806:), a vaginal-microbicide gel (0.5%), sparked hope that it might provide modest protection against HIV. The results of a larger trial released in December 2009 showed that PRO 2000 was safe as administered, but was ineffective in reducing the risk of HIV infection. That trial (MDP 301) was sponsored by the Microbicides Development Programme. MDP 301 was conducted in South Africa, Tanzania, Uganda and Zambia with more than 9,300 women volunteers. No significant difference was found in the number of women who contracted HIV in the group given PRO 2000 compared to the group given a placebo. While this trial did not result in an effective product, it served as a model for future HIV-prevention trials; it provided scientific information and lessons from its social-science component, community engagement and preparation undertaken by the trial staff.
764:
No tenofovir-resistant virus was detected in the women who acquired HIV infection during the study. In addition to demonstrating efficacy against HIV, CAPRISA 004 found evidence that tenofovir gel also prevents the transmission of herpes simplex virus type 2 (HSV-2). HSV-2 is a lifelong, incurable infection which can make those infected with the virus two-to-three times more likely to acquire HIV. Data collected during the CAPRISA 004 study indicate that tenofovir gel provided 51% protection against HSV-2. Tenofovir, developed by Gilead
Sciences, is a nucleotide reverse-transcriptase inhibitor (NRTI) which interferes with the replication of HIV and is approved in tablet form for use in combination with other ARVs to treat HIV. CAPRISA 004 was a collaboration among CAPRISA,
850:
infected. Individuals would receive ARVs before they were exposed to HIV, with the goal of lowering their risk or preventing infection. One of the potential advantages of PrEP is that an individual could use it autonomously (without the need to negotiate with a partner), and it is not dependent on the time of sex. It is hoped that those unable to negotiate condom use with their sexual partners would be able to reduce their risk of HIV infection with the use of an oral (or injectable) prophylactic drug. Current PrEP candidates in development include tenofovir and
Truvada (a combination of two ARV compounds, tenofovir and emtricitabine). One potential risk of the PrEP approach is that drugs present in systemic circulation might, over time, create ARV-resistant HIV strains.
845:
need to be confirmed by other clinical trials before the microbicide tenofovir gel is made available to the public. This decision rests with regulators, particularly in South Africa. In 2013, the VOICE study (MTN 003), another large-scale trial, is scheduled to release results. VOICE is evaluating three different strategies to prevent HIV in women: one ARV-based microbicide and two regimens consisting of oral ARVs on a daily basis. The VOICE trial is testing 1% tenofovir vaginal gel in a once-daily formulation. It is not known at this time if VOICE will be considered a
795:
676:). ARV-based microbicides may be formulated as long-acting vaginal rings, gels and films. The results of the first efficacy trial of an ARV-based microbicide, CAPRISA 004, tested 1% tenofovir in gel form to prevent male-to-female HIV transmission. The trial showed that the gel (which was applied topically to the vagina), was 39% effective at preventing HIV transmission. CAPRISA 004 was the 12th microbicide-efficacy study to be completed, and the first to demonstrate a significant reduction in HIV transmission. The results of this trial are
475:
563:
40:
744:
621:(in a test tube). The compound displayed a high level of efficacy against HIV and HSV. While the results are encouraging, the study did not evaluate VivaGel's effect in the body. It is still unknown what the results mean for women who would use the product in real-life settings; for example, the effect of sexual intercourse (or semen) on the gel (which often affects the protective properties of a drug) is unknown. The
714:
for this is that the rectum has a thinner epithelium, greater surface area and lower degree of elasticity than that of the vagina. Due to these factors, a microbicidal preparation that is effective when applied vaginally might have a different degree of effectiveness when applied rectally. In
January 2010, the National Institutes of Health awarded two grants totaling $ 17.5 million to the
759:, was conducted among 889 women to evaluate the ability of 1% tenofovir gel to prevent male-to-female HIV transmission. The study found a 39% lower HIV infection rate in women using 1% tenofovir gel compared with women using a placebo gel. In addition, tenofovir gel was shown to be safe as tested. The results of the
528:. PRO 2000 was demonstrated to be safe, but it did not reduce the risk of HIV infection in women (as explained in the MDP 301 trial results, released in December 2009). Similarly, the phase III efficacy trial of Carraguard showed that the drug was safe for use but ineffective in preventing HIV transmission in women.
700:
microbicides were formulated as semi-solid systems, such as gels, tablets, films, or creams, and were designed to be applied to the vagina before every act of intercourse. However, vaginal rings have the potential to provide long-term controlled release of microbicide drugs. Long-acting formulations,
820:
The phase III clinical trial for carrageenan-based
Carraguard showed that it had no statistical effect on HIV infection, according to results released in 2008. The study showed that the gel was safe, with no side effects or increased risks. The trial also provided information about usage patterns in
713:
use lubricants containing nonoxynol-9. This suggests that they might be receptive to the concept of using topical rectal microbicides if such products were to become commercially available. However, the development of rectal microbicides is not as advanced as that of vaginal microbicides. One reason
844:
Efforts are underway to develop safe and effective topical microbicides. Several different gel formulations are currently undergoing testing in phase III clinical efficacy trials, and about two dozen other products are in various phases of development. Results from CAPRISA 004, while promising, may
763:
trial provide statistically significant evidence that ARVs, topically applied to the vaginal mucosa, can offer protection against HIV and (potentially) other pathogens. During the study, 38 of the women who used the tenofovir gel acquired HIV and 60 women who used a placebo gel became HIV-infected.
