Following is a roundup of treatment and prevention news announced at IAS 2017. The references appearing in parentheses in each item pertain to the original conference reports. Go to ias2017.org for details.
Bictegravir found non-inferior to Tivicay
The experimental drug bictegravir (BIC) was found to be non-inferior to dolutegravir (DTG, brand name Tivicay, found in Triumeq).
Both HIV medications are from the drug class called integrase strand transfer inhibitors, or INSTIs. Of note, all the INSTIs currently on the market are recommended for first-time use in HIV therapy.
Results are from 48-week data from two Phase 3 clinical trials, Studies 1489 and 1490. BIC was given as a single-tablet regimen (STR), with two other medications in it (emtricitabine and tenofovir alafenamide, or FTC/TAF). DTG was given with FTC/TAF in one study and as the Triumeq single-tablet regimen in the other (the two other drugs in it are lamivudine and abacavir, or 3TC/ABC). (MOAB01 and TUPDB02)
Bictegravir is being developed by Gilead Sciences, while Tivicay and Triumeq are from ViiV Healthcare. FDA approval for a BIC single-tablet regimen is anticipated for next year.
Single-tablet regimen with Prezista
There are several STRs on the market for HIV, but none contain a protease inhibitor (PI) medication, the drug class that started it all for conquering the virus.
That’s changing with continuing good results of research with an STR with darunavir (brand name Prezista), the last PI standing among recommended drugs for first-time therapy under U.S. HIV treatment guidelines.
The EMERALD study looked at switching patients from a Prezista-based HIV combination to a Prezista-based STR. At 24 weeks, the 763 patients switched to the Prezista STR in development maintained their undetectable viral load. (TUPEB0372)
The Prezista STR combines darunavir with emtricitabine (FTC) and tenofovir alafenamide (TAF) and a booster drug, cobicistat.
Prezista is also available as Prezcobix, where it is combined with cobicistat.
Switching because of lipids
A European study looked to see if switching patients from a PI-based therapy to one with dolutegravir would improve lipids in people who had high cardiovascular risk or were over the age of 50.
For the patients switched to the INSTI, they found a statistically significant improvement in all lipid fractions (total cholesterol, non-HDL cholesterol, triglycerides, LDL cholesterol, and TC/HDL ration) except HDL, the “good” cholesterol.
Of the 415 study patients, 205 were switched to dolutegravir while the rest were kept on their PI regimen. (TUAB0102)
Doravirine, a new non-nuke
An STR combining the investigational drug doravirine with lamivudine and tenofovir DF (3TC/TDF) was found to be non-inferior to Atripla. Like the efavirenz (brand name Sustiva) found in Atripla, doravirine is a non-nucleoside analog medication. The DRIVE-AHEAD study reported Phase 3 results from 48 weeks. There were statistically significantly fewer neuropsychiatric events and a favorable lipid profile with the doravirine STR. Half of the 728 participants received the doravirine STR and the other half received Atripla. (TUAB0104LB)
LATTE-2: long-acting injectable HIV therapy
You gotta love a latte. What about the results of LATTE-2?
The “LATTE” in this study stands for Long-Acting Antiretroviral Treatment Enabling. Two HIV drugs were combined into one injectable, injected either every four weeks or every eight weeks.
Individuals started during a 20-week induction period on a once daily oral combination of an integrase inhibitor (cabotegravir) plus Epzicom (a combination of abacavir and lamivudine, or ABC/3TC).
For years there’s been good results reported from this study. Now there’s two-year data. At 96 weeks, 94% of the patients on the 8-week injection had undetectable viral load vs. 87% of those on the 4-week injection (and 84% of the people continued on the all-oral regimen of the meds). Still, the clinical trial is going ahead with studying an injection taken every four weeks.
Participants were switched to the injectable from their all-oral HIV therapy, with all of them having undetectable viral load before the switch. LATTE-2 was looking at the injectable, therefore, as a maintenance treatment.
The two drugs in the injectable are the investigational cabotegravir and the already FDA-approved (in oral form) rilpivirine (brand name Edurant, found in Complera and Odefsey). (MOAX0205LB)
Long-acting PrEP with cabotegravir
An injectable form of the experimental drug cabotegravir was reported to be “well tolerated” by HIV-negative people. The HPTN 077 research abstract concluded that the results support going ahead with study of a 600 mg intramuscular dose every eight weeks for the use of PrEP (pre-exposure prophylaxis, or prevention of HIV).
The injections followed an induction period of four weeks with daily doses of an oral formulation of cabotegravir. A total of 199 participants received a 600 mg cabotegravir injection, an 800 mg shot, or placebo. Three out of four participants received all of the injections called for in the study, out to 29 or 33 weeks (depending on the dose they were given). Injection site pain and injection site reactions were more common in the active drug doses compared to placebo. These are still early Phase 2 results. (TUAC0106LB)
Long-acting PrEP with rilpivirine
An injectable form of rilpivirine has been studied for PrEP over the years. The HIV Prevention Trials Network (HPTN) took a look at the acceptability of this injectable for PrEP among women here in the U.S. and in Africa.
HPTN 076 reported that, “Continuing high HIV incidence rates coupled with low adherence to HIV prevention agents (daily oral and topical) in clinical trials among African women underscore the need for more acceptable and easier to use HIV prevention. Strong global demand for injectable contraception suggests that new, long-acting, injectable HIV pre-exposure prophylaxis (PrEP) formulations could meet this need.”
The 100 African women and 36 U.S. women received bimonthly injections for 28 weeks.
“Most aspects of the injectable were highly acceptable,” the research team reported, “although about two-thirds of participants experienced some injection site pain. Most recommendations for improving acceptability were related to reducing injection pain.” (WEPEC0956)
Daily vs. on demand PrEP
Dutch researchers used data from the Amsterdam PrEP (AmPrEP) demonstration study to look at daily or event-driven use (also called “on demand”).
Of 376 men who have sex with men (MSM) in the study, 273 chose daily use of the HIV prevention pill, while 103 chose event-driven use.
A great many reasons were listed for picking daily (dPrEP) or event-driven (edPrEP) use, or later switching.
“Among the reasons to use dPrEP were the convenience of daily routine (n=133), perceived higher dPrEP efficacy (n=34), and fear of side-effects relating to edPrEP re-initiation (n=5). Perceived toxicity and burden of daily medication were reasons to choose edPrEP (n=38). Infection risk was also considered: dPrEP was preferred for unplanned and/or frequent sexual risk behavior (n=79), while edPrEP was chosen when risk was more predictable (n=57),” were among the findings reported by the researchers.
In their conclusion, they wrote, “A great variety of personal and contextual factors determine the choice for PrEP regimens, related switches and stops. In order to successfully support future PrEP users, a tailored approach, addressing choices for PrEP regimens as a continuum of flexible and changeable choices, is essential.” (WEAC0106LB)
Prevention vaccine
Janssen Pharmaceutical Companies of Johnson & Johnson presented “the first look at in-human data for investigation ‘mosaic’-based, prime-boost regimens that are designed to elicit an immune response against a variety of HIV subtypes prevalent worldwide.”
According to a press release from the NIH, which funded pre-clinical development, “Further research will be needed because the ability to elicit anti-HIV immune responses does not necessarily indicate that a candidate vaccine regimen can prevent HIV acquisition.” NIH reported that should a larger study move forward, it could begin enrolling late this year or early 2018. As with this part of the study, the APPROACH vaccine research will take place with South African women. Further results from another study, TRAVERSE, are awaited to make a decision about moving forward, NIH reported. (See the session “Progress in Antibody-Mediated Preventive Vaccine Strategies.”)