Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses. Mechanism of action When HIV infects a cell, reverse transcriptase copies the viral single stranded RNA genome into a double-stranded viral DNA. The viral DNA is then integrated into the host chromosomal DNA, which then allows host cellular processes, such as transcription and translation, to reproduce the virus. RTIs block reverse transcriptase's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying. A similar process occurs with other types of viruses. The hepatitis B virus, for example, carries its genetic material in the form of DNA, and employs an RNA-dependent DNA polymerase to replicate. Some of the same compounds used as RTIs can also block HBV replication; when used in this way they are referred to as polymerase inhibitors. Types RTIs come in three forms: Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs) Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs) Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) Nucleoside reverse transcriptase translocation inhibitor (NRTTIs). The antiviral effect of NRTIs and NtRTIs is essentially the same; they are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NtRTIs lack a 3′-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5′–3′ phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors. Unfortunately, NRTIs/NtRTIs compete as substrates for not only viral but also host DNA synthesis, acting as chain terminators for both. The former explains NRTIs'/NtRTIs' antiviral effect, while the latter explains their drug toxicity/side effects. In contrast, NNRTIs have a completely different mode of action. NNRTIs block reverse transcriptase by binding directly to the enzyme. NNRTIs are not incorporated into the viral DNA like NRTIs, but instead inhibit the movement of protein domains of reverse transcriptase that are needed to carry out the process of DNA synthesis. NNRTIs are