The Weekly NewsDigest is a compilation of HIV prevention research media coverage and relevant science in peer-reviewed journals; material on
other reproductive health issues; and matters of policy and politics relevant to HIV prevention research, development and advocacy.
Its purpose is to raise awareness around the range of opinions and information about HIV prevention research disseminated in the press and
scientific journals and provide a neutral, objective basis for decision-making and evidence-based advocacy.
The Treatment Action Campaign (TAC) says it's ready to litigate against the Gauteng Health Department should it not clear its outstanding debt to suppliers by the end of this week. The TAC adds that the closure of health laboratories in Gauteng and KwaZulu-Natal has severely impacted on people who are HIV-positive and those with TB. Chairperson of the Treatment Action Campaign, TAC, Nonkosi Khumalo says the closure of health laboratory services impacts on patients on Anti-retroviral treatment (ARVs) and those who need to be tested for TB. Blood tests are not being done due to the closures. Khumalo says some health care facilities are unable to initiate new patients on ARV treatment because they can't get their blood tests to laboratories. "People have been calling our offices and we have been to some of the sites that have challenges, like Kaalfontein clinic in Tembisa, Eastbank clinic in Alexandra and ART clinic in Edenvale. These are clinics that started saying to us: 'We are just not coping because we can't do laboratory tests, we can't initiate people on treatment unless we know what their CD4 counts are, we can't screen for TB because we won't get the results'," Khumalo says.
The National Health Laboratory Service, NHLS, is owed about R2 billion. The Gauteng and KwaZulu-Natal Health Departments owe R1.7billion collectively. About 30 of its sites have already shut down. The Health Department has so far committed to clearing all outstanding debt by June this year. Khumalo says the crisis needs to be sorted out now... "TAC is ready to litigate on an urgent basis and get a proper plan. An answer saying by June is not good enough. Something has to happen and it has to happen now. We are definitely litigating. This has been going on forever. We didn't just find out about it", says Khumalo. There are currently more than 200 NHLS labs across the country. CEO Dr Sagie Pillay says the body has had to take drastic measures to centralise the facilities because of these closures.
The female condom, also known as the Femidom, provides women with a condom of their own to use for protection against unplanned pregnancies and sexually transmitted diseases, such as HIV and AIDS. However, negative perceptions from the product's intended users and a perceived low demand for female condoms have considerably slowed its distribution and accessibility...
Tian Johnson, a Strategist for the African Alliance for HIV Prevention, says there are a lot of misconceptions around Femidoms. "There is the incorrect perception that there is no demand for the product. And the argument has always been that: How do you demonstrate demand in the absence of product? We still have some areas in this country where women have never seen female condoms", says Tian Johnson. Johnson also rubbished the arguments that Femidoms are noisy and uncomfortable during sex. "Who has silent sex? Why are we using the noise of a female condom during sex as a basis to deprive women and men of another tool to prevent HIV? On the issue of discomfort, we have a lot of research that proves that the more you use it, the more comfortable it becomes", says Tian Johnson. Currently, 5 million female condoms have been distributed across provinces. But, Johnson says although it's difficult to gauge the actual demand for female condoms, this number is not nearly enough. "We have 5 million that have been distributed. But if no more are procured, we foresee a shortage where there will be no stock in provinces", says Tian Johnson.
A Roman Catholic archbishop has asked the Philippines Department of Health not to hand out condoms to couples on Valentine's Day, as it did last year. "The Church is against the distribution of condoms... because we know how the use of contraceptives affects the morality of our people and our society in general," Jaro Archbishop Angel Lagdameo said Friday. The key to a society without HIV/AIDS, he said, is "abstinence, fidelity to one's spouse, and obedience to God's will."
If caught, any Swazi engaged in a same-sex relationship will be arrested and jailed. But public health officials are using Valentine's Day to urge gays to trust promises of confidentiality and test for HIV. "February is known as the month of love, when couples express their love for each other through gifts, especially on Valentine's Day. The purpose of our new campaign, called 'The Love Test', is to encourage couples to undergo HIV testing," said Simon Zwane, Deputy Director of Health. He acknowledged that in Swazi society gay sex is taboo but said the health ministry was actively extending its reach to include gay couples in HIV counselling and testing. "Couples need to be consistently aware of their HIV status. This will result in them making joint decisions on risk reduction in their relationships," said Zwane. Swaziland's HIV prevalence has remained the world's highest for years, with about a quarter of all adults living with HIV. Several NGOs, including the Alliance of Mayors' Initiative on Coordinated Action against AIDS at the Local Level (AMICAALL) and the family planning company, PSI International, are partners in the nationwide campaign, the first health initiative in the small impoverished country to acknowledge the existence of gays and welcome them to make use of HIV testing and counselling services. "Just admitting that there are gays in Swaziland is a big step for a government ministry," said Alicia Dlamini, a HIV testing counsellor in Manzini, the country's industrial hub... Dlamini's fellow HIV counsellor, Thamie Shongwe, feels the health ministry's Valentine's campaign to test couples will fail to attract same-sex couples. Lucky Gama (not his actual name), 24, a gay auto mechanic, agreed. "A lot of gays are afraid that if they go to get tested they will be found out and disgraced. Maybe the police will be called to arrest you, because this is Swaziland." ...
Uganda will starting next month produce a new low cost and more effective life saving HIV/AIDS drug. 104.9 Ssuubi FM has learnt that the new anti-retroviral (ARV) drug, Tenofovir, will be manufactured by local company Quality Chemicals Pharmaceutical Company... A monthly dose of the drug will cost 20 U.S. dollars compared to 600 dollars for the same drug in Europe, the paper reported... "One pill a day is recommended as opposed to two pills used in the first line of treatment," said Samuel Opio, a pharmacist at Quality Chemicals Pharmaceutical Company... Government health centers are expected to start receiving the new drug next year, in a move that will partly improve compliance to ARVs.
