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NNRTIs are a class of antiretroviral medicines used to treat HIV/AIDS. Unlike nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs do not require phosphorylation to function and instead bind directly to the reverse transcriptase enzyme. This reduces the enzyme's capacity to transform viral RNA into DNA, which is a critical stage in viral reproduction. One of the distinguishing features of NNRTIs is their affinity for the HIV-1 reverse transcriptase enzyme. This selectivity reduces the likelihood of deleterious impacts on human biological processes. NNRTIs that are routinely used in HIV therapy regimens include efavirenz, nevirapine, and etravirine. Efavirenz, a first-generation NNRTI, became popular due to its once-daily dose and strong antiviral action. However, it has been linked to negative effects of the central nervous system, including vivid nightmares and dizziness. Nevirapine, another first-generation NNRTI, is widely used in resource-limited settings due to its low cost. However, it necessitates a lead-in period to limit the chance of rash, a potentially harmful reaction. Etravirine, a second-generation NNRTI, was created to overcome resistance difficulties caused by first-generation medicines. It is active against both the wild-type and select resistant HIV-1 strains. Importantly, etravirine provides a variable dose schedule that allows for tailoring to individual patient demands. NNRTIs are typically well tolerated, however they can cause rash, hepatotoxicity, and drug interactions. Furthermore, the establishment of resistance mutations complicates long-term HIV management, highlighting the significance of regular monitoring and adherence to treatment regimens. The usual strategy to HIV management is combination therapy, which frequently includes NNRTIs in addition to other types of antiretrovirals. The use of NNRTIs has greatly contributed to the success of highly active antiretroviral therapy (HAART), which has transformed HIV infection from a devastating disease to a chronic, manageable condition for many people. Ongoing research is investigating new NNRTIs and optimizing treatment techniques to improve efficacy, tolerability, and accessibility in the global fight against HIV/AIDS.