601:
have awarded grants totaling $ 25.7 million for VivaGel's development and testing. VivaGel is being developed as a standalone microbicide gel and an intra-vaginal microbicide. It is also being evaluated for use in condoms. It is hoped that VivaGel will provide an extra resource to mitigate the
861:
are an effective method for blocking the transmission of most sexually transmitted infections (with HPV a notable exception). However, a variety of social factors (including, but not limited to, the sexual disempowerment of women in many cultures) limit the feasibility of condom use. Thus, topical
734:
A major breakthrough in microbicide research, announced in July 2010, reported that an ARV-based microbicide gel could partially prevent HIV. A trial led by the Centre for the AIDS Programme of
Research in South Africa (CAPRISA), conducted in South Africa, demonstrated that the ARV tenofovir, when
705:
began the first study in Africa to test the safety and acceptability of a vaginal ring containing dapivirine. Drugs might also be administered systemically through injectable or oral formulations known as PrEP. Injectable formulations may be desirable since they could be administered infrequently,
849:
for CAPRISA 004, which used a different dosing strategy. Products known as Pre-Exposure
Prophylaxis, or PrEP, are also being tested at various stages of the development process. These products, administered orally or via injection, would contain ARVs to protect HIV-negative people from becoming
865:
Some sub-Saharan
African cultures view vaginal lubrication as undesirable. Since some topical microbicide formulations currently under development function as lubricants, such "dry sex" traditions may pose a barrier to the implementation of topical microbicidal programs. Recent data on product
429:
surfaces, they are less desirable than other agents. Additionally, clinical trials have not demonstrated these agents to be effective at preventing HIV transmission. Consequently, laboratory and clinical trials testing this class of products as microbicides have largely been discontinued.
725:
Ultimately, successful topical microbicides might simultaneously employ multiple modes of action. In fact, long-acting formulations such as vaginal rings could provide the technology needed to deliver multiple active ingredients with different mechanisms of action.
836:, is ineffective as a topical microbicide in preventing HIV infection. Although nonoxynol-9 has been shown to increase the risk of HIV infection when used frequently by women at high risk of infection, it remains a contraceptive option for women at low risk.
545:
had been stopped because preliminary results suggested a potential increased risk of HIV in women who used the compound. There is no satisfactory explanation as to why application of cellulose sulfate was associated with a higher risk of HIV infection than
656:) and UC-781. These next-generation microbicides have received attention and support because they are based on the same ARV drugs currently used to extend the survival (and improve the quality of life) of HIV-positive people. ARVs are also used to prevent
360:
Although there are many approaches to preventing sexually transmitted infections in general (and HIV in particular), current methods have not been sufficient to halt the spread of these infections (particularly among women and people in
706:
possibly once a month. It is likely, however, that such products would need to be monitored closely and would be available only through prescription. This approach also carries the risk of emergence of ARV-resistant strains of HIV.
701:
like vaginal rings, are potentially advantageous since they could be easy to use, requiring replacement only once a month. This ease of use could prove very important to make sure that products are used properly. In 2010, the
637:(ARV) agents. ARVs work either by preventing the HIV virus from entering a human host cell, or by preventing its replication after it has already entered. Examples of ARV drugs being tested for prevention include
466:
and microbicidal gel formulated to maintain the natural protective acidity of the vagina. Candidates in this category (including BufferGel) have proven to be ineffective in preventing HIV infection.
554:
on March 16, 2007, a large number of compounds (more than 60 in early 2007) are under development; at the beginning of that year, five phase III trials testing different formulations were underway.
1985:
581:
molecule (which binds to viruses and prevents them from affecting an organism's cells). Experimental results with VivaGel indicate 85–100% effectiveness at blocking transmission of both HIV and
1410:
Carballo-Diéguez A, O'Sullivan LF, Lin P, Dolezal C, Pollack L, Catania J (March 2007). "Awareness and attitudes regarding microbicides and
Nonoxynol-9 use in a probability sample of gay men".
