22 JULY 2011, VOLUME 12, ISSUE 29

There appears to be real excitement at the International Aids Society conference in Rome... There is still no vaccine on the horizon - once the biggest hope - but the news from recent studies that taking antiretroviral drugs protects people without HIV from infection and reduces the risk of people with HIV passing it to their partners (here) has changed the landscape. Suddenly we are in a world where Aids is more preventable than ever before - and both prevention and treatment come pill-shaped. So there is no shortage of important people calling for more funds and more action to roll out drugs to the nine million people in developing countries estimated to need them right now. Michel Sidibe, executive director of UNAIDS, said it was an affront to humanity that there were gaps in coverage. "We have to remember that history will judge us not by our scientific breakthroughs, but how we apply them," he said. There are practical difficulties in the way of getting the drugs to all who need them, but beyond the rhetoric and the big picture, there are organisations which are trying to find better ways forward. The Drugs for Neglected Diseases Initiative, for instance, which has been doing excellent work on a select group of conditions - human African trypanosomiasis, leishmaniasis, Chagas disease and malaria - has decided to take on the needs of children with HIV... And also on the drugs issue, Medecins Sans Frontieres have been castigating the big pharma companies for slashing their Aids drug prices for the lowest-income countries, such as most of those in Africa, but refusing to allow the same sort of discount for middle-income countries. Brazil and Thailand may be richer than Uganda or Sierra Leone, say MSF, but they have major HIV epidemics and will not be able to afford the drugs they will need to treat their people for the future...

A campaign to encourage African men to get circumcised to prevent infection by HIV gained a powerful boost Wednesday by three new studies unveiled at the world AIDS forum in Rome. New cases of HIV among men fell by an astonishing 76 percent after a circumcision programme was launched in a South African township, researchers reported. Had no circumcisions been carried out, the tally of new infections among the overall population, men and women combined, would have been 58 percent higher... The new study was conducted between 2007 and 2010 in Orange Farm, a township of 110,000 adults, where more than 20,000 circumcisions had been performed, especially in the 15-24 age group which is most sexually active. Two other studies released in Rome added to the good news about circumcision:

-- Circumcised men say they experience greater sexual pleasure after surgery, a finding that should help overcome unease about the operation. Investigators at the University of Makerere interviewed 316 men, average age 22, who had been circumcised between February and September 2009. A year after the operation, 220 of the volunteers said they were sexually active, of whom a quarter said they used condoms. A total of 87.7 percent said they found it easier to reach an orgasm after being circumcised, and 92.3 percent said they experienced more sexual pleasure.

-- Newly-circumcised men are just as likely as uncircumcised men to practice safe sex, according to interviews conducted among 2,207 men in western Kenya, six months after they had had the operation. This helps ease concerns that circumcised men are tempted to abandon condom use in the belief they are completely shielded from HIV... On the downside, male circumcision does not reduce the risk for women who have intercourse with an HIV-infected man, and the protective benefit does not seem to apply to homosexual intercourse. There is an indirect advantage, though. The fewer men who are infected with HIV, the smaller the risk of infection for others.

Using microwaves to kill malaria parasites and developing a way to give fetuses immunity to HIV are among the dozen ideas the Bill & Melinda Gates Foundation thinks are worth more research dollars, after giving more than 500 scientists seed money to take an initial look at some far-out concepts. A dozen scientists or teams of researchers will each get an additional $1 million over five years to take their ideas to the next level and see if they have the potential to save lives, the foundation announced Wednesday. The foundation initially chose more than 500 scientific ideas out of nearly 20,000 proposals for its Grand Challenges Explorations grants, worth $100,000 each, saying it would be taking a calculated risk by giving money for whatever wacky idea the world's best minds come up with to combat malaria, HIV and other world health problems...

Collaboration among different kinds of scientists is an attribute of many of the Grand Challenges projects. Mike McCune, professor of medicine at the University of California San Francisco, said working in multidisciplinary teams has helped a number of researchers from his university get a Gates grant. His project, to fight HIV infection while a fetus is in the uterus, takes a number of known scientific principles and combines them in a new way. He is working to utilize what scientists already know about the unique and effective immune system of the human fetus, plus the way vaccines work on newborns and the success so far at decreasing the number of HIV transmissions from mother to child in this country... His goal is to strengthen and prolong a child's natural immunity. For now, McCune is testing his theories on non-human primates, by giving vaccines to mothers who hopefully will pass immunity along to their fetuses. "This is not science fiction. Everything I've told you has a longstanding history to it," McCune said. "The Gates grant allows me and others to take existing dogmas and paradigms and throw them out the window."...

