Due to the ongoing COVID-19 pandemic, this year’s Annual ACTG Network Meeting will be held virtually during the week of June 14, 2021. We will share additional details soon!
Romidepsin Doesn’t Activate HIV-1 Expression in People Living with HIV on ART (A5315)

This exploratory study sought to determine whether romidepsin could awaken latent (‘sleeping’) HIV from its reservoir as part of an HIV cure “kick and kill strategy.” Romidepsin is a histone deacetylase inhibitor drug used to treat cutaneous T cell lymphoma.

In A5315, a randomized, double-blind, placebo-controlled study, investigators evaluated single doses of romidepsin at different amounts for three Cohorts. There were 43 participants with suppressed viral loads on ART that enrolled to prove this approach was safe. Sixteen participants were then enrolled in a final Cohort to receive romidepsin or placebo. Specialized techniques were used to look for HIV in different ways to see if the romidepsin worked.

All romidepsin doses were found to be safe and well-tolerated. However, there were no significant increases in HIV levels (meaning it did not activate sleeping HIV), and romidepsin did not appear to reawaken dormant virus from the reservoir at the doses studied, despite evidence that romidepsin had the expected effect on human cells.

Because studies of histone deacetylase (HDAC) inhibitors as single latency reversal agents, including this study, have failed to show a reduction in the inducible HIV-1 reservoir, other approaches will be needed to achieve a cure for HIV infection.

Bottom line: HDAC inhibitors like romidepsin will not get us closer to finding a way to eliminate the HIV in people. Negative studies like this help scientists move on to more promising approaches.

McMahon, D. K., Zheng, L., Cyktor, J. C., Aga, E., Macatangay, B. J., Godfrey, C., Para, M., Mitsuyasu, R. T., Hesselgesser, J., Dragavon, J., Dobrowolski, C., Karn, J., Acosta, E. P., Gandhi, R. T., Mellors, J. W., & ACTG A5315 Team (2020). A phase I/II randomized, placebo-controlled trial of romidepsin in persons with HIV-1 on suppressive antiretroviral therapy to assess safety and activation of HIV-1 expression (A5315). The Journal of infectious diseases, jiaa777. Advance online publication.

Lower Quality of Life and Lower Adherence Predict Early Virological Failure (A5273/9)

Lower health-related quality of life and lower adherence have been found to be independent predictors of virologic failure among people starting ART in U.S. clinical trials. A5273 evaluated whether quality of life and self-reported adherence could predict early second-line antiretroviral virological failure in less resource-rich countries. 

A5273 evaluated two second-line ART regimens among individuals from 15 sites in nine low-middle income countries: Brazil, India, Kenya, Malawi, Peru, South Africa, Tanzania, Thailand, and Zimbabwe. The study defined early virological failure as confirmed HIV-1 RNA viral load higher than 400 copies/mL after 24 weeks of second-line ART. Participants completed the quality of life questionnaire (ACTG SF-21), which has eight domains: General Health Perceptions, Physical Functioning, Role Functioning, Social Functioning, Cognitive Functioning, Pain, Mental Health, and Energy/Fatigue.

Of 500 individuals (51% women, median age 39 years) included in this study, 79% and 75% self-reported complete adherence (no missing doses in the past month) at 4 and 24 weeks after starting second-line ART, respectively. Early virological failure was experienced by 7% and was more common among those who self-reported incomplete adherence. Participants with low quality of life had higher rates of early virological failure.

A5273 verified that lower quality of life adds to self-reported incomplete adherence in predicting early virological failure. These findings indicate that quality of life and adherence assessments after second-line ART initiation could be implemented as real-time measurements to identify individuals at higher risk of subsequent virological failure in low-middle income countries. These individuals may benefit from interventions to improve quality of life, such as social self-value empowerment and yoga, or to optimize adherence, such as text-message reminders.

Bottom line: No matter where you live or how you feel about yourself, your quality of life influences your success or failure in taking medicines to treat HIV.

Torres, T. S., Harrison, L. J., La Rosa, A. M., Zheng, L., Cardoso, S. W., Ulaya, G., Akoojee, N., Kadam, D., Collier, A. C., Hughes, M. D., & for AIDS Clinical Trials Group (ACTG) A5273 Study Group (2021). Poor quality of life and incomplete self-reported adherence predict second-line ART virological failure in resource-limited settingsAIDS care, 1–10. Advance online publication.

Evaluating Physical Function Impairment and Frailty in Middle-Aged People Living with HIV (A5361s/2)

As the lifespan of people living with HIV increases, so too do the number of people aging with HIV (nearly half of people living with HIV in the United States are now at least 50 years old). Compared to people without HIV, physical function impairment and frailty are more common and occur at an earlier age in people living with HIV; both have been associated with increased risk of falls, hospitalizations, and death. This paper describes physical function impairment and frailty in middle-aged people living with HIV on stable ART when they enrolled in A5361S (PREPARE), a substudy of REPRIEVE.

A5361S evaluated 266 people living with HIV in the United States, nearly all in their 40s or 50s (81% male, 47% White, 45% Black, 18% Latinx). Many had high body mass index (BMI) and levels of physical activity were low. The investigators found that while overt frailty was uncommon (6%), physical function impairments and pre-frailty were present in nearly half of participants. Physical function impairments appeared mostly in power (the ability to rise from a chair) or strength (grip), important manifestations of skeletal muscle function.

These findings suggest that the time it takes you to stand up from a chair may be a useful screening tool in this relatively young population to detect subtle changes in physical function earlier in age. Additionally, greater BMI, physical inactivity, smoking, and hypertension were associated with physical function impairments. These are important modifiable factors to help target interventions to potentially delay or reduce physical function impairments. The team is continuing to assess physical function yearly to understand any effects of statins over time.

Bottom line: In this relatively younger population with HIV, changes in healthy physical function appeared earlier. Need to learn more about why this happens and the best ways to combat it.

Umbleja, T., Brown, T. T., Overton, E. T., Ribaudo, H. J., Schrack, J. A., Fitch, K. V., Douglas, P. S., Grinspoon, S. K., Henn, S., Arduino, R. C., Rodriguez, B., Benson, C. A., & Erlandson, K. M. (2020). Physical Function Impairment and Frailty in Middle-Aged People Living With Human Immunodeficiency Virus in the REPRIEVE Trial Ancillary Study PREPAREThe Journal of infectious diseases222(Suppl 1), S52–S62.
Martha Tholanah, Zimbabwe

Martha Tholanah is a Zimbabwean woman openly living with HIV who is passionate about women’s health and rights, access to basic services and HIV related treatment, the development of functional health systems, and environment and conservation issues. She serves on the East and Southern Africa (ESA) Regional Think Tank on HIV, Human Rights and Social Justice that is coordinated by the UNAIDS ESA RST. She has served as board chair of GALZ (Zimbabwe LGBTI association) and as a member of the International Community of Women Living with HIV (ICW) Southern Africa and ICW Global, and the Technical Review Committee of the Medical Research Council of Zimbabwe (MRCZ). Martha's current work involves grant support for civil society organizations working on sexual and reproductive health. She also volunteers in community health education.
Martha first became involved with ACTG in 2004 when she joined the Community Constituency Group (CCG), now the Community Scientific Subcommittee (CSS). She is currently serving her third term on the CSS and is also a member of the Community Advisory Board at the Milton Park CRS, where she is the current chair. Martha is the community representative for the A5391 (Do-It Study) protocol team, as well as the Comorbidities Transformative Science Group (CTSG). She has previously served on various ACTG protocol teams and committees.
An avid volunteer, Martha has joined many local organizations in order to help others. She has volunteered with Zimbabwe Health Ministry Hospitals, GALZ (the only LGBTI organization in Zimbabwe), Network of Zimbabwean Positive Women, Zimbabwe AIDS Network, and Just Associates (JASS). She has held various positions within these organizations to best support them and help her community.
Martha has received a number of awards for her work over the years. These include the 2015 David Kato Vision and Voice Award, awarded annually to an individual who demonstrates courage and outstanding leadership in advocating for the sexual rights of LGBTI people, particularly in environments where these individuals face continued rejection, marginalization, isolation and persecution; the 2015 Community Impact Award (since renamed Sharon Maxwell Community Impact Award), presented on 26th June 2015 by the ACTG Global Community Advisory Board; and the 2016 Elizabeth Taylor Human Rights Award.
Martha finds serving as a community member with the ACTG highly motivating and inspiring. Working with various professionals, understanding research processes, and interfacing with grassroots communities keeps her excited about clinical research.
This year the ACTG Network added five new core ACTG Clinical research sites. Over the next few months, we will spotlight each one so the network can get to know more about them.

Nutrición-Mexico, CRS, Mexico City, Mexico

The Instituto Nacional de Ciencias Medicas Y Nutrición Salvador Zubirán (INCMNSZ) HIV Research Unit belongs to the Infectious Diseases Department at INCMNSZ, which is a main teaching, academic medical center in Mexico City. The INCMNSZ HIV Research Unit has conducted HIV clinical and epidemiologic research throughout the last two decades, and includes three experienced infectious disease physicians, four study coordinators, nurses, mental health specialists, laboratory technicians, and administrative personnel with experience in clinical trials. They have a specialized microbiology lab and experience in fungus and Tuberculosis research.

Since 2004, the INCMNSZ clinic has participated in most of the pivotal phase 2 and 3 clinical trials of antiretroviral (ARV) drugs. The site has been very successful in recruiting participants across studies. Since 2007, the clinic has been one of seven sites of Region 2 (Caribbean, Central and South America Network, CCASANET) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) network, participating in almost all of the network’s initiatives focused on research in opportunistic infections, comorbidities, aging, mortality, and late diagnosis, among others. Recently, INCMNSZ has been one of three Mexico sites in the MOSAICO preventive vaccine study (HVTN), for which they are currently actively recruiting. They are thrilled to be joining the ACTG as a core site and continuing their important work.
March 20 marked National Native HIV/AIDS Awareness Day. We are fortunate to share the insight of Bill Hall, University of Washington ACTU CAB Member and Tlingit Tribal Member, on the importance of this day and making sure our Native communities are represented in our clinical trials.

"I became a Community Advocate for the Native American community on HIV/AIDS because, through my involvement with various AIDS organizations, I realized that the reason Native Americans are the most under-served community on HIV/AIDS was because no one was speaking up. HIV stigma is very strong and limits Native American participation in important research. We need to educate our community that research is safe, and that the regulations for research studies are quite high, and that if they feel uncomfortable at any time, they can quit the study. We need to make sure that all HIV treatments that we develop work in the Native American body. The only way to do that is to have Native participants in research studies."
Follow the ACTG on all of our social media accounts! Follow us throughout CROI for updates on ACTG presentations. Additionally, March 10 is National Women and Girls HIV/AIDS Awareness Day (#NWGHAAD)! Check out our social media pages to hear from our network about the importance of highlighting the experiences of women and girls living with HIV. 

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