Principles of therapy
- HIV replication damages the immune system and results in AIDS.
- HIV replication may be estimated by measuring plasma HIV RNA levels. CD4+T-cell counts indicate the immune system condition.
- HIV infection develops differently and, therefore, the treatment should be individualized, based upon plasma HIV RNA levels and CD4+T-cell counts.
- Antiretroviral therapy is not able to kill the virus, but it slows down the virus replication and postpone the development of AIDS. The treatment should be initiated as soon as possible (even when the HIV infection is not confirmed as prophylaxis). Once the viral load decreases the risk of transmission is reduced.
- The most effective is the treatment which includes the combination of anti-HIV drugs with which the patient hasn’t been treated in the past and that are not cross-resistant to other drugs that the patient has already received. Monotherapy is not recommended as drug resistance develops.
- The combinations of antiretroviral drugs should be used according to the appropriate schedules and dosages. The HIV treatment regimens include at least 3medicines from 2 or more ART classes.
- The drugs for treatment of HIV are limited. Every therapy will have an impact on future treatment for this person as resistance to certain medicines may occur.
- Women should receive antiretroviral therapy, even during pregnancy.
- The same principles apply to children and adults..
- The regimen should be as simple as possible, to make it easy for an infected individual. This will improve the compliance and adherence to treatment.
Indications to antiretroviral therapy
- Acute retroviral syndrome
- Chronic infection
- Symptomatic disease
- Asymptomatic diseases:
- CD4+T-cell count <350/µL or/and viral load >100,000 copies/mL;
Antiretroviral therapy (ART) may be administered combined antiretroviral therapy (cART) or highly active antiretroviral therapy (HAART).
Four groups of drugs are available now for the treatment of HIV infection:
- Reverse trancriptase inhibitors
Zidovudine (300 mg bid), didanosine (125-200 mg bid), zalcitabine (0.75 mg tid), stavudine (30-40 mg bid), lamivudine (150 mg bid), abacavir (300 mg bid)
Nucleotide analogue tenofovir (300 mg qd)
Nonnucleoside reverse transcriptase inhibitors:
Nevirapine (200 mg/day for 14 days, later 200 mg bid), delavirdine (400 mg tid), and efavirenz (600 mg qhs)
These medicines affect the reverse transcription (the synthesis of DNA based on the viral RNA). However, reverse transcriptase inhibitors alter DNA polymerization reactions causing various side effects such as anemia, granulocytopenia, myopathy, lactic acidosis,
hepatomegaly with steatosis, pancreatitis, peripheral neuropathy, headache, nausea, malaise etc.
HAART therapy with reverse transcriptase inhibitors is known to cause a syndrome of hyperlipidemia, glucose intolerance/insulin resistance, and fat redistribution (lipodystrophy syndrome).
- Protease inhibitors
Saquinavir (1000-1200 mg bid), indinavir (800 mg q8h), ritonavir (600 mg bid), nelfinavir (750 mg tid or1250 mg bid), amprenavir (1200 mg bid), fosamprenavir (1400 mg bid), atazanavir (400 mg qd)), tipranavir (500 mg daily), and darunavir (600 mg daily)
The medicines suppress the activity of protease.
The major adverse reactions include: diarrhea, nausea, headaches,
hyperglycemia, fat redistribution, lipid abnormalities, abdominal
pain, nephrolithiasis, indirect hyperbilirubinemia, etc.
- Entry inhibitors (CCR5 co-receptor antagonists)
Enfuvirtide (90 mg bid), maraviroc (150-600 mg bid)
Entry inhibitors affect the binding of HIV to its receptor or co-receptor.
The side effects of these drugs are: local injection reactions, hypersensitivity reactions, increased rate of bacterial pneumonia, hepatotoxicity, nasopharyngitis, fever, cough, rash, abdominal pain, dizziness, fever, musculoskeletal symptoms.
- Integrase inhibitors
Raltegravir (400 mg bid)
Raltegravir suppresses the activity of the viral integrase.
Nausea and rash are the side effects of this medicine.