MTN-009: The HIV Drug Resistance Study
Study Overview
Nowhere in the world is HIV cutting a wider, more destructive swath than in sub-Saharan Africa, and women, who account for 60 percent of those getting infected, are bearing the brunt of the epidemic. The extent that these infections involve drug resistant virus is not known. MTN-009, also called the HIV Drug Resistance Study, aims to provide a reliable assessment of the prevalence of HIV drug resistance in a representative population of women from KwaZulu-Natal, South Africa, where a woman’s HIV risk is among the highest. MTN-009 seeks also to understand if certain risk behaviors are associated with resistance. The study expects to enroll 350 newly diagnosed HIV-positive women and approximately 650 HIV-negative women, all between the ages of 18 and 40. Understanding the prevalence of HIV drug resistance will not only help inform public health decisions concerning the selection of ARVs that should or should not be used as part of antiretroviral therapy (ART), but will also help to guide HIV prevention efforts focused on testing different antiretroviral (ARV)-based approaches.
MTN-009 is being conducted at seven sites affiliated with the South African Medical Research Council (MRC) HIV Clinical Trials Unit in Durban and the surrounding KwaZulu-Natal region of South Africa. These same sites are also currently conducting VOICE–Vaginal and Oral Interventions to Control the Epidemic, a major HIV prevention trial testing daily use of a vaginal microbicide containing the ARV tenofovir and another approach called pre-exposure prophylaxis (PrEP), which involves daily use of the ARV tablet tenofovir or Truvada®. Both VOICE and MTN-009 are studies of the Microbicide Trials Network (MTN), an HIV/AIDS clinical trials network established and funded in 2006 by the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), all components of the U.S. National Institutes of Health (NIH). Leading MTN-009 are Urvi Parikh, Ph.D., of the University of Pittsburgh, and Photini Kiepiela, Ph.D., of the MRC.
The study started in September 2010 and is expected to take about two years to complete.
Why the Study is Important
Several African countries are beginning to expand access to ARVs for treatment as well as step up efforts to prevent mother to child transmission of HIV with the use of ARVs. At the same time, several large-scale trials are testing the promise of ARVs for preventing HIV in different at-risk populations. The widespread use of ARVs brings with it an inherent concern: drug resistance. Drug resistance refers to the ability of some microorganisms, including viruses such as HIV, to adapt so they can survive and multiply in the presence of drugs that would normally weaken or kill them.
In countries such as the United States, where ART is widely used, about 10 percent of new infections occur with drug-resistant HIV. Where ART use is more limited, new infections are far less likely to be from drug-resistant HIV. According to the Southern African Treatment and Resistance Network, less than 5 percent of newly infected individuals in the sub-Saharan region have drug-resistant virus. These numbers could increase with scale-up of ART, however. If not recognized and properly managed, high rates of drug resistance could facilitate its spread and eventually compromise the effectiveness of mainstay drugs. As such, information on the prevalence of HIV resistance will have critical bearing on the success of both current and future treatment and prevention programs.
For its part, MTN-009 will contribute important data about the prevalence of and risks for HIV drug resistance in women of reproductive age, who face the greatest risk of acquiring HIV, primarily through unprotected sex with a male partner. Importantly, the study will help determine if virus being transmitted to women has strains that are resistant to the ARVs currently being evaluated in HIV prevention trials like VOICE.
How the Study is Being Conducted
Women who contact one of the MRC sites to inquire about taking part in an HIV prevention trial, including VOICE, will first be offered enrollment in MTN-009. Those who voluntarily enroll will be asked to complete a private, computer-assisted questionnaire about behaviors that could potentially increase the risk of drug resistance, such as prior use of ARVs by either the participant or her sexual partner. Participants will then be tested for HIV infection. If a woman tests negative, her participation in the HIV Drug Resistance Study concludes at that time and she will be referred to the HIV prevention trial for screening. A woman who tests HIV positive will have additional tests of her blood to determine if there is evidence of drug resistant virus and to assess the effect that her HIV is having on the health of her immune system. One test will measure the amount of virus in the blood (viral load). Another test, called CD4+ T cell count, will provide an estimate of the number of healthy immune cells that remain uninfected. At subsequent study visits, participants will be counseled on the results of these tests, told how the results may impact the effectiveness of certain types of ARV medications as well as be referred to appropriate health care and counseling services. Although MTN-009 does not provide HIV treatment, the results of study tests may help doctors who are treating the infection to make better medical choices. With a participant’s permission, study staff will share results of laboratory tests performed as part of the study with her healthcare providers.
Detecting Resistance
Special laboratory tests can detect drug resistance from just a small sample of blood. These tests look for changes, or mutations, in the genetic makeup of HIV and identify those that have signatures for different types of drug resistant virus. As such, a drug resistance test can indicate a particular drug or drug class that should be avoided as well as those ARVs that may have reduced effectiveness. In recently infected or newly diagnosed people, resistance testing can help determine the best combination of ARVs to consider when treatment is later needed. During the time that a person is being treated with ART, routine resistance testing helps in monitoring the effectiveness of drug combinations so that adjustments can be made promptly as needed.
Two types of resistance tests will be used in MTN-009. The standard test detects resistance by casting a wide net. But this technique cannot always capture every mutation present in a sample, so the sensitive test is used to seek out specific mutations that may have been missed. These tests will be particularly important for characterizing HIV drug resistance within a population for whom there is currently very little data – South African women. Most information about drug resistance involves the HIV B subtype, which is most common in the Americas and Europe. Yet, in Africa, the predominant virus is C subtype, with other subtypes seen as well. This means that the drug resistant varieties that are usually seen in the United States or elsewhere may not necessarily be the same that arise in Africa.
Funding
MTN-009, the HIV Drug Resistance Study, gets its funding from the Division of AIDS, NIAID and the NIH Office of AIDS Research.
# # #
Additional information about MTN-009—the HIV Drug Resistance Study, VOICE and more generally about HIV drug resistance, is available at http://www.mtnstopshiv.org/news/studies/mtn009 and http://www.mtnstopshiv.org/news/studies/mtn003.
About the Microbicide Trials Network
The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. Based at Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international investigators and community and industry partners who are devoted to preventing or reducing the sexual transmission of HIV through the development and evaluation of products applied topically to mucosal surfaces or administered orally.
3-September-10
See Also
