Editing Nevirapine (section)

==Medical uses==
Nevirapine is used in people six years of age and older infected with HIV-1 as part of combination antiretroviral treatment (ART or cART). Monotherapy with nevirapine is not indicated due to rapid emergence of resistance.<ref name="Viramune FDA label">{{cite web | title=Viramune- nevirapine suspension Viramune- nevirapine tablet | website=DailyMed | date=28 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ec05500-6333-4bd0-ac83-464fad0d5162 | access-date=19 November 2020}}</ref><ref name="Viramune XR FDA label">{{cite web | title=Viramune- nevirapine tablet, extended release | website=DailyMed | date=25 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82598cb3-a0eb-4ff2-8b8d-d8da96c25388 | access-date=19 November 2020}}</ref>

Nevirapine in triple combination therapy has been shown to suppress [[viral load]] effectively when used as initial antiretroviral therapy (''i.e.'', in antiretroviral-naive patients).<ref name="INCAS_1998" /> Some clinical trials have demonstrated comparable HIV suppression with nevirapine-based regimens to that achieved with regimens based on a [[protease inhibitor (pharmacology)|protease inhibitor]] (PI)<ref>{{cite journal | vauthors = van Leeuwen R, Katlama C, Murphy RL, Squires K, Gatell J, Horban A, Clotet B, Staszewski S, van Eeden A, Clumeck N, Moroni M, Pavia AT, Schmidt RE, Gonzalez-Lahoz J, Montaner J, Antunes F, Gulick R, Bánhegyi D, van der Valk M, Reiss P, van Weert L, van Leth F, Johnson VA, Sommadossi JP, Lange JM | display-authors = 6 | title = A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients | journal = AIDS | volume = 17 | issue = 7 | pages = 987–999 | date = May 2003 | pmid = 12700448 | doi = 10.1097/00002030-200305020-00007 | s2cid = 25420787 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Podzamczer D, Ferrer E, Consiglio E, Gatell JM, Perez P, Perez JL, Luna E, González A, Pedrol E, Lozano L, Ocaña I, Llibre JM, Casiró A, Aranda M, Barrufet P, Martínez-Lacasa J, Miró JM, Badía X, Casado A, Lupo S, Cahn P, Maños M, Estela J | display-authors = 6 | title = A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study) | journal = Antiviral Therapy | volume = 7 | issue = 2 | pages = 81–90 | date = June 2002 | pmid = 12212928 | doi = 10.1177/135965350200700202 | s2cid = 31574879 | doi-access = free }}</ref> or [[efavirenz]].<ref name="2NN">{{cite journal | vauthors = van Leth F, Andrews S, Grinsztejn B, Wilkins E, Lazanas MK, Lange JM, Montaner J | title = The effect of baseline CD4 cell count and HIV-1 viral load on the efficacy and safety of nevirapine or efavirenz-based first-line HAART | journal = AIDS | volume = 19 | issue = 5 | pages = 463–471 | date = March 2005 | pmid = 15764851 | doi = 10.1097/01.aids.0000162334.12815.5b | s2cid = 20933620 | doi-access = free }}</ref>

This drug is generally only to be considered for use if the CD4 cell count is very low.<ref name="Viramune FDA label" />

Although concerns have been raised about nevirapine-based regimens in those starting therapy with high viral load or low CD4 count, some analyses suggest that nevirapine may be effective in this group of people.<ref name="2NN" />

Nevirapine may also form a useful component of salvage regimens after virological failure, usually in combination with one or more PIs as well as [[nucleotide reverse transcriptase inhibitor]] (NRTIs), especially in those who have not previously taken an NNRTI.

Dosing in children is based on [[body surface area]] (BSA),<ref name="Viramune FDA label" /> however, weight-based dosing algorithms have been released. These guidelines include dosing algorithms for as young as newborn babies.<ref>{{Cite web|url=http://aidsinfo.nih.gov/guidelines|title=Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children: Guidelines for the use of antiretroviral agents in pediatric HIV infection.|date=March 2016|publisher=AIDSinfo, U.S. Department of Health and Human Services (HHS).|access-date=2016-11-05|url-status=live|archive-url=https://web.archive.org/web/20161107221758/https://aidsinfo.nih.gov/guidelines|archive-date=2016-11-07}}</ref>

