Recently Published Article by CHIPTS Researcher, Arleen Leibowitz, Ph.D.
Condom Distribution in Jail to Prevent HIV Infection
by Arleen A. Leibowitz, Nina Harawa, Mary Sylla, Christopher C. Hallstrom and Peter R. Kerndt
Download PDF here: [Download not found]
by Mark Mascolini at natap.org
CLICK HERE to read the full article
from Jules: as the meeting ended the FDA’s Debra Birnkrant, M.D. Director, Division of Antiviral Products said this was a “landmark” meeting and indeed it was. The meeting started at 8am and ended at 8:30pm. However, this was not the longest meeting. This is the longest FDA Antiviral Ad Board meeting since the FDA hearing for ritonavir & indinavir, a joint hearing for both drugs on back to back days, the ritonavir hearing as I recall was held over night, the FDA & the sponsor had to meet in the hotel overnight & the meeting was resumed the next day, this was under FDA Commissioner Kessler, I was there. Both meeting were landmarks, the IDV/RTV & this one, this one because this is the first hearing to discuss approval for a prevention drug, which will open an unchartered era and will be full of surprises. The discussions today by the panel were controversial & complicated, as lots of concerns were raised including what baseline tests & monitoring tests should be used and how often, including testing for HIV, viral load, HBV, STIs, renal function, bone dexas and more.
By large majorities, the FDA’s Antiviral Drugs Advisory Committee voted to recommend extending Truvada’s license to include pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) and for HIV-discordant couples (with one partner positive and one negative). The advisory panel also supported Truvada (coformulated tenofovir/emtricitabine) as PrEP for “other individuals at risk for acquiring HIV through sexual activity,” but less enthusiastically than they endorsed the first two indications.
The committee voted 19 to 3 to recommend Truvada PrEP for HIV-negative MSM and 19 to 2 (with 1 abstention) for HIV-negative partners in serodiscordant couples. The vote favoring PrEP for “other individuals at risk for acquiring HIV through sexual activity” was 12 to 8 with 2 abstentions.
Committee members voiced uncertainty about who the “other individuals” are, although completed and ongoing trials offer ample suggestions. In the two placebo-controlled trials Gilead Sciences advanced to support the PrEP indication, participants were MSM in iPrEx [1] and HIV-discordant heterosexual African couples in Partners PrEP [2]. A third trial that found daily Truvada helps protect people from HIV during sex, TDF2, enrolled high-risk Batswana women and men not necessarily in discordant partnerships [3]. Some MSM in iPrEx lived in the US, but most were from South America, South Africa, and Thailand. These trials included no heterosexual US men or women.
A fourth trial, FEM-PrEP, found no protective effect with Truvada taken by high-risk African women [4], while the VOICE PrEP/microbicide trial closed its microbicide arm and its oral tenofovir-only arm because those strategies were not protecting high-risk women from HIV [5]. FEM-PrEP investigators found that only 15% of women who got HIV in the Truvada group had detectable tenofovir levels at two visits. In its briefing document for the Truvada PrEP hearing, the FDA noted that “adherence to prescribed interventions appears to play a key role” in success or failure of PrEP [6].
Both iPrEx and Partners PrEP randomized HIV-negative participants to Truvada or placebo; Partners PrEP also tested tenofovir alone to prevent HIV acquisition by HIV-negative partners with an HIV-positive partner. In their primary analyses, iPrEx documented a 42% lower HIV acquisition risk with Truvada, while Partners PrEP found a 75% lower risk with Truvada and a 67% lower risk with tenofovir alone. An FDA analysis presented at the hearing indicated that iPrEx men with measurable intracellular drug concentrations had an 87.5% lower risk of HIV infection than men taking placebo.
The licensing change formally requested by Gilead is that “Truvada is indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults.” Recommendation for an extended indication by the Antiviral Drugs Advisory Committee does not oblige the FDA to follow suit, but it seems likely the FDA will do so. On the way to the committee vote, FDA analysts presented a largely favorable review of Truvada PrEP findings, concluding that “safety and efficacy of [Truvada] for the prevention of HIV-1 infection in high-risk individuals is supported by two large clinical trials” [iPrEx and Partners PrEP].
