The Heavy Co$T Of AIDS – With Global Funds To Dry Up, Jamaica In Peril

Prepared by Byron Buckley

CARIBBEAN AIDS prevention advocates fear that crucial funding to sustain hard-won gains over the last decade could dry up by year end. Financial support from the Geneva-based Global Fund could cease because Jamaica and other Caribbean states, having been classified as ‘middle-income’ countries, no longer qualify as recipients of funding.

Dr Edward Greene - File

In addition, a South-South agreement between the Organisation of Eastern Caribbean States (OECS) and Brazil, which facilitates universal access to antiretroviral drugs to treat HIV/AIDS, comes up for renegotiation later this year.

Faced with this spectre, Dr Edward Greene, United Nations special envoy for HIV in the Caribbean, says the world body will be working with Jamaica and other countries in the region to protest the ‘middle-income’ designation and secure its reversal.

Warns Greene: “With Jamaica experiencing its current level of financial constraints and renegotiating its debt with the International Monetary Fund, we are concerned about the possibility of the country being forced to suspend its social programmes. It would be catastrophic, in particular, for people living with HIV (PLHIV), if a withdrawal of support were to take place.”

The UN envoy flays the World Bank’s flawed study, based on income, which resulted in Jamaica’s reclassification. He notes: “Income does not tell you the burden of debt nor disease.”

It is the easing of the burden of HIV/AIDS on Caribbean societies that Greene and fellow advocates wish to sustain. A cessation of funding would threaten the fragile gains made in the Caribbean over the last decade. From 2001-2009:

The number of AIDS-related deaths declined by 9,000;
The number of new HIV infections decreased by 3,000;
The number of PLHIV in Haiti and Guyana declined;
The number of PLHIV in Jamaica remained the same;
Adult HIV prevalence rate declined in Jamaica, Haiti and Guyana;
Adult HIV prevalence remained stable in Suriname, the Dominican Republic, and The Bahamas.
In addition to these positive trends, Greene has high praise for Jamaica’s efforts to ramp up its HIV response. “It is obvious that Jamaica is on the path to the elimination of mother-to-child transmission by 2015, and that the Caribbean, as a whole, can aim to be the first region in the world to achieve this goal,” he says.

The OECS could eliminate mother-child HIV infection by 2015. Fifty per cent of people in the Caribbean have access to antiretroviral treatment (ART) drugs, 70 per cent in Guyana, and universal in Barbados.

Challenges remain

But challenges remain in the regional efforts to control the spread of HIV/AIDS. Overall, between 2001 and 2009, the number of PLHIV increased by four per cent, including in Cuba, Jamaica’s nearest neighbour. During the same period, the HIV adult prevalence rate increased in four Caribbean countries: Barbados, Belize, Trinidad and Tobago, and Cuba.

One area of grave concern in Jamaica is the 30 per cent HIV prevalence among gay men. This is among the highest in global terms, and is followed in the region by Trinidad and Tobago (20 per cent), Dominican Republic (11 per cent), and The Bahamas (10 per cent). Overall, the Caribbean, with an adult HIV prevalence rate of one per cent, is ranked second to Africa (five per cent). This makes the Caribbean anomalous in the Americas, where the adult/HIV prevalence is 0.5 per cent in both Central/South America and North America/Mexico.

Indeed, any reversal of the gains from the Caribbean’s HIV/AIDS prevention programme would give a black eye to the optimism that characterises the global outlook on the status of the epidemic. Over the last 10 years, there has been a decline in mortality rates for HIV/AIDS across the globe. The mortality rate is down because more people have access to medication.

Greene explains: “Having access to antiretroviral drugs is a lifesaver because it allows people to live a very active and normal life. In the Caribbean, we can almost safely say we can eliminate the disease. I think we are in a more optimistic position than we were 10 years ago.”

