Rectal microbicide

Last updated
Rectal microbicide
Specialty Gastroenterology, general surgery

A rectal microbicide is a microbicide for rectal use. Most commonly such a product would be a topical gel inserted into the anus so that it make act as protection against the contract of a sexually transmitted infection during anal sex.[ citation needed ]

Contents

Along with vaginal microbicides, rectal microbicides are currently the subject of medical research on microbicides for sexually transmitted diseases to determine the circumstances under which and the extent to which they provide protection against infection.

Less commonly, rectal microbicides can have other purposes also; for example, they could be used to treat certain medical conditions as a suppository would.

History

Early development of topical microbicides starting around 1998 focused on preventing of HIV transmission during vaginal intercourse. [1] The entire field lacks a proof of concept that a vaginal microbicide exists. [1] As of 2008, 16 topical microbicides entered phase I or II clinical trial and 7 advanced to an additional trial. [1] Previous studies both showed promise in new areas of research and gave disappointing results from the first generation products, as surfactants like nonoxynol-9 and entry inhibitors like carrageenan showed no efficacy in preventing HIV and were associated with risk of inflammation which raised the risk of contracting HIV in some circumstances. [1]

In 1998, researchers noted that gay men using products containing nonoxynol-9 as part of their infection prevention strategy despite lack of evidence of efficacy or any safety data for that practice. [2] At the time, the drug was under evaluation as a vaginal microbicide. [2]

Because of expected similarities between the efficacy of vaginal and rectal microbicides, some researchers have called for all vaginal microbicides to be tested for efficacy when used rectally. [3]

Motivation

There are two fundamental reasons to research and develop rectal microbicides for HIV prevention:

Concerted advocacy for the research and development of safe, effective, acceptable and accessible rectal microbicides began in 2005, when International Rectal Microbicide Advocates was founded with colleagues representing the AIDS Foundation of Chicago, the Canadian AIDS Society, the Community HIV/AIDS Mobilization Program, and the Global Campaign for Microbicides.[ citation needed ]

The political and sociocultural context reinforced the dismissal of rectal microbicides. Pervasive homophobia across the globe has resulted in a lack of adequate attention and resources devoted to gay men and other men who have sex with men (MSM) despite the disproportional HIV burden borne by this population. [7] Few knew, or acknowledged, that anal intercourse is a widespread practice among heterosexuals, both men and women, gay men and other MSM, as well as transgender people. Thus, evidence-free assumptions relegated the rectal portion of the microbicide field to a small, dark corner.[ citation needed ]

The field has moved from simply being an adjunct to vaginal studies to a force in its own right. This is due to a handful of visionary, passionate, and dogged scientists; funding from the United States (which has supported approximately 97% of all rectal microbicide research); and growing community engagement. [8]

Research

Preclinical testing

Preclinical testing for rectal microbicides has been conducted in macaques to get a nonhuman primate model of drug behavior. [9]

UC-781 trial

Scientists working on the University of California, Los Angeles (UCLA's) Microbicide Development Program initiated the first Phase I RM safety trial, investing the safety and acceptability of UC-781, in December 2006. Rectal application of UC-781 gel, a potent antiretroviral (ARV) drug, was shown to be safe and acceptable to the 36 men and women in the trial. Phase I trials normally focus solely on safety and acceptability, but researchers used a novel approach in this trial: taking rectal tissue biopsies from participants and exposing them to HIV ex vivo in the laboratory. The drug significantly reduced HIV transmission in these essays. [10]

RMP-02/MTN-006

RMP-02/MTN-006 Tested the same vaginal formulation of tenofovir gel that reduced HIV acquisition by an estimated 39 percent overall in the CAPRISA (Centre for the AIDS Programme of Research) 004 trial that was conducted in South Africa. [11] In September 2009, 18 men and women began enrolling in the trial, which was sponsored by the Microbicide Trials Network (MTN) and UCLA's Microbicide Development Program. The study tested the safety and acceptability of single- and multiple-day rectal applications of tenofovir, a single oral dose of tenofovir, and a placebo.[ citation needed ]