Data presented by the iPrEx and Partners PrEP principal investigators showed that resistance did not emerge in anyone randomized to Truvada who became infected during the course of the trial. Resistance developed in a few people who took Truvada or tenofovir during early HIV infection that had gone undetected. Neither trial found evidence of risk compensation–the possibility that people using PrEP will ignore other measures that protect them from HIV, such as consistent condom use. In fact, study participants generally practiced safer sex after enrolling in the trials.
The FDA advised that “regular HIV testing, adherence and behavioral counseling on safer sex practices, including condom use, are essential components of healthcare delivery around PrEP.”
FDA officials did raise some safety concerns in their analysis of iPrEx and Partners PrEP. Noting that renal failure or Fanconi syndrome did not occur among Truvada takers in iPrEx, the FDA cautioned that cases of concurrent proteinuria, glycosuria, and hypophosphatemia primarily in the Truvada arm “may be potentially concerning for subclinical proximal renal tubulopathy, although the limited numbers and poor adherence observed in this trial, as assessed by drug level monitoring, preclude reliable interpretation” [6].
In Partners PrEP only 7 people permanently withdrew because of adverse events, and 6 withdrawals were attributed to grade 2 renal toxicity, 3 in people taking tenofovir alone, 2 in people taking Truvada, and 1 in the placebo group [6]. All renal toxicity (creatinine clearance below 50 mL/min) resolved in 5 women when they stopped study drugs. Results are pending on the 1 man who endured renal toxicity.
Analyzing renal toxicity in other ways, the FDA found no evidence linking toxicity to tenofovir or Truvada in Partners PrEP [6]. Treatment-emergent creatinine increases affected 5% taking tenofovir, 7% taking Truvada, and 5% taking placebo. “Drug-related” creatinine toxicity affected only 8 people overall (0.2%), and 5 of those 8 were taking placebo.
Truvada PrEP trials completed so far include few African-American men, who have a higher risk of renal disease than white men. And because HIV incidence has been climbing in African-American MSM, they are likely candidates for Truvada PrEP.
The FDA noted that men enrolled in iPrEx had lower bone mineral density (BMD) when they entered the trial than does the general population. Men randomized to Truvada had small but statistically significant drops in BMD compared with the placebo group throughout the trial. BMD declines of more than 5% from baseline affected 14% of iPrEx participants taking Truvada versus 6% taking placebo. The FDA pointed to similar BMD declines among MSM in a CDC study of tenofovir safety [7].
The FDA mentioned renal toxicity in its overall premeeting briefing conclusion of Truvada PrEP efficacy and safety: “The decision to prescribe [Truvada] for the prevention of sexual acquisition of HIV infection should carefully weigh the individual risks for acquiring HIV, their understanding of the importance of adherence to medication, and their potential for development of renal toxicity” [6].
Before clinicians start Truvada PrEP, the FDA said in its premeeting document, they should (1) test the person for HIV, (2) measure renal function and serum phosphorous, and (3) assess risk factors for renal and bone toxicity [6]. Clinicians might also consider supplementing vitamin D and calcium in someone taking Truvada PrEP, the FDA advised. Everyone using Truvada for PrEP should get tested regularly for HIV and monitored for renal problems. Some Truvada takers may benefit from DEXA bone scans before and during PrEP, the FDA suggested.
The FDA offered this final conclusion in its briefing document: “If physicians prescribe and individuals utilize [Truvada] in the manner described for PrEP, in combination with other strategies to prevent HIV infection, the individual at risk may be spared infection with a serious and life-threatening illness that requires lifelong treatment with a three-drug antiretroviral regimen. That regimen, in line with current treatment guidelines for HIV-infected treatment-naive patients, will almost certainly contain [Truvada]” [6].