1194:
1978:
1054:
617:(HSV). In 2009, Starpharma released its results for a study investigating VivaGel's antiviral activity against HIV and HSV in humans by testing cervico-vaginal samples
755:(CAPRISA) released results of a study establishing proof of concept that an ARV-based, topical microbicide can reduce the likelihood of HIV transmission. The trial,
752:
377:) and secondary protection (if a condom breaks or slips off during intercourse). It is hoped that microbicides may be safe and effective in reducing the risk of HIV
1971:
2103:
2139:
1367:
598:
52:
258:
1901:
1623:
1117:
773:
251:
1497:
1286:
1167:
1136:
1652:
1348:
1272:
609:
It is also hoped that microbicides will block the transmission of HIV and other sexually transmitted infections, such as those caused by certain
574:
VivaGel is a sexual lubricant with antiviral properties manufactured by
Australian pharmaceutical company Starpharma. The active ingredient is a
1994:
1593:
991:
718:
to fund research into rectal microbicides. That research will include investigations into product acceptability of rectal microbicides with
1934:
1806:
2065:
2060:
702:
1746:
1563:
1311:
1198:
1061:
915:
566:
The chemical structure of dendrimers is typically symmetric around the core, and often adopts a spherical three-dimensional
1086:
1704:
1871:
866:
acceptability, however, show that many men and women enjoy using gels during sex that would contain a microbicidal drug.
672:
microbicides to be administered locally in the rectum or vagina or systemically through oral or injectable formulations (
2075:
1776:
17:
2070:
1836:
1371:
1220:
2129:
649:
122:
76:
1912:
425:
of microorganisms. Since detergent microbicides also kill host cells and impair the barrier function of healthy
521:
270:
1631:
1251:
1121:
964:
594:
777:
516:
preparations (such as 0.5% PRO 2000 and 3% Carraguard vaginal microbicide gels) have failed to demonstrate
175:
1505:
1290:
1171:
1140:
765:
534:
is another microbicide found ineffective in preventing the transmission of HIV. On
February 1, 2007, the
2080:
1660:
535:
1352:
735:
used in a vaginal gel, was 39% effective at preventing HIV transmission from men to women during sex.
1476:
1154:
665:
551:
373:. In such situations, the use of microbicides could offer both primary protection (in the absence of
1386:
890:
715:
677:
673:
1601:
1030:
454:
can neutralize vaginal pH. One potential class of microbicides acts by reducing the pH of vaginal
1963:
684:
that ARVs, topically applied to the vaginal mucosa, can offer protection against HIV (and other)
499:
378:
1930:
1528:
1682:
314:
1814:
1734:
593:
in Australia and the United States, which will be followed by initial human safety tests. The
2134:
769:
657:
653:
410:
382:
148:
2124:
2034:
803:
614:
610:
567:
184:
1653:"Experimental Microbicide Carraguard Does Not Provide Protection Against HIV, Study Finds"
8:
2013:
139:
1754:
942:
458:, which may kill (or otherwise inactivate) pathogenic microorganisms. One such agent is
2008:
1435:
1022:
885:
846:
603:
362:
334:
301:. Multiple compounds are being developed and tested for their microbicidal activity in
279:
1902:"2007 U.N.Declaration of Commitment on HIV/AIDS and Political Declaration on HIV/AIDS"
1571:
815:
1427:
1266:
1014:
880:
710:
625:
trial demonstrated that topical tenofovir gel provided 51% protection against HSV-2.
525:
369:
is not a realistic option for women who want to bear children, or who are at risk of
366:
342:
326:
294:
104:
91:
1454:
1319:
1026:
919:
1536:
1439:
1419:
1006:
681:
646:
590:
582:
575:
506:. Thus, carrageenan and other microbicides of its class act as decoy receptors for
298:
200:
60:
1564:"Microbicide Gel Ineffective At Preventing HIV Infection Among Women, Study Finds"
992:"Microbicides and other topical strategies to prevent vaginal transmission of HIV"
495:
483:
426:
370:
2090:
1712:
1094:
634:
491:
414:
302:
1879:
1423:
2118:
1594:"Understanding the results from trials of the PRO 2000 microbicide candidate"
1087:"Understanding the results from trials of the PRO 2000 microbicide candidate"
719:
503:
422:
322:
306:
283:
1844:
1784:
862:
microbicides might provide a useful woman-initiated alternative to condoms.