There's little to cheer biomedical researchers in the president's budget proposal released today: the proposal would hold the National Institutes of Health's (NIH's) budget at the current level of $30.86 billion. While the budgets of most of NIH's 27 institutes are remaining flat, NIH would move some money around through "prioritization," said NIH Principal Deputy Director Lawrence Tabak after a press briefing today. The agency wants to add $64 million, an 11% increase, to the National Center for Advancing Translational Sciences (NCATS). The increase would include $40 million more for the Cures Acceleration Network (now funded at $10 million). To free up these funds, NIH wants to cut $51 million from the IDeA program, which are grants for states that get relatively little NIH funding and that are administered by the National Institute of General Medical Sciences. Last year Congress gave NIH a large increase over what it had requested, so it was a place to trim, Tabak said...
In order to squeeze more grants out of the flat budget--the target is an 8% increase in new grants, to 672, for a total of 9415--NIH will put in place new grant management policies. Continuing grants will be cut 1% below the 2012 level, competing grants wouldn't get inflationary increases in future years, and NIH will add a new layer of review for proposals from investigators who already have at least $1.5 million in funding. Still, the success rate is projected to bump up only slightly from this year's all-time low of 18% to 19%, NIH says. And although new grants will rise, the overall number of funded grants will actually drop by 56 to 35,888.
Tabak pointed to the positive: "I think that this budget enables us to support an increase in the number of new and competing grants--it's up 8%. This budget allows us to continue the implementation of NCATs which we feel is very important. And this budget allows us to continue our priorities in basic sciences, innovative science, and of course support for new investigators." But advocates of biomedical research were disappointed. "Overall, we're aware of the overall budget situation, but we're still very concerned about the proposed freeze," says David Moore, senior director of government relations for the Association of American Medical Colleges. It would be the 10th year in a row that NIH's budget has not kept pace with biomedical research inflation, he says. As a result, in inflation-adjusted dollars, "we'd be 20% below where we were a decade ago," Moore says.
The Centers for Disease Control and Prevention (CDC) would see a minuscule increase in total funding in the 2013 budget--$39 million--bringing its total to $11.2 billion. However, more than half of that total is not from discretionary funds but comes from other sources, including almost $4.3 billion for a mandatory program to vaccinate children. CDC's discretionary budget would drop from $5.7 billion, the level of the past 2 years, to $5 billion in 2013. The agency is getting some extra wiggle room thanks to $903 million it would get from the "Prevention Fund," money that comes through President Barack Obama's health care legislation and that funds disease prevention at different levels of government. The Prevention Fund dollars will go, among other things, to promoting rapid detection of disease outbreaks and reducing the spread of various diseases.
During the Super Bowl, a representative of the pharmaceutical company Eli Lilly posted on the company's corporate blog that the average cost of bringing a new drug to market is $1.3 billion, a price that would buy 371 Super Bowl ads, 16 million official NFL footballs, two pro football stadiums, pay of almost all NFL football players, and every seat in every NFL stadium for six weeks in a row. This is, of course, ludicrous. The average drug developed by a major pharmaceutical company costs at least $4 billion, and it can be as much as $11 billion. The drug industry has been tossing around the $1 billion number for years... But as Bernard Munos of the InnoThink Center for Research in Biomedical Innovation has noted, just adjusting that estimate for current failure rates results in an estimate of $4 billion in research dollars spent for every drug that is approved... Wanting to make this even more rigorous, Forbes... took Munos' count of drug approvals for the major pharmas and combined it with their research and development spending as reported in annual earnings filings going back fifteen years... The range of money spent is stunning... At $12 billion per drug, inventing medicines is a pretty unsustainable business. At $3.7 billion, you might just be able to make money... There are lots of expenses here. A single clinical trial can cost $100 million at the high end, and the combined cost of manufacturing and clinical testing for some drugs has added up to $1 billion. But the main expense is failure...
Rising HIV prevalence rates around the world have changed how we date and how we love, at least in theory. The sexual history discussion comes up earlier in dating, and HIV testing as a couple is just a step below becoming "official". Then comes figuring out how to navigate love and also HIV. For Pholokgolo Ramothwala, media owner and a father of two whose partner is HIV-negative, being an HIV activist made disclosing his positive HIV status easier, but the decision was still accompanied by fear of rejection... In May 2011, the HPTN-052 trial, conducted among couples in which only one partner was HIV-positive - discordant couples - showed that that treating an HIV-infected individual can reduce the risk of sexual transmission of HIV to an uninfected partner. It's not all stress, says JP Mokgethi-Heath, an Anglican priest who, like his husband, Paul - also a priest - is living with HIV. For JP, HIV has proven to be a blessing in disguise...
Ramothwala and his partner, now years into the relationship and with two children, have figured out safer sex. He and his partner have had to talk it through - from sexual positions in which they can both be sure the condom is still on, to what kind of condoms to use and how to have children safely. For their first child they used sperm washing - a procedure that separates an HIV-positive man's sperm from the semen, which is thought to pose most of the HIV infection risk to women... To conceive their youngest daughter, the couple used post-exposure prophylaxis (PEP) - ARVs that reduce the risk of HIV infection if taken within 72 hours of possible exposure. The couple timed unprotected sex to coincide with ovulation and ensured that she took PEP within the prescribed window period...
Hundreds of people marched in New Delhi on Friday to protest an ambitious free-trade agreement being negotiated between India and the European Union that patient groups and health activists say could severely curtail India's production and export of affordable drugs for millions living with HIV in developing countries. About 80 percent of the HIV medicines distributed in poorer African, Latin American and Central Asian nations come from India. In recent years, with the U.S. government, U.N. agencies and organizations such as Doctors Without Borders and the Bill and Melinda Gates Foundation all using the relatively inexpensive Indian-made generic cocktails of antiretroviral drugs in their aid programs, India has earned the nickname "pharmacy of the developing world."... The proposed free-trade pact between India and the European Union would be the world's largest, covering about 1.7 billion people. No such pact exists between India and the United States, but the two nations have consulted on bringing about a bilateral investment treaty, which activists say is often the first step toward a free-trade agreement. David Lipman, the E.U. ambassador to Thailand, said in a statement Friday that "nothing in the proposed agreement would limit India's freedom to produce and export medicines." But activists who have accessed leaked drafts say it includes measures to enforce intellectual property rights--including stricter enforcement of port controls and expansion of drug manufacturers' ability to challenge Indian government decisions in court--that could do just that... Indian Prime Minister Manmohan Singh said Friday that he hoped negotiators could quickly iron out their differences on a stringent intellectual property regime, as well as on issues such as barriers to automobiles and banking... The HIV and hepatitis C patients who joined activists in the streets of the capital carried a giant capsule-shaped balloon and urged India to reject the treaty proposals. India has about 2.5 million HIV-infected people, according to the National AIDS Control Organization...
