Integrase Inhibitor Bictegravir Matches Dolutegravir for First-Line HIV Treatment

from CROI 2017

Bictegravir, an investigational integrase inhibitor from Gilead Sciences, was highly potent, well tolerated and worked as well as dolutegravir (Tivcay) in a Phase 2 clinical trial, according to study results presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) this week in Seattle and published online in The Lancet HIV.

Integrase inhibitors, also known as integrase strand transfer inhibitors (INSTIs), are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment of HIV infection, but they could be applied to other retroviruses.

The discovery and development of integrase inhibitors led to the first integrase inhibitor approval by the U.S. Food and Drug Administration (FDA) on October 12, 2007, for raltegravir (brand name Isentress). Research results published in the New England Journal of Medicine on July 24, 2008, concluded that "raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks."

Since integrase inhibitors target a distinct step in the retroviral life cycle, they may be taken in combination with other types of HIV drugs to minimize adaptation by the virus. They are also useful in salvage therapy for patients whose virus has mutated and acquired resistance to other drugs.

Due to their high potency and good tolerability, integrase strand transfer inhibitors are an increasingly important part of initial antiretroviral therapy and are included in most recommended regimens for first-line treatment in U.S. and European HIV treatment guidelines.

Bictegravir (formerly GS-9883) is an investigational integrase inhibitor that can be taken once-daily and does not require a booster -- unlike Gilead's older integrase inhibitor elvitegravir, which must be boosted with cobicistat.

As previously reported, bictegravir demonstrated high potency against wild-type and resistant strains of HIV, favorable pharmacokinetics, and an improved resistance profile compared to older integrase inhibitors. In a 10-day monotherapy study, it rapidly reduced viral load by more than 2 login people with HIV.

At CROI Joseph Custodio from Gilead reported that bictegravir was safe and well-tolerated at doses ranging from 5 mg to 600mg in healthy volunteers. Bictegravir inhibits renal tubule transporters, which lowers creatinine levels and leads to a decline in estimated glomerular filtration rate, but it does not cause actual kidney function impairment, he explained.

Bictegravir is metabolized equally bythe CYP3A4 and UGT1A1 pathways. Custodio said it has low potential to be either a "victim" or "perpetrator" of drug-drug interactions. Bictegravir levels rose by more than 300% when administered with both CYP3A4 and UGT1A1 inhibitors, and fell by up to 75% when given with both CYP3A4 and UGT1A1 inducers. The drug had a half-life of approximately 18 hours, indicating it is suitable for once-daily dosing. Bictegravir had no effect on a common oral contraceptive or ledipasvir/sofosbuvir (Harvoni) for hepatitis C, and administering it 2 hours before or after minimises interactions with antacids.

Paul Sax of Brigham and Women's Hospital in Boston and colleagues conducted a Phase 2 placebo-controlled clinical trial comparing bictegravir to dolutegravir for initial HIV therapy.

The study included 98 previously untreated adults. Almost all were men, more than half were white, and the median age was about 32 years. They generally had asymptomatic HIV infectionwith a median CD4 T-cell count of approximately 450 cells/mm3 and a median viral load of about 4.4 log copies/mL at baseline. They had normal kidney function and people with hepatitis B or C coinfection were excluded.

Participants in this double-blind study were randomly assigned (2:1) to receive 75 mg bictegravir or 50 mg dolutegravir, each with matching placebos. Both drugs were combined with 25 mg tenofovir alafenamide (TAF) and 200 mg emtricitabine, taken once daily with or without food for 48 weeks. The primary endpoint was the proportion of people with HIV RNA below 50 copies/mL at 24 weeks.

Results

Both treatments were highly effective.

97% of participants in the bictegravir arm and 94% in the dolutegravir arm achieved viral suppression at 24 weeks.

97% and 91%, respectively, had undetectable HIV RNA at 48 weeks.

Given the small number of patients, these differences were not statistically significant and this study was not powered to determine full non-inferiority.

1 person in the bictegravir arm and 2 in the dolutegravir armhad HIV RNA >50 copies/mL, but no significant resistance was detected in either arm.

CD4 cell gains were 258 cells/mm3 in the bictegravir arm compared 192 cells/mm3 in the dolutegravir arm, not a significant difference.

Both regimens were generally safe and well-tolerated, with no treatment-related serious adverse events and no deaths.

The most frequent adverse events were diarrhea (12% in each arm) and nausea (8% with bictegravir and 12% with dolutegravir).

1 bictegravir recipient with a previous history of allergic dermatitis stopped treatment early due to hives after 24 weeks.

Estimated glomerular filtration rate declined by -7.0 mL/min in the bictegravir arm and -11.3 mL/min in the dolutegravir arm at week 48, but there were no discontinuations due to kidney-related adverse events and no cases of tubulopathy.

Bictegravir and dolutegravir taken with TAF and emtricitabine "both demonstrated high virologic response rates at week 24 that were maintained at week 48," the researchers concluded. "Both treatments were well tolerated, and no significant safety signal was detected in either arm."

These results were promising enough to proceed with Phase 3 trials using a single-tablet regimen of bictegravir, TAF, and emtricitabine. Custodio noted that optimising the formulation allowed for a lower 50 mg bictegravir dose in the coformulation.

Sax said that 4 Phase 3 studies are now fully enrolled; 2 of these are similar to the current study but will use the bictegravir single-tablet regimen rather than separate pills. Another is comparing the bictegravir single-tablet regimen against a coformulation of dolutegravir, abacavir, and lamivudine (Triumeq).

"The high virologic response rates seen in this study show that the pairing of bictegravir with [TAF/emtricitabine] could potentially offer patients and physicians a new HIV treatment option with pre-clinical data supporting few drug interactions and a high barrier to resistance," Sax said in a Gilead press release.

2/14/17

Sources

H Zhang, JM Custodio, X Wei, et al. Clinical Pharmacology of the HIV Integrase Strand Transfer Inhibitor Bictegravir. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 40.

P Sax, E DeJesus, G Crofoot, et al. Randomized Trial of Bictegravir or Dolutegravir with FTC/TAF for initial HIV therapy. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 41.

PE Sax, E DeJesus, G Crofoot, et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. The Lancet HIV. February 14, 2017 (online ahead of print).

Gilead Sciences. Gilead Presents New Phase 2 Data on Bictegravir, an Investigational Integrase Strand Transfer Inhibitor for the Treatment of HIV. Press release. February 13, 2017.

Switching course, Gilead markets HIV drug for prevention ..........

Gilead Sciences Inc has begun marketing its HIV treatment Truvada in a way thousands of consumers already use it – to prevent infection with the virus that causes AIDS.

The company introduced Truvada to the U.S. market in 2004 for HIV treatment. In 2012, Gilead won approval to market it for prevention after two large, peer-reviewed studies showed it also was effective at preventing infections in healthy people.

But the company decided against promoting the drug as a preventative treatment, deferring to patient advocates who feared it could encourage promiscuity and unsafe practices, such as having sex without condoms.

