NIH Restructures HIV Clinical Trial Networks; AIDS Director Touts Milestones

The National Institutes of Health (NIH) wound down its latest seven-year HIV research cycle with a reflection on its successes and a rollout of new clinical trial priorities heading into 2021. On Nov. 30, the agency announced the clinical investigators and institutions that will lead four federally funded HIV/AIDS clinical trials networks over the next seven years.

It also announced a new round of grants to 35 U.S. and international institutions selected as HIV/AIDS clinical trial units.

The restructuring happens every seven years, as NIH renews its funding of the HIV/AIDS clinical trials networks and realigns those networks to be more effective and efficient in its research aimed at ending the HIV epidemic.

“You could think of this as ‘who is in and who is out,’ but in reality [restructuring] is more like changing chairs,” said Carl Dieffenbach, Ph.D., the director of the Division of AIDS (DAIDS) within the NIH’s National Institute of Allergies and Infectious Diseases (NIAID).

The next seven-year cycle will be led by four networks, down from five in the prior cycle:

• HIV Vaccine Trials Network (HVTN)
• HIV Prevention Trials Network (HPTN)
• AIDS Clinical Trials Group (ACTG)
• International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT)

The biggest structural changes relative to the past seven years are the elimination of the Microbicide Trials Network, which will be folded into HPTN, and the absorption of adolescent HIV prevention and vaccine research into HPTN and HVTN, respectively.

DAIDS Director Hails 7 Years of Scientific Progress

Dieffenbach said that the NIH’s trial networks have brought huge strides in HIV research over the past seven years—in both treatment and prevention, as well as among both adults and children. In an interview with TheBodyPro, he cited several specific advances:

• Improvements in antiretroviral therapy and progress in development of an HIV vaccine.
• Demonstrated efficacy of next-generation pre-exposure prophylaxis (PrEP), including long-acting injectables, for both men and women.
• Effective use of antiretroviral therapy to prevent acquisition of HIV during pregnancy.
• Promising prophylaxis for tuberculosis, a disease that can be difficult to manage for coinfected people living with HIV.

Diffenbach said he was especially proud of two breakthroughs that came out of NIH vaccine trials. The first is downward label changes for the use of dolutegravir in pediatric antiretroviral therapy. “This means at a few weeks of age, babies can get the best meds and not stuck be stuck on AZT [zidovudine, Retrovir], and this makes a huge difference in their life expectations,” he said.

The second is the development of the dapivirine vaginal ring for HIV prevention, which is now prequalified for a global license through the World Health Organization. Dieffenbach added that he expects breakthroughs soon in research on other forms of long-term HIV protection for men and women, including patches, implants, and oral medications lasting 30 to 60 days per dose.

Impact of COVID-19 on Federally Funded HIV Research

The COVID-19 pandemic had teams doing double duty in 2020, Dieffenbach said—but that the process of restructuring the clinical trials network and issuing a new round of research awards was able to continue unaffected.

Diffenbach recalled that when COVID-19 hit the U.S., NIAID director Anthony Fauci, M.D., said all network teams must help address the newly emerging coronavirus pandemic as well as HIV. This meant an emergency adjustment in priorities, Diffenbach said: “While clinical research shut down due to COVID-19, we selectively kept large high-value projects running—using telemed[icine], ... remote meetings and so on, to keep the research moving.”

Network leaders stepped up, forming the COVID-19 Prevention Network, and trial sites absorbed the additional SARS-CoV-2-related workload, including trials of the Moderna vaccine and monoclonal antibodies.

“This work is a credit to how researchers were able to be flexible and do two things at once,” Dieffenbach said. “Even while restructuring networks, we worked across the institute, and worked with pharmaceutical companies to ensure that the studies [on COVID-19 vaccines and treatments] were done right.”

Another valuable trial was on the efficacy of hydroxychloroquine—which, although touted relentlessly by President Donald J. Trump, was ineffective as a COVID-19 treatment. Diffenbach said that the data regarding the drug’s failure were clear enough on the drug’s failure (the trial was ended early) to cut through the politicization.

Finding Synergy in HIV and Coronavirus Research

Diffenbach, who has been involved with HIV research for nearly three decades, said that there’s some synergy between the work on HIV and COVID-19, and that some of the rapid development of COVID-19 vaccines and treatments could have implications for HIV and other viruses.

“The success of the SARS-CoV-2 vaccine trials is due in large part to the HIV vaccine researchers that have helped to lead the vaccine effort,” he said. “The lessons learned, particularly on vaccine design, will help the HIV field. Also, [SARS-CoV-2 monoclonal antibodies] are being produced at a scale and a speed that will translate into making [them] less expensive and more available.”

[Related: Can the mRNA Technology Used for COVID-19 Vaccines Also Give Us an HIV Vaccine?]

More synergy: Moderna, whose COVID-19 vaccine was authorized for emergency use by the Food and Drug Administration on Dec. 18, has also been working with the NIH on number of viral vaccines, including HIV. And additional COVID-19 vaccines in the pipeline from Oxford/AstraZenica and Janssen use vector delivery systems first used in HIV vaccine trials, although their development has led to concerns about potential increases in HIV susceptibility among vaccine recipients.