Laboratory tests showed that HIV was significantly inhibited in rectal tissue samples from participants who applied tenofovir gel to their rectums daily for one week compared to tissue from those who used a placebo gel. Although a slight anti-HIV effect was noted in tissue from participants who applied a single dose of tenofovir gel, the finding was not statistically significant. The single dose of oral tenofovir did not provide any protection against HIV in rectal tissue samples. The study also discovered that only 25 percent of the participants liked tenofovir gel, compared to 50 percent who had used the placebo gel. Some individuals who used tenofovir gel experienced gastrointestinal distress, cramps, and diarrhea. Results were presented at the 18th Conference on Retroviruses and Opportunistic Infections, or CROI. [12]

MTN-007

MTN-007 studied a reformulated version of the tenofovir gel. Researchers retained the same concentration of tenofovir (one percent), but reduced the glycerin in the gel in an attempt to make it more acceptable and “rectal friendly.” This Phase I safety and acceptability study, launched in October 2011, included 65 men and women from three sites in the United States. Results were presented at the 19th CROI in March 2012. [13] This reduced glycerin formulation of 1 percent tenofovir gel was found to be safe and acceptable. Researchers recommended advancing this candidate to Phase II.[ citation needed ]

MTN-017

MTN-017, the follow-up to MTN-007, represented a major milestone: the first Phase II expanded safety and acceptability study of an RM. The trial was officially launched in October 2013 [14] at sites in the United States, Peru, Thailand, and South Africa. The 195 gay men, other MSM, and transgender women recruited into MTN-017 more than doubled the total number of human beings who have participated in RM clinical trials to date, and the trial was also the first to include participants from countries outside of the United States.[ citation needed ]

The study investigated the safety and acceptability of the reduced glycerin tenofovir gel and directly compared acceptability and adherence to daily oral Truvada. MTN-017 featured an open-label, crossover design in which each individual followed three different regimens, each lasting eight weeks. One regimen consisted of the participant applying the gel to the rectum daily. A second regimen asked participants to apply the gel rectally before and after anal intercourse. In the third regimen, participants took oral Truvada every day. The order in which participants followed the study regimens was assigned randomly, with a break between each regimen.[ citation needed ]

The procedures carried out as part of MTN-017 determined how much of each drug is absorbed in blood, rectal fluid, and tissue, and also assessed any changes in cells or tissue. Study participants were asked about any side effects, what they liked and disliked about using the gel either daily or with sex, and whether they would consider using the gel in the future. Gel acceptability and adherence were directly compared to oral Truvada, which has been shown to reduce the risk of HIV acquisition in a number of studies among different populations. [15] [16]

Use

Rectal microbicides can reduce the risk of transmission of HIV during anal intercourse, particularly during sex when condoms are not used. [1] Researchers have explored using personal lubricant as a vehicle for delivering a rectal microbicide. [17]

Culture

Research into rectal microbicides and funding for exploring their use as public health tools has faced barriers historically because of the taboo in discussing anal health and anal sex. [18] Researchers have reported feeling disinclined to request funding for "anal research" because of biases against anything to do with an anus, and public policy writers have at times faced opposition to promoting discussion on anal topics. [18]

Future

Scientists at the Population Council are trying to develop a microbicide that would be both safe and effective in either the vagina or the rectum. They have conducted early work on a combination product containing MIV-150 (an investigational ARV), zinc acetate, and carrageenan gel. Further evaluation of this combination is dependent on funding. [19]

Related Research Articles

<span class="mw-page-title-main">Safe sex</span> Ways to reduce the risk of acquiring STIs

Safe sex is sexual activity using methods or contraceptive devices to reduce the risk of transmitting or acquiring sexually transmitted infections (STIs), especially HIV. "Safe sex" is also sometimes referred to as safer sex or protected sex to indicate that some safe sex practices do not eliminate STI risks. It is also sometimes used colloquially to describe methods aimed at preventing pregnancy that may or may not also lower STI risks.

<span class="mw-page-title-main">Nonoxynol-9</span> Chemical compound

Nonoxynol-9, sometimes abbreviated as N-9, is an organic compound that is used as a surfactant. It is a member of the nonoxynol family of nonionic surfactants. N-9 and related compounds are ingredients in various cleaning and cosmetic products. It is widely used in contraceptives for its spermicidal properties.