The word 'cure' -- long a taboo in HIV/AIDS circles -- is being bandied about freely here at the 2011 meeting of the International AIDS Society. The word has been used in symposia, satellite meetings, and even a formal "Rome Statement for an HIV Cure" launched by the society and backed by a who's who of scientists, research organizations, and activists. It is "the right time to accelerate research on an HIV cure," said Francoise Barre-Sinoussi, PhD, of France's Pasteur Institute in Paris. Barre-Sinoussi has rock-star status on the scientific side of the HIV/AIDS community. She is president-elect of the AIDS Society and shared the 2008 Nobel Prize in medicine for identifying the human immunodeficiency virus. She is co-chairing a scientific working group of some 40 people whose goal is to chart a research path to guide future study. The group, which has support from the NIH, the French AIDS research agency, and the Treatment Action Group among others, hopes to have that pathway mapped by the 2012 International AIDS Conference in Washington...

The scientific working group that has signed on includes such well-known U.S. clinician-researchers as John Mellors, MD, of the University of Pittsburgh, Martin Markowitz, MD, of New York's Aaron Diamond AIDS Research Center, and Steven Deeks, MD, of the University of California San Francisco...  In essence, what has been proposed here is a proposal to develop a road map to a scientific strategy. Actual research proposals -- let alone research -- will have to wait and in any case will be dependent on international agreements both that a cure is possible and that there's money to support study that could last for several decades. Aside from the purely scientific questions, researchers will have to take into account the ethics of conducting clinical trials of possible cures among people whose HIV may be controlled by currently available treatment, said Mark Harrington of the New York-based Treatment Action Group, one of the organizations supporting the Rome statement. There will be a "lot of failed trials along the way," he said, and many participants -- even in trials that yield important scientific information -- "will not obtain any benefit."...

Middle-income countries with large numbers of people living with HIV will no longer benefit from preferential pricing when buying antiretroviral drugs from large pharmaceutical companies, according to the annual Medecins Sans Frontieres drug pricing report, Untangling the Web of ARV Price Reductions. "The main bad news in the study is the fact that a number of pharmaceutical companies will no longer be providing preferential pricing to middle-income countries like Brazil, China, India and Thailand," Nathan Ford, medical director at MSF's Campaign for Access to Affordable Medicines, said at the launch of the report at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome. According to the report, pharmaceutical firm ViiV Healthcare -- owned by Pfizer and GlaxoSmithKline -- no longer offers reduced prices to middle-income countries, even when their programmes are fully funded by the Global Fund to fight HIV, Tuberculosis and Malaria. Merck has also ceased to offer discounted prices to all lower middle- and upper middle-income countries, proposing instead to negotiate discounts on a case-by-case basis. Of particular concern is the price of UN World Health Organization-recommended third-line drug, raltegravir -- an integrase inhibitor that blocks retroviral replication -- which costs up to US$5,870 per person per year in Brazil, compared with $675 in sub-Saharan Africa. Janice Lee, pharmacist at MSF's Campaign for Access to Essential Medicine, noted that drug company discount programmes were not a long-term solution, and governments would have to start using trade-related aspects of intellectual property rights (TRIPS) measures to override patents...

There is some good news, though; a once-daily combination pill containing tenofovir -- a WHO-recommended first- and second-line drug -- costs $173 per person per year, compared with $613 five years ago... The reductions in price for less toxic medications such as tenofovir also ease the pressure on over-burdened health systems...

A group of 35 scientists and stakeholders on Monday published "The Rome Statement for an HIV Cure," which asserts, "Now, more than ever, it is time to seriously start looking for an HIV cure." The statement -- released in Rome at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention -- kicks off a new global scientific strategy, "Towards an HIV Cure," which targets the virus' remarkable resiliency ... The statement advocates for the "development of, at least, a functional cure that, without completely eliminating the virus from the body, would permanently suppress its replication and considerably diminish viral reservoirs, possibly leading to the long-term remission of patients. "Not only would such a strategy act as therapy at the individual level but, considering the growing evidence that HIV transmission is dramatically reduced in the absence of detectable viral load, it would most probably contribute to HIV prevention at the population level," the statement says. The new strategy "aims at building a global consensus on the state of HIV reservoirs research and defining scientific priorities that need to be addressed by future research to tackle HIV persistence in patients undergoing antiretroviral therapy."...