His optimism is also based on developments in medical science of formulas to eventually eliminate HIV/AIDS, just like what occurred with smallpox and polio in the 1980s. This upbeat posture, perhaps overblown, is also reflected in UNAIDS’s goals of getting to zero by 2015:

Zero AIDS infection
Zero AIDS-related deaths
Zero discrimination
Eliminating discrimination
Lifting the burden of the disease, importantly, involves the elimination of discrimination against PLHIV. Discrimination is considered an important driver of HIV infection rate, according to health advocates, because people refuse to be tested. Studies carried out in the OECS by the Caribbean HIV/AIDS Alliance found that even among medical practitioners, there was the perception of stigma. This often leads to some form of discrimination, – giving more legs to the disease because people don’t want to go to the clinic.

Commenting on the hot-button issue in Jamaica of repealing the buggery law, the UN envoy says it is secondary to addressing discrimination and promoting human rights in general.

“For me, that (repealing the buggery law) is not the main problem. The main problem we are dealing with is the human rights, generally speaking,” he reasons. “People are entitled to access care, because if they don’t, that could affect society on a whole.”

Greene believes the State has an obligation to protect citizens on a whole to ensure that people with communicable diseases have access to care and treatment.

He reasons: “If I put the accent on reducing stigma and discrimination and human rights, I am ensuring that there is no overt discrimination for PLHIV in the workplace and in the school. This is because I don’t want to exclude one per cent of the population, or 30 per cent of men who have sex with men (MSM), from having access to those things that other people have. Just like how I would not exclude people from certain services because of their race, gender or where they live – as happens to job applicants living in inner-city communities.”

According to the UN envoy, it is important that PLHIV have certain responsibilities – to go and get tested, to adhere to their regime of treatment, to ensure that they educate their family and friends.

“So homosexuals have the right to health care,” Greene argues, “but they also have to behave in particular ways to conform to the norms of the communities. If they expect to be treated a certain way, they can’t behave in ways that are subversive to the community.” For example, he notes, members of the homosexual community should not “prey on young, vulnerable boys”. They must act responsibly, thus balancing the human rights structure.

Faith-based organisations

The goals of zero infection, deaths and discrimination require the involvement of the faith-based community. Greene is hopeful that after recent consultations with local church leaders, they will be able to adopt a message of abstinence, faithfulness to one’s partner and condom use. He points to the role played by faith-based organisations in East Asian societies in producing the lowest HIV/AIDS prevalence rate of 0.1 per cent per population.

“Notwithstanding its religious tenets, East Asia promoted safe sex as a practice for a fairly long time. It has not allowed its religious precepts to get into the way of practical sexuality.

“This is one reason we are seeing the very low prevalence rate, overall,” Greene observes.

The situation in East Asia contrasts with what obtains in the Caribbean where family life is breaking down; sexual promiscuity is rampant; and communities foster a culture of fear that leaves young girls vulnerable to sexual predators.

Of course, per capita income is quite high in East Asia, and the level of poverty there does not compare with prevalence rates in India and South/Southeast Asia.

Greene points out: “We have to see AIDS also as a development issue. Enhancing development could impact positively on AIDS outcome.”

He was in Jamaica to discuss a number of issues with governmental and non-governmental organisations, particularly surrounding human rights and HIV, as well as the financial sustainability of HIV programmes. As a result of these discussions, it has been agreed that Jamaica will hold a national consultation on human rights and the reduction of stigma and discrimination on World AIDS Day, December 1, 2012.

Byron Buckley is associate editor at The Gleaner. Email feedback to columns@gleanerjm.com and byron.buckley@gleanerjm.com.
Low HIV prevalence in East Asia linked to:

Religious and family patterns;
Historical cultural mores, spiritualism;
Less multiple partners in sex;
Greater degree of abstinence before marriage;
Higher degree of faithfulness to partners

Rectal Formulation of Tenofovir Gel Found Safe and Acceptable in Early Phase Clinical Study