Women who rely on injectable contraception are being strongly advised by the World Health Organisation (WHO) to also use condoms to protect them against the increased risk of HIV infection. A study in the Lancet last October found that women living in AIDS-hit countries using progestogen-only injections, such as Depo-Provera, were twice as likely to become HIV positive as other sexually active women. The findings caused huge consternation, particularly among family planning experts. In sub-Saharan Africa, the centre of the AIDS epidemic, the contraceptive most women choose is a long-lasting injection, which they can keep secret from their partner. The WHO convened an expert group to examine the evidence. It concluded that hormonal contraception--whether the pill or injection--was safe for women at risk of HIV to use if they wanted to prevent pregnancy. But the guidance says: "It is critically important that women at risk of HIV infection use condoms and, where appropriate, other measures to prevent and reduce their risk of HIV infection and sexually transmitted infections." Current evidence is not strong enough to prove or disprove an increased risk of HIV from hormonal contraception, according to the experts. They agreed that the use of hormonal contraception should remain unrestricted if a strong clarification was added to the medical advice "which reflected the difficulties the group had with the data, the need for an enhanced message about condom use and other HIV prevention measures and the need for couples to have access to as wide a range of contraceptive methods as possible".
About half of the 34 million people living with HIV are women. In sub-Saharan Africa, nearly 60% of all new infections occur in women. There is an urgent need for women to have better means of protecting themselves against HIV, particularly if their partner refuses to wear a condom. "Women need safe contraceptive and HIV prevention options that they can own and manage," said Michel Sidibe, executive director of UNAIDS. "New investments into research for female controlled HIV prevention options and safe contraceptive methods are essential." About 25% of the 128 million married or cohabiting women in sub-Saharan Africa aged 15 to 49 want but cannot obtain contraception. UnAIDS said there was an urgent need for dual solutions to prevent HIV as well as conception.
The budget proposal unveiled yesterday by President Barack Obama is getting negative reviews from some public health advocates. In particular, they say the Global Health Initiative, which targets HIV/AIDS, tuberculosis, and neglected diseases, is slated for roughly a $300 million cut to about $8.5 billion. The cuts are "deeply disappointing and a far cry from what [Obama] has promised," Sophie Delaunay, head of Doctors Without Borders said in a statement. While the 2013 budget calls for increasing spending by $350 million for the Global Fund to Fight AIDS, TB and Malaria, an analysis by Health Global Access Project (GAP), a nonprofit organization of HIV/AIDS advocates and human rights activists, suggests this is a "bait and switch." That's because the proposed budget also chops more than $500 million from the President's Emergency Plan for AIDS Relief (PEPFAR). "Robbing Peter to pay Paul in the global AIDS fight is likely to leave both Peter and Paul dead without access to lifesaving services--services that would have been there if the president were not proposing to cut global AIDS programs," said Matthew Kavanagh, Health GAP's director of U.S. advocacy. According to Kaiser Family Foundation's Policy Tracker, the budget cuts $546.4 million from HIV/AIDS and $25 million from tuberculosis treatment, but adds $350 million to the Global Fund. The shifts bring the overall drop in the Global Health Initiative's budget to $310 million.
A plan to use an approved HIV-fighting drug from Gilead Sciences Inc. as prevention to the AIDS virus will get priority review by the Food and Drug Administration, the agency said Monday. The move means that the use of Truvada as a way to reduce HIV risk could be approved by June 15, rather than face a standard 10-month agency review. If approved, Truvada would be the first drug for uninfected people to reduce the risk of acquiring HIV. But Foster City-based Gilead faces a rough road on its way to winning approval of Truvada as a preventative treatment. At least one AIDS patient advocacy group has opposed the plan. The Los Angeles-based AIDS Healthcare Foundation has argued that a study of 2,499 gay men showed that Truvada was effective as a preventative 44 percent of the time -- not enough to warrant approval by the FDA, it claims -- and that men might believe taking the drug is a fail-safe measure and will stop using condoms. The group has set up a web page, called nomagicpills.org, created mailers and taken out ad space in newspapers to spread its message. What's more, the FDA news closely follows a finding by researchers at the University of California, San Francisco, and the San Francisco Veterans Administration Medical Center that found that one of Truvada's ingredients, tenofovir, is associated with a significant risk of kidney damage and chronic kidney disease that increases over time. The study of 10,000 patients used VA electronic health records to find that for each year of exposure to tenofovir, the risk of protein in urine rose 34 percent and the risk of developing chronic kidney disease increased 33 percent. Protein in urine is a marker of kidney damage. The study's principal investigator was Dr. Michael Shlipak, chief of general internal medicine at the VA Medical Center and a professor of medicine and epidemiology and biostatistics at UCSF. Truvada faces a May meeting in front of the FDA's antiviral drugs advisory committee, Gilead said in a press release. That panel will give a non-binding recommendation to the agency. A once-a-day pill that combines two AIDS-fighting drugs, Truvada originally was approved by the FDA in 2004 for patients who already have HIV. The drug, which costs $12,000 a year, registered sales of $1.4 billion in 2011. In filing its application with the FDA in December, Gilead said the 44 percent effectiveness of the drug was compared to those in the study who received a placebo. That rate rose to 73 percent for men who took the drug consistently. The study included researchers at the Gladstone Institutes in San Francisco. Some 50,000 people each year are newly infected with HIV in the United States, with about 61 percent of new infections occurring among men who have sex with men.