Even without Gilead's help, many consumers learned Truvada was more than 90 percent effective in tests at preventing HIV infection. In 2014, the U.S. Centers for Disease Control and Prevention recommended it as an option for people at high risk for HIV infection.

As many as 90,000 people in the United States used the drug for prevention, or pre-exposure prophylaxis (PrEP), last quarter. That's up from 60,000 to 70,000 earlier this year, the company said. Usage also is growing in France, where about 2,000 people have been prescribed Truvada for prevention since January.

In July, the drugmaker began marketing Truvada for PrEP to doctors through professional publications, digital advertising and other channels, including the website PreventHIV.com.

And this fall, the drugmaker began marketing directly to consumers with print advertisements in publications geared toward the lesbian, gay, bisexual and transgender community, including OUT, Advocate and SWERV. It plans soon to expand to social media and digital.

Gilead said it wants to reach people whose doctors are either unaware or reluctant to prescribe Truvada for prevention.

The marketing "is primarily driven by demand by patients," said David Piontkowsky, Gilead's vice president of HIV Medical Affairs, in an interview.

Attitudes toward Truvada started to change a couple years ago as doctors, AIDS activists and potential users saw its effectiveness, he said. The "criticism now is we're not saying enough."

Truvada is helping bolster Gilead's profits as sales of its biggest moneymakers – treatments for hepatitis C – decline.

U.S. net product sales of Truvada for the first nine months of 2016 were $1.8 billion compared with $1.5 billion for the same period in 2015. The company said in its earnings report that the gain was driven by price increases as well as "increased usage of Truvada for PrEP."

"We expect PrEP to continue to be a significant part of Gilead's growth in HIV going forward, particularly in the U.S.," Gilead Chief Operating Officer Kevin Young recently told investors.

The new Truvada campaign has been well received, even by those who once opposed promoting the drug for prevention. They include David Duran, a writer and HIV advocate, who helped popularize the term "Truvada Whore" in a 2012 article describing his fear that it would encourage people to have sex without condoms.

Duran began rethinking that concern about a year later in light of newer research showing that PrEP helped prevent more cases of HIV, without a rise in other sexually transmitted disease, which suggested people were using condoms.

"I'm thrilled they are starting to pump some money into marketing and awareness," Duran said. "There is a solid base of folks who know about PrEP, but it's still not a topic the country as a whole knows about."

GROWTH POTENTIAL

As a preventive measure, the blue Truvada pill is taken once daily. Some people experience nausea, vomiting or headaches during the first few weeks on the drug.

Users must be tested every three months to ensure they don't have HIV or other sexually transmitted diseases and to monitor kidney function and bone density.

Some Medicaid programs and most private insurance cover the treatment, which lists for $1,500 a month before any negotiated discounts. With greater awareness and favorable coverage for preventative treatments, the number of Americans using Truvada could rise, said the company and healthcare providers.

An estimated 50,000 new U.S. HIV infections are diagnosed each year.

The CDC estimated in 2015 that about 1.2 million Americans were at substantial risk of HIV infection and could benefit from PrEP.

That includes men who have sex with men, transgender women who have sex with men, partners of people who are HIV-positive and intravenous drug users who share needles.

The number of high risk groups "is much broader than one might think," said Dr. Jennifer Childs-Roshak, president and CEO of Planned Parenthood League of Massachusetts. "It is not just men with multiple partners. There are a whole host of folks who could benefit."

At least 15 patients have gone on Truvada for prevention since Planned Parenthood's six Massachusetts clinics began offering it this fall. Planned Parenthood of New York City plans to offer the treatment to all of its 50,000 patients, said Julia Sullivan, associate director of quality management.

Wider use also could buffer Gilead when Truvada, the only drug currently approved in the United States for PrEP, loses patent protection in 2021. Gilead has a successor treatment in the works. The once-daily F/TAF (emtricitabine/tenofovir alafenamide) has been approved for HIV treatment and is under study as a preventative.

"PrEP is indeed a significant part of Truvada," said Leerink Partners analyst Geoffrey Porges. "It can certainly keep Truvada relatively flat but the key question is, when will they show that TAF works for PrEP?"

In the meantime, the concept of taking an HIV drug to prevent infection is making inroads in popular U.S. culture. It came up in an episode of "Transparent," the Emmy award-winning Amazon series about a family with a transgender parent, when a character was contemplating sex with an HIV-positive partner.

"We were trying to make the conversation reflect what happens in real life," said a writer on the show who works under the name Our Lady J. "PrEP is a big part of that conversation. As an HIV positive person, I'm struck with the level of ignorance around PrEP."

(Reporting By Jilian Mincer; Editing by Michele Gershberg and Lisa Girion)

Concerns Mount As Transsexual Adolescents Push Up Jamaica's HIV Rates ................

As usual the transgender community is still being lumped with MSM either by the response and by populations overall it seems and it makes the previous studies on MSM HIV prevalence rates of 32% in 2007 and others since problematic while it may be higher trans-persons who merge into the MSM community get counted as gay. The article below touches the very conflation and to think the very named agency is partly guilty of not making the stark differences between the groups even as trans voices screamed to them to pay attention.

The Gleaner carried this:

As a HIV-positive transgender youth, 22-year-old *Tory belongs to the at-risk group that is considered to be most in need of intervention if Jamaica has any hope of seeing further reductions in the number of persons living with HIV/AIDS.

According to a study that was released last week by the Jamaica AIDS Support for Life (JASL), transgender persons who are HIV-positive are more likely to experience homelessness, stigma, forced sex and physical violence. Of the 71 transgender participants polled, more than 52 per cent were involved in sex work for accommodation and food, among other things.

"Now we are seeing where they are at increased risk more than gay men, and more than sex workers, of course, and so it's really just about how we are going to ensure that our programmes are attending to the needs of these persons," said executive director of JASL, Kandasi Levermore.

A UNAIDS report ahead of the commemoration of World AIDS Day on December 1 warned that 15-24 years is a dangerous time for women. It noted that an estimated 45 per cent of all new HIV infections globally in 2014 were among members of key populations and their sexual partners, and warned that new HIV infections are continuing to increase among people who inject drugs and men who have sex with men. The report went on to say that HIV was not declining in sex workers and transgender people.

Tory, a male who identifies as a female, has found himself in several of these categories. He became homeless at 16 years old and became a sex worker shortly after to provide for himself. His clients were mostly professional men, and at 18, he decided to go and live with a police officer who he said was a "regular buyer". He said he contracted HIV from the lawman.

"Being 16 and a sex worker, you get more clients because you are young, because you are new, because they like young people because they think you are not very smart. But I was very smart. Why I was homeless is because I was kicked out of high school because of my sexual orientation," he told The Sunday Gleaner.

MISTREATMENT AT CLINIC

He said due to the mistreatment he received at the first clinic he visited after his diagnosis, he did not take any medication for the first year. He, however, went to a different clinic where the attitude of health professionals was better, and he has since seen vast improvement in his health. He said he is now focused on becoming stable because his greatest desire now is to have a child, although he admitted that he had never had sexual intercourse with a woman.