China is reporting progress from Henan Province, where thousands of poor farmers were infected with HIV through an unsanitary blood-buying scheme in the 1990s. The Henan Provincial Health Department said 3,173 cases of HIV infection were reported last year, the lowest figure in three years. After a years-long crackdown on the illegal blood trade, 45 percent of infections logged in 2010 resulted from sexual contact, which surpassed blood sales and drug use as the main routes of transmission. Preventing infections among men who have sex with men remains a challenge, as the proportion of cases attributable to MSM sex grew to 4 percent last year from .06 percent in 2004.

A drug developed by GlaxoSmithKline Plc (GSK) and Pfizer Inc. (PFE) controlled HIV faster and more safely than Bristol-Myers Squibb Co. (BMY)'s Sustiva in a study, suggesting the experimental medicine may one day be preferred to Bristol's. Dolutegravir, a product of Glaxo and Pfizer's ViiV Healthcare joint venture, reduced HIV to undetectable levels in 90 percent of patients after 48 weeks, compared with 82 percent of those who got Sustiva, according to results presented at an AIDS meeting in Rome today. Dolutegravir also caused a significantly lower rise in bad cholesterol than Sustiva, at one-twelfth of the dose size. Sustiva is one of three drugs in Gilead Sciences Inc. (GILD)'s Atripla, the world's best-selling AIDS pill, and brought New York-based Bristol $1.4 billion in sales last year... Sustiva is recognized by the U.S. Department of Health and Human Services as a component of preferred combination HIV therapy regimens for patients who are new to treatment, said Cristi Barnett, a Bristol-Myers spokeswoman, in an e-mail...

Clinical trials of a monoclonal antibody produced in transgenic tobacco plants, a potentially low-cost, scalable system, have begun in Europe. In 2004 industrial and academic partners began work on a system for producing proteins in plants. Delays in development of a regulatory pathway for plant-produced proteins meant the project overran but a manufacturing system is now working and a clinical trial underway. "We now have a facility in Europe for producing modern medicines in transgenic plants that is unique in the world, although this has taken many years and much investment to establish", said Rainer Fischer, Pharma-Planta coordinator and Fraunhofer IME director. Transgenic tobacco plants are grown for 45 days before being processed at a biotechnology facility in Aachen, Germany. Leaves are chopped and shredded in 250kg batches and then undergo downstream processing to extract more than five grams of pure antibody. As well as developing a practical production system the team had to make sure it was acceptable to regulators and this, according to Pharma-Planta, was the most difficult phase of the project. Pharma-Planta worked with regulators to overcome the lack of manufacturing guidelines for production in greenhouses. Greenhouse conditions were tweaked and equipment for purifying the active ingredient from the leaves under GMP (good manufacturing practice) was built and tested. Having gone through this process and gained UK Medicines and Healthcare products Regulatory Agency (MHRA) approval for a Phase I trial the team think other plant-produced proteins can be developed. "This is a red letter day for the field. [MHRA approval] is an acknowledgement that monoclonal antibodies can be made in plants to the same quality as those made using existing conventional production systems", said Julian Ma, scientific coordinator for Pharma-Planta. Now Pharma-Planta has shown an anti-HIV microbicide, P2G12, can be manufactured in green plants the hope is other products will follow. Widespread use of plant-based production could, say its supporters, ensure an affordable supply of vaccines and other drugs for the developing world.

The Drugs for Neglected Diseases Initiative (DNDi) has launched a new drug development program to address treatment needs of children with HIV. While developed countries can claim victory in virtually eliminating HIV infection in children due to effective prevention of mother-to-child transmission, there is little market incentive for pharmaceutical companies to develop antiretroviral drugs specifically for children in developing nations. This is why DNDi exists. DNDi was launched in 2003 by research organizations around the world to develop medicine for diseases that impact the world's poor and fall through the cracks of R&D efforts of Big Pharma. The group is developing new treatments for malaria, visceral leishmaniasis, sleeping sickness (human African trypanosomiasis, HAT) and Chagas disease. Now, they're adding pediatric HIV to the list.