Talks are underway between the Swiss drug maker Lonza and the government of South Africa to produce HIV medicines in that nation, where 5.6 million people are infected. "This joint venture, named Ketlaphela ["I will survive" in the Sotho language], will establish the first pharmaceutical plant to manufacture active pharmaceutical ingredients for antiretroviral medicines in South Africa," said Science Minister Naledi Pandor. The plant will help control the price of AIDS drugs in South Africa, which currently imports the main ingredients needed. South Africa will invest 1.1 billion rand (US $143 million) in the project, while Lonza will commit 500 million rand (US $65 million), said Pandor. "Lonza's high Swiss standards, plus their superb track record of establishing and maintaining successful commercial operations in developing countries, make them a valuable and desirable partner," Pandor noted. On its website, Lonza said discussions are "still in an early stage and nothing has been signed." But talking to media in Cape Town, spokesperson Simon Edwards said the company is "looking forward to a long-term involvement in this project ... and to long-term success."
Preliminary city data show an increase in reports for several STDs last year for the sixth straight year. It is unclear whether the continued climb represents an increase in risky behavior or reflects the Department of Public Health (DPH)'s push to get more people tested for STDs. In the past, health officials have suggested a lack of condom use among gay and bisexual men who use serosorting as an HIV prevention measure could account for rising STD rates among men. Gonorrhea cases increased from 1,943 in 2010 to 2,243 last year, an increase of 15.4 percent compared with 2010's 8.6 percent increase. Chlamydia cases grew from 4,603 two years ago to 4,741 last year, a 3 percent gain compared with a 10 percent jump in 2010. Male rectal gonorrhea cases increased from 479 in 2010 to 622 last year - a 38.2 percent increase, compared with a 6.3 percent rise two years ago. Male rectal chlamydia cases increased nearly 5 percent to 959 - well below the 23.4 percent increase in 2010, when the city logged 914 cases. Early syphilis cases rose from 659 in 2010 to 682 in 2011 - a 3.5 percent increase, compared to the 26.4 percent increase in 2010. The city's STD chief, Dr. Susan Philip, did not comment by press time on the 2011 data, which are unofficial and came from the San Francisco Monthly STD Report. Final DPH data will be published later this year in the 2011 Annual Summary.
When they first got married six years ago, Mary and William Simiyu were a typical newly-wed couple - full of love and hope about their future together. Three years into their marriage Mary fell sick and they reluctantly agreed to get tested for HIV. Her result was HIV positive but her husband's wasn't. Suddenly, they had become discordant... Mary said her husband couldn't share anything with her, including their bed, and when he disclosed her positive status to his mother, pressure mounted on him to send her away... After being counselled by community health workers and the church pastor, the couple agreed to stay together, but both said that at times it is difficult... His desire to have more children also adds to the tension... Experts say the desire to have children could be fuelling the spread of HIV in marriages. "Many people still view children as the epitome of a successful and fulfilling marriage," noted Lucy Waweru, a psychology lecturer at the University of Nairobi... An estimated 6 percent of Kenyan couples - about 344,000 - are HIV discordant, while a further 22 percent of couples know the HIV status of their sexual partners.
Although Kenya has national guidelines for promoting prevention among people living with HIV, implementing them has proved to be a challenge. Dr Charles Okal, the AIDS and Sexually Transmitted Diseases (STD) Coordinator for Nyanza Province says providing services for discordant couples is made difficult by the fact that testing is the only way to find them, yet couples rarely turn out for testing together. According to the Kenya AIDS Strategic Plan 2009/13, the higher level of HIV testing amongst women (43 percent) compared to men (25 percent) is mainly due to antenatal testing and the uptake of prevention of mother-to-child transmission programmes... The Kenya AIDS Indicator Survey 2007 notes that 45 percent of all new HIV infections occur in marriages, but the fear of disclosure remains a major problem.
Biotechs butted heads with their far-larger pharmaceutical allies over a key lobbying issue, and lost. As Bloomberg reports, biotechnology companies threw their weight behind a plan drafted by North Carolina Democratic Sen. Kay Hagan to launch a more rapid FDA approval program, using fewer human trials, for orphan drugs or treatments that address fatal diseases. Pharmaceutical companies beat back the measure, however, apparently not wanting to dilute existing safety measures.
In a word: awkward. Both industry sectors lobby as part of the Biotechnology Industry Organization, a group that theoretically represents both sides' interests equally as drug development increasingly overlaps between each side. BIO board members representing the far smaller biotechs supported the proposal, but their pharmaceutical industry counterparts nixed the idea... Biotechs want the plan because they'd gain a more rapid approval timeline by redefining what efficacy means, using things like biomarkers that measure a drug's potential effectiveness, early trial results, or interim data to support regulatory approval. The idea arguably reflected a more innovative approach typical for biotechs, but they are also still relatively small and not generating significant revenue, so they'd welcome anything that could help better manage the financially punishing cost of traditional, extensive clinical trials. On the other hand, larger pharmaceutical companies want to preserve the existing system, citing safety concerns, but the status quo also helps preserve an important financial stake... BIO, perhaps not surprisingly, is pushing a compromise plan that would add other orphan drug or fatal disease-treatments to an existing program that accelerates approval for both cancer and HIV drugs... Hagan will submit the new proposal to Congress later this year ... and it may be folded into larger legislation that renews the drug industry fee system that funds FDA regulatory reviews. The compromise throws biotechs another bone: the use of surrogate endpoints, which show how a drug affects biological activity. But regulators would still require companies to prove clinical outcomes at some point.
-In 2010 for the first time there was a plateau in the growth of the AIDS epidemic, but the current global financial crisis and drop in AIDS funding are threatening the sustainability of this achievement.
-Growing evidence suggests that HAART is not just life-saving for those with HIV, but also a highly effective means of preventing HIV transmission. Despite this evidence, there is lingering ambivalence about the expansion of HAART coverage.
-In this Essay we argue that the cost-effectiveness of HAART roll out has been significantly underestimated, as economic analyses have thus far not considered the secondary benefits of HAART, chief among them the impact of HAART on HIV transmission.