794:
1624:"Trial Shows Anti-HIV Microbicide Is Safe, but does Not Prove it Effective"
1431:
1018:
338:
275:
31:
2098:
2029:
1541:
875:
829:
760:
756:
622:
487:
406:
1409:
1228:
345:(s) over a longer period). Some of these agents are being developed for
1192:
1165:
1134:
833:
661:
642:
463:
447:
402:
236:
159:
1312:"Ongoing Clinical Trials of Topical Microbicide Candidates (May 2011)"
633:
Researchers have begun to focus on another class of microbicides, the
2044:
968:
895:
802:
Results released in February 2009 from a clinical trial of PRO 2000 (
776:(USAID) and the South African Department of Science and Technology's
638:
578:
539:
478:
Cellulose sulfate (also known as sulfate cellulose or sulfocellulose)
459:
455:
398:
286:
that commonly cause sexually transmitted infection (for example, the
130:{(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid
1368:"Research:New vaginal ring borrows from birth control to fight AIDS"
1010:
814:
Carrageenan may prevent HPV and HSV transmission, but not HIV. See
664:, and are used to prevent HIV infection from developing immediately
474:
2039:
789:
685:
517:
354:
1993:
1477:"$ 17 million grant to help Pitt researcher develop anti-HIV gel"
669:
586:
547:
542:
330:
668:
to the virus. Such ARV-based compounds could be formulated into
858:
418:
374:
350:
346:
318:
550:. According to a review of microbicide drug candidates by the
562:
507:
451:
743:
39:
443:
1055:"Anti-HIV Gel Shows Promise in Large-scale Study in Women"
1680:
753:
Centre for the AIDS Programme of Research in South Africa
310:
287:
1807:"Vaginal and Oral Interventions to Control the Epidemic"
589:
monkeys. It has passed the animal-testing phases of the
1195:"Research: Daily Telegraph c/o Australian News Network"
1168:"Research: Cellulose sulfate microbicide trial stopped"
1137:"Research: Cellulose sulfate microbicide trial stopped"
439:
1958:
989:
599:
National Institute of Allergy and Infectious Diseases
1529:"Nature News: Microbicide gel may help againstn HIV"
709:
Substantial numbers of men who have sex with men in
297:
that exert their activity by a variety of different
1931:""Dry sex" worsens AIDS numbers in southern Africa"
1342:
1340:
1338:
774:United States Agency for International Development
282:that are capable of killing or destroying certain
1365:
2116:
1335:
490:. Carrageenans are a family of linear sulfated
147:
1995:Microbicides for sexually transmitted diseases
990:Lederman MM, Offord RE, Hartley O (May 2006).
1979:
1346:
1193:Daily Telegraph c/o Australian News Network.
1166:Cellulose sulfate microbicide trial stopped.
1135:Cellulose sulfate microbicide trial stopped.
962:
413:and Savvy (1.0% C31G), act by disrupting the
2140:Sexually transmitted diseases and infections
1115:
729:
446:, with a pH value of around 4. However, the
433:
305:. Microbicides can be formulated in various
27:Pharmacologic agents and chemical substances
1526:
1452:
1384:
1271:: CS1 maint: numeric names: authors list (
940:
2066:International Partnership for Microbicides
2061:International Rectal Microbicide Advocates
1986:
1972:
1492:
1490:
703:International Partnership for Microbicides
38:
1540:
1474:
183:
1674:
793:
742:
561:
473:
1866:
1864:
1862:
1747:"PEPFAR Statement on CAPRISA 004 Trial"
1487:
1249:
557:
538:announced that two phase III trials of
388:
14:
2117:
1221:"VivaGel™ – Clinical trials Under Way"
486:category of microbicides includes the
85:
1967:
1928:
333:(which must be used near the time of
293:Microbicides are a diverse group of
98:
1859:
1937:from the original on 25 August 2007
1685:. Geneva: World Health Organization
839:
798:Chemical structure of MDP1 molecule
660:of HIV from mother to child during
498:, which many microbes utilize as a
341:(or other devices that release the
24:
2076:Microbicides Development Programme
1681:World Health Organization (2002).
913:
628:
520:in preventing HIV transmission in
229:
25:
2151:
1952:
1733:Global Campaign for Microbicides
853:
2071:Global Campaign for Microbicides
738:
217:
211:
1922:
1894:
1829:
1799:
1769:
1739:
1727:
1697:
1683:"HIV/AIDS Topics: Microbicides"
1645:
1616:
1586:
1556:
1520:
1475:Templeton, David (2010-01-09).
1468:
1446:
1403:
1378:
1359:
1304:
1279:
1243:
1213:
1186:
747:Chemical structure of tenofovir
691:
271:sexually transmitted infections
1929:Hyena, H. (10 December 1999).
1159:
1128:
1109:
1079:
1047:
983:
965:"Research: rectalmicrobicides"
956:
934:
907:
824:
809:
502:for initial attachment to the
223:
205:
13:
1:
1705:"Microbicide Clinical Trials"
901:
722:men ages 18 to 30 years old.
595:National Institutes of Health
469:
393:
1659:. 2008-02-20. Archived from
1630:. 2008-02-18. Archived from
1349:"Research:BasedMicrobicides"
1118:"Research: HIV transmission"
778:Technology Innovation Agency
288:human immunodeficiency virus
7:
1498:"Caprisa 004 Study Details"
869:
783:
766:Family Health International
10:
2156:
2081:Microbicide Trials Network
1387:"Research:global-campaign"
999:Nature Reviews. Immunology
787:
536:International AIDS Society
385:with an infected partner.
195:Chemical and physical data
2089:
2053:
2022:
2001:
1777:"AVAC-About Microbicides"
1424:10.1007/s10461-006-9128-0
1155:World Health Organization
730:Completed clinical trials
678:statistically significant
604:sub-Saharan AIDS pandemic
552:World Health Organization
434:Vaginal defense enhancers
353:use by those engaging in
248:
235:
199:
194:
174:
158:
138:
118:
113:
75:
70:
51:
46:
37:
943:"Research: microbicides"
891:Supramolecular chemistry
816:Carrageenan#Medical Uses
716:University of Pittsburgh
674:pre-exposure prophylaxis
1481:Pittsburgh Post-Gazette
1366:control to fight AIDS.
1252:"Research: CAPRISA 004"
804:Indevus Pharmaceuticals
772:. It was funded by the
2130:Prevention of HIV/AIDS
799:
748:
615:herpes simplex viruses
611:human papillomaviruses
571:
494:chemically related to
479:
411:sodium dodecyl sulfate
363:less-developed nations
1872:"Ongoing PrEP Trials"
1735:Product Pipeline List
797:
746:
658:vertical transmission
654:reverse transcriptase
591:drug-approval process
565:
477:
405:microbicides such as
349:application, and for
1542:10.1038/news.2009.91
1527:Nature News (2009).
916:"Research: hiv aids"
821:trial participants.
558:Nanoscale dendrimers
500:biochemical receptor
389:Mechanisms of action
299:mechanisms of action
2014:Vaginal microbicide
1817:on 27 November 2016
1347:BasedMicrobicides.
1201:on October 22, 2008
1174:on February 8, 2007
1143:on February 8, 2007
963:rectalmicrobicide.
711:developed countries
442:is typically quite
280:chemical substances
94:(Prescription only)
34:
2009:Rectal microbicide
1757:on 14 October 2012
1628:Population Council
1568:Medical News Today
1116:HIV transmission.
971:on 30 October 2020
886:Rectal microbicide
847:confirmatory trial
800:
749:
572:
526:multicenter trials
480:
337:) and sponges and
335:sexual intercourse
295:chemical compounds
269:Microbicides for
30:
2112:
2111:
1657:kaisernetwork.org
1455:"global-campaign"
1453:global-campaign.
1412:AIDS and Behavior
1385:global-campaign.
1231:on 7 January 2008
941:global-campaign.
881:Cellulose sulfate
751:In July 2010 the
532:Cellulose sulfate
367:Sexual abstinence
343:active ingredient
266:
265:
102:
89:
18:Cellulose sulfate
16:(Redirected from
2147:
1988:
1981:
1974:
1965:
1964:
1947:
1946:
1944:
1942:
1926:
1920:
1919:
1917:
1911:. Archived from
1906:
1898:
1892:
1891:
1889:
1887:
1878:. Archived from
1868:
1857:
1856:
1854:
1852:
1843:. Archived from
1833:
1827:
1826:
1824:
1822:
1813:. Archived from
1803:
1797:
1796:
1794:
1792:
1783:. Archived from
1773:
1767:
1766:
1764:
1762:
1753:. Archived from
1743:
1737:
1731:
1725:
1724:
1722:
1720:
1711:. Archived from
1701:
1695:
1694:
1692:
1690:
1678:
1672:
1671:
1669:
1668:
1649:
1643:
1642:
1640:
1639:
1620:
1614:
1613:
1611:
1609:
1600:. Archived from
1590:
1584:
1583:
1581:
1579:
1570:. Archived from
1560:
1554:
1553:
1551:
1549:
1544:
1524:
1518:
1517:
1515:
1513:
1508:on 14 March 2011
1504:. Archived from
1494:
1485:
1484:
1472:
1466:
1465:
1463:
1461:
1450:
1444:
1443:
1407:
1401:
1400:
1398:
1396:
1391:
1382:
1376:
1375:
1370:. Archived from
1363:
1357:
1356:
1351:. Archived from
1344:
1333:
1331:
1329:
1327:
1318:. Archived from
1308:
1302:
1301:
1299:
1298:
1289:. Archived from
1283:
1277:
1276:
1270:
1262:
1260:
1258:
1247:
1241:
1240:
1238:
1236:
1227:. Archived from
1217:
1211:
1210:
1208:
1206:
1197:. Archived from
1190:
1184:
1183:
1181:
1179:
1170:. Archived from
1163:
1157:
1152:
1150:
1148:
1139:. Archived from
1132:
1126:
1125:
1120:. Archived from
1113:
1107:
1106:
1104:
1102:
1093:. Archived from
1083:
1077:
1076:
1074:
1072:
1067:on 13 March 2016
1066:
1060:. Archived from
1059:
1051:
1045:
1044:
1042:
1041:
1035:
1029:. Archived from
996:
987:
981:
980:
978:
976:
967:. Archived from
960:
954:
953:
951:
949:
938:
932:
931:
929:
927:
918:. Archived from
911:
840:Current research
698:first generation
682:proof of concept
647:diarylpyrimidine
438:Healthy vaginal
307:delivery systems
262:
261:
254:
243:
231:
225:
219:
213:
207:
187:
151:
100:
97:
87:
84:
42:
35:
33:
29:
21:
2155:
2154:
2150:
2149:
2148:
2146:
2145:
2144:
2115:
2114:
2113:
2108:
2091:Clinical trials
2085:
2049:
2018:
1997:
1992:
1955:
1950:
1940:
1938:
1927:
1923:
1915:
1909:U.N.Declaration
1904:
1900:
1899:
1895:
1885:
1883:
1882:on 6 March 2012
1870:
1869:
1860:
1850:
1848:
1847:on 6 March 2012
1835:
1834:
1830:
1820:
1818:
1805:
1804:
1800:
1790:
1788:
1787:on 25 July 2011
1775:
1774:
1770:
1760:
1758:
1745:
1744:
1740:
1732:
1728:
1718:
1716:
1715:on 16 July 2011
1703:
1702:
1698:
1688:
1686:
1679:
1675:
1666:
1664:
1651:
1650:
1646:
1637:
1635:
1622:
1621:
1617:
1607:
1605:
1604:on 25 July 2011
1592:
1591:
1587:
1577:
1575:
1574:on 14 June 2011
1562:
1561:
1557:
1547:
1545:
1525:
1521:
1511:
1509:
1496:
1495:
1488:
1473:
1469:
1459:
1457:
1451:
1447:
1408:
1404:
1394:
1392:
1389:
1383:
1379:
1364:
1360:
1345:
1336:
1325:
1323:
1322:on 16 July 2011
1310:
1309:
1305:
1296:
1294:
1287:"Study Details"
1285:
1284:
1280:
1264:
1263:
1256:
1254:
1248:
1244:
1234:
1232:
1219:
1218:
1214:
1204:
1202:
1191:
1187:
1177:
1175:
1164:
1160:
1146:
1144:
1133:
1129:
1114:
1110:
1100:
1098:
1097:on 16 July 2011
1085:
1084:
1080:
1070:
1068:
1064:
1057:
1053:
1052:
1048:
1039:
1037:
1033:
1011:10.1038/nri1848
994:
988:
984:
974:
972:
961:
957:
947:
945:
939:
935:
925:
923:
922:on May 29, 2004
912:
908:
904:
872:
856:
842:
827:
812:
792:
786:
741:
732:
694:
631:
629:Antiretrovirals
560:
496:heparan sulfate
492:polysaccharides
472:
436:
396:
391:
383:sexual activity
371:sexual violence
303:clinical trials
257:
255:
252:(what is this?)
249:
241:
228:
222:
216:
210:
190:
170:
154:
134:
131:
126:
125:
109:
66:
28:
23:
22:
15:
12:
11:
5:
2153:
2143:
2142:
2137:
2132:
2127:
2110:
2109:
2107:
2106:
2101:
2095:
2093:
2087:
2086:
2084:
2083:
2078:
2073:
2068:
2063:
2057:
2055:
2051:
2050:
2048:
2047:
2042:
2037:
2032:
2026:
2024:
2020:
2019:
2017:
2016:
2011:
2005:
2003:
1999:
1998:
1991:
1990:
1983:
1976:
1968:
1962:
1961:
1954:
1953:External links
1951:
1949:
1948:
1921:
1918:on 2009-03-25.
1893:
1858:
1828:
1798:
1768:
1738:
1726:
1696:
1673:
1644:
1615:
1585:
1555:
1519:
1486:
1467:
1445:
1402:
1377:
1374:on 2010-06-11.
1358:
1355:on 2011-07-17.
1334:
1303:
1278:
1242:
1212:
1185:
1158:
1127:
1124:on 2008-03-06.
1108:
1078:
1046:
982:
955:
933:
905:
903:
900:
899:
898:
893:
888:
883:
878:
871:
868:
855:
854:Social factors
852:
841:
838:
826:
823:
811:
808:
785:
782:
740:
737:
731:
728:
693:
690:
666:after exposure
635:antiretroviral
630:
627:
583:genital herpes
559:
556:
471:
468:
435:
432:
423:lipid membrane
415:viral envelope
395:
392:
390:
387:
323:aerosol sprays
284:microorganisms
264:
263:
246:
245:
239:
233:
232:
226:
220:
214:
208:
203:
197:
196:
192:
191:
189:
188:
180:
178:
172:
171:
169:
168:
164:
162:
156:
155:
153:
152:
144:
142:
136:
135:
133:
132:
129:
121:
120:
119:
116:
115:
111:
110:
108:
107:
95:
81:
79:
73:
72:
68:
67:
65:
64:
57:
55:
49:
48:
44:
43:
26:
9:
6:
4:
3:
2:
2152:
2141:
2138:
2136:
2133:
2131:
2128:
2126:
2123:
2122:
2120:
2105:
2102:
2100:
2097:
2096:
2094:
2092:
2088:
2082:
2079:
2077:
2074:
2072:
2069:
2067:
2064:
2062:
2059:
2058:
2056:
2054:Organizations
2052:
2046:
2043:
2041:
2038:
2036:
2033:
2031:
2028:
2027:
2025:
2021:
2015:
2012:
2010:
2007:
2006:
2004:
2000:
1996:
1989:
1984:
1982:
1977:
1975:
1970:
1969:
1966:
1960:
1957:
1956:
1936:
1932:
1925:
1914:
1910:
1903:
1897:
1881:
1877:
1873:
1867:
1865:
1863:
1846:
1842:
1838:
1832:
1816:
1812:
1808:
1802:
1786:
1782:
1778:
1772:
1756:
1752:
1748:
1742:
1736:
1730:
1714:
1710:
1706:
1700:
1684:
1677:
1663:on 2009-07-21
1662:
1658:
1654:
1648:
1634:on 2008-03-06
1633:
1629:
1625:
1619:
1603:
1599:
1595:
1589:
1573:
1569:
1565:
1559:
1543:
1538:
1534:
1530:
1523:
1507:
1503:
1499:
1493:
1491:
1482:
1478:
1471:
1456:
1449:
1441:
1437:
1433:
1429:
1425:
1421:
1417:
1413:
1406:
1388:
1381:
1373:
1369:
1362:
1354:
1350:
1343:
1341:
1339:
1321:
1317:
1313:
1307:
1293:on 2010-07-24
1292:
1288:
1282:
1274:
1268:
1253:
1250:CAPRISA 004.