"I am gay because I won't be in a long-term relationship with a woman," said Tory, before explaining that he is open to having sex with a woman for the sake of having a child.

"I want a child with my genes. Adoption is so hard in Jamaica at this point. She can be a lesbian or she can also be positive and virally suppressed, like myself. So there is a lot of hope to get a child if I want a child when I am ready," he said.

According to a report released recently by JASL, which was funded by the Canadian Institute of Health Research, there is very little knowledge about the HIV prevalence among transgender women in Jamaica.

However, the National HIV/STI programme noted that, "In contrast with the estimated HIV prevalence of 0.4 and 0.5 per cent reported in adolescent girls and boys aged 15-19 at the national level through the UNAIDS 2014 estimates, the HIV prevalence among gay and bisexual adolescent boys is estimated to be 14 per cent, while HIV prevalence in transgender adolescents is estimated to be 27 per cent."

Renae*, who came out as a transgender at 21 years old, said he is concerned that HIV is highest among transgender youths, and blamed this on the fact that those who adopt this lifestyle were often stigmatised or forced to engage in transactional sex.

"Being gay is a taboo, but being transgender is a greater taboo, and because of that, you have a lot of parents who actually do put out their children for these type of things, and you are out on the streets, you have no formal education, you have no way to really provide for yourself," he said.

"So you have to come up with means and ways to provide for yourself, and one of those methods is to become prey to sexual predators out there, or to offer yourself up as collateral, and oftentimes it is to persons who maybe know that they have the virus, but they don't care."

Although Renae was born male, he identifies as a female and is now an advocate for those living in the transgender community. He believes that while there have been improvements in access to treatment for those who are HIV-positive, stigma and discrimination are still forcing some to go underground instead of seeking help.

"That's why I work so hard within the health sector to make things better for trans people on a whole," he said.

[* Names changed to protect identity]

ENDS

And the signs continue to show us that the forward thinking in as far as the NGOs are concerned is still lacking and why are more persons being captured way better given the resources?

The more things change the more they stay the same.

Peace & tolerance

H

also see:

Continued oversight or deliberate overlooking of Jamaican SGL Women in HIV Prevention ............ 

Continued Trans erasure/invisibility by Jamaican advocates ......... 2012

International Study Finds High Levels of Adherence to Use of Rectal Microbicide Gel

Participants as adherent to using gel with sex as taking a daily pill for HIV prevention

CHICAGO, October 20, 2016 – Participants enrolled in a rectal microbicide study were just as likely to follow through using an anti-HIV gel with anal sex as they were to using daily oral pre-exposure prophylaxis (PrEP), according to adherence results presented today at the HIV Research for Prevention conference (HIVR4P). The study, led by the U.S. National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN), was the first extended safety study of a rectal microbicide for prevention of HIV infection from anal sex, which initially reported that the gel was safe in February 2016.

The Phase II study, MTN-017, began in September 2013 and enrolled 195 men who have sex with men (MSM) and transgender women at sites in Peru, Thailand, South Africa and the United States, including Puerto Rico. MTN-017 participants –12 percent of whom were transgender women – cycled through three study regimens which each lasted eight weeks: reduced glycerin tenofovir gel used daily, reduced glycerin tenofovir gel used before and after anal sex, and daily use of the antiretroviral tablet Truvada® (emtricitabine/tenofovir disoproxil fumarate) as PrEP, developed by Gilead Sciences, Inc.

Researchers found that most participants were highly adherent during the course of MTN-017, using study products 80 percent of the time or more. Participants were similarly adherent to using gel before and after sex (93 percent) as they were to taking daily oral Truvada (94 percent). They were less adherent when using the gel on a daily basis (83 percent).

“Overall adherence to the three regimens in MTN-017 was high,” said Alex Carballo-Diéguez, Ph.D., HIVR4P abstract co-author and professor of medical psychology, Columbia University. “What we found most remarkable was that even though efficacy of the gel has not been established, its adherence was similar to oral Truvada, which we know is effective. This tells us that rectal microbicide gels, provided they are proven effective, could be a potential alternative for people who don’t want to use daily oral PrEP.”

Adherence in MTN-017 was measured by a combination of responses to daily questions sent by text message, number of returned gel applicators, and blood tests to confirm the presence or absence of drug. Throughout the study, researchers employed real-time pharmacokinetics (PK), in which they regularly tested participants’ blood to assess the presence of drug – a determinant of whether they were using their assigned study products – and shared the results with participants as part of their adherence counseling sessions. These sessions also included convergence interviews, collaborative conversations to engage participants and clarify discrepancies among adherence measures.

In a related HIVR4P poster session (P24.11), Iván C. Balán, Ph.D., assistant professor of clinical psychology, Columbia University, found that convergence interviews conducted in MTN-017, which were aimed at improving the accuracy of adherence data, were feasible and acceptable to both adherence counselors and study participants. They also provided important context to understanding discrepancies in product use assessments and PK results. Engaging study participants as allies in the process was critical to avoid making them feel confronted and thus becoming defensive, noted Dr. Balán.

In addition to Dr. Carballo-Diéguez, abstract co-authors include Dr. Balán, Rebecca Giguere, M.P.H., Curtis Dolezal, Ph.D., Cheng-Shiun Leu, Ph.D., William Brown III, Ph.D., Titcha Ho, Ph.D., Camagu Tuswa-Haynes, M.S., all with the New York State Psychiatric Institute and Columbia University; Javier Lama, M.D., IMPACTA PERU Clinical Trials Unit; Jeanna Piper, M.D., Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID) at the NIH; Barbra Richardson, Ph.D., University of Washington and Fred Hutchinson Cancer Research Center; Ian McGowan, M.D., Ph.D., University of Pittsburgh; and Ross Cranston, M.D., Microbicide Trials Network.

Dr. Cranston is protocol chair of MTN-017 and Dr. Lama is protocol co-chair.

MTN-017 was funded by NIAID and the National Institute of Mental Health, both components of the NIH. Tenofovir gel was developed by Gilead Sciences, Inc., of Foster City, Calif., which assigned the rights for tenofovir gel to CONRAD, of Arlington, Va., and the International Partnership for Microbicides of Silver Spring, Md., in December 2006. Clinical input and study supplies of reduced glycerin tenofovir gel were provided by CONRAD, with funding from USAID.

# # #

Dr. Carballo-Diéguez’s abstract (QA20.01) is part of the HIV R4P oral presentation session Trust But Verify: Understanding Adherence taking place from 10:30-noon CDT, Wed., October 20. It is one of 22 MTN abstracts being presented at the HIVR4P 2016 conference. Webcasts of all HIVR4P 2016 sessions, along with the conference program and more information on the meeting is available at hivr4p.org.

More information and materials about MTN-017 and rectal microbicides are available athttp://www.mtnstopshiv.org/news/studies/mtn017.



About the Microbicide Trials Network

The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. Based at Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international investigators and community and industry partners whose work is focused on the development and rigorous evaluation of promising microbicides – products applied inside the vagina or rectum that are intended to prevent the sexual transmission of HIV – from the earliest phases of clinical study to large-scale trials that support potential licensure of these products for widespread use. More information about the MTN is available at www.mtnstopshiv.org.