-We argue that the strategic value of expanded HIV testing and expansion of HAART coverage has dramatically increased. This has opened the door for the possibility of wide-scale implementation of "Seek, Test, Treat and Retain" programs as a means to control HIV- and AIDS-related morbidity, mortality, and transmission at once.
One of the frustrations for scientists working on HIV/AIDS treatments has been the human immunodeficiency virus' ability to evade the body's immune system. Now an Indiana University researcher has discovered a compound that could help put the immune system back in the hunt... In laboratories at the Indiana University School of Medicine, Andy Qigui Yu, M.D., Ph.D., assistant professor of microbiology and immunology, is testing a promising compound that may counteract HIV's ability to hijack the immune system's protection mechanism... In November, the Bill & Melinda Gates Foundation announced it had awarded nine new Grand Challenges Explorations Phase II grants, one of them to Dr. Yu. The Phase II grants were awarded to researchers who had received initial $100,000 awards and had shown promising results. The new grant will support not only Dr. Yu's research into compounds that may block the ability of HIV to hide behind the CD59 "cloak," but also his work to identify the mechanism the virus uses to incorporate CD59...
Scientists from the Antwerp Institute of Tropical Medicine, Antwerp University Hospital and Antwerp University have tested a new 'therapeutic vaccine' against HIV on volunteers. The participants were so to say vaccinated with their own cells. The researchers filtered certain white blood cells out of the volunteer's blood, 'loaded' them outside the body and then gave them back. The immune system of the testees was better than before in attacking and suppressing the virus, the scientists reported in the journal AIDS. But they still cannot cure the disease... The volunteers received four times, with four-week intervals, a small quantity of their own reworked dendritic cells. And indeed, after each vaccination the CD8 battle cells in their bodies recognised the virus better and better, while the vaccination had virtually no side effects. The most important result was that the vaccine-activated battle cells became better and better in suppressing the virus, in test tubes for the moment. But HIV remains a disguise artist; it still succeeds in changing its proteins sufficiently fast and often to let at least a few viruses escape the attack. So it remains impossible to cure AIDS, but the results are encouraging: the vaccine, made of the participant's own dendritic cells, is safe and has some therapeutic effect, be it a limited one.
Van Gulck E, Vlieghe E, Vekemans M, Van Tendeloo VFI, et al. mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients. AIDS, 2012; 26 (4)
Phase III clinical studies for multi-drug resistant HIV need to evolve from traditional superiority or non-inferiority designs to a new approach in which clinical improvements are demonstrated through short, step-wise efficacy and safety trials, argues a US-based stakeholder group. The proposals come from the Washington-based Forum for Collaborative HIV Research, which represents government, industry, researchers, patient advocates, healthcare providers and private foundations... The proposed new pathway for Phase III trials features in the 1 February 2012 electronic issue of the journal AIDS. According to the Forum, what is now a "robust" drug development pipeline for HIV risks being undermined by the challenge of showing efficacy and safety in clinical trials of promising new antiretrovirals in either 'treatment-experienced' or 'treatment-naive' patients. In these circumstances, the Forum says, superiority or non-inferiority trials are "no longer useful" as a means of demonstrating clinical improvements.
The new pathway outlined in the AIDS paper focuses on HIV trials in multi-drug resistant patients, where rates of accrual into HIV clinical trials have declined "precipitously", the Forum notes... For these patients, short, cumulative superiority trials would allow sponsors to demonstrate efficacy without the risk of patients developing resistance to the new drug or additional resistance to old drugs, it argues. The pathway described in the AIDS paper calls for a multi-phase study design... These options are not so applicable to studies in treatment-naive patients, "where results of both superiority and non-inferiority trials are difficult to interpret", the Forum points out... As the paper notes, there are now 26 unique antiretroviral drugs (plus alternative formulations and fixed-dose combinations) in six different therapeutic classes available to treat HIV. Together they have achieved viral suppression rates of between 70% and 90%. However, the authors also highlight growing problems with drug-resistant strains of HIV and the ongoing need for new treatment options...
Operational research in low-income countries has a key role in filling the gap between what we know from research and what we do with that knowledge--the so-called know--do gap, or implementation gap. Planned research that does not tangibly affect policies and practices is ineffective and wasteful, especially in settings where resources are scarce and disease burden is high. Clear parameters are urgently needed to measure and judge the success of operational research. We define operational research and its relation with policy and practice, identify why operational research might fail to affect policy and practice, and offer possible solutions to address these shortcomings. We also propose measures of success for operational research. Adoption and use of these measures could help to ensure that operational research better changes policy and practice and improves health-care delivery and disease programmes.
Nephrotoxicity is observed in 1.6 % of patients treated with tenofovir disoproxil fumarate.
We report a 37 year old late presenting HIV positive male patient... Since its introduction in 2001 the nucleotide analogue tenofovir is one of the most frequently used substances in HIV treatment. Our case showed that tenofovir can induce a renal damage in patients with renal agenesis despite initially non-impaired renal function. Due to our experience we suggest that tenofovir should not be used in these patients regardless of a normal renal function.
US investigators have identified a possible association between the use of antiretroviral therapy during pregnancy and an increased risk of having a baby with a cleft lip or palate. The study, published in the January edition of Cleft Palate-Craniofacial Journal, found preliminary evidence seven anti-HIV drugs may increase the risk of this birth abnormality. However, the investigators emphasise that their their findings are far from definitive. "Our report, although the first to report this signal, is merely a starting point; further investigations on these drugs' side effects are required to follow." Appropriate use of antiretroviral therapy during pregnancy can reduce the risk of mother-to-child transmission of HIV to below 1%. However, it is important to understand the possible risks associated with the use of anti-HIV drugs during pregnancy. The protocols of clinical trials routinely exclude pregnant and nursing mothers. Therefore, investigators scrutinised the Food and Drug Administration's (FDA's) Adverse Events Reporting System (AERS) to see if therapy with antiretrovirals during pregnancy increased the risk of cleft lip or palate. Data from April 2004 to October 2009 were examined by the researchers. They calculated crude reporting odds ratios (ROR) to detect potential associations between specific antiretroviral drugs and the birth abnormality. "Readers should be cognizant of the fact that the RORs calculated in this study should not be interpreted as definitive measure of the associations' strength without further validation in well-controlled and prospective or retrospective epidemiological studies," write the authors.