<span class="mw-page-title-main">Microbicides for sexually transmitted diseases</span> Pharmacologic agents and chemical substances

Microbicides for sexually transmitted diseases are pharmacologic agents and chemical substances that are capable of killing or destroying certain microorganisms that commonly cause human infection.

<span class="mw-page-title-main">Personal lubricant</span> Substance to reduce friction, usually during sexual acts

Personal lubricants are specialized lubricants used during sexual acts, such as intercourse and masturbation, to reduce friction to or between the penis and vagina, anus or other body parts or applied to sex toys to reduce friction or to ease penetration. Surgical or medical lubricants or gels, which are similar to personal lubricants but not usually referred to or labelled as "personal" lubricants, may be used for medical purposes such as speculum insertion or introduction of a catheter. The primary difference between personal and surgical lubricants is that surgical lubricants are thicker, sterile gels, typically containing a bacteriostatic agent. As of 2015 the personal lubricant market was estimated to be worth at least $400 million.

<span class="mw-page-title-main">Pre-exposure prophylaxis</span> HIV prevention strategy using preventative medication for HIV-negative individuals

Pre-exposure prophylaxis (PrEP) is the use of medications to prevent the spread of disease in people who have not yet been exposed to a disease-causing agent, usually a virus. The term typically refers to the use of antiviral drugs as a strategy for the prevention of HIV/AIDS. PrEP is one of a number of HIV prevention strategies for people who are HIV negative but who have a higher risk of acquiring HIV, including sexually active adults at increased risk of contracting HIV, people who engage in intravenous drug use, and serodiscordant sexually active couples.

<span class="mw-page-title-main">HIV Prevention Trials Network</span>

The HIV Prevention Trials Network (HPTN) is a worldwide collaborative clinical trials network that brings together investigators, ethicists, community and other partners to develop and test the safety and efficacy of interventions designed to prevent the acquisition and transmission of HIV. HPTN studies evaluate new HIV prevention interventions and strategies in populations and geographical regions that bear a disproportionate burden of infection. The HPTN is committed to the highest ethical standards for its clinical trials and recognizes the importance of community engagement in all phases of the research process.

iPrEx

iPrEx was a phase III clinical trial to determine whether the antiretroviral medication emtricitabine/tenofovir could safely and effectively prevent HIV acquisition through sex in men who have sex with men and transgender women. iPrEx was the first human study of an HIV prevention strategy known as pre-exposure prophylaxis, or PrEP.

CAPRISA 004 is the name of a clinical trial conducted by CAPRISA. This particular study was the first to show that a topical gel could reduce a person's risk of contracting HIV. The gel used in the study contained a microbicide.

CONRAD is a non-profit organization scientific research organization that works to improve the reproductive health of women, especially in developing countries. CONRAD was established in 1986 under a cooperative agreement between Eastern Virginia Medical School (EVMS) and the United States Agency for International Development(USAID). CONRAD’s products are developed primarily for women in low-resource settings, in that they are designed to be safe, affordable and user-friendly. CONRAD is led by Scientific and Executive Director Gustavo Doncel, M.D., Ph.D. Primary funding for CONRAD comes from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID), with additional funding from The Bill & Melinda Gates Foundation and the National Institutes of Health (NIH).

HIV prevention refers to practices that aim to prevent the spread of the human immunodeficiency virus (HIV). HIV prevention practices may be undertaken by individuals to protect their own health and the health of those in their community, or may be instituted by governments and community-based organizations as public health policies.

HVTN 505 is a clinical trial testing an HIV vaccine regimen on research participants. The trial is conducted by the HIV Vaccine Trials Network and sponsored by the National Institute of Allergy and Infectious Diseases. Vaccinations were stopped in April 2013 due to initial results showing that the vaccine was ineffective in preventing HIV infections and lowering viral load among those participants who had become infected with HIV. All study participants will continue to be monitored for safety and any long-term effects.