MTN is funded by the U.S. National Institutes of Health grants UM1AI068633, UM1AI068615 and UM1AI106707.

Click here for PDF version of this document.

News From the 2016 International AIDS Conference

The 21st International AIDS Conference in Durban, South Africa (AIDS 2016), held July 18 to 22, featured numerous pivotal presentations on HIV science. Conference goers absorbed cutting-edge information about antiretrovirals (ARVs), including treatment for the virus, treatment as prevention (TasP) and pre-exposure prophylaxis (PrEP), as well as the effort to test and treat the global HIV population, HIV among women, and the search for a vaccine and a cure.

Below is a recap of the major scientific findings presented at the conference. To read more about any of these studies, click the hyperlinks. To see a newsfeed of all AIDS 2016 reporting from POZ, click here or on the #AIDS2016 hashtag at the bottom of any article, including this one.

Vaccine:

Following a pilot study’s promising findings of an HIV vaccine’s ability to spur the immune system, researchers intend to begin enrolling participants into the Phase IIb/III HVTN 702 vaccine trial in southern Africa this fall. This will be the seventh major HIV vaccine efficacy trial. The vaccine under investigation is a retooled version of the one that in 2009 showed some success in preventing HIV among Thai participants.

Long-Acting HIV Treatment:

A long-acting injectable version of the ARVs cabotegravir and Edurant (rilpivirine), dosed every four weeks, will enter Phase III trials during the latter half of 2016, with initial results coming two years later. The Phase IIb LATTE-2 trial tested injections of the treatment given every four and eight weeks and found that the more frequent dosing schedule suppressed HIV more effectively.

Treatment as Prevention (TasP):

Three major studies underlined the considerable power of HIV treatment to prevent the spread of the virus, adding greater scientific heft to the notion that it may in fact be impossible to transmit HIV with a fully suppressed viral load.

In 2011, interim results from the HPTN 052 trial found that starting HIV treatment early rather than delaying was associated with a 96 percent reduced risk of transmission among mixed-HIV-status heterosexual couples. Now, final results from the study have showed that there were no transmissions within couples when the HIV-positive member was on ARVs and had a fully suppressed virus.

Interim results from the PARTNER study, which included both heterosexual and male-male mixed-HIV-status couples, also found no transmissions between partners when the virus was fully suppressed.

Also, the Partners PrEP study examined the effect of providing mixed-HIV-status heterosexual couples Truvada (tenofovir/emtricitabine) as pre-exposure prophylaxis (PrEP) for the HIV-negative partner as a “bridge” to the HIV-positive partner being on ARVs for at least six months. This protocol slashed HIV risk by 95 percent.

PrEP:

Gilead Sciences, manufacturer of Truvada, conducted an analysis of data from 80 percent of U.S. retail pharmacies and found that nearly 80,000 people had filled at least one prescription for the drug’s use as PrEP between January 2012 and December 2015. (If all sources of PrEP prescriptions could be accounted for, this number would likely be quite a bit greater.) Between the fourth quarters of 2012 and 2015, quarterly new PrEP prescriptions rose 738 percent, from 1,671 to 14,000, largely among men. This upward trend shows no signs of abating.

The IPERGAY study of an intercourse-based PrEP dosing protocol among men who have sex with men (MSM) in France and Canada found that the participants used condoms less frequently after they shifted from the trial’s placebo-controlled phase to its open-label portion in which everyone knew they were receiving Truvada. Despite such a shift in sexual risk taking, the men’s HIV rate was low during the open-label phase. The study’s researchers believe they now have enough evidence to support the notion that the dosing protocol itself was indeed responsible for reducing the risk of HIV among the men, rather than the mere fact that men were on average taking Truvada about four times a week. (Previous research has shown that taking Truvada that often offers maximum protection.)

Researchers found that teenagers given PrEP may need monthly monitoring to adhere well to a daily Truvada regimen. (PrEP is not currently approved for minors in the United States, and current guidelines stipulate monitoring every three months.) A separate studyfound that Truvada-related bone loss is reversible after young men stop PrEP and that the drug was not associated with fractures during the study’s follow-up period.

Another study found that among black MSM receiving PrEP, men were more likely to adhere to the regimen if they were older than 25, had more than a two-year advanced degree, did not use multiple medications that they were not prescribed and had a primary partner.

Women:

A follow-up of the previously reported MTN-020/ASPIRE study of an ARV-containing vaginal ring found that HIV-negative women who used the monthly ring well had a 56 percent reduced risk of contracting the virus compared with women receiving a placebo ring. Those who used the ring at the highest level cut their HIV risk by 75 percent or greater.

Two studies provided excellent news regarding the prevention of mother-to-child transmission of HIV. A nationally representative study found that just 4 percent of children born to HIV-positive women in South Africa contracted the virus by 18 months of age. Another trial found that HIV treatment could practically halt the transmission of HIV through breast feeding.

A collection of three studies provided new insight into why HIV rates among young women in South Africa are so high. In one study, researchers found that HIV transmission among adolescent girls and young women is driven by their sexual relations with men who are an average of eight years older. Two other studies suggest that particular bacteria in women’s vaginas may facilitate transmission.

Cure:

Researchers have developed a consortium to help develop and study stem-cell transplant cures for HIV that would replicate the success of the pair of such transplants that cured the famed Berlin Patient while also treating his leukemia. They already have a few transplant recipients who, while still taking HIV treatment, show very small amounts of the virus in their viral reservoirs. These individuals would need to stop taking ARVs for researchers to determine whether they may have been cured of the virus.

A study found that treating HIV within 15 days of infection prevented the development of antibodies to the virus among a group of South African women. Such early treatment also preserved their immune function. The study’s ethics committee believes the women should remain on treatment for two to three years before researchers may discuss with the participants the possibility of taking them off treatment to see whether the virus rebounds.

On the subject of viral rebound after a treatment interruption, an experimental treatment with the HDAC inhibitor (a kind of cancer drug) vorinostat, the immunosuppressant hydroxychloroquine and the ARV Selzentry (maraviroc) had no effect on viral rebound after an HIV treatment interruption.

90-90-90:

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has called for, by 2020, getting 90 percent of the world’s HIV population diagnosed, 90 percent of that group on treatment for the virus, and 90 percent of that group virally suppressed. Achieving the 90-90-90 targets would mean that, of all people living with the virus, 90 percent would know their status, 81 percent would be treated and 73 percent would be virally suppressed.

Research suggests that nations are advancing toward these targets, with 17 million people on treatment in 2015. One intervention in particular has surpassed the targets in certain rural Ugandan and Kenyan communities. But UNAIDS executive director Michel Sidibé raised serious concerns at AIDS 2016 that a retreat of major donor commitments from paying for HIV care and treatment worldwide could stymie such progress.

An analysis of spending by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) found that foreign aid dollars go disproportionately to epidemics more generalized across a national population than to those concentrated among MSM or injection drug users (IDUs).