"There are millions of children with HIV/AIDS in low- and middle-income countries, but their needs are absent from the HIV research and development agenda, and this is largely because they are poor and voiceless and do not represent a lucrative market," Dr. Bernard Pecoul, DNDi's executive director, said in a statement. "Working with partners, we hope to help fill this terrible gap and offer improved treatment options for children with HIV/AIDS." According to the DNDi release, the World Health Organization recommends immediate antiretroviral therapy (ARV) for all HIV-positive children less than two years old. The problem, though, is that nobody has established safe dosing guidelines for use of ARV in very young children. "Current pediatric ARV formulations are unpalatable for these children, are impractical for caregivers due to multiple liquid preparations that have to be adjusted according to weight, and have undesirable interactions with tuberculosis (TB) drugs," the release said. DNDi's first priority will be to develop an improved first-line protease inhibitor-based regimen for children under three years old.

Antiretroviral prevention methods are not in competition, and policy makers and providers need to start to thinking about how antiretrovirals, pre-exposure prophylaxis and microbicides will be provided as part of a combination prevention package -- and who will benefit most from each method, delegates heard at a satellite meeting on the opening day of the Sixth International AIDS Society Conference in Rome. "You don't want to have the family planning clinic here, the pills clinic here, the injections clinic here, and the microbicides clinic over here," said Dr Stephen Becker of the Bill and Melinda Gates Foundation. Delegates were discussing the rapidly changing landscape of HIV prevention methods that use antiretroviral drugs...

The first tenofovir-containing microbicide could receive regulatory approval by the end of 2013, subject to positive results from a confirmatory trial now taking place in South Africa... A second CAPRISA study (008) is testing the roll-out of tenofovir gel through family planning clinics in KwaZulu-Natal, comparing the monthly testing and follow-up schedule used in the original CAPRISA study with a three-monthly schedule, in order to examine the feasibility and acceptability of providing a microbicide through existing health services that target sexually active women. Although the South African government has already begun investing in the scale-up of production facilities to manufacture the gel, the extent of demand for the microbicide is still unclear. Studies of women's attitudes towards the microbicide will be needed to gauge demand, but a lot of work will also be needed to develop demand -- and to make sure that women understand how they could benefit from using the microbicide. Provider and donor preferences for particular prevention methods could also overshadow the need to think about prevention technologies as a spectrum of methods that will suit different people at different times... Defining the niches of different antiretroviral-based prevention methods will depend on up to date information about local epidemics and behavioural patterns, applied through mathematical modelling to generate options for policy makers, what Willard Cates of Family Health International called "the science of prioritisation, to make scarce resources go further to maximise impact".

...Microbicides may have unique introductory challenges, said David Stanton of USAID, whose agency is strongly committed to supporting microbicide scale-up in sub-Saharan Africa. The tenofovir microbicide will have to clear the hurdles of confirmatory trials, as well as differences in regulatory requirements between countries before it can even be distributed. The South African Medicines Control Agency has not yet given a clear opinion on what data it will require for registration, leaving the danger that further studies could be needed to achieve registration in South Africa. There is also the challenge of ensuring that the gel is manufactured to a consistently high standard, so that it contains the right quantity of tenofovir in each dose, and the challenge of organising an efficient distribution system. WHO and UNAIDS are working with CONRAD and the South African Ministry of Science and Technology, two of the sponsors of the satellite meeting, to plan for introduction of tenofovir gel, and WHO will develop guidance on use of the microbicide so that it can be released as soon as the first regulatory approval is granted.

But perhaps the biggest challenge for introduction will be the accessibility of the microbicide gel for a group at particularly high risk of infection in southern Africa -- young women and girls... While circumcising male adolescents is easy and socially acceptable, social and legal constraints on the sexuality of women will continue to undermine the central promise of microbicides -- a prevention tool to empower women -- unless confronted head-on.

Abstract
Background: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.

Methods: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.

Results: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01).

Conclusions: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy.

Abstract
We report a 46-year-old man who has sex with men (MSM) patient, of Scottish descent, who had no history of arterial hypertension, diabetes, or illicit drug use, was hepatitis C virus (HCV) negative but underwent right nephrectomy for urothelial tumor in 2006. Before starting antiretroviral therapy, he had a CD4 cell count of 316/mm(3) and plasma HIV RNA level was 1,020,537 copies per milliliter. He developed acute renal failure only 2 weeks after introduction of tenofovir-based antiretroviral therapy and then required 3 months of hemodialysis. After the end of hemodialysis, antiviral therapy was resumed with abacavir (300mg x 2/day), lamivudine (300mg every day), and lopinavir/ritonavir (400/100mg twice daily). Renal biopsy revealed severe and diffuse toxic acute tubular necrosis Two years after tenofovir discontinuation, the patient's renal function remained subnormal. Although severe renal toxicity due to tenofovir is rare, patients receiving tenofovir must be monitored closely for renal dysfunction especially during the first weeks of tenofovir therapy.

An in-depth review of consent forms provided to volunteers for HIV/AIDS research in the United States and abroad about study procedures, risks and benefits has found that the forms were extremely long and used wording that may have been complex enough to hinder full understanding, according to bioethicists at The Johns Hopkins University. A systematic analysis of 124 informed-consent documents for U.S. government-sponsored, multinational HIV/AIDS research conducted in 2006 revealed that the forms spanned more than 20 pages, says the study's lead investigator, Nancy Kass, Sc.D., deputy director for public health at the Johns Hopkins Berman Institute of Bioethics.

Their study, described in the August issue of the Journal of General Internal Medicine, and funded by the National Institute of Allergy and Infectious Diseases, also found that commonly misunderstood research concepts -- namely, randomization and placebos -- seemed to be explained with far less attention... Kass also found that the majority of the forms weren't as readable as they should be... Such findings, while still not meeting commonly agreed-upon standards, demonstrate lower readability than consent form studies from decades past. By making informed-consent documents so long and complex, Kass concludes, researchers neglect their ethical duty to describe their research in ways that help participants truly understand. The authors cite data on literacy rates in the United States and abroad -- in light of the rise in research in developing countries, where half or more of the populations are illiterate... Almost half of Americans read at or below the eighth-grade level, the authors state. As long as these template forms, which come from research funders, remain lengthy, the investigators and review boards in the field will assume they must use those forms, Kass says. So, the overall goal of the study is to supply hard facts that policy specialists can use as they consider developing recommendations for shortening and simplifying consent forms, or for, otherwise, helping participants in complex clinical research understand what they are joining.

Journal Reference:
Kass NE, Chaisson L, Taylor HA, Lohse J. Length and Complexity of US and International HIV Consent Forms from Federal HIV Network Trials. Journal of General Internal Medicine, 2011

Two studies of the use of oral pre-exposure prophylaxis (PrEP) in heterosexual people show that oral PrEP will protect women against HIV. The 6th International AIDS Society Conference in Rome heard the additional data from two trials of pre-exposure prophylaxis in heterosexuals yesterday. First results from these trials, the Partners PrEP trial and the TDF2 trial, were announced on Wednesday, 13 July... The new data on PrEP in men and women were keenly anticipated because another study of PrEP in women, FEM-PrEP, had closed recently after finding zero efficacy for Truvada, and it had been theorised that oral PrEP might not work for women because drug concentrations in the genital tract were too low... In the Partners PrEP study, the HIV-negative partner was female in 38% of the 4758 couples. There was no difference in efficacy of either tenofovir or Truvada between men and women. The efficacy of tenofovir was 68% in women and 58% in men versus placebo; the efficacy of Truvada was 62% in women and 83% in men. None of the differences between men and women, or between tenofovir and Truvada, was statistically significant.

Unadjusted figures in the TDF2 study at first suggested there might be some difference in efficacy between men and women. It is important to note that this study was not 'powered' to demonstrate efficacy; this means that -- due to there being fewer infections than expected -- even a statistically significant positive result is based on too few cases for it to be regarded as a truly convincing efficacy result. Nonetheless, the headline finding of 63% efficacy against placebo was statistically significant. In this study, 45% of the 1200 participants were women. The efficacy of Truvada in men was 80% (two HIV infections in men on Truvada versus ten on placebo) and this was statistically significant. The efficacy in women was 49% (seven infections on Truvada versus 14 on placebo), and this lost statistical significance...

Journal Reference:
Baeten J. Antiretroviral Pre-Exposure Prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP Study. Sixth IAS Conference, Rome, abstract MOAX0106, 2011.

Oral Abstract
Background: The Preexposure Prophylaxis Initiative (iPrEX) study found that pre-exposure prophylaxis using antiretroviral medications (PrEP) significantly reduced HIV transmission among men who have sex with men. However, the FemPrEP study among high risk women showed no such protective effect. Therefore, additional safety and efficacy data among heterosexual men and women are needed.

Methods: We randomly assigned HIV-seronegative participants 18-39 years of age to receive either oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) or matching placebo once daily. Participants attended monthly visits for HIV testing and risk reduction counseling, sexually-transmitted infection management, and adverse event monitoring.

Results: Of 2532 volunteers screened, 1219 were randomized; 45.7% female. Participants were followed for 1549 person-years (median 1.1 years; maximum 3.7 years). Adherence by pill count was similar in both arms (TDF-FTC 84.1% vs. placebo 83.7%, p=0.79). Comparable proportions of participants in both arms reported >1 sexual partner in the prior month and percentage of vaginal episodes with condom use (TDF-FTC 14.2% vs. placebo 14.1%, p=0.86; TDF-FTC 81.9% vs. placebo 79.7%, p=0.21, respectively). Nausea/vomiting and dizziness occurred more commonly among TDF-FTC participants compared to placebo (28.8% vs. 11.9%, p< 0.0001; 15.3% vs. 10.5%, p=0.0143, respectively). There was no difference in serious adverse events between groups (TDF-FTC 9.2% vs. placebo 8.5%, p=0.58). Using modified intent-to-treat analysis including the 33 participants who became HIV-infected during study participation (63.6% female), 9 received TDF-FTC and 24 received placebo correlating to an overall protective efficacy of 62.6% (95% confidence intervals, CI, 21.5, 83.4; p=0.0133). Limiting analysis to participants on study medication when infected, the protective efficacy was 77.9% (95% CI 41.2, 93.6; p=0.0053).

Conclusion: Daily TDF-FTC was effective and safe for prevention of HIV infection among heterosexual men and women compared to placebo. Data from two ongoing studies and TDF-FTC drug level testing in TDF2 participants will further define the role of PrEP among heterosexual populations.

A man who is in a relationship with an HIV-positive woman has a three times higher risk of acquiring HIV if his partner also has bacterial vaginosis, Craig Cohen told the Sixth International AIDS Society conference in Rome today. Whereas it has been previously established that bacterial vaginosis increases a woman's risk of acquiring HIV, this is the first time that it has been shown to increase her risk of transmission to sexual partners. Bacterial vaginosis (BV) is a condition which occurs when the normal balance of bacteria in the vagina becomes disrupted...

Studies on men's risk of acquiring HIV when their sexual partners have bacterial vaginosis have not previously been conducted... Craig Cohen presented an analysis of data on couples recruited to the Partners in Prevention study, conducted in seven countries of southern and eastern Africa. There were 2236 HIV-negative men in the cohort who had an HIV-positive female partner. Both partners were followed for up to two years... After controlling for a large number of potentially confounding factors (sociodemographic, behavioural and biological), men whose partners had BV had a three times higher risk of acquiring HIV than other men (hazard ratio 3.06, 95% confidence interval 1.35 -- 6.95)... He advanced two other hypotheses that could explain the increased risk to male partners. Firstly, that normal bacteria may be virucidal against HIV, reducing the proportion of virus that is infectious. Secondly, that bacterial vaginosis could indirectly increase the male partner's susceptibility to HIV. Cohen noted that long-term sexual partners share genital flora, with men acquiring bacteria from their partners. It is possible, he suggested, that bacteria may activate Langerhans cells and CD4+ T-cells, making the man more susceptible to HIV infection. A significant challenge in acting on this research is that current treatment strategies for bacterial vaginosis are inadequate, with low cure rates and the problem often recurring.

Reference:
Cohen CR et al. Association of bacterial vaginosis with female-to-male HIV-1 transmission among HIV-1 discordant couples in Sub-Saharan Africa. Sixth International AIDS Society conference, Rome, abstract MOAC0202, 2011.

A drug that suppresses herpes simplex-2 (HSV-2) also curtails the progression of HIV, a researcher reported here. In a randomized controlled trial in Uganda, acyclovir (Zovirax), taken twice a day, increased the time before co-infected participants needed HIV treatment or suffered an AIDS-defining illness, according to Steven Reynolds, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. In places where access to antiretroviral drugs is limited, the approach may ease the pressure on treatment resources, Reynolds told a session at the 2011 meeting of the International AIDS Society here. He added that more research is needed to confirm the findings, but acyclovir treatment "may be warranted" in people with both HIV and HSV-2. The study enrolled 440 people with both infections and assigned them randomly to get 400 mg of acyclovir twice daily or placebo, Reynolds reported... The goal was to measure the impact of acyclovir over a two-year period on the risk of reaching a level of 250 cells per microliter or fewer, or suffering a World Health Organization stage 4 event, Reynolds said. At either point, therapy would be indicated...

But the study may be missing the point, in the light of recent findings in treatment as HIV prevention, according to Pedro Cahn, MD, of Fundacion Huesped in Buenos Aires and a former president of the IAS. Cahn himself is involved in a study testing a similar drug -- valacyclovir (Valtrex) -- for the same purpose, but he told MedPage Today that such strategies can only have an application as long as it's necessary to delay treatment because resources are scarce. Cahn and others here are arguing that most resources should be put into expanding access to treatment, rather than using them to delay the medical need for therapy...

Reference:
Reynolds SJ, et al. "Impact of HSV-2 suppressive therapy with daily acyclovir on HIV-1 disease progression: a randomized placebo-controlled trial in Rakai, Uganda" IAS 2011; Abstract TUAB0104.

The use of the anti-herpes-simplex-2 treatment valacyclovir (Valtrex) in pregnant, HIV-infected women does not appear to harm their infants when administered along with therapy to prevent mother-to-child transmission of HIV, researchers said here... "The results of this study are what we would have expected to see," said Julio Montaner, MD, of the University of British Columbia, Vancouver. He told MedPage Today that the trial confirms that use of valacyclovir to suppress herpes simplex virus 2 helps the mother without causing harm to the child. The researchers enrolled women who were diagnosed with co-infections in 2008 in Nairobi, Kenya. They received 500 mg of valacyclovir twice daily from 34 weeks' gestation until 12 months postpartum. The study did not enroll women with late-stage HIV infection or women with CD4-positive counts less than 250 cells/microliter. Women were treated with zidovudine 300 mg after 28 weeks or longer gestation during pregnancy and every three hours during labor. Single dose nevirapine was administered during labor and administered to the infant after birth. The women were given questionnaires regarding adverse events and adherence to the regimen 10 times during the course of the study, which extended from enrollment to 12 months postpartum.

Reference:
Drake A, et al. "MOPE174 -- Safety of prolonged maternal valacyclovir administration in infants receiving antiretroviral HIV-1 prophylaxis" IAS 2011; Abstract Book, p. 68.

Abstract
Objective: Clients of female sex workers (FSWs) are an important target group for human immunodeficiency virus/sexually transmitted infection (HIV/STI) prevention. This study aimed to estimate their HIV and other STI prevalence, examine their risk behaviors, and evaluate their role as a bridge population in the spread of HIV/STIs.

Methods: A cross-sectional study was performed among 553 clients recruited in commercial sex sites in the province of Escuintla, Guatemala. They were interviewed and tested for HIV and other STIs.

Results: Half of the clients who were approached refused participation. Median age was 28.9 years; 57.7% had a regular partner, of whom, 10.1% had concurrent noncommercial partnerships. Consistent condom use with FSWs and regular partners was 72.5% and 17.1%, respectively. Approximately 18% formed a bridge, and 40.0% a potential bridge. Among those who provided samples (70.5% provided a blood sample and 89.7%, urine sample), prevalence of HIV, syphilis, gonorrhea, chlamydia, and herpes simplex virus 2 was 1.5%, 1.0%, 0.8%, 5.5%, and 3.4%, respectively. Unprotected sex with FSWs and drug use just before sex were risk factors for having any STI (9.8% of participants). Bridge clients were significantly less educated, more employed, paid lower prices to the FSW just visited, and had a previous STI.

Conclusion: There is a relatively high prevalence of HIV in clients compared to national estimates, and a substantial proportion of them act as a bridge for HIV/STI transmission between FSWs and the general population in Escuintla. Given that this is fuelling the current HIV epidemic, preventive interventions addressing this hard-to-reach group are urgently required.

Abstract
Objective: Sexual behavior changes are widely cited as contributing factors to sexually transmitted disease trends. We explore a rarely examined aspect of behavior trends in an open cohort--the relative impact of individuals' changing reported behavior versus new responses due to a changing respondent base.

Methods: Respondents from an open cohort in Uganda annually answer questions on sexual behavior. We describe the impacts on behavior trends of: respondents' changing reported behavior, migration, mortality, changing eligibility for indicator inclusion, changing survey participation, and misreporting. We report contributions to trends on the following factors: condom use, ever had sex, age at first sex, and number of sexual partners and casual partners.

Results: Main trend contributions varied by indicator. Condom use trends were influenced by individuals' changing responses and by increasing condom use among in-migrants and newly interviewed people. Sexual partners were driven by fewer partners among newly interviewed people, although increase of partners in 1999, 2004, and 2006 stemmed mainly from people changing answers. Thirty-nine percent of responses to age at first sex among 17- to 20-year-olds were inconsistent--different ages in different years. Early trends in the factor "ever had sex" among 15- to 19-year-olds were driven by people changing their answers--including ever to never, an impossible sequence. Comparing behavior in one year to mortality in the next, we found little evidence of higher mortality among higher risk takers.

Discussion: In an open cohort, various factors contribute to sexual behavior trends. When reporting sexual behavior trends, researchers should acknowledge the contributing factors and attempt to separate the role of interindividual versus intraindividual changes.

Abstract
Background: Increased duration of hormonal contraceptive (HC) use may be positively associated with the risk of invasive cervical cancer.

Methods: This is a secondary analysis from the HPV Sentinel Surveillance Study. The authors examined the association between type-specific human papillomavirus (HPV) detection and current HC use among 7718 women attending 26 sexually transmitted disease, family planning and primary care clinics in the USA.

Results: There was an association between HC use and HPV-16 detection (adjusted prevalence rate ratio 1.34 (95% CI 1.05 to 1.71) for oral contraceptive users and 1.41 (1.01 to 2.04) for depot-medroxyprogesterone acetate users); there was no association between HC use and detection of other HPV types or any HPV overall.

Conclusions: Longitudinal studies are needed to better define this type-specific association and its clinical significance.

A landmark study by the BC Centre for Excellence in HIV/AIDS (BC-CfE) and the University of British Columbia (UBC) shows that patients in Africa receiving combination antiretroviral therapy (cART) for HIV can expect to live a near normal lifespan. The study, published in the Annals of Internal Medicine, is the first large-scale analysis of life expectancy outcomes in Africa for HIV patients on cART and shows significant variance between patient subgroups. Females have a significantly higher life expectancy than men, and in all participants, early initiation of treatment was associated with longer life expectancy... The authors believe that the study, conducted in Uganda, reflects the situation in many other settings in Africa, where simplified HIV/AIDS care in rural, semi-rural and urban settings is available. The study analyzed a cohort of 22,315 individuals aged 14 or older, who initiated cART at The AIDS Support Organization (TASO) clinics between 2000 and 2009... The study found a strong association between baseline CD4 cell status and mortality when controlling for factors such as age, year of cART initiation and gender. Those who started cART earlier, at a higher CD4 cell status, lived longer. "These benefits will only be sustained if there is continued support for cART scale up by the international donor community and national governments," said study author Dr. Jean Nachega, Professor of Medicine and director of the Centre for Infectious Diseases at Stellenbosch University, Cape Town, South Africa. "We require sustainable investment and simplified treatment options to deliver long-term care and access more people in Africa with HIV."

The researchers report that they have designed molecular inhibitors that target specific proteins associated with Alzheimer's disease and HIV to prevent them from forming amyloid fibers, the elongated chains of interlocking proteins that play a key role in more than two dozen degenerative and often fatal diseases. "By studying the structures of two key proteins that form amyloids, we were able to identify the small chain of amino acids responsible for amyloid fiber formation and engineer a 'molecular cap' that attaches to the end of the fibers to inhibit their growth," said research leader David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator. The study was published online June 15 in the journal Nature and will be available in an upcoming print edition... Unlike the tau protein, the SEVI (semen-derived enhancer of viral infection) protein is a far more accessible target for a molecular blocker because it builds amyloid fibers in a vaginal environment, a key process in the sexual transmission of HIV, Eisenberg said. "The presence of SEVI makes the rate of HIV infection through sexual transmission up to 100,000 times more likely," he said. "By blocking SEVI, we have a method for inhibiting the sexual transmission of HIV." ...The SEVI blocker proved to be equally effective in preventing fiber growth, bolstering the idea that blockers can be designed for other diseases associated with amyloid fibers as well. "Though many tests remain, it seems we could be on the way to developing a therapeutic," Eisenberg said. "Our hope is that we could make a blocker that could be applied with a vaginal gel or spray that would help to prevent HIV infection."...

Abstract
Background: Improving the outcomes of HIV/AIDS treatment programs in resource-limited settings requires successful linkage of patients testing positive for HIV to pre-antiretroviral therapy (ART) care and retention in pre-ART care until ART initiation. We conducted a systematic review of pre-ART retention in care in Africa.

Methods and Findings: We searched PubMed, ISI Web of Knowledge, conference abstracts, and reference lists for reports on the proportion of adult patients retained between any two points between testing positive for HIV and initiating ART in sub-Saharan African HIV/AIDS care programs. Results were categorized as Stage 1 (from HIV testing to receipt of CD4 count results or clinical staging), Stage 2 (from staging to ART eligibility), or Stage 3 (from ART eligibility to ART initiation). Medians (ranