antiretroviral therapy should be given during pregnancy. There is a possibility of antiretroviral prophylaxis in newborns.
If there is an accident with HIV-containing material (mucosal exposure or parenteral exposure), the implementation of HIV post-exposure prophylaxis (PEP) should be evaluated.
Reporting
According to §7, paragraph 3 of the Infection Protection Act, there is a non-nominal obligation to report the detection of an HIV-1 or HIV-2 infection to the Robert Koch Institute (RKI). Notification must be made within 2 weeks.