In another wrinkle, the first major study of the public-health effects of programs to aggressively test and treat HIV found that, in South African communities receiving such an intervention, providing immediate treatment rather than following national guidelines was not associated with any difference in the rate of new HIV cases.

Antibody Mediated Prevention Study ...........

source Gettyimages

AMP stands for Antibody Mediated Prevention. This is the idea of giving people antibodies to see if they will protect against HIV infection.

This study, also referred to as HVTN 704/HPTN 085, tests a new idea for HIV prevention. In traditional vaccine studies, we give people a vaccine and wait to see if their bodies will make antibodies against HIV in response. In this study, we’ll be skipping that step, and just giving people the antibodies directly. We will do this through an infusion, which some people know better as getting an IV or getting a drip. This is the first study testing whether this antibody can prevent HIV infections in people.
READY TO GET AMPED?

HVTN and HPTN Announce initiation of antibody mediated prevention (AMP) study
SEATTLE and DURHAM, N.C. - The HIV Vaccine Trials Network (HVTN) and the HIV Prevention Trials Network (HPTN) today announced the initiation of HVTN 704/HPTN 085, also known as Antibody Mediated Prevention (AMP), a Phase 2b clinical trial to evaluate the safety and efficacy of VRC01, a broadly neutralizing monoclonal antibody (bnAb). AMP is the first study to evaluate whether bnAbs are effective in reducing acquisition of HIV-1 infection among at risk populations.

"Injections or infusions of antibodies to prevent acquisition of an infectious disease have been utilized in medicine for decades," said Larry Corey, M.D., study chairperson for HVTN 704/HPTN 085 and principal investigator for the HVTN. "The remarkable advance in technologies to isolate and manufacture human monoclonal antibodies in concentrations high enough to potentially prevent HIV is a major advance and provides the underlying principle for our enthusiasm for these trials."

The clinical trial is a randomized, double-blind, placebo-controlled, multi-center, global effort conducted in the U.S., Brazil, and Peru and will enroll 2700 men or transgender persons (TG) who have sex with men or TG persons. Study participants will be randomized to receive VRC01 or placebo by intravenous (IV) infusion every eight weeks. Infusions will continue for 72 weeks for HIV-uninfected participants in all groups, with follow up for 20 additional weeks. A parallel study, HVTN 703/HPTN 081, will be initiated later this year in sub-Saharan Africa and will enroll 1500 sexually active women.

AMP is being sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The NIAID Vaccine Research Center discovered the VRC01 antibody and manufactured it for this trial.

"This study represents an important next step in developing agents that can prevent HIV infection by using bnAbs," said Myron Cohen, M.D., study chairperson for HVTN 704/HPTN 085 and principal investigator for the HPTN. "AMP will leverage the research expertise, resources and reach of two NIAID-funded HIV prevention trial networks, and underscores our commitment to innovation and identification of new interventions to prevent HIV transmission."

"New HIV infections have continued to increase in our most vulnerable populations in the United States including African American men who have sex with men," said Srilatha Edupuganti, M.D. M.P.H., co-chairperson of HVTN 704/HPTN 085 and associate professor of medicine, Emory University School of Medicine. "The use of bnAbs offers new hope to stem that tide as we have for other at-risk populations here and around the world."

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About HVTN

The HIV Vaccine Trials Network (HVTN) is the largest worldwide clinical trials network dedicated to the development and testing of HIV/AIDS vaccines. The HVTN is an international collaboration that conducts all phases of clinical trials, from evaluating experimental vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy. Support for the HVTN comes from the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH). The Network's HIV Vaccine Trial Units are located at leading research institutions in 27 cities on four continents. The Network's headquarters are at the Fred Hutchinson Cancer Research Center in Seattle, Washington. For more information, visit http://www.hvtn.org.

About HPTN

The HIV Prevention Trials Network (HPTN) is a worldwide collaborative clinical trials network that brings together investigators, ethicists, community and other partners to develop and test the safety and efficacy of interventions designed to prevent the acquisition and transmission of HIV. HPTN studies evaluate new HIV prevention interventions and strategies in populations and geographical regions that bear a disproportionate burden of infection. The HPTN research agenda is focused primarily on the use of integrated strategies: use of antiretroviral drugs (antiretroviral therapy and pre-exposure prophylaxis); interventions for substance abuse, particularly injection drug use; behavioral risk reduction interventions and structural interventions. For more information, visit http://www.hptn.org.

also see: Newly Discovered "Teenage" Antibody Could Mean Knocking Out HIV for Good

Combination Inhibitor BMS-986197 Demonstrates Good Anti-HIV Activity in Early Study

A long-acting bioengineered "combinectin" molecule with a triple mechanism of action demonstrated potent antiviral activity and worked against HIV that developed resistance to any of the 3 separate mechanisms in a laboratory study, and lowered viral load in humanized mice, according to research presented at theConference on Retroviruses and Opportunistic Infections (CROI 2016)last month in Boston.

Modern antiretroviral therapy is highly safe and effective for most people with HIV, but there is still room for more convenient agents that could help improve adherence, as well as drugs for people with highly resistant virus.

BMS-986197 is an injectable biologic agent which investigators think could potentially be self-administered as a long-acting subcutaneous injection; combining different modes of action in a single agent could avoid the need for multiple injections.

Mark Krystal, formerly of Bristol-Myers Squibb and now at ViiV Healthcare, presented findings from early laboratory and animal studies of BMS-986197, which is part of the portfolio of Bristol-Myers Squibb's investigational HIV agents recently acquired by ViiV.

BMS-986197 is made up of adnectins, small proteins with modifiable binding loops resembling certain antibody regions. Researchers combined adnectins targeting the CD4 cell surface receptor and HIV's gp41 protein subunit, along with a peptide fusion inhibitor, to build a so-called combinectin inhibitor that uses independent mechanisms to interfere with 3 routes of HIV entry. Finally, this combinectin was attached to human serum albumin to improve its pharmacokinetics.

The anti-CD4 adnectin appears to allow HIV's gp120 envelope protein to bind to the receptor, but prevents conformational changes needed for binding to co-receptors (CCR5 or CXCR4). The second adnectin attacks the N17 sequence of the HIV gp41 envelope protein subunit. The fusion inhibitor component works similarly to enfuvirtide (T20 or Fuzeon).

The EC50, or 50% effective concentration, of the anti-CD4 adnectin, the anti-gp41 adnectin, and the fusion inhibitor peptide were 8.5, 5.4, and 0.4 nM (nanoMolar), respectively. Linking these 3 inhibitors into a single molecule led to synergistic effects greater than the sum of the parts. The optimal combination of the 2 adnectins increased potency by more than 100-fold, while adding the fusion inhibitor appeared to increase the barrier to resistance. The addition of human serum albumin decreased potency but made the combinectin last longer in the body.

In the laboratory BMS-986197 demonstrated antiviral activity against a wide range of clinical virus isolates of different subtypes obtained from people with HIV. It retained potency against viruses that were resistant to any 1 of the 3 separate entry inhibition mechanisms and it showed no loss of potency in human blood serum.