Follow-up study planned to further assess gel’s potential as a rectal microbicide to prevent HIV
March 5, 2012 – A gel formulation of the antiretroviral drug tenofovir designed specifically for rectal use was found safe and acceptable, according to a Phase I clinical study led by the U.S. National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN), and presented today at the 19th Conference on Retroviruses and Opportunistic Infections (CROI). The results of the study, which included HIV-negative men and women who used the gel rectally once a day for one week, serve as an important step toward the development and testing of arectal microbicide to prevent HIV from anal sex. 
Microbicides, products applied on the inside of the rectum or vagina, are being studied as an approach for preventing or reducing the sexual transmission of HIV. The majority of microbicide research has focused on products to prevent HIV through vaginal sex, yet the risk of becoming infected with HIV from unprotected anal sex may be 20 times greater than unprotected vaginal sex. Developed as a vaginal microbicide, tenofovir gel was reformulated with less glycerin, a common additive found in many gel-like products, in the hopes of making it more appropriate for rectal use. 
The study, known as MTN-007, began in October 2010 and enrolled 65 men and women at three sites – the University of Pittsburgh, University of Alabama at Birmingham and Fenway Health in Boston. It is a follow-up trial to an earlier study, RMP-02/MTN-006, which assessed the rectal use of the vaginal formulation of tenofovir gel. That study found the gel produced a significant antiviral effect when used in the rectum, but gastrointestinal side effects were problematic.
In MTN-007, study participants were randomly assigned to one of four study groups. Three of these groups were assigned to use one of the following products for a one-week period: a rectal formulation of tenofovir gel; a placebo gel containing no active ingredient; or a gel containing the spermicide nonoxynol-9. A fourth group did not use any gel but took part in all of the study-related procedures and tests, including physical and rectal exams.
Study results indicated no significant differences in side effects among the three gel groups. Eighty percent of participants reported only minor side effects related to the use of study products, while 18 percent reported moderate side effects. (Two study participants reported severe adverse events, but they were not deemed to be related to use of the study products.) Participants’ adherence to the use of their assigned study products was high, with 94 percent using the products daily as directed. When asked about the likelihood that they would use the gel in the future, 87 percent of the participants who used the rectal formulation of tenofovir gel indicated they would likely use the gel again, compared to 93 percent of the placebo gel group, and 63 percent of the nonoxynol-9 gel group. In addition to assessing safety and acceptability, researchers also conducted preliminary gene expression testing, and noted changes in the activation of some genes in the tenofovir gel group, which they are continuing to evaluate to understand more fully.
“These findings tell us that the ‘rectal-friendly’ version of tenofovir gel was much better tolerated than the vaginal formulation of the gel when used in the rectum,” said Ian McGowan, M.D., Ph.D., co-principal investigator of the MTN and professor of medicine, Division of Gastroenterology, Hepatology and Nutrition and Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine. “We are very encouraged that the rectal gel was quite safe, and that most people who used it said they would be willing to use it in the future.”
As follow-up to MTN-007, researchers are now planning a Phase II, multi-site trial called MTN-017that will involve186 men who have sex with men and transgender women at clinical sites in Peru, South Africa, Thailand, and the U.S. Participants will cycle through three study regimens: rectal tenofovir gel used daily, rectal tenofovir gel used before and after anal sex, and daily use of the antiretroviral tablet Truvada®. MTN-017 will allow researchers to collect additional information about the gel’s safety and acceptability in the rectum, and compare it to the use of Truvada.                                         
In addition to Dr. McGowan, other authors of MTN-007 are Craig Hoesley, M.D., University of Alabama; Ross Cranston, M.D., University of Pittsburgh; Philip Andrew, FHI 360; Laura Janocko, Ph.D., MTN and Magee-Womens Research Institute; James Dai, Fred Hutchinson Cancer Research Center; Alex Carballo-Dieguez, Ph.D., Columbia University; Ratiya Kunjara Na Ayudhya, BSMT, MTN; Jeanna Piper, M.D., Division of AIDS, National Institute of Allergy and Infectious Diseases; and Ken Mayer, M.D., Fenway Health.
MTN-007 is funded by the National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) 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. 
The reduced glycerin formulation of tenofovir gel that was evaluated in MTN-007 is not the same formulation developed for vaginal use. The vaginal formulation of tenofovir gel was found safe and effective in reducing the risk of HIV in women who used it before and after vaginal sex in a study called CAPRISA 004. More recently, however, MTN researchers conducting the VOICE Studyclosed the tenofovir gel arm of the trial after a routine review of study data determined that the gel, while safe, was not effective in preventing HIV among the women in that study group, who were asked to apply it vaginally every day. In the meantime, a Phase III trial called FACTS 001 is currently evaluating the vaginal formulation of tenofovir gel using the same regimen as CAPRISA 004, with results expected in 2014. 

