1. Mutations in the Reverse Transcriptase Gene Associated With Resistance to Reverse Transcriptase Inhibitors
Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors (nRTIs)
69 Insertion Complex (affects all nRTIs currently approved by the US FDA)
Multi-nRTI
Resistance
151 Complex (affects all nRTIs currently approved by the US FDA except tenofovir)
Multi-nRTI
Resistance
Thymidine Analogue-Associated Mutations (TAMs; affect all nRTIs currently approved by the US FDA other than emtricitabine and lamivudine)
This slide summarizes NNRTI resistance patterns. There is a clustering of mutations between codons 100 and 106 and codons 181 and 190, with several others occurring in the low 200s. There is broad cross-resistance in these patterns, although subtle differences can be seen.1
Multi-nRTI
Resistance
1. D’Aquila RT, Schapiro JM, Brun-Vezinet F, et al. Drug resistance mutations in HIV-1. Top HIV Med. 2002;10:11-15.

2. Mutations in the Reverse Transcriptase Gene Associated With Resistance to Reverse Transcriptase Inhibitors (cont’d)
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zidovudine
This slide summarizes NNRTI resistance patterns. There is a clustering of mutations between codons 100 and 106 and codons 181 and 190, with several others occurring in the low 200s. There is broad cross-resistance in these patterns, although subtle differences can be seen.1
1. D’Aquila RT, Schapiro JM, Brun-Vezinet F, et al. Drug resistance mutations in HIV-1. Top HIV Med. 2002;10:11-15.

3. Mutations in the Reverse Transcriptase Gene Associated With Resistance to Reverse Transcriptase Inhibitors (cont’d)
Nonnucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs)
Etravirine
Efavirenz
Nevirapine
Rilpivirine
This slide summarizes NNRTI resistance patterns. There is a clustering of mutations between codons 100 and 106 and codons 181 and 190, with several others occurring in the low 200s. There is broad cross-resistance in these patterns, although subtle differences can be seen.1
1. D’Aquila RT, Schapiro JM, Brun-Vezinet F, et al. Drug resistance mutations in HIV-1. Top HIV Med. 2002;10:11-15.

4. Mutations in the Protease Gene Associated With Resistance to Protease Inhibitors
Atazanavir +/-ritonavir
Darunavir/ ritonavir
Fosamprenavir/ ritonavir
Indinavir/ ritonavir
Lopinavir/ ritonavir
Many mutations in the protease gene, as shown in this recent representation,1 confer significant cross-resistance across the entire class. The mutations highlighted in yellow generally develop in patients who receive the individual PIs for the first time with or without nucleosides.
Indinavir—46 and 82
Ritonavir—84 and 82
Saquinavir—48 and 90
Nelfinavir—30 and 90, occasionally 88
Amprenavir—50, 54, and 84
Lopinavir/ritonavir—It is unclear which mutation develops first in patients, but the mutations shown all contribute to lopinavir resistance, based on phenotypic and genotypic analyses of clinical isolates. It has been suggested that as few as 4 mutations may be associated with high-level resistance to lopinavir/ritonavir. Although L63P causes no appreciable increase in IC50, it is shown for only lopinavir/ritonavir because, along with other mutations, it predicts a lack of viral load response to regimens containing this agent.
1. D’Aquila RT, Schapiro JM, Brun-Vezinet F, et al. Drug resistance mutations in HIV-1. Top HIV Med. 2002;10:11-15.

5. Mutations in the Protease Gene Associated With Resistance to Protease Inhibitors (cont’d)
Nelfinavir
Saquinavir/ ritonavir
Tipranavir/ ritonavir
Many mutations in the protease gene, as shown in this recent representation,1 confer significant cross-resistance across the entire class. The mutations highlighted in yellow generally develop in patients who receive the individual PIs for the first time with or without nucleosides.
Indinavir—46 and 82
Ritonavir—84 and 82
Saquinavir—48 and 90
Nelfinavir—30 and 90, occasionally 88
Amprenavir—50, 54, and 84
Lopinavir/ritonavir—It is unclear which mutation develops first in patients, but the mutations shown all contribute to lopinavir resistance, based on phenotypic and genotypic analyses of clinical isolates. It has been suggested that as few as 4 mutations may be associated with high-level resistance to lopinavir/ritonavir. Although L63P causes no appreciable increase in IC50, it is shown for only lopinavir/ritonavir because, along with other mutations, it predicts a lack of viral load response to regimens containing this agent.
1. D’Aquila RT, Schapiro JM, Brun-Vezinet F, et al. Drug resistance mutations in HIV-1. Top HIV Med. 2002;10:11-15.

6. Mutations in the Envelope Gene Associated With Resistance to Entry Inhibitors
Enfuvirtide
Maraviroc
User Notes available at
This slide summarizes NNRTI resistance patterns. There is a clustering of mutations between codons 100 and 106 and codons 181 and 190, with several others occurring in the low 200s. There is broad cross-resistance in these patterns, although subtle differences can be seen.1
1. D’Aquila RT, Schapiro JM, Brun-Vezinet F, et al. Drug resistance mutations in HIV-1. Top HIV Med. 2002;10:11-15.

7. Mutations in the Integrase Gene Associated With Resistance to Integrase Strand Transfer Inhibitors
Dolutegravir
Elvitegravir
Raltegravir
This slide summarizes NNRTI resistance patterns. There is a clustering of mutations between codons 100 and 106 and codons 181 and 190, with several others occurring in the low 200s. There is broad cross-resistance in these patterns, although subtle differences can be seen.1
1. D’Aquila RT, Schapiro JM, Brun-Vezinet F, et al. Drug resistance mutations in HIV-1. Top HIV Med. 2002;10:11-15.

8. 2017 Update of the Drug Resistance Mutations in HIV-1
IAS–USA Drug Resistance Mutations Group
2017 Update of the Drug Resistance Mutations in HIV-1
Annemarie M. Wensing, MD, PhD; Vincent Calvez, MD, PhD; Huldrych F. Günthard, MD; Victoria A. Johnson, MD; Roger Paredes, MD, PhD; Deenan Pillay, MD, PhD; Robert W. Shafer, MD; Douglas D. Richman, MD
Top Antivir Med. 24(4). Updates available at
IAS–USA is a not-for-profit, HIV clinical specialist–education organization. It is entirely different from and not affiliated with the International AIDS Society.