Transmission rate modeling estimated secondary infections from those aware and unaware of their HIV infection. An estimated 49% of transmissions were from the 20% of persons living with HIV unaware of their infection. About 8 transmissions would be averted per 100 persons aware of their infection; with more infections averted the higher the percentage of persons with viral suppression and linked to care. Improving all stages of HIV care would substantially reduce transmission rates.
Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends.
In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34,189 HIV-infected (55% MSM, 19% other men, 26% women) and 114,260 HIV-uninfected individuals (90% men).
Among men, the unadjusted anal cancer incidence rates per 100,000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7"-151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5"-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100,000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8"-6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5"-2.2). In comparison with the period 2000"-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3"-.9) in 1996"-1999 and 0.9 (95% CI, .6"-1.2) in 2004"-2007.
Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
While the balance of recent evidence supports the efficacy of antiretroviral (ARV)-based pre-exposure prophylaxis (PrEP) against HIV-1 infection, recent negative trial results are perplexing. Of seven trials with available HIV endpoints, three different products have been tested: tenofovir 1% vaginal gel, oral tenofovir disoproxil fumarate (TDF) tablets, and TDF/emtricitabine (TDF/FTC or Truvada) tablets. Six of these trials were conducted exclusively in sub-Saharan Africa; all found the products to be safe, and four (CAPRISA004; iPrEX; Partners for PrEP; TDF2) demonstrated effectiveness. Furthermore, HPTN 052 recently confirmed that ARV treatment leads to 96% reduction in transmission to HIV-negative partners in HIV-serodiscordant couples. These results, along with human and animal data, provide substantial evidence for the efficacy of ARV-based HIV prevention. Yet assessment of oral Truvada in the FEM-PrEP study and of oral and vaginal tenofovir in the VOICE study was stopped for futility. How do we make sense of these discrepant results? We believe that adherence is a key factor, although it cannot be the only factor. Expanding upon a recent editorial in the Lancet, we discuss the impact of suboptimal product adherence on PrEP efficacy in the context of variable drug concentration at the exposure site, integrity of the vaginal epithelium, and the role of acute infection.
Lack of education and an economic dependence on men are often suggested as important risk factors for HIV infection in women. We assessed the efficacy of a cash transfer programme to reduce the risk of sexually transmitted infections in young women.
In this cluster randomised trial, never-married women aged 13-22 years were recruited from 176 enumeration areas in the Zomba district of Malawi and randomly assigned with computer-generated random numbers by enumeration area (1:1) to receive cash payments (intervention group) or nothing (control group). Intervention enumeration areas were further randomly assigned with computer-generated random numbers to conditional (school attendance required to receive payment) and unconditional (no requirements to receive payment) groups. Participants in both intervention groups were randomly assigned by a lottery to receive monthly payments ranging from US$1 to $5, while their parents were independently assigned with computer-generated random numbers to receive $4-10. Behavioural risk assessments were done at baseline and 12 months; serology was tested at 18 months. Participants were not masked to treatment status but counsellors doing the serologic testing were. The primary outcomes were prevalence of HIV and herpes simplex virus 2 (HSV-2) at 18 months and were assessed by intention-to-treat analyses.
88 enumeration areas were assigned to receive the intervention and 88 as controls. For the 1289 individuals enrolled in school at baseline with complete interview and biomarker data, weighted HIV prevalence at 18 month follow-up was 1.2% (seven of 490 participants) in the combined intervention group versus 3.0% (17 of 799 participants) in the control group (adjusted odds ratio [OR] 0.36, 95% CI 0.14-0.91); weighted HSV-2 prevalence was 0.7% (five of 488 participants) versus 3.0% (27 of 796 participants); adjusted OR 0.24, 0.09-0.65). In the intervention group, we noted no difference between conditional versus unconditional intervention groups for weighted HIV prevalence (3/235 [1%] vs 4/255 [2%]) or weighted HSV-2 prevalence (4/233 [1%] vs 1/255 [<1%]). For individuals who had already dropped out of school at baseline, we detected no significant difference between intervention and control groups for weighted HIV prevalence (23/210 [10%] vs 17/207 [8%]) or weighted HSV-2 prevalence (17/211 [8%] vs 17/208 [8%]).
Cash transfer programmes can reduce HIV and HSV-2 infections in adolescent schoolgirls in low income settings. Structural interventions that do not directly target sexual behaviour change can be important components of HIV prevention strategies.
Between a quarter and a third of young women in sub-Saharan Africa are infected with HIV by the time they reach their early 20s. Structural factors such as poor education, poverty, and gender and power inequalities are important determinants of young women's vulnerability to HIV infection. However, until now, no rigorously assessed intervention targeting this group has significantly reduced HIV infection and no intervention that targets structural factors has directly affected HIV infection. In The Lancet, Sarah Baird and colleagues report the results of a randomised controlled trial done with adolescent girls in rural Malawi, examining the effects of a cash transfer programme on risk of HIV infection. The investigators report that schoolgirls who received monthly cash payments of varying amounts were significantly less likely than girls who did not receive payments to be infected with HIV... and HSV-2..., to have an older male partner, and to have sexual intercourse once per week at follow-up (18 months for biological outcomes and 12 months for behavioural outcomes)...
To plan the next step, it would be helpful to understand the precise mechanism by which the intervention worked... However, the study was not powered to detect heterogeneous effects on biological outcomes between the CCT and the UCT interventions, and the reduced rates of pregnancy in the UCT group and small but significant effect of the CCT on school attendance suggest that some potential differences exist in the causal pathways between the two treatment groups. Although these findings are exciting, they are attenuated by the key weakness of this study: the investigators did not measure HIV incidence, the gold standard in HIV prevention trials. However, the balance of covariates between study groups at baseline and the consistency of effects across outcomes suggest that the intervention was probably effective in reducing HIV and HSV-2 infections. Additionally, few HIV infections were detected (n=24) and the programme had little effect on intermediate outcomes when absolute (rather than relative) measures of effect were used...