1246:
1230:
1226:
1222:
1216:
1200:
1196:
1189:
1173:
1169:
1162:
1156:
1142:
1138:
1131:
1123:
1119:
1112:
1096:
1092:
1088:
1082:
1063:
1056:
1050:
1036:on 2015-07-01
1032:
1028:
1024:
1020:
1016:
1012:
1008:
1005:(5): 371–82.
1004:
1000:
993:
986:
970:
966:
959:
944:
937:
921:
917:
910:
906:
897:
894:
892:
889:
887:
884:
882:
879:
877:
874:
873:
867:
863:
860:
851:
848:
837:
835:
831:
822:
818:
817:
807:
805:
796:
791:
781:
779:
775:
771:
767:
762:
758:
754:
745:
739:Tenofovir gel
736:
727:
723:
721:
717:
712:
707:
704:
699:
689:
687:
683:
679:
675:
671:
667:
663:
659:
655:
651:
648:
644:
640:
636:
626:
624:
620:
616:
612:
607:
605:
600:
596:
592:
588:
584:
580:
577:
569:
564:
555:
553:
549:
544:
541:
537:
533:
529:
527:
523:
519:
515:
511:
509:
505:
504:cell membrane
501:
497:
493:
489:
485:
476:
467:
465:
461:
457:
453:
449:
445:
441:
431:
428:
424:
420:
416:
412:
408:
404:
400:
386:
384:
380:
376:
372:
368:
364:
358:
356:
352:
348:
344:
340:
339:vaginal rings
336:
332:
328:
324:
320:
316:
312:
308:
304:
300:
296:
291:
289:
285:
281:
277:
276:pharmacologic
273:
272:
260:
253:
247:
240:
238:
234:
204:
202:
198:
193:
186:
182:
181:
179:
177:
173:
166:
165:
163:
161:
157:
150:
146:
145:
143:
141:
137:
128:
127:
124:
117:
112:
106:
96:
93:
83:
82:
80:
78:
74:
69:
62:
59:
58:
56:
54:
50:
47:Clinical data
45:
41:
36:
19:
2135:Microbicides
1939:. Retrieved
1924:
1913:the original
1908:
1896:
1884:. Retrieved
1880:the original
1875:
1849:. Retrieved
1845:the original
1840:
1837:"About PrEP"
1831:
1819:. Retrieved
1815:the original
1810:
1801:
1789:. Retrieved
1785:the original
1780:
1771:
1759:. Retrieved
1755:the original
1750:
1741:
1729:
1717:. Retrieved
1713:the original
1708:
1699:
1687:. Retrieved
1676:
1665:. Retrieved
1661:the original
1656:
1647:
1636:. Retrieved
1632:the original
1627:
1618:
1606:. Retrieved
1602:the original
1597:
1588:
1576:. Retrieved
1572:the original
1567:
1558:
1546:. Retrieved
1532:
1522:
1510:. Retrieved
1506:the original
1501:
1480:
1470:
1458:. Retrieved
1448:
1418:(2): 271–6.
1415:
1411:
1405:
1393:. Retrieved
1380:
1372:the original
1361:
1353:the original
1324:. Retrieved
1320:the original
1315:
1306:
1295:. Retrieved
1291:the original
1281:
1255:. Retrieved
1245:
1233:. Retrieved
1229:the original
1224:
1215:
1203:. Retrieved
1199:the original
1188:
1176:. Retrieved
1172:the original
1161:
1145:. Retrieved
1141:the original
1130:
1122:the original
1111:
1099:. Retrieved
1095:the original
1090:
1081:
1069:. Retrieved
1062:the original
1049:
1038:. Retrieved
1031:the original
1002:
998:
985:
973:. Retrieved
969:the original
958:
946:. Retrieved
936:
924:. Retrieved
920:the original
909:
864:
857:
843:
828:
819:
813:
801:
750:
733:
724:
708:
697:
696:Most of the
695:
692:Formulations
632:
618:
608:
573:
531:
530:
513:
512:
488:carrageenans
481:
437:
397:
379:transmission
359:
292:
268:
267:
256:
250:
77:Legal status
71:Legal status
2125:Antiseptics
2099:CAPRISA 004
2030:Nonoxynol-9
1225:Star Pharma
876:Antiseptics
830:Nonoxynol-9
825:Nonoxynol-9
810:Carrageenan
761:CAPRISA 004
757:CAPRISA 004
623:CAPRISA 004
579:dendrimeric
514:Carrageenan
464:spermicidal
407:nonoxynol-9
278:agents and
244: g·mol
149:147127-20-6
114:Identifiers
2119:Categories
1689:August 28,
1667:2008-03-12
1638:2008-03-12
1297:2010-10-01
1040:2013-03-22
902:References
834:spermicide
788:See also:
720:homosexual
680:and offer
662:childbirth
643:dapivirine
613:(HPV) and
568:morphology
470:Polyanions
456:secretions
403:surfactant
394:Detergents
309:including
237:Molar mass
185:W4HFE001U5
160:ChemSpider
140:CAS Number
123:IUPAC name
2045:BufferGel
2035:Tenofovir
896:Tenofovir
686:pathogens
650:inhibitor
639:tenofovir
576:nanoscale
540:cellulose
524:clinical
522:phase III
510:binding.
484:polyanion
460:BufferGel
399:Detergent
32:Tenofovir
2040:PRO 2000
2023:Products
1935:Archived
1432:16775772
1267:cite web
1027:28270072
1019:16639430
914:gender.
870:See also
790:PRO 2000
784:PRO 2000
619:in vitro
597:and the
518:efficacy
448:alkaline
355:anal sex
259:(verify)
53:ATC code
1941:1 April
1886:1 April
1851:1 April
1821:1 April
1791:1 April
1761:1 April
1719:1 April
1608:1 April
1578:1 April
1548:1 April
1512:1 April
1502:Caprisa
1460:1 April
1440:2722261
1395:1 April
1326:1 April
1257:1 April
1235:1 April
1205:1 April
1178:1 April
1147:1 April
1101:1 April
1071:1 April
975:1 April
948:1 April
926:1 April
859:Condoms
670:topical
652:of HIV
587:macaque
548:placebo
543:sulfate
427:mucosal
381:during
375:condoms
347:vaginal
327:tablets
319:lotions
242:287.216
201:Formula
61:J05AF07
1751:PEPFAR
1533:Nature
1438:
1430:
1025:
1017:
770:CONRAD
450:pH of
444:acidic
419:capsid
351:rectal
315:creams
105:℞-only
103:
90:
63:
2104:VOICE
2002:Types
1916:(PDF)
1905:(PDF)
1436:S2CID
1390:(PDF)
1065:(PDF)
1058:(PDF)
1034:(PDF)
1023:S2CID
995:(PDF)
508:viral
452:semen
331:films
1959:AVAC
1943:2018
1888:2018
1876:AVAC
1853:2018
1841:AVAC
1823:2018
1793:2018
1781:AVAC
1763:2018
1721:2018
1709:AVAC
1691:2006
1610:2018
1598:AVAC
1580:2018
1550:2018
1514:2018
1462:2018
1428:PMID
1397:2018
1328:2018
1316:AVAC
1273:link
1259:2018
1237:2018
1207:2018
1180:2018
1149:2018
1103:2018
1091:AVAC
1073:2018
1015:PMID
977:2018
950:2018
928:2018
832:, a
768:and
482:The
462:, a
401:and
311:gels
274:are
176:UNII
167:none
1811:MTN
1537:doi
1420:doi
1007:doi
645:(a
585:in
421:or
365:).
329:or
290:).
92:POM
2121::
1933:.
1907:.
1874:.
1861:^
1839:.
1809:.
1779:.
1749:.
1707:.
1655:.
1626:.
1596:.
1566:.
1535:.
1531:.
1500:.
1489:^
1479:.
1434:.
1426:.
1416:11
1414:.
1337:^
1314:.
1269:}}
1265:{{
1223:.
1153:,
1089:.
1021:.
1013:.
1001:.
997:.
780:.
688:.
641:,
606:.
440:pH
417:,
409:,
357:.
325:,
321:,
317:,
313:,
215:14
99:US
86:UK
1987:e
1980:t
1973:v
1945:.
1890:.
1855:.
1825:.
1795:.
1765:.
1723:.
1693:.
1670:.
1641:.
1612:.
1582:.
1552:.
1539::
1516:.
1483:.
1464:.
1442:.
1422::
1399:.
1332:9
1330:.
1300:.
1275:)
1261:.
1239:.
1209:.
1182:.
1151:.
1105:.
1075:.
1043:.
1009::
1003:6
979:.
952:.
930:.
570:.
230:P
227:4
224:O
221:5
218:N
212:H
209:9
206:C
101::
88::
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