On Tuesday, Food and Drug Administration reviewers affirmed clinical trial data suggesting the HIV drug Truvada is safe and effective in cutting HIV infection risk when taken daily. The positive review comes ahead of an FDA advisory panel’s meeting on Thursday to discuss whether to approve Truvada for people at high risk of acquiring HIV sexually. The drug from Gilead Sciences already is approved to treat persons infected with HIV.
The panel will take separate votes on approval to market Truvada as an HIV prevention option among:
*gay and bisexual men,
*people in serodiscordant relationships and
*others at risk for acquiring HIV sexually.
Truvada only worked to prevent HIV when taken every day, reviewers emphasized. Adherence to the once-daily pill was less than perfect in clinical trials, which included condom use and HIV counseling, and adherence may be even less ideal in the real world, reviewers said.
Some researchers note that condoms are still the best prevention against HIV, and that a pill is not the same. Some drugs on the horizon also may prove to be better for HIV prevention than Truvada, which has had mixed results for preventing infection in women, critics say. Nonetheless, many advocates say Truvada should be an option, along with condoms, counseling, and other prevention measures.
Side-effects associated with Truvada include dizziness, diarrhea, nausea, and vomiting. More serious adverse events include liver toxicity, bone thinning, and kidney problems.
FDA does not have to follow the advice of its advisory panels, but usually does so.
By Tim Horn at POZ.com
on May 4, 2012
Roughly a year ago, I was asked by Jose Zuniga of the International Association of Physicians in AIDS Care (IAPAC) to serve as a writer and member of the first-ever blue-ribbon panel assigned with the task of developing international guidelines for improving engagement in HIV care and treatment adherence. The Guidelines for Improving Entry into and Retention in Care and Antiretroviral Adherence for Persons with HIV were first made available online ahead of print by Annals of Internal Medicine on March 5 and were eventually published in the May 1 issue of the journal.
The experience was eye-opening, to say the least. Working most closely with two of the smartest, dedicated and caring HIV-treating clinicians and researchers I can name–Michael Mugavero, MD, of the University of Alabama, Birmingham, and Melanie Thompson, MD, of the AIDS Research Consortium of Atlanta–I was most heavily involved in the sections focusing on entry into and retention in care. Basically, I was charged with reviewing to what extent people living with HIV are actually receiving regular care–irrespective of whether or not actual HIV treatment is prescribed–and coming up with recommendations to shore up weaknesses. How hard could this possibly be?
Well, it turned out to be much easier than I thought, only because the national portrait of entry into and retention in HIV care has been consistently abysmal and the astounding dearth of data from well-designed studies exploring entry and retention strategies that could be used to construct well-formed recommendations.
In retrospect, I would have liked for my job to have been much, much harder.
Reading through the rest of the IAPAC guidelines, it is abundantly clear that the pharmaceutical industry, along with public and private research networks, have done a bang-up job improving our ability to adhere to HIV treatment. Millions, if not billions, have been spent on transforming fistfuls of relatively toxic pills, taken multiple times a day, into safer coformulations and novel combinations that involve taking no more than one or two tablets or capsules once or twice a day. There have also been several well-designed studies exploring the utility of treatment adherence strategies, such as directly observed therapy, electronic pill bottle caps, text messaging, phone calls, educational programming and a variety of counseling methods.
Synthesizing all of the treatment adherence data for the sake of best-practices guidelines wasn’t easy, for sure, but the end result was a clear set of conclusive recommendations based on strong scientific conclusions.
However, none of this–the ability to prescribe easy, highly effective treatment regimens and a plethora of adherence tools to prolong our health and prevent ongoing transmission of the virus on a massive scale–matters if we can’t first get people living with HIV connected to regular care.
The situation is direr than I, for one, ever imagined. Only in recent years have data emerged, underscoring how far off we are from a central tenet of the National AIDS Strategy: Ensuring that all people living with HIV are well supported in a regular system of care.
Consider the following….
This coming Thursday, May 10, the United States Food and Drug Administration (FDA) will convene its Antiviral Drugs Advisory Committee at a public session in Washington D.C. to review data and public input related to the potential use of the antiretroviral drug Truvada for HIV prevention. The Committee will vote on whether or not daily oral intake of Truvada is safe and effective when used to prevent HIV infection, an approach known as pre-exposure prophylaxis (PrEP).
