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Human immunodeficiency virus (HIV)
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Richard Basilan, William Salzer
For ARV-naive, nonpregnant patients who meet criteria for initiation of ARV therapy, present guidelines recommend the use of an NNRTI-based, a PI-based, or an integrase inhibitor–based regimen. All regimens would also include two NRTIs. Purely NRTI-based regimens, such as Trizivir (a combination of zidovudine, lamivudine, and abacavir), are no longer recommended as they have been found to have higher rates of virologic failure. For an NNRTI-based regimen, the preferred agents include efavirenz with emtricitabine and tenofovir (available as combination pill Atripla™). Use of efavirenz should be avoided during the first trimester of pregnancy, as well as in women who are of reproductive age and are not taking sufficient steps to avoid pregnancy, given its known teratogenicity in animal and human studies. An alternative NNRTI-based regimen would include nevirapine with zidovudine and lamivudine (Combivir™). It should be noted that nevirapine should be avoided in patients with moderate-to-severe hepatic impairment (Child Pugh B or C), as well as females with a CD4 count >250 cells/mL as both groups have an increased risk for potentially fatal hepatitis.
Micronutrients in Prevention and Improvement of the Standard Therapy in HIV/AIDS
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
The evolution of antiviral therapy for the treatments of HIV/AIDS has led to the development of HAART that includes combination of three or more classes of antiviral drugs. They represent nucleoside and nucleotide reverse transcriptase inhibitors (nNRTI), non-nucleoside nucleotide reverse transcriptase inhibitors (NNRTI), protease inhibitors, integrase inhibitors, and entry inhibitors. NNRTI inhibits reverse transcriptase by incorporating themselves into the newly synthesized viral DNA preventing its function; nNRTI inhibits reverse transcriptase directly by binding to the enzyme and prevents further transcription of viruses; protease inhibitor stops the viral replication by inhibiting activity of protease, which is needed to complete the final assembly of HIV; integrase inhibitor inhibits enzyme integrase, which is responsible for integration of viral DNA into the DNA of infected cells, and thus stops virus production, and entry inhibitors help to prevent the virus from entering and infecting cells.
Nevirapine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Nevirapine (previously known as BI-RG-587) is a dipyridodiazepinone derivative and a potent and highly specific inhibitor of the reverse transcriptase of HIV-1. It has no activity against HIV-2 or any other retrovirus. It is a member of a class of structurally diverse nonnucleoside reverse transcriptase inhibitor (NNRTI) compounds that share part, or all, of the same binding site on the HIV reverse transcriptase enzyme.
Effect of dolutegravir-based first-line antiretroviral therapy on weight and body mass index among adult people living with HIV on follow up at health facilities in Hawassa city administration, Southern Ethiopia: a retrospective cohort study
Published in Annals of Medicine, 2023
Agete Tadewos Hirigo, Daniel Yilma, Ayalew Astatkie, Zelalem Debebe
Ninety-seven (18.5%) PLWH had a history of tuberculosis infection, 72 (74.2%) of them had pulmonary tuberculosis, and 25 (25.8%) had extra-pulmonary tuberculosis. Likewise, 47(8.9%) subjects had opportunistic infections other than tuberculosis (Herpes zoster (n = 29), pneumocystis pneumonia (n = 4), toxoplasmosis (n = 4), and candidiasis infection (n = 10)). Of the 524 adults, 70% (367/524) initiated ART with the NNRTI-based regimens, while 30% (157/524) initiated the TLD regimen. Of those who initiated the NNRTI-based regimens, 98.4% received TDF + 3TC + EFV, while 1.1%, 0.3%, and 0.3% received Zidovudine (ZDV) + 3TC + EFV, TDF + 3TC + NVP and abacavir (ABC)+3TC + EFV, respectively (Table 2). One hundred seventy-nine (34.1%) participants continued receiving the NNRTI-based regimens for 24 months; while 35.9% (188/524) adults were switched from the NNRTI-based regimens to TLD regimen before 24 months of treatment as per the WHO guidelines. Forty-two out of 524 (8.0%) adults had no documented height values to calculate the BMI and only 482 adults were considered for the BMI analysis. Of the 482 participants, 69.5% (335/482) initiated ART with the NNRTI-based regimens, while the remaining 30.5% (147/482) initiated the TLD regimen. About 33.8% (163/482) participants continued receiving the NNRTI-based regimens; while 35.7% (172/482) were switched from NNRTI-based regimens to the TLD regimen as per the WHO directions.
An evaluation of long-acting cabotegravir + rilpivirine for the treatment of virologically suppressed adults living with HIV
Published in Expert Opinion on Pharmacotherapy, 2022
Hamdi Qazzaz, Christopher Parganas, Theodore James Cory
RPV is a 2nd generation nonnucleoside reverse transcriptase inhibitor, NNRTI. The mechanism by which the drug exhibits its effect is via binding to the hydrophobic pocket of the reverse transcriptase that stops the transformation of viral RNA to DNA in infected human cells. RPV can reduce viral loads within the body by 1.2 log10 copies/ml [4]. This is usually achieved by administrations of 25 mg, once daily [4]. In addition, the EC50 of naive and pretreated patients is 65 ng/ml for a 25 mg oral RPV [4]. Further studies targeting patients with wild-type HIV-1 concluded that the drug had an EC50 of 0.73 nmol/ml, compared to 5220 nmol/L for patients who had HIV-2 infections [19]. In addition to studies outlined above, there has also been work conducted on the antiviral activity of RPV in combination with other drugs, particularly other NNRTIs to gauge efficacy. These studies concluded that there were no significant changes in the effectiveness and the pharmacokinetic profile upon the addition of an NNRTI.
Alanine transaminase and hemoglobin appear to predict the occurrence of antituberculosis medication hepatotoxicity; findings and implications in Botswana
Published in Expert Review of Anti-infective Therapy, 2021
Boikobo Kesenogile, Brian Godman, Godfrey Mutashambara Rwegerera
TB/HIV co-infection rate in Botswana is as high as 59.2% [13]. The different classes of ARTs have the potential to cause hepatotoxicity; however, this is more commonly associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Botswana has now moved away from an NNRTI-based regimen to a dolutegravir (DTG) first-line regimen [66]. The majority of HIV positive patients on ART in this study (70.2%) were on a DTG-based regimen that is rarely associated with hepatotoxicity [67,68]. The different types of ART regimen were not significantly associated with hepatotoxicity in our study, which may be partly due to a small sample size that was not powered to show any difference. On the other hand, the switch of guidelines to replace NNRTIs such as efavirenz, which has a high propensity to cause hepatotoxicity as compared to DTG, might also have played a part.