Even so, Baird and colleagues' study provides a proof of concept that alteration of the structural environment with cash payments can affect HIV risk in young women... Although the results of this study are intriguing, advocating the halt of HIV prevention campaigns focused on strategies that include sexual and reproductive health information, education, and behaviour change is premature. More experiments and mixed-methods research should be done to better understand the mechanism of action through which CCT and UCT programmes work to reduce risk--this mechanism will probably differ, depending on the target population and context...
An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance.
Subjects were followed for 180 days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions.
Setting: Two managed care organizations in California.
Number of 189,629 women who received greater than or equal to 1 dose of HPV4 between 08/2006 and 03/2008.
Outcome: Potential new-onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with greater than or equal to 12-month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC).
Overall, 1014 potential new-onset cases were electronically identified; 719 were eligible for case review; 31-40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto's disease [IRR = 1.29, 95% confidence interval: 1.08-1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study.
No autoimmune safety signal was found in women vaccinated with HPV4.
Empirical research on informed consent has shown that study participants often do not fully understand consent information. This study assessed participant understanding of three mock consent approaches describing an HIV-prevention clinical trial in Lilongwe, Malawi prior to trial implementation. Pregnant women (n = 297) were systematically selected from antenatal-care waiting lines and sequentially allocated to receive an enhanced standard consent form (group 1), a context-specific consent form (group 2), or context-specific counseling cards (group 3). Understanding of research concepts and study procedures was assessed immediately postintervention and at 1-week follow-up. At postintervention, participants in groups 2 and 3 understood more about research concepts and study procedures compared with group 1. Group 3 participants also understood more about study procedures compared with group 2. At follow-up, participants in groups 2 and 3 continued to understand more about research concepts and study procedures. Context-specific approaches improved understanding of consent information in this study.
Microbicide trials aim to measure the effect of a microbicide in reducing the risk of acquiring human immunodeficiency virus. Such trials present a number of challenging issues from design and conduct through to analysis and reporting. This begins with the initial identification of the target trial population. Prevention trials need to identify those at risk of human immunodeficiency virus infection. This can be more difficult in the general population compared with treatment trials that can target specific patient groups who have a confirmed diagnosis of the disease of interest. Consequently, microbicide trial participants will inevitably be recruited who are never at risk of HIV infection. In this chapter we outline the main features of microbicide trial design, key issues during conduct and analysis, and discuss the challenges specific to these types of clinical trials.
This report presents data on participation in online or offline prevention activities among a sample of New York City men who have sex with men (MSM) recruited online between April-August of 2007 who use the Internet to meet sex partners. The analysis focuses on the 1,124 men who reported sex with a main or casual partner in the past 12 months. Over half (53%) of the MSM reported unprotected anal intercourse (UAI) in the past year. Data from our multivariate analysis indicate that MSM who participate in online or offline prevention activities were less likely to engage in UAI.
Second generation electronic medication adherence monitors provide real-time data on pill bottle opening behavior. Feasibility, validity, and acceptability, however, have not been established. Med-eMonitor is a multi-compartment adherence device with reminder and education capacity that transmits data through a telephone connection. Monthly adherence levels were measured for 52 participants over approximately 3 months using the Med-eMonitor (unadjusted and adjusted for participant confirmed dosing) and unannounced pill counts. HIV RNA was assessed before and after the 3-month period. Acceptability of Med-eMonitor was determined. Over 92% of Med-eMonitor data was transmitted daily. Unannounced pill counts significantly correlated with adjusted Med-eMonitor adherence (r = 0.29, P = 0.04). HIV RNA significantly correlated with unannounced pill counts (r = -0.34, P = 0.02), and trended toward a significant correlation with unadjusted Med-eMonitor adherence (r = -0.26; P = 0.07)... Most, but not all, participants liked using the Med-eMonitor. Med-eMonitor allows for real-time adherence monitoring and potentially intervention, which may be critical for prolonging treatment success.
The role of circumcision in the transmission of human immunodeficiency virus (HIV) among men who have sex with men (MSM) in resource restricted regions is poorly understood. This study explored the association of circumcision with HIV seroprevalence, in conjunction with other risk factors such as marriage and sex position, for a population of MSM in India. Participants (n = 387) were recruited from six drop-in centers in a large city in southern India. The overall HIV prevalence in this sample was high, at 18.6%. Bivariate and multivariable analyses revealed a concentration of risk among receptive only, married, and uncircumcised MSM, with HIV prevalence in this group reaching nearly 50%. The adjusted odds of HIV infection amongst circumcised men was less than one fifth that of uncircumcised men [adjusted odds ratio (AOR) 0.17; 95% CI 0.07-0.46; P < 0.001]. Within the group of receptive only MSM, infection was found to be lower among circumcised individuals (AOR, 0.30, 95% CI 0.12-0.76; P < 0.05) in the context of circumcised MSM engaging in more UAI, having a more recent same sex encounter and less lubricant use when compared to uncircumcised receptive men. To further explain these results, future studies should focus on epidemiologic analyses of risk, augmented by social and sexual network analyses of MSM mixing.
Little is known of the acceptability of male circumcision (MC) to adolescent boys, a key target group for HIV prevention. We conducted a cluster design survey among adolescent boys and their parents/guardians in two villages in Botswana. Of 1300 households visited, 398 boys were eligible; 269 boys and 210 parents/guardians participated. MC was described correctly by 80% of boys, and 76% identified that MC reduces the risk of male HIV acquisition. After a brief informational session, 75% of boys stated that they would definitely want to be circumcised and 96% of parents/guardians would want their boy circumcised. Boys most frequently reported pain (49%) and possible health problems (19%) as concerns undergoing MC; concerns about peer or partner acceptance, sexual function, or cultural appropriateness were uncommon. Adolescent MC is likely to be highly acceptable in Botswana if done safely, for free and with adequate pain control in a hospital setting.