Relevant background materials for the session became available today, which include the FDA’s initial evaluation of research data related to Truvada’s safety and efficacy in the context of PrEP. Using the Committee’s recommendations and its own evaluation, the FDA is expected to make a final decision on approval by June 15, 2012.
If approved, PrEP will become part of the existing suite of evidence-based HIV prevention tools. Although many questions remain regarding high costs, operational challenges, accessibility and additional implications of PrEP both within and outside the United States, the FDA’s Committee will limit their assessment to Truvada’s safety and efficacy.
You can submit data, information or views concerning this meeting to the FDA Advisory Committee in written or electronic format until May 17, 2012. Click this link to learn how to make a submission. Additional links to key documents are provided below to help advocates better understand PrEP and the FDA review process.
Additional Resources:
A vaccine that elicits broadly neutralizing antibodies (bNAbs) to HIV has long seemed at least as elusive as the Holy Grail. But as more and more such antibodies are isolated from HIV-infected volunteers—revealing rare vulnerabilities on HIV—researchers are increasingly hopeful of coaxing that coveted humoral response.
Some 400 attendees at the Keystone Symposia, which paired the annual HIV Vaccines meeting with the Viral Immunity and Host Gene Influence meeting, got an update on the quest to make such vaccines. A number of talks at the conference, held March 21-26, illuminated how structural and computational biology are being applied to reverse-engineer immunogens that might induce bNAbs. Others described how next-generation DNA sequencing technologies are unraveling the genetic origins and evolution of those antibodies.
CLICK HERE to read the full article.
As the global campaign against AIDS enters its fourth decade, the development of a broadly preventive HIV vaccine remains among its most vexing challenges.
In his opening remarks at the 19th Conference on Retroviruses and Opportunistic Infections (CROI), held March 5-8 in Seattle, Tufts University virologist John Coffin, the scientific organizer of the event, noted that the failure of previous vaccine candidates had convinced many scientists that antibodies capable of preventing HIV infection could not be elicited through vaccination.
But the 31.2% efficacy demonstrated in the RV144 vaccine trial in Thailand—which, though modest, provided the first evidence of vaccine-induced protection from HIV—has helped lift the gloom from such speculations. Volunteers in that trial who received the prime-boost vaccine combination developed low titers of gp120-binding antibodies that subsequent analyses revealed are correlated with the risk of HIV infection. Separately, a dramatic expansion in the number of broadly neutralizing antibodies (bNAbs) against HIV isolated from volunteers, and the data describing their mechanisms of action, have renewed optimism about the prospects of this vaccine strategy.
“We’re now thinking much more seriously about developing vaccines that might be based on eliciting specific antibodies,” Coffin told the international gathering of more than 4,200 HIV researchers and clinicians.
Reflecting this shift in strategy, CROI organizers selected pioneering antibody researcher Dennis Burton, professor of immunology and microbial science and director of IAVI’s Neutralizing Antibody Center (NAC) at The Scripps Research Institute in La Jolla, California, to kick off the conference. Burton observed that the recent discovery of more than two dozen potent bNAbs by his lab and others, and the elucidation of some of their structural targets on HIV’s Envelope glycoprotein, have revealed weaknesses that can be exploited for both drug and vaccine development. “The tools are all there,” said Burton. “It remains to be seen if immunogen design can take advantage of all these tools.”
But antibodies were far from the only item on CROI’s four-day agenda. The conference also highlighted investigations of the structure of HIV’s Envelope trimer and updates on the continuing analysis of samples collected in the RV144 trial. Other talks of particular interest covered new findings on how a subset of T cells influences antibody development, the evolutionary pathways of HIV and SIV, and the results of several recent studies on ARV-based prevention, which dominated the conference and provoked more than a few animated discussions.
