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cross resistance
May 31, 2005

DEAR DON, I M HAPPY ENOUGH THAT U GAVE ME VALUABLE INFORMATIONS AB FUZEON. FOR THIS TIME I HAVE 2 QUESTIONS FOR U.

1. I READ IN HARRISSON'S INTERNAL MEDICINE THAT NEVIRAPINE AND ENFUVIRTIDE PRODUCE ALMOST THE SAME POSITIONAL MUTATION IN HIV1 GENOME INSPITE OF BEING TOTALLY DIFFERENT TYPES OF AGENTS.IS IT POSSIBLE TO SHOW FUZEON RESISTANCE IN NEVIRAPINE EXPERIENCED PATIENT? 2.ANOTHER Q IS THAT , IF A PATIENT RESISTANT TO NRTIand NNRTI INFECT A HEALTHY ONE, WILL THERE BE ANY SCOPE FOR THE NEWLY INFECTED PATIENT TO USE NRTI and NNRTI? IF THE NEW PATIENT LOSES THE 1ST OPTION (NRTI n NNRTI), THEN THE WHOLE SCENARIO WILL BE DEVASTATING. ISNT IT DON? WITHIN 10 YEARS ALL STRAINS OF HIV WILL B RESISTANT TO ALL CURRENTLY AVAILABLE DRUGS. WHAT U THINK DON? PLESE INFORM ME. THANK U TITAS MEDICAL STUDENT(BENGAL,INDIA) 24.5.5

Response from Mr. Kurtyka

Titas,

I have been exploring Harrison's Online and cannot find anything that suggests cross-resistance between NNRTs and enfuvirtide. NNRTI resistant-mutations occur in the reverse transcriptase gene roughly between codons 100-190 with the K103N and Y181C being among the most common. There is broad cross-resistance between the currently available NNRTI agents (efavirenz, nevirapine and delavirdine).

Resistance to enfuvirtide occurs in the GP41 envelope gene generally between codons 36-43. I am not aware of any data suggesting cross resistance between NNRTIs and enfuvirtide (or PIs or CCR5 inhibitors for that matter). You may wish to review the IAS-USA drug resistance mutations chart (see link below).

With regards to your second question, if a patient with HIV that is resistant to antiretroviral agents infects (or reinfects) another individual, it is likely that the patient will acquire the HIV resistant mutations from the source patient, thus potentially limiting the availability of susceptible agents for the newly infected patient. I don't know if anyone can predict that in 10 years all strains of HIV will be resistance to all currently available drugs. This is a concern however and it clearly demonstrates the need for healthcare providers, community educators, and others to continually reinforce the need for safer sex and safer needle use among everyone to reduce the transmission of HIV and other STIs.

IAS-USA Mutation Chart


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