We conducted a cross-sectional study to determine whether the time between two consecutive sexual partnerships (gap) is associated with sexually transmitted infections (STIs) in Russia. A self-administered questionnaire was administered to STI clinic patients in St. Petersburg and participant's STI data at the time of enrollment in the study was collected from medical charts. The length of the gap between partnerships was divided into four categories: overlapping (0 or negative gap), short gaps (1-90 days), mid-length gaps (91-365 days), and long gaps (366 days or more). Among the 659 respondents, 22.6% had overlapping partnerships, and 13.7, 4.2, and 59.5% had short, mid-length and long gaps, respectively. Short gaps (OR 2.34; 95% CI 1.38-3.95), but not overlapping relationships, were independently associated with STIs when contrasted against long term gaps. HIV prevention programs for Russian STI clinic patients should therefore focus also on prolonging the gap between consecutive, monogamous sexual partnerships.
To determine correlates of concurrent sexual partnerships among high-risk low-income urban African American women, survey responses of 337 women who had main sexual partners for over 6 months and reported high-risk behaviors were analyzed; 142 of these women also reported other sexual partnerships within the past 90 days. Unadjusted analyses showed that concurrency was significantly associated with relationship status, sexual debut, forced sex, incarceration of self and partners, depression, drug use, known or suspected partner nonmonogamy, and partner drug use. Age of sexual debut, relationship status, and indicators of problem drug use remained significantly associated with concurrency when controlling for individual factors, and only indicators of problem drug use and known or suspected partner nonmonogamy remained significantly associated with concurrency when also controlling for partner characteristics. Our results suggest the presence of extensive sexual networks within this population and document the need for interventions that address drug abuse and partnership instability. Moreover, the strong association between concurrency and perceptions of partners' nonmonogamy suggest the need for intervention to target men and women in this core group.
This paper explores the roles of acute infection and concurrent partnerships in HIV transmission dynamics among young adults in Zimbabwe using realistic representations of the partnership network and all published estimates of stage-specific infectivity. We use dynamic exponential random graph models to estimate partnership network parameters from an empirical study of sexual behavior and drive a stochastic simulation of HIV transmission through this dynamic network. Our simulated networks match observed frequencies and durations of short- and long-term partnerships, with concurrency patterns specific to gender and partnership type. Our findings suggest that, at current behavior levels, the epidemic cannot be sustained in this population without both concurrency and acute infection; removing either brings transmission below the threshold for persistence. With both present, we estimate 20-25% of transmissions stem from acute-stage infections, 30-50% from chronic-stage, and 30-45% from AIDS-stage. The impact of acute infection is strongly moderated by concurrency. Reducing this impact by reducing concurrency could potentially end the current HIV epidemic in Zimbabwe.
Black men who have sex with men (MSM) are disproportionately affected by HIV infection. Black MSM in San Francisco may have higher rates of unrecognized HIV infections. Increased HIV testing among Black MSM may reduce the numbers of unrecognized infections, inform more men of their status and thus reduce the potential for ongoing transmissions. Social network HIV testing programs have focused on asking HIV-positive and/or high-risk negative men to recruit their social or sexual contacts. We used a network approach to deliver HIV testing to Black MSM in San Francisco and collected risk assessment data. Participants were asked to recruit any of their social contacts who were also Black MSM. Recruitment by risk level and HIV status was heterogeneous. HIV infection among this population is associated with older age, having a high school education or higher and currently being homeless. Fully 23% of HIV positive Black MSM are unaware of their infection. Only a third of unrecognized infections were recruited by a known HIV-positive participant. Linkage to care was a challenge and underscores the need for comprehensive systems and support to link Black MSM to care and treatment.
Social network analysis was used to examine the relationship between HIV/AIDS stigmatization, perceived risk, and centrality in the community network (via participation in community groups). The findings from respondents in Keetmanshoop, Namibia (N = 375) showed an interaction between stigma and risk perceptions\those who perceived higher HIV risk and stronger HIV stigma participated in fewer community groups and participated in groups with members who participated less widely across the network. In contrast, those who perceived higher HIV risk and weaker HIV stigma participated more, and were in community groups that are located on a greater share of the paths between entities in the network. Taboo, secrecy, resistance, knowing a person living with HIV/AIDS, and desire for diagnosis secrecy were also related to centrality. Findings suggest that the interaction of perceived HIV risk and HIV stigma are related to structural-level features of community networks based on participation in community groups.
Today, we're one small but significant step closer to figuring out how to get certain cells to fight back against HIV infection. Specifically, scientists with the NYU Langone Medical Center and colleagues in Rochester, NY, and France have determined how a little protein known as SAMHD1 appears to resist HIV in certain cells. The key? Starvation. This discovery, detailed online in the journal Nature Immunology, is the kind of finding that will matter more years from now, as future researchers try to figure out new drug targets. In theory, another team of scientists could build a vaccine or pill that harnesses SAMHD1 throughout the body to completely beat back HIV, now that they know how the proteins resist the virus. But it may be years before we know whether this is possible in humans.
Their finding links two previously known discoveries. The virus grows by eating a cell's deoxynucleotide triphosphates (dNTPs)--DNA building blocks--to replicate itself. And they already know immune cells called dendritic cells containing SAMHD1 appear to resist HIV infection. They've also been experimenting with HIV vaccines and have recently generated some promising results, at least in monkeys. So the big question was: How does SAMHD1 work? It turns out it protects the immune cell from such viruses as HIV by wiping out the food supply--the dNTP--so the HIV starves.
The discovery reveals the challenge and opportunity implicit in treatment development. The belief is HIV has evolved so it tries to infect cells that don't have SAMHD1 but have plenty of dNTPs--CD4 T-cells, according to the researchers. Co-lead investigator Nathaniel Landau of the NYU School of Medicine explains the discovery aided by researchers at the University of Rochester Medical Center and the Cochin Institute in Paris as a bid to decipher HIV in order to anticipate its moves and defeat it. "We want to understand how the enemy fights so that we can outsmart it in the end," he said in a statement announcing the news.