An Important Issue In Antiviral Therapy Is The Emergence Of Resistant Strains

Summary of resistance

A very important issue in Antiviral therapy is the emergence of resistant strains on the latest drug resistance mutations. The reasons for the emergence of drug-resistant strains include increased virus transmission, HIV virus evolution to escape the efficacy of drugs, HAART treatment of patients lack of medication compliance and so on. In this regard, the successful development of monotherapy with three drugs combined with TDF, FTC and EFV once a day will help improve patient compliance.

Recent studies have shown that HIV resistance increases with the duration of treatment, in the past 6 years, the antiviral treatment of patients resistant to at least 20% to 25%. The resistance detected in the untreated population, commonly referred to as primary resistance, is known as secondary resistance in the treatment of individual patients. The occurrence of drug resistance appears to be independent of the subtype of HIV-1. More importantly, the likelihood of drug-resistant mutations is increased in patients who have previously received Antiviral therapy and are resistant to an antiviral agent, and the selectivity of the drug is reduced in future treatments. In the initial drug resistance study, the most common genetic variation associated with AZT, drug resistance was a change in the two bases, resulting in a change in the amino acid at position 215 from threonine to tyrosine or phenylalanine, and later found at least There are five genetic variants associated with AZT resistance. Resistance mutations also occur in the treatment of other NRTIs (ddC, ddI and 3TC) and PIs.

Whether in vitro or in vivo, have been found PIs resistant strains. PI-resistant strains can appear in untreated individuals, due to the spontaneous mutation of the virus or the spread of drug-resistant strains. In terms of structure and function, the protease is more elastic, which makes it more resistant to other HIV virus enzymes. In order to avoid the production of resistance, the concentration of PI in the body need to be maintained at a certain concentration. When used in combination with other drugs, the frequency of resistance appears to be lower. Some mutations can lead to cross-resistance to five different structural protease inhibitors. The use of two protease inhibitors (NFV and APV) produces resistant mutations that are not cross-resistant to other protease inhibitors, so other PIs may remain effective when resistant to NFV or APV. However, if these drugs continue to be used, mutations that are resistant to other protease inhibitors will also occur. In turn, if the first to produce resistance to other PIs, usually also resistant to NFV and APV.

Virus strains resistant to four different Antiviral drugs have been found in the laboratory. It has been reported that five NRTIs and one NNRTI drug have been used in one infected person, and their drug-resistant strains are resistant to all NRTIs and most of the NNRTIs. It is clear that this treatment is not To prevent the emergence of multiple drug-resistant strains, and multi-resistant strains still maintain a certain level of replication. Recent cases have reported that individuals infected with multiple drug-resistant R5 / X4 strains spread rapidly and progressed to AIDS.

Resistance to inhibitors of inhibitors such as CCR5 has also been reported that resistance to CCR5 receptor inhibitors does not seem to be the use of CXCR4, but a virus with higher affinity for receptors. The same problem exists for CD4 therapy. It is important to identify whether the use of CCR5 receptor inhibitors leads to the presence of X4 viruses when mixed virus strains are present. T20-resistant viruses have also been identified, but the ability to replicate the virus is declining and more sensitive to neutralizing antibodies, which explain why drugs like T20 are not suitable for monotherapy. It is important to have a lower prevalence of drug resistance in areas where medication compliance is emphasized.