International Rectal Microbicide Advocates (IRMA) is an international non-profit organization which promotes awareness of rectal microbicides.

PRO 2000 is an experimental vaginal microbicide which has been proposed as a preventive medicine for reducing the risk of contracting HIV. It has never been recommended as an effective medicine to be used for any purpose. Some clinical trials have shown that under some conditions it may provide some protection against HIV.

A vaginal microbicide is a microbicide for vaginal use. Most commonly such a product would be a topical gel or cream inserted into the vagina so that it may treat some infection in the vagina, such as types of vaginitis.

BufferGel is the brand name of a spermicide and microbicide gel which is being tested for its potential development into a preventive medicine to stop the transmission of HIV.

Since reports of emergence and spread of the human immunodeficiency virus (HIV) in the United States between the 1970s and 1980s, the HIV/AIDS epidemic has frequently been linked to gay, bisexual, and other men who have sex with men (MSM) by epidemiologists and medical professionals. It was first noticed after doctors discovered clusters of Kaposi's sarcoma and pneumocystis pneumonia in homosexual men in Los Angeles, New York City, and San Francisco in 1981. The first official report on the virus was published by the Center for Disease Control (CDC) on June 5, 1981 and detailed the cases of five young gay men who were hospitalized with serious infections. A month later, The New York Times reported that 41 homosexuals had been diagnosed with Kaposi's sarcoma, and eight had died less than 24 months after the diagnosis was made.

<span class="mw-page-title-main">Quarraisha Abdool Karim</span>

Quarraisha Abdool Karim is an infectious diseases epidemiologist and co-founder and Associate Scientific Director of CAPRISA. She is a Professor in Clinical Epidemiology, Columbia University, New York and Pro-Vice Chancellor for African Health, University of KwaZulu-Natal, South Africa.

<span class="mw-page-title-main">Rectal douching</span> Act of rinsing the rectum with liquid

Rectal douching is the act of rinsing the rectum with intent to clean it. An instance of this rinsing or a tool used to perform the rinse may be called a rectal douche.

<span class="mw-page-title-main">Dapivirine Ring</span> Antiretroviral vaginal ring

Dapivirine (DPV) Ring is an antiretroviral vaginal ring pioneered by the International Partnership for Microbicides (IPM) pending for regulatory review. It is designed as a long-acting form of HIV prevention for at-risk women, particularly in developing nations such as sub-Saharan Africa. IPM has rights to both the medication and the medical device. A total of four rings with different drug diffusion systems and polymer composition have been developed by IPM. The latest design, Ring-004, is a silicone polymer matrix-type system capable of delivering DPV intravaginally in a sustained manner.

Sharon Louise Hillier is an American microbiologist. She is the Richard Sweet Endowed Chair in Reproductive Infectious Disease and vice chair of the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh Medical Center (UPMC) and Magee-Women's Research Institute.