FDA ASKED TO APPROVE NEW HIV PREVENTION METHOD, PRE-EXPOSURE PROPHYLAXIS (PrEP)

 

For Immediate Release                          Contact

December 15, 2011                                  Mark Aurigemma; 646-270-9451mark@aucomm.net

                        Pedro Goicochea; 415-490-8350pgoicochea@gladstone.ucsf.edu                                                                                                      

 

FDA ASKED TO APPROVE NEW HIV PREVENTION METHOD, PRE-EXPOSURE PROPHYLAXIS (PrEP)

 

An application from Gilead Sciences, Inc. has been filed with the U.S. Food and Drug Administration toapprove an HIV antiretroviral therapy to reduce the risk of HIV infection among uninfected men who have sex with men (MSM) and heterosexual women and men. The application to approve the new HIV prevention method called pre-exposure prophylaxis, or PrEP, is based partly on data from the Global iPrEx study, the first human efficacy study to prove that PrEP reduces HIV infection risk inpeople (http://www.iprexnews.com).

 

The PrEP drug is a single-tablet once-daily combination of emtricitabine (FTC 200 mg) and tenofovir (TDF 300 mg), marketed under the brand name Truvada®. The iPrEx study found that MSM who were prescribed a single daily FTC/TDF tablet experienced an average of44% fewer HIV infections than those who received a placebo pill. Among a study sub-set those who took the tablet frequently enough for drug to be detected in their bodies, the rate of protection against HIVinfection was more than 90%. All participants in the iPrEx study received condoms and comprehensive HIV prevention support. The HIV prevention benefits of PrEP were in addition to the benefits obtained from other prevention methods.

 

iPrEx study results were first reported in the New England Journal of Medicine in November, 2010 (http://www.nejm.org/doi/pdf/10.1056/NEJMoa1011205).

 

Data supporting the use of PrEP to reduce HIV infection risk in heterosexual men and women were provided by the Partners PrEP study, which involved 4758 HIV serodiscordant couples (couples in which one partner is HIV-infected and the other is not) at nine trial sites in Kenya and Uganda. Both the iPrEx and Partners PrEP studies found that PrEP is safe, with very low levels of sideeffects and limited risk of HIV drug resistance.

 

“With 2.6 million new HIV infections occurring each year, and fewer than half of people with HIV receiving treatment, the world needs new and effective HIV prevention strategies,” said iPrEx Protocol Chair Robert Grant, MD, MPH of the Gladstone Institutes and the University of California at San Francisco. “Men who have sex with men have borne an enormous burden in this epidemic, and have also beenconsistently at the head of efforts to help reverse it. The 2,499 men and transgender women who participated in the iPrEx study Brazil, Ecuador, Peru, South Africa, Thailand and the United States have made an historic contribution to the effort to help end this epidemic.”

 

“The data are clearly strong enough to warrant FDA approval of Truvada for HIV prevention,” said Dana Van Gorder, Executive Director of the AIDS advocacy group Project Inform. “The decision about whether to approve Truvada for prevention should be made with compassion, based on science rather than ideology, and without judgment regarding the behaviors of people at risk for HIV. We firmly believe in the right of people at risk of becoming infected with HIV to choose PrEP, which has been shown to be effective when used with condoms, as an additional method of HIV prevention.”

An Open Label Extension of the iPrEx study (iPrEx OLE; http://www.iprexole.com/index.html) is currently underway at 11 clinical trials sites in the United States, Peru, Ecuador, Brazil, South Africa and Thailand. iPrEx OLE is designed to provide additional information about the safety of PrEP and the behavior of people taking PrEP over a longer term.

 

The iPrEx study was sponsored by the U.S. National Institutes of Health (NIH) through a grant to the Gladstone Institutes, a non-profit independent research organization affiliated with the University of California at San Francisco. Additional support for iPrEx was provided by the Bill & Melinda Gates Foundation.

# # #

 

Mark Aurigemma
212.600.1960 (office)
646.270.9451 (mobile)


HIV May Reproduce in Cells Other Than CD4s, Which Might Explain Brain-Related Problems

For the first time, researchers have shown that HIV can actively reproduce in a cell type other than CD4 cells, according to a new paperpublished October 6 by the online journal PLoS Pathogens. These findings, the authors explain, may help explain why antiretroviral therapy may not offer complete protection against HIV-associated neurological problems.

According to the paper authored by Ronald Swanstrom, PhD, and his colleagues at the University of North Carolina Center for AIDS Research in Chapel Hill, some people diagnosed with HIV-associated dementiahave two genetically distinct HIV types in their cerebrospinal fluid (CSF), the clear fluid found in the spaces around and inside the brain and spinal cord.

These variants, the authors point out, are not detected in HIV circulating in the blood, and one of them could be present years before the onset of dementia and potentially contribute to mild forms of neurologic disease, including HIV-associated neurocognitive disorder (HAND). The detection of these viruses in the CSF, Swanstrom and his colleagues point out in an accompanying press release, is evidence that they are growing in the central nervous system.

One of the two HIV variants found in CSF reproduces in CD4 cells, as does the virus growing in the blood. But the other type does not. It infects and replicates in macrophages, another white immune cell that engulfs and digests foreign material, including bacteria.

“This is the first time that anyone has demonstrated active replication of HIV virus in a cell type other than [CD4] cells,” Swanstrom said in the press release.

Researchers have known for many years that macrophages trap HIV—macrophage means “big eaters”; their role is to engulf harmful pathogens and diseased cells in tissues of the body. Once a macrophage encases a pathogen like HIV, the macrophage displays pieces of the virus on its membranes and produces chemicals, known as cytokines, to alert other cells of the immune system to the presence of the pathogen in bodily tissues.

CD4s are among the immune system cells to respond to the macrophage’s plea for help. For years, researchers believed that the only way HIV can escape the macrophages is by being passed on to the CD4 cells, where the virus can begin replicating. The new research by Swanstrom’s group suggests that HIV can reproduce in macrophages without any help from CD4 cells.

Swanstrom’s group had been collecting blood and CSF samples from patients who had either HIV-associated dementia or other severe neurological defects.

“After the start of therapy, we looked at the rate at which the virus disappeared,” Swanstrom said. “We know that HIV in the blood disappears quickly when you go on therapy, and that’s because the virus is growing in [CD4] cells, which have a very short half-life,” referring to the period of time it takes for a substance undergoing decay to decrease by half. “Infected [CD4] cells decay by half every one to two days.”

But for half of the patients in the new study, HIV growing in the cerebrospinal fluid decayed very slowly, several weeks to one month. “This is evidence the virus is actually being produced by a cell with a longer half-life, and not a [CD4] cell,” Swanstrom said.
The researchers also found that the slow-decaying HIV had a particular attraction, or “tropism,” to macrophages and were able to infect them.

“Those viruses are known to exist in autopsy brain studies. It has been known for 10 years that a subset of HIV-infected patients have slow decay of the virus in the CSF, and it’s also been known for a long time that you can find macrophage-tropic virus in the brain,” Swanstrom said. “But no one has ever brought the two together in a way that makes sense and could give you a tool to evaluate what’s going on the brain by looking at cerebrospinal fluid.”

The study also found HIV-infected macrophages present in a CSF sample two years before the patient was diagnosed with dementia. Swanstrom said this tells us there’s information in the CSF that potentially could predict disease progression. “Is it bad to have these viruses around even if you don’t get a diagnosis of dementia? And are they potentially causing cognitive damage that can be reversed with HAART?”

To explore these and other questions, Swanstrom’s University of North Carolina group will continue collaborating with researchers and the University of California at San Francisco to expand the research in HIV patients who don’t have dementia and are starting therapy. A new study will look for biomarkers in the CSF in the form of HIV variants or other immune protein information that may predict improvement, stability or decrease in cognitive capacity during therapy.

