HIV drugs: drug interactions and resistance
At the 44th Interdisciplinary Conference on Antimicrobials and Chemotherapy, held in Washington in October 2004, a number of reports were devoted to the subject of HIV infection and the drugs used to treat it.
At the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, ICAAC, held in Washington in October 2004, the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, several reports were devoted to the subject of HIV infection, as well that means used in its treatment, including the number of drug interactions of antiretroviral drugs.
As you know, between a number of drugs used in the treatment of HIV infection, there is a pharmacokinetic interaction, which must be taken into account when prescribing them. Thus, the ability of ritonavir to increase the absorption of other drugs by inhibiting cytochrome P-450 in the intestinal wall has been demonstrated. To a lesser extent, it inhibits cytochrome P-450 of the liver, which leads to an increase in the concentration in the blood of the drugs metabolized in this organ. Another antiviral medication, atazanavir, works primarily on the liver's cytochrome P-450.
The above effect has been demonstrated by the example of the interaction of saquinavir with ritonavir and atazanavir. It has been found that with the simultaneous administration of saquinavir and ritonavir, they do not affect the half-life of saquinavir, but only change the time of onset of maximum concentration. However, with the addition of atazanavir, the half-life of saquinavir is significantly increased, due to the effect of the drug on the metabolism of saquinavir in the liver. Another study examined the effect of residual ritonavir concentrations 12 hours after administration on the concentration of saquinavir. Despite the continued high concentration of ritonavir in the blood, the absorption of saquinavir has been significantly reduced, indicating the need for simultaneous administration of these drugs to achieve their maximum effect.
Another important problem is the increase in HIV resistance to antimicrobials. According to a 2003 study of 317 previously untreated patients from 40 cities in the United States, 23% of patients showed a decrease in the sensitivity of HIV to at least 1 drug, and in 14%, mutations have been found that have led to the emergence of resistance in the HIV strain. The most common was resistance to non-nucleoside reverse transcriptase inhibitors, and in 6% of HIV-infected people tested, the virus was resistant to all drugs in this class.
With the introduction of tenofovir into clinical practice, the K65R mutation, which causes resistance to this drug, has become an object of great attention. Taking tenofovir in combination with didanosine and abacavir has significantly increased the likelihood of a mutation (especially when taking 3 drugs at the same time), while taking zidovudine and lamivudine together reduced the risk of this phenomenon. A K65R mutation has rarely been seen in patients treated with protease inhibitors. In general, it should be noted that although the incidence of the K65R mutation increased with the introduction of tenofovir into clinical practice, it has now stabilized at 4.3%.
A significant relationship was found between the incidence of HIV resistance and the patient's race: resistance was found in 27% of Caucasians, 23% of African Americans and 6% of Hispanics, which probably reflects the availability of therapy in these social groups.
A high level of resistance indicates the need to determine sensitivity to basic therapy for HIV-infected people not previously treated when selecting a drug. When resistance appears during treatment, in order to avoid the occurrence of new mutations, it is recommended to change the drug, even if the patient's condition is clinically stable.