References

  1. 1 2 3 4 5 McGowan, I. (2008). "Rectal microbicides: A new focus for HIV prevention". Sexually Transmitted Infections. 84 (6): 413–417. doi:10.1136/sti.2008.031328. PMID   19028937. S2CID   37411175.
  2. 1 2 Michael Gross; Susan Buchbinder; Connie Celum; Patrick Heagerty; George R. Seage III (July 1998). "Rectal Microbicides for U.S. Gay Men: Are Clinical Trials Needed? Are They Feasible?". Sexually Transmitted Diseases. 25 (6): 296–302. doi: 10.1097/00007435-199807000-00005 . PMID   9662763. S2CID   27971070.
  3. ↑ McGowan, I.; Anton, P. (2008). "Rectal microbicides". Current Opinion in HIV and AIDS. 3 (5): 593–598. doi:10.1097/COH.0b013e32830891cf. PMID   19373027. S2CID   38476514.
  4. ↑ Microbicide Trials Network. "Rectal Microbicides: Fact Sheet". Pittsburgh, PA: Microbicide Trials Network. Retrieved 1 April 2018.
  5. ↑ Leynaert, B.; Downs, A. M.; de Vincenzi, I. (1998). "Heterosexual Transmission of Human Immunodeficiency Virus: Variability of Infectivity Throughout the Course of Infection". American Journal of Epidemiology. European Study Group on Heterosexual Transmission of HIV. 148 (1): 88–96. doi: 10.1093/oxfordjournals.aje.a009564 . PMID   9663408.
  6. ↑ Vitinghoff, E.; Douglas, J.; Judon, F.; McKiman, D.; MacQueen, K.; Buchinder, S. P. (1999). "Per-Contact Risk of Human Immunodeficiency Virus Transmission Between Male Sexual Partners". American Journal of Epidemiology. 150 (3): 306–311. doi: 10.1093/oxfordjournals.aje.a010003 . PMID   10430236.
  7. ↑ "Achieving an AIDS-Free Generation for Gay Men and Other MSM: Financing and Implementation of HIV Programs Targeting MSM" (PDF). amfAR and Johns Hopkins Bloomberg School of Public Health. Archived from the original (PDF) on 2017-05-10. Retrieved 1 April 2018.
  8. ↑ IRMA. "Safety of Lubricants for Rectal Use: Questions & Answers for HIV Educators and Advocates" (PDF). Retrieved 1 April 2018.
  9. ↑ Patton, D. L.; Sweeney, Y. T. C.; Paul, K. J. (2009). "A Summary of Preclinical Topical Microbicide Rectal Safety and Efficacy Evaluations in a Pigtailed Macaque Model". Sexually Transmitted Diseases. 36 (6): 350–356. doi:10.1097/OLQ.0b013e318195c31a. PMC   2749653 . PMID   19556929.
  10. ↑ Anton; Saunders; Elliot; Khanukhova; et al. (2011). "First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy". PLOS ONE. 6 (9). e23243. Bibcode:2011PLoSO...623243A. doi: 10.1371/journal.pone.0023243 . PMC   3182160 . PMID   21969851.
  11. ↑ Karim; Karim; Frohlich; Grobler; et al. (2010). "Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women". Science. 329 (5996): 1168–1174. Bibcode:2010Sci...329.1168A. doi:10.1126/science.1193748. PMC   3001187 . PMID   20643915.
  12. ↑ Anton; McGowan. RMP-02/MTN-006: A Phase 1 Placebo-controlled Trial of Rectally Applied 1% Vaginal TFV Gel with Comparison to Oral TDF. 18th Conference on Retroviruses and Opportunistic Infections.
  13. ↑ McGowan; Hoesley; Janocko; et al. MTN-007: A Phase 1 Randomized, Double-blind, Placebo-controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel. 19th Conference on Retroviruses and Opportunistic Infections.
  14. ↑ "Researchers Launch First-Ever Phase II Safety Study of a Rectal Microbicide to Prevent HIV" (Press release). Microbicide Trials Network. 2 October 2013. Retrieved 15 December 2016.
  15. ↑ Grant, Robert M.; Lama, Javier; Anderson, Peter L.; McMahan, Vanessa; et al. (2010). "Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men". New England Journal of Medicine. 363 (27): 2587–2599. doi:10.1056/nejmoa1011205. PMC   3079639 . PMID   21091279.
  16. ↑ Baeten; Donnell; Mugo; Mujugira; Celum; et al. (Partners PrEP Study Team) (2012). ARV PrEP for HIV-1 Prevention among Heterosexual Men and Women. 19th Conference on Retroviruses and Opportunistic Infections.
  17. ↑ Exner, T. M.; Correale, J.; Carballo–Diéguez, A.; Salomon, L.; Morrow, K. M.; Dolezal, C.; Mayer, K. (2008). "Women's Anal Sex Practices: Implications for Formulation and Promotion of a Rectal Microbicide". AIDS Education and Prevention. 20 (2): 148–159. doi:10.1521/aeap.2008.20.2.148. PMID   18433320.
  18. 1 2 Straube, Trenton (July–August 2011). "The Anal Dialogues". POZ . Retrieved 17 November 2011.
  19. ↑ Pickett, Jim (August 2012). "Ready, Set, Rectal Microbicides: An Update on Rectal Microbicide Research and Advocacy". AIDSTAR-One Spotlight on Prevention.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.