In bio-engineered mice with humanized immune systems BMS-986197 produced dose-dependent decreases in viral load, and at the highest dose most became undetectable. Cell receptors remained occupied and pharmacokinetics were consistent over 36 days. In cynomologous monkeys a subcutaneous injection had a half-life of 30 hours and the researchers projected a half-life in humans of about 40 hours -- potentially adequate for once-weekly dosing.

"BMS-986197 is a long-acting (projected weekly dose) biologic molecule containing 3 individual inhibitors of HIV-1 entry that can be dosed subcutaneously," the researchers concluded. "BMS-986197 is effective at lowering viral loads in a mouse model of infection."

3/14/16

Reference

M Krystal, DWensel, Y Sun, et al. HIV-1 Combinectin BMS-986197: A Long-Acting Inhibitor With Multiple Modes of Action. Conference on Retroviruses and Opportunistic Infections. Boston, February 22-25, 2016. Abstract 97.

JASL Receives US$99,738 grant from the Embassy of Japan for HIV Prevention

also see: Health Minister Says Boldness Needed to Change Buggery Laws for HIV Prevention Work to be Effective with at Risk Groups 

Persons living with HIV are set to benefit from improved facilities for treatment, care and support, at the Jamaica AIDS Support for Life (JASL), through a US$99,738 grant from the Embassy of Japan, under its 'Grassroots Human Security Project'. The funds will facilitate an expansion in medical services and increased counselling support for persons living with HIV.

"The value of being able to increase the number of clients who receive treatment and counselling here, based on the renovations and expansion, cannot be captured in monetary terms. That more persons living with HIV will have accessible, available and affordable services, in a friendly and comfortable environment, is priceless," stated Minister of Health Dr Fenton Ferguson in his address at the contract signing and handover ceremony held at JASL on Friday.

The Kiwanis Club of Constant Spring, which will provide contribution, in terms of volunteer labour, was lauded by the minister for the selflessness of its members and continued commitment and support to JASL for the past seven years.

improvement

In expressing his thanks to Japanese ambassador, His Excellency Yasuo Takase, Dr Ferguson said, "we trust that you will be heartened by the significant improvement you will see in our health services due to your kind contribution."

"the strengthening of the multi-sectoral response will be the key to how readily we will be able to advance towards the very ambitious but inspiring UNAIDS targets of zero discrimination, zero transmission and zero AIDS related death."

This event came within 24 hours of the Japanese Embassy providing funding for six ambulances worth US$73,350 to the St John National Council.

Dr Ferguson also thanked the government of Japan for its continued support of the health sector in Jamaica.

Press release from JASL read as follows:

PRESS RELEASE
The Jamaica AIDS Support for Life receives JMD $11,000,000 to expand clinic from the Embassy of Japan in Jamaica The National Health Sector stands to benefit from the $11 Million grant received by JASL to expand its clinic. Jamaica AIDS Support for Life is the only non Government treatment site in the island and since its relocation to its new home, the organisation has seen a 419 % increase in clinic attendance without an expansion of the clinic space.. In light of this JASL was able to secure a grant to assist with the cost for the much needed expansion, with the kind assistance of The Kiwanis Club of Constant Spring.
The Embassy of Japan in Jamaica through its Grassroots and Human Security Grant Project has donated $11,000,000 to assist with the renovation and expansion of the clinic space. The Ambassador of Japan in Jamaica, His Excellency Yasuo Takase, said he would like to leave a legacy in Jamaica and JASL’s clinic expansion is one of his final projects before his diplomatic tour of duty ends.
The clinic which serves members of key populations (persons living with HIV, men who have sex with men and sex workers) will be expanded to include: counselling/ VCT (testing) room; a pharmacy dispensary to provide anti-retroviral and drugs for opportunistic infections; phlebotomist station; and an extending waiting area.
Through this expansion, JASL has estimated that the clinic will be able to serve almost 1,000 additional persons.

The Grant details were as follows:

A) Grassroots Human Security Project

Grassroots Human Security Project provides non-refundable financial assistance for development projects designed to meet the diverse needs in Jamaica. The project does not offer direct government-to-government grant assistance. However this project aims to provide flexible and timely support to development projects at the grassroots levels such as NGOs, hospitals, schools, local authorities and other non-profit organizations. The following are priority areas for the project:

Poverty Reduction

Primary Health

Education

Environment

Natural disaster response

Other global issues within the local context

Since 1995 Japan has provided a total of US$ 5 million to 80 local projects through the project. To see more details on the project, please click here for the guideline. 

Jamaica's National Flower Lignum Vitae Found to Have Bio-activity to Fight HIV

Jamaica’s national flower the Lignum Vitae has been found to contain properties that could be used to treat persons living with the Human Immune Virus, HIV, the virus that causes Acquired Immune Deficiency Syndrome, AIDS, by depleting the immune systems of infected persons the researchers who worked on the discovery were led by noted Jamaican scientist and entrepreneur Dr Henry Lowe, the research team noted that the Lignum Vitae has potent bioactivity that could work against HIV.

The study outlined in part:

Aim: Jamaica is rich in medicinal plants. Guaiacum oficinale is the “National Flower”, with reported uses in folk medicine for the treatment of various conditions including inflammation. In our search for plants with anticancer and anti-infective properties, we evaluated Guaiacum oficinale for activity against HIV-1.

Methodology: The leaf, seed and twig extracts of G. oficinale were screened for anti HIV-1 properties in primary peripheral blood mononuclear cels (PBMCs) infected with the reference HIV-1 BaL strain.

Results: Al the tested extracts inhibited HIV-1 p24 production by infected cells, with EC50 concentrations of 2.35µg/ml, 23.42µg/ml and 25.04µg/ml, respectively for the leaf, seed and twig extracts. As comparison, Betulinic acid had an EC50 value of 27.50µg/ml. The tested extracts had IC50/EC50 selectivity index (SI) values of ≥ 3, which compared favorably to Betulinic acid SI value of 1.09.

Conclusion: The results of this study suggest that extracts of G. oficinale may provide leads for the discovery of new drug agents against HIV-1.

Dr Henry Lowe

A statement from Dr Lowe’s Environmental Health Foundation, EHF Group of Companies said that although known from last year test results were repeated several times to ensure data accuracy it says since then the findings were published April 2014 issue of the prestigious European Journal of Medicinal Plants, according to the statement since publication a significant amount of data has been developed, the work of Dr Lowe and his research team has been lauded by Dr Joseph Bryant of the Institute of Human Virology at the University of Maryland Medical School where the global viral network is located. Dr Bryant said Dr Lowe and his researchers need to be recognised and commended for bringing a gift of a major potential magic bullet from a Jamaican tree to the potential management of HIV.

The EHF Group says it is currently pursuing potential drugs from the Lignum Vitae in collaboration with the US based National Products Division of the Research Triangle International which is known for its discoveries of anti HIV drugs, based on this collaboration the EHF Group believes it is one the verge of discovering a potent major anti HIV drug from the plant, Dr Lowe who is the founder and the scientist at the Kingston based Biotech R & D Institute plans to do further research on the isolates of the Lignum Vitae this in order to develop a treatment that could be used alone or as part of a cocktail for the management of HIV/AIDS.

In the interim a nutraceutical product is being developed the EHF group says a US patent has so far been filed in order to protect this vital intellectual property.

The tree is found almost everywhere and in even dry rocky conditions, it is also available in the United States and the Caribbean but as different varieties and is a home remedy for tonsillitis by soaking the bar until the water turns red then gargle or drunk for fever, in the Virgin Islands it is used for fish poisoning and in other parts of the Caribbean for even abortion when specially prepared, it seems this plat we have here and I have no doubt many others have properties that we must explore and unearth. Some parts of Latin America use the leaves for tea to treat stomach aches or as an energy booster when soaked overnight and drunk unsweetened. It is also said to have anti bacterial properties in a subsequent interview with Dr Lowe on Nationwide radio.

He said in that interview also that it could be a potential foreign exchange earner for Jamaica.

Another household use in Jamaica is that of a makeshift broom when a few branches are tied together and is an excellent insect repeller in kitchens in a similar bunched set of green leaves and used to chase away flies and such from meats and fruits. It is rested and amongst fruits, tubers and other foods to supposedly slow down drying out of them when stored in a container or typical food basket and also chasing away fruit flies, moths that feed or surround the aforementioned. During Christmas it attracts thousands of butterflies to its purple flowers and said thousands of caterpillars can be seen on its trunk and branches as they feed prior to pupating.

the trunk often used to make a tea or broth or bark is stripped off and used separately

It seems this plant has some properties just by its natural use and the attraction or repulsion of insects and so on. Not to mention its use as a disciplinary tool for whipping but cut in very slim stick strips as it does not break easily.

Hope we can find the active properties and develop on this as an alternative for the other manufactured and still expensive antiretroviral and highly active antiretroviral therapies available and given the push on PrEP as treatment cheaper drugs are needed as Truvada locally is not so cheap and is partially distributed via the free national system.

Download the PDF file on the research HERE written by Dr Henry Lowe

Peace and tolerance

H

US University Claims its Found Way To Eliminate HIV from Cells

TEMPLE UNIV. TEAM MAKES BREAKTHROUGH IN HIV-AIDS RESEARCH 

ABC 6 news carried this news item on their website on July 21, 2014

PHILADELPHIA (WPVI) --

Local researchers have made a breakthrough in attacking HIV, and it could be the first step toward a cure.

Currently, HIV has been difficult to stop because it doesn't just float around in the bloodstream - it inserts itself into someone's DNA.

Current drugs won't take it out. But for the first time, researchers at Temple University have been able to eliminate it from human cells.

Dr. Kamel Khalili from Temple University School of Medicine explains, "The current therapy for AIDS does not eliminate viruses, but rather suppresses virus replication."

Dr. Khalili says current drugs do a good job of keeping patients alive, but they don't cure HIV-AIDS.

If there's a break in taking the drugs, the virus starts building again.

That's what happened with a baby in Mississippi. Experts had previously said the baby was "cured" of AIDS.

So instead, Dr. Khalili's team has created a protein combo that targets and attaches itself to the HIV in a cell's DNA. It then cuts out the infected part. The cell repairs itself and becomes a healthy cell again.

"Precise, fast, and has no harm to the cells," Dr. Khalili said.

The process has worked on human cells in the laboratory, and animal tests have begun, to make sure it kills all the HIV.

Dr. Khalili says the next challenge is to determine the best way to give it to humans. It may take several years, but his team believes it will work... and may even go a step further.

He says, "We hope that the technology that we have developed can also help protect individuals - uninfected individual - from HIV."

The results of the Temple team's work were published Monday by the National Academy of Science, and it's getting a lot of attention.

Dr. Khalili believes the process will also work on other viral infections, and possibly for cancer.

Having trouble seeing the video above then go HERE

Jamaica Increasing Funding For HIV/AIDS Programmes

Minister of Health, Hon. Dr. Fenton Ferguson (centre) greets Prime Minister of St. Kitts and Nevis, Dr. Denzil Douglas (left) prior to the start of a Global Fund press briefing at the Jamaica Pegasus Hotel in Kingston on April 9. Also sharing in the moment is Executive Director, Global Fund, Mark Dybul. The Global Fund provides support for HIV/AIDS, tuberculosis, and malaria projects around the world. It is an international financing institution that supports countries in their fight against three of the world’s most devastating diseases.

Minister of Health, Hon. Dr. Fenton Ferguson says while funding support from international agencies is crucial in combating HIV/AIDS, the country is taking gradual ownership of specific programmes related to the disease.

The Health Minister was responding to questions during a Global Fund press briefing at the Jamaica Pegasus Hotel in Kingston on Wednesday, April 9.

“In spite of the difficulty, we are moving from a position of 80 per cent external funding where we are now at about 46 per cent (local funding) in support of the HIV/AIDS programme, and so while we have gotten what we could consider transitional funding that will be specific for the high risk groups, Jamaica has demonstrated, in relation to the antiretroviral drugs, that we are taking gradual ownership in that regard,” he said.

Through the Global Fund, a total of US$16 billion has been allocated for disbursement to small, developing states, like Jamaica, to fight debilitating diseases such as HIV/AIDS, tuberculosis, and malaria.

The sum is being provided under the Fund’s revised financing model for 2014 to 2016, and is available for distribution to eligible nation states, with each country having a specific allotment, depending on its national income level and disease burden.

The sum is 20 per cent higher than the amount disbursed by the Global Fund over the previous period.

Under the revised plan, Jamaica is eligible for US$19 million draw down over the next two years, to tackle the diseases.

Jamaica was originally slated to receive US$11 million from the Fund but following further discussions, the allocation was increased.

Dr. Ferguson noted that the funding will be used to facilitate the needs of the most at-risk groups.

The Minister also noted that despite the reclassification of Jamaica and other Caribbean states as ‘upper middle income’ countries, which has affected their ability to access funding from international agencies, other factors need to be taken into consideration when determining funding support.

“Even as we look at country classification, it is important also to take into account health indicators in the country, the debt to GDP ratio in the countries, so that in the final analysis we would be able to get a real appreciation as to a country’s ability to fund not just HIV but to carry forward the overall national health agenda,” he said.

He said the country continues to tackle HIV/AIDS, which is as much a public health matter as it is a developmental issue.

“Any phenomenon relative to the disease process that has a profound effect on public health, robs a society of productive capacity. This is in relation to productive capacity, which will ultimately affect development, therefore we continue to make the point that health issues are developmental issues and we will continue to press this agenda,” he said.

Executive Director of the Global Fund, Mark Dybul, said Jamaica has had tremendous success in combating HIV.

He also noted that reduction rates regarding mother to child transmission “are very close to what are seen in the United States and Europe,” adding that this success is mirrored throughout the region.

He added that significant declines have also been seen in tuberculosis and that the region is on a path towards eliminating malaria.

The Global Fund provides financial support for HIV/AIDS, tuberculosis and malaria projects around the world. It is an international financing institution that supports countries in their fight against three of the world’s most devastating diseases.