CLICK HERE to read the full article at www.iavireport.org
Through the Department of Public Health, Substance Abuse and Prevention Control division, The Wall-Las Memorias Project (TWLMP) is doing is conducting a study on the accessibility, availably and social norms of alcohol and other substance abuse in Southeast Los Angeles which includes the cities of Huntington Park, Bell Gardens, South Gate, Maywood, Bell, and Cudahy.
In an effort to gather comprehensive data TWLMP will be conducting focus groups for young adults, ages 18-24 who are LGBTQ. Would it be possible to open up an invitation to any community groups/members that you may know in your community whether they be 18 year olds who are in high school or 18-24 year olds who are in college or working?
In appreciation of participants time a $20 gift card to Target will be given to each participant, light snacks and refreshments will be provided as well. The focus group will be recorded (with participant consent) and notes will be taken to make sure we capture the most accurate information. We will conduct the focus group at a convenient location in the community unless you have a location in mind that we can utilize.
I appreciate your time and hope to hear from you soon.
Please feel free to contact me at your earliest convenience regarding this request @ (323) 257-1056 ex.23 or lvelasquez@thewalllasmemorias.org
UNITED STATES: “FDA Panel Considers HIV Drug for New Use”
Wall Street Journal (05.06.12):: Jennifer Corbett Dooren
On Thursday, a Food and Drug Administration advisory panel will consider whether to recommend that FDA approve the first drug for high-risk but healthy people to take to prevent HIV infection. Truvada, made by Gilead Sciences Inc., is already one of the most widely used drugs to treat HIV infection. Gilead has submitted data from two large clinical trials to support marketing Truvada as pre-exposure prophylaxis (PrEP).
Gilead submitted one study involving about 2,500 at-risk gay and bisexual men that found the drug, in addition to other prevention measures like condom use, reduced their HIV infection risk by 44 percent. In another involving about 4,800 serodiscordant heterosexual couples, HIV infection risk was cut 73 percent among HIV-negative partners taking Truvada, interim data showed. But a study among some 2,000 women was stopped last year after it was determined it was unlikely to show whether Truvada helped prevent infection among them.
The AIDS Healthcare Foundation filed a petition in March urging FDA to reject the application, saying PrEP data are not strong enough. AHF also cited worries over side-effects, the drug’s $14,000-a-year cost, and adherence problems. However, the prevention advocacy group AVAC is among 14 organizations calling for FDA’s approval.
Dr. Rodney Wright, AHF’s board chair, said he is concerned about “a blanket approval” of Truvada for PrEP and the lack of data for it among women. Wright and other physicians already prescribe Truvada as PrEP on a limited basis, including for serodiscordant couples wishing to have children. CDC last year released interim PrEP guidelines for certain men who have sex with men, and it is weighing similar guidance for heterosexuals.
“PrEP will be the most beneficial for people at very high risk of HIV infection,” but strict adherence to the daily regimen is essential, said Jonathan Mermin, director of CDC’s Division of HIV/AIDS Prevention.
HAVANA — Yudelsy García O’Connor, the first baby known to have been born with AIDS in Cuba, is not merely still alive. She is vibrant, funny and, at age 25, recently divorced but hoping to remarry and have children.
Her father died of AIDS when she was 10, her mother when she was 23. She was near death herself in her youth.
“I’m not afraid of death,” she said. “I know it could knock on my door. It comes for everyone. But I take my medicine.”
Ms. García is alive thanks partly to lucky genes, and partly to the intensity with which Cuba has attacked its AIDS epidemic. Whatever debate may linger about the government’s harsh early tactics — until 1993, everyone who tested positive for H.I.V. was forced into quarantine — there is no question that they succeeded.
Cuba now has one of the world’s smallest epidemics, a mere 14,038 cases. Its infection rate is 0.1 percent, on par with Finland, Singapore and Kazakhstan. That is one-sixth the rate of the United States, one-twentieth of nearby Haiti.
The population of Cuba is only slightly larger than that of New York City. In the three decades of the global AIDS epidemic, 78,763 New Yorkers have died of AIDS. Only 2,364 Cubans have.
Other elements have contributed to Cuba’s success…..
CLICK HERE to read the full article on nytimes.com