===Preventing mother-to-child transmission===

Although a single dose of nevirapine given to both mother and child reduced the rate of HIV transmission by almost 50% compared with a very short course of [[zidovudine]] (AZT) prophylaxis, in a clinical trial in [[Uganda]],<ref>{{cite journal | vauthors = Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Ducar C, Deseyve M, Emel L, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Dransfield K, Bray D, Mmiro F, Jackson JB | display-authors = 6 | title = Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial | journal = Lancet | volume = 354 | issue = 9181 | pages = 795–802 | date = September 1999 | pmid = 10485720 | doi = 10.1016/S0140-6736(99)80008-7 | s2cid = 6740488 | doi-access = free }}</ref> that trial was found in an Associated Press investigation to be riddled with "sloppy recordkeeping" and possibly fraud.<ref>{{cite news | vauthors = Solomon J |title=Research Flawed on Key AIDS Medicine |url=https://www.washingtonpost.com/archive/politics/2004/12/14/research-flawed-on-key-aids-medicine/3a4caf23-4576-4165-ab70-83ba2976b9cf/}}</ref> A subsequent study in [[Thailand]] showed that prophylaxis with single-dose nevirapine in addition to zidovudine is more effective than zidovudine alone.<ref name="Lallemant">{{cite journal | vauthors = Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V | display-authors = 6 | title = Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand | journal = The New England Journal of Medicine | volume = 351 | issue = 3 | pages = 217–228 | date = July 2004 | pmid = 15247338 | doi = 10.1056/NEJMoa033500 | doi-access = free }}</ref> These and other trials have led the [[World Health Organization]] to endorse the use of single-dose nevirapine prophylaxis in many developing world settings as a cost-effective way of reducing mother-to-child transmission. However, in the United States the Ugandan study was deemed flawed <ref>The HIVNET 012 Study and the Safety and Effectiveness of Nevirapine in Preventing Mother-to-Infant Transmission of HIV, {{cite web |url=http://www3.niaid.nih.gov/news/newsreleases/2004/hivnet012.htm |title=The HIVNET 012 Study and the Safety and Effectiveness of Nevirapine in Preventing Mother-to-Infant Transmission of HIV |access-date=2009-01-23 |url-status=dead |archive-url=https://web.archive.org/web/20090201162348/http://www3.niaid.nih.gov/news/newsreleases/2004/hivnet012.htm |archive-date=2009-02-01 }}</ref> and as of 2006 the FDA has not approved of such nevirapine prophylaxis.<ref>Celia Farber, "Out of Control: AIDS and the Corruption of Science" {{cite magazine |url=https://harpers.org/archive/2006/03/out-of-control/ |title=&#91;Article&#93; Out of control, by Celia Farber |magazine=Harper's Magazine |date=March 2006 |volume=March 2006 |access-date=2009-06-11 |url-status=live |archive-url=https://web.archive.org/web/20090504174126/http://www.harpers.org/archive/2006/03/0080961 |archive-date=2009-05-04 | vauthors = Farber C }}</ref> However, supporters of HIVNET 012 experiment argued that the flaws in this experiment were largely due to bureaucratic incompetence, while the findings regarding the safety and efficacy of single-dose nevirapine from this study were scientifically solid and too important to discard.<ref name="pmid21553555">{{cite journal | vauthors = Crane J | title = Adverse events and placebo effects: African scientists, HIV, and ethics in the 'global health sciences' | journal = Social Studies of Science | volume = 40 | issue = 6 | pages = 843–870 | date = December 2010 | pmid = 21553555 | doi = 10.1177/0306312710371145 | s2cid = 26027925 }}</ref> Moreover, it was argued that holding African researchers who operated under resource-poor situations to the same moral and procedural standards to their Western counterparts was unrealistic, and would further marginalize African researchers' role in the science community and impede the progress of African science.<ref>Lock, M. & Nguyen, V 2010, an Anthropology of Biomedicine, Malden, Wiley-Blackwell.</ref> Another clinical trial, ''Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding'', was completed in September 2013.<ref>{{cite web |url=http://clinicaltrials.gov/show/NCT00074412 |title=Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding - Full Text View - ClinicalTrials.gov |access-date=2009-01-23 |url-status=live |archive-url=https://web.archive.org/web/20081205094051/http://clinicaltrials.gov/show/NCT00074412 |archive-date=2008-12-05 }}</ref>  	

A major concern with this approach is that NNRTI resistance mutations are commonly observed in both mothers and infants after single-dose nevirapine,<ref>{{cite journal | vauthors = Johnson JA, Li JF, Morris L, Martinson N, Gray G, McIntyre J, Heneine W | title = Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated | journal = The Journal of Infectious Diseases | volume = 192 | issue = 1 | pages = 16–23 | date = July 2005 | pmid = 15942889 | doi = 10.1086/430741 | doi-access = free }}</ref> and may compromise the response to future NNRTI-containing regimens.<ref>{{cite journal | vauthors = Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M | display-authors = 6 | title = Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy | journal = The New England Journal of Medicine | volume = 351 | issue = 3 | pages = 229–240 | date = July 2004 | pmid = 15247339 | doi = 10.1056/NEJMoa041305 | doi-access = free }}</ref> A short course of maternal [[Lamivudine/zidovudine]] is recommended by the U.S. Public Health Service Task Force to reduce this risk.<ref name=perinatal/>

===Nonoccupational Post-Exposure Prophylaxis===
Nevirapine is contraindicated for non-occupational post-exposure-prophylaxis including for pregnant and nonpregnant women due to severe liver toxicity.<ref>{{cite web |title=Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV—United States, 2016 |url=https://stacks.cdc.gov/view/cdc/38856 |publisher=Centers for Disease Control}}</ref>