Created in 2002, the Global Fund is a unique partnership between governments, civil society, the private sector, and affected communities. The Fund channels approximately US$3 billion a year to health professionals to treat and prevent AIDS, tuberculosis, and malaria in their countries.

It does not implement or manage programmes, relying instead on local experts to select and administer the programmes that save the most lives.

Long-acting antiretrovirals may improve survival for people with poor adherence

Produced in collaboration with hivandhepatitis.com

Long-acting antiretroviral formulations taken once-monthly or less have the potential to improve survival and quality of life for people with HIV, especially those who have difficulty achieving good adherence, but cost may be a barrier, according to a presentation at the Second IDWeek conference taking place this week in San Francisco.

Long-acting antiretroviral therapy (ART) administered as monthly or quarterly injections may be a more convenient way for some people to receive treatment, which could lead to improved adherence and in turn better viral suppression. Two such formulations, a long-acting version of rilpivirine known as TMC278-LA and the experimental HIV integrase inhibitor GSK1265744, have shown promising pharmacokinetics, safety and antiviral activity in early studies.

Eric Ross from Massachusetts General Hospital in Boston and colleagues used mathematical modelling to predict the impact of long-acting ART on survival and cost-effectiveness for people who have not taken ART before (treatment naive) in four scenarios:
Current standard of care using daily oral antiretrovirals, starting with a regimen based on an NNRTI (non-nucleoside reverse transcriptase inhibitor), moving on to protease inhibitors and finally to integrase inhibitors and salvage regimens.

Late long-acting ART starting after multiple treatment failures.
Second-line long-acting ART starting after first-line NNRTI failure.
First-line long-acting ART used as an initial regimen.

The model assumed a hypothetical cohort of previously untreated people with HIV based on demographic, CD4 cell count and adherence data from published studies. Most (84%) were men, the mean age was 43 years, the baseline CD4 count was 320 cells/mm3 and they maintained 89% adherence on average. The analysis assumed that viral suppression rose linearly with increasing adherence when using daily ART, but that both adherence and suppression remained consistently high when using long-acting injections.

The researchers projected changes in CD4 count, viral load and retention in care over a lifetime. They looked at life expectancy, quality-adjusted life years (QALYs) and cost estimates based on 2012 US price data:

Average first-line regimen: USD$24,000/year.
Boosted protease inhibitor regimen: USD$28,000/year.
Integrase inhibitor regimen: USD$39,000/year.
Integrase inhibitor salvage regimen: USD$40,000/year.
Long-acting ART regimen: USD$53,000/year.

Importantly, they estimated that long-acting ART would cost 85% more than boosted protease inhibitor regimens, based on historical information about relative costs of novel long-acting formulations of drugs for other diseases.

Cost-effectiveness was determined by calculating whether the incremental cost per QALY gained was above or below USD$100,000, a commonly used threshold in the US.

Compared with a life expectancy of 23.0 years after ART initiation for people taking daily therapy, the model predicted that those using long-acting formulations would increase their survival by several months: 23.5 years with late long-acting ART, 23.6 with second-line long-acting ART and 23.7 with first-line long-acting ART.

Lifetime costs for long-acting ART under the late, second-line, and first-line scenarios were USD$420,000, USD$490,000 and USD$670,000, respectively, compared with USD$400,000 for current daily regimens.

Late long-acting ART after multiple treatment failures was found to be cost-effective, coming in under the threshold at USD$90,000 per QALY. Second-line long-acting ART was ten-fold more expensive at USD$980,000 per QALY. The cost of starting long-acting ART as first-line therapy was an exorbitant USD$6,190,000 per QALY.

But the cost picture improved when the model took into account adherence. Amongst individuals with very high adherence to daily regimens (as seen in some clinical trial populations), long-acting ART did not significantly improve survival, so it was not cost-effective under any scenario. People with poor adherence to daily therapy, however, could see enough improvement in life expectancy that long-acting ART became feasible.

The researchers calculated that the cost of long-acting ART would have to drop into the $27,000 to $34,000 per year range to become cost-effective for second-line therapy – close to the current price of boosted protease inhibitor regimens.

"Long-acting ART has the potential to improve survival of HIV patients, especially those with barriers to adherence," the investigators concluded. "With a high cost, long-acting ART will be good value when used selectively in poorly adherent patients with multiple failures. With a cost near that of currently available regimens, long-acting ART could be cost-effective as second-line therapy."

The researchers stressed that because survival benefits of long-acting ART could be negligible for highly adherent patient groups, future studies of this strategy "may underestimate its value" if they do not include individuals with barriers to adherence.

They also noted that this model did not incorporate the potential impact of long-acting ART on reducing the risk of HIV transmission, which would likely improve its value.

The historical 85% cost increase for novel long-acting drug formulations is perhaps the most flexible factor in this model. If advocates succeed in demanding lower prices, or if national health programs refuse to pay such a high premium, long-acting ART could become cost-effective for more people.

MORE HERE

Background:

Long-acting antiretroviral formulations (LA-ART), currently in development, aim to achieve monthly or quarterly ART dosing; this could improve health benefits of ART for HIV-infected individuals who have difficulty maintaining daily adherence. We sought to identify the clinical and economic circumstances under which differing clinical roles of LA-ART might be cost-effective in the US.

Methods:

We used a microsimulation model of HIV disease progression (CEPAC-US) to project the impact of 3 potential roles of LA-ART (compared to daily ART only): 1) initial therapy for all ART-naïve patients, 2) 2nd-line therapy for those failing 1st-line, and 3) use for patients with multiple prior failures on NNRTI- and PI-based regimens. Model outcomes include quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER); strategies with ICER < $100,000/QALY are designated “cost-effective”. We simulate a cohort with mean adherence (medication possession ratio) of 89% (SD = 22%). Depending on adherence, HIV RNA < 400c/mL at 48 weeks on daily ART ranges from 0 to 91%, and loss to follow-up ranges from 41 to 4/100PY. We assume LA-ART's efficacy is 91% regardless of adherence to daily ART, and that LA-ART costs $60,000/patient-year (vs. $28,000 for daily PI-based regimens). In sensitivity analysis, we vary LA-ART's cost, efficacy, and quality of life (QOL) impact (due to benefits of reduced pill burden or detrimental side effects).

Results:

In the base case, LA-ART increases overall life expectancy (LE) compared to daily ART by 0.5-0.6 years, and LE of patients with the lowest adherence by 2.3-3.0 years, depending on clinical role; only LA-ART for patients with multiple failures is cost-effective ($86,000/QALY, Table). With a cost of $30,000/year and a favorable QOL impact, 2nd-line LA-ART is cost-effective ($94,000/QALY); varying efficacy of LA-ART has minimal impact on cost-effectiveness results.

Conclusion:

LA-ART could improve survival of US HIV patients, especially those with barriers to adherence and poor outcomes on daily ART. With a high cost, it will be a good value for use in patients with multiple prior failures; a cost close to current regimens combined with demonstrable QOL benefit would support broader use.