People living with HIV sometimes delay going on antiretroviral therapy, Swanstrom said. “Our research will help further understand what’s going on in the central nervous system of patients who are still alive and in tissue that’s accessible in the clinical setting, i.e. CSF. If these individuals knew there was an AIDS virus replicating independently in their CNS, it might affect their decision when to start treatment with [antiretrovirals].”

also see

Distinct AIDS viruses found in cerebrospinal fluid of people with HIV dementia

Discordant HIV Levels in the Brain and Blood Are More Common Than Expected says US study

Source

Up to 10 percent of people on antiretroviral (ARV) therapy have active HIV replication in the brain and spinal fluid despite having undetectable HIV levels in the blood, according to a study published online November 4 in The Journal of Infectious Diseases. This could explain why low-level inflammation and cognitive decline persist in people being successfully treated with HIV drugs. It may also have implications for treatment recommendations and the ongoing study of different treatment strategies.
A number of studies in recent years have documented two key findings about HIV in the brains of people taking ARVs. First, that HIV reproduction in the brain and central spinal fluid (CSF) is sometimes different from what occurs in the blood; and second, that immune inflammation and cognitive decline are frequently detected in people who otherwise have very good control of their HIV on ARV therapy.

Another key factor that some researchers believe can significantly affect HIV’s activity in the brain and CSF is the ability of individual drugs to cross the blood-brain barrier. Some ARVs cross easily, while others have poor penetration into these compartments.

In an effort to explore the interaction of these three factors—differences in viral replication in blood and brain, signs of immune inflammation, and the brain penetration potential of a person’s regimen—Arvid Edén, MD, from the Sahlgrenska Academy at the University of Gothenburg, in Sweden, and his colleagues examined blood and CSF samples from 69 HIV-positive people taking ARV therapy.

The blood and brain samples were taken between 2002 and 2010. To be included in the study, in which CSF levels were obtained by a lumbar puncture, a person needed to have been on ARVs for at least six months and to have had undetectable HIV levels in the blood for at least three months.

All of the people were taking either Sustiva (efavirenz), Norvir (ritonavir)-boosted Reyataz (atazanavir) or Kaletra (ritonavir plus lopinavir). These drugs were combined with either Viread (tenofovir), Ziagen (abacavir) or Retrovir (zidovudine), plus either Emtriva (emtricitabine) or Epivir (lamivudine).

Edén and his colleagues found that 10 percent of the participants had detectable HIV levels in CSF, many more than they expected. When the team compared the characteristics of those with measurable virus in CSF with those who did not have measurable virus in CSF, they found that people with measurable CSF levels were more likely to have been on ARVs longer, to have had periodic increases in HIV in the blood (blips), and to have taken a treatment interruption.

Edén’s team also found that people with measurable CSF HIV levels were more likely to have high levels of brain inflammation, as determined by measuring neopterin levels.

The makeup of the ARV regimen was not statistically meaningful in regards to discordant viral load responses in the blood and brain. However, there was a trend toward an increased risk of HIV replication in the brains of those who took either Viread or Ziagen compared with those who took Retrovir.

Interestingly, a new method of calculating the likelihood of good ARV control of HIV in the brain, called the central nervous system penetration effectiveness (CPE) rank, was not a good predictor of neither discordant blood and brain HIV levels nor the likelihood of brain inflammation.

Though the brain penetration of the regimens did not significantly affect the likelihood of having discordant HIV levels in the blood and brain, other studies have found that it does. In an accompanying editorial, David Clifford, MD, from Washington University in St. Louis, said this issue needs critical attention, as the most commonly used ARVs today often have only minimal to moderate brain penetration. “If these findings are replicated by others, suggesting 10 percent failure rate of current therapy in the critical CNS compartment, this would be a serious shortcoming for present therapy,” he warned.

“This topic also touches on the interaction of HIV with aging, particularly as it affects the brain and cognitive status,” he continued, noting that cognitive decline from HIV replication and activation could hasten or worsen age-related cognitive problems.

“If control of virus in the brain becomes increasingly difficult to maintain over time,” he concluded, “this implies that increasing neurologic symptoms associated with the virus might augment the cognitive decline of aging, resulting in much more serious late-life neurological issues for HIV-infected patients.”

Ultimately, both doctors, along with Edén’s colleagues, emphasize that this is a very important area of exploration that demands larger studies going forward.

See also:

“Cerebrospinal fluid”