Long-acting therapies headlined a year of continued drug development, both in the treatment and prevention of HIV. Meanwhile, CDC recommended a third dose of a COVID-19 mRNA vaccine for certain patients living with advanced or untreated HIV to boost their protection.

Cabotegravir’s Big Year

The year started with the approval of cabotegravir-rilpivirine (Cabenuva), the first long-acting injectable antiretroviral therapy (ART). The drug, which can be administered monthly, was approved for people living with HIV who are virologically suppressed on a stable ART regimen with no history of treatment failure.

The FDA also approved an oral version of cabotegravir (Vocabria) to be taken with an oral version of rilpivirine (Edurant) for a month prior to starting the injectable therapy to ensure the medication is well tolerated.

Injectable cabotegravir was also found to be superior as HIV prevention compared with oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF/FTC; Truvada) in men who have sex with men (MSM) and transgender women in the phase II/III HPTN-083 trial.

While the trial was previously stopped for efficacy by a data and safety monitoring board, data from December 2016 to May 2020 from the blinded phase of the trial found 13 incident HIV infections in the cabotegravir arm versus 39 in the TDF/FTC arm (HR 0.34, 95% CI 0.18-0.62).

However, while the injectable was safe, there were four incident infections in the intervention group despite on-time administration and adequate levels of cabotegravir, raising questions about both PrEP failure and integrase strand-transfer inhibitor (INSTI) resistance.

Long-Acting PrEP Implant Moves Forward

Other long-acting therapies continued to make progress, particularly in HIV prevention. An early trial of an islatravir implant for PrEP presented at this year’s virtual Conference on Retroviruses and Opportunistic Infections (CROI) revealed it may protect against HIV for an entire year.

Pharmacokinetic data from people at low risk of HIV infection found that islatravir at three different doses had blood levels of the drug considered sufficient for protection against infection at week 12, though the highest dose — 56 mg — was projected to yield adequate islatravir blood levels for at least 52 weeks.

The implants were placed in the patients’ upper arms and remained in place for 12 weeks. Side effects included redness, injection site pain, tenderness, and some pruritus.

Lead researcher Randolph Matthews, MD, PhD, of Merck in Kenilworth, New Jersey, said data from this trial support further study “in a larger, longer phase II trial” and could “provide an attractive option for individuals in whom adherence to a daily PrEP regimen is challenging.”

Novel Drug Makes Waves in Super-Refractory Patients

Another long-acting injectable, the investigational drug lenacapavir, showed promise for HIV patients who were resistant to multiple drug classes in a study presented at CROI.

Eighty-eight percent of patients who had lenacapavir added to their failing regimen achieved a reduction in viral load within 15 days of treatment versus 17% of patients on placebo. Indeed, 72% of patients receiving failing regimens achieved viral suppression.

All the patients reported adverse events during the trial — most frequently headache, nausea, cough, diarrhea, and rash — but none led to study discontinuation.

“I was blown away by these results,” said Sharon Hillier, PhD, of the University of Pittsburgh School of Medicine, who moderated the CROI press conference where the results were shared. “This new generation of long-acting molecules that could be given in a sustained delivery way, I think, are going to revolutionize prevention and treatment.”

Additional results from the ongoing phase II/III trial were presented at the virtual International AIDS Society (IAS) Conference on HIV Science, where the treatment proved its durability. At week 26, 81% of these heavily treatment-experienced patients achieved viral suppression, and 89% had viral loads less than 200 copies/mL.

Median CD4 count increased by 82 cells/μL, and no patients had a CD4 count below 50 cells/μL at week 26, despite eight patients with a very low CD4 count at baseline.

Two large phase III trials assessing the drug for HIV prevention are ongoing.

COVID and the HIV Patient

An analysis of WHO data on over 15,000 people living with HIV in Asia, Europe, and Africa presented at the IAS meeting found that HIV is an independent risk factor for severe or critical COVID-19 (OR 1.13, 95% CI 1.09-1.17). Even after adjusting for age, sex, and comorbidities, HIV infection was also tied to a higher risk of in-hospital mortality (adjusted HR 1.30, 95% CI 1.24-1.36).

“This study underscores the importance of countries including all people living with HIV in the list of priority populations for national COVID-19 vaccine programs,” said IAS President Adeeba Kamarulzaman, MBBS.

CDC classified HIV as a risk factor for severe COVID, and recommended that people living with advanced or untreated HIV infection receive a third dose of mRNA COVID-19 vaccine at least 28 days following a two-dose primary series.

Patients will self-attest if they have these conditions, and this does not require “medical sign-off” from any clinician or prescriber.

Other research released this year included:

Black Women With HIV Face Higher Early Death Risk

Certain Groups Left Behind in HIV Preventive Care

Shingrix OK’d for Immunocompromised Adults

Drug Resistance in People on PrEP Who Acquire HIV

Therapeutic HIV Vax Trial Takes Its First-in-Human Steps

Last Updated November 12, 2021