Preventive care changes HIV care

Last month, the US Food and Drug Administration (FDA) granted Cabotegravir’s breakthrough therapy designation. HIV Pre-exposure prophylaxis (PrEP).

This designation is based on the efficacy and safety results of the HPTN083 trial. This study compared long-acting injectable cabotegravir for HIV prophylaxis with daily oral emtricitabine / tenofovir disoproxil fumarate (FTC / TDF, tolbada) 200 mg and 300 mg Phase 2b / 3 randomization. It was a multicenter, double-blind study. Transgender women, men who have sex with men, and women who are at high risk of becoming infected with HIV.

The final analysis showed that cabotegravir was 66% more effective in preventing HIV when compared to FTC / TDF tablets. This corresponds to an HIV incidence of 0.41% (95% CI, 0.22% -0.69%) in the Cabotegravir group and 1.22% (95% CI, 0.87% -1.67%) in the FTC / TDF group. 4566 participants.

A partner HIV prophylaxis study, HPTN084 (The LIFE Study), evaluated the safety and efficacy of cabotegravir in PrEP in non-HIV-infected women compared to daily oral FTC / TDF. It showed even greater efficacy in the patient population. .. This is the first study of long-acting injections for the prevention of HIV in women.

The study enrolled 3,223 women aged 18-45 in 20 locations in seven countries in sub-Saharan Africa (Botswana, Kenya, Malawi, South Africa, Eswatini, Uganda and Zimbabwe).

The Data Safety Oversight Committee met on November 5th to discuss the exam and found impressive data to change some courses in the exam.

“They recommended that the blind phase of HPTN084 be discontinued as it demonstrated the superiority of Cabotegravir over Tolbada,” said Dr. Alex Reinhardt, Senior Director of Global HIV Prevention Strategy for ViiV Healthcare. I did.

Rinehart noted that the study had a total of 38 HIV infections, 34 of which were in the Truvada group and 4 in the cabotegravir group, resulting in an 89% reduction in the number of infections in the study.

When this news came out, Dr. Carlos Del Rio tweeted his excitement: “Game Changer” in talking about treatment. Del Rio is a prominent professor of medicine at Emory University School of Medicine and an executive associate Dean of Emory University. He is also a professor of global health and epidemiology at the Rollins School of Public Health, a co-director of the Emory AIDS Research Center, and a co-principal investigator of the Emory Vaccines and Treatment Evaluation Unit.

Rinehart reports that the overall safety profile is very good, injections are well tolerated, and only a small percentage (2.5%) of injection site reactions report grade 2 or higher. These were considered mild to moderate and none of the participants stopped testing for injection site reactions.

Regarding the potential benefits of taking Cabotegravir over traditional PrEP therapy, Rinehart points out the simplicity and privacy aspects of taking injections every 8 weeks.

“They’re cautious … we’re talking about giving six injections a year, rather than having to take pills every day,” Reinhardt said. “This is a huge problem for women because they can protect themselves and do not have to negotiate HIV prevention with their partners.”

The studies mentioned above are part of the HIV Prevention Trials Network, a global collaborative network of clinical trials, and bring together researchers to develop and test HIV interventions.

The breakthrough designation makes it easier for the FDA and ViiV Healthcare, the manufacturer of Cabotegraville, to work together and work towards approval of Cabotegraville. “We look forward to working closely with the FDA to make this prevention option available to people at risk of becoming infected with HIV,” said Kimberly Smith, MD, MPH, Senior Vice President. R & D manager ViiV Healthcare,Said.

HIV Care Challenges

While exciting new treatments such as cabotegravir are in late development, barriers to PrEP care remain. Studies have shown challenges, including access and compliance, despite advances in treatment and clinical care.

A large study found that in Africa, PrEP users in three sub-Saharan countries repeatedly turn medication on and off. The results of these findings were presented earlier this year at the International AIDS Society (IAS) AIDS2020 Virtual Session...

The study investigated 41,459 patients in Kenya, Lesotho and Tanzania. Their PrEP regimen included daily non-event-driven dosing. Of these three countries, 10,809 (26.1%) discontinued PrEP at least once and then resumed it. 20.7%, 27.5% and 51.8% remain from PrEP for less than 30 days, 30-60 days and 61 days or more, respectively.

These findings show that PrEP users do not continue to use it indefinitely. This suggests that it is not the patient’s goal, according to researchers.

This is a problem that is also experienced in the United States. The study, conducted by Kaiser Permanente San Francisco Medical Center, also found adherence problems in the PrEP Continuum of Care and new HIV infections: long-term follow-up in a large clinical cohort. Researchers have followed people for several years since they were identified as potential beneficiaries of this treatment.

“It was mainly the first year when we dropped out in the PrEP continuum and lost in follow-up. After the first year of treatment, most people maintained and continued to take the drug. “The infectious disease clinician, Kaiser Permanente San Francisco Medical Center, and Research Investigator Jonathan Volk, MD, said.

He said there was a 27% decrease within the first year.

To interview When Contagion Earlier this year, Volk talked about many steps needed to start and continue the PrEP regimen, including receiving prescriptions, filling out prescriptions, and starting treatment.

They pointed out that failure to perform these steps could lead to HIV infection.

“There were two important steps: we lost people in a continuum and there was a preventable HIV infection we observed,” Volk said. “The first was a link to care that had a clinical encounter with a PrEP referral and did not receive a prescription. The second was a care-related patient who started and later discontinued treatment. was.”

In both of these groups, Volk said HIV prevalence was above 1% during the follow-up period.

In this study, researchers also reported that blacks were less likely to receive a prescription, less likely to start PrEP, and more likely to discontinue PrEP.

Volk also mentioned access to care issues. For example, he mentioned the cost of prescriptions and the costs that are perceived as barriers to PrEP. However, because of this latter barrier, many people are unaware that they can get prescription assistance.

“Last year, PrEP received a Grade A recommendation from the US Preventive Medicine Commission, which allows us to offer PrEP to almost any patient for free,” Volk said.

Thus, he says, more awareness is needed to overcome this barrier to care.

Care strategy

Obviously, the COVID-19 pandemic made it difficult to visit the clinic directly. That’s why Kaiser Permanente is adapted for virtual visits with patients and secure email.

Through these online visits and email communications, Volk said he had discussed PrEP with the patient and started it remotely.

One of the other aggressive strategies they are implementing is the ability to identify potential PrEP beneficiaries early.

“We are trying to identify people further upstream from linkage to care,” Volk said. “These are candidates for PrEP, but may be people who are not linked to care.”

They attempt to partially achieve this by examining patient electronic medical records, adopting existing HIV prediction models, and increasing the number of variables in the model to identify new potential patients with PrEP. is.

New variables will include whether the patient has had an STI test, erectile dysfunction and penicillin prescriptions, and a mental health diagnosis, Volk said. The new forecast model has over 40 variables.

“By flagging the top 1% or 2% risk course of our population, we were able to identify about 50% of the incidence infections in the male population,” Volk said. “One of the most exciting things for us is that this model worked for black patients as well as for white patients when it comes to predicting HIV risk.”

According to Volk, one of their projects was to incorporate this new predictive model into their primary care settings. This facilitates discussions between the patient and the clinician, especially with PrEP care when needed.

This type of conversation between clinicians and patients moves towards removing barriers to traditional care such as access and adherence and gaining more people who can benefit from PrEP therapy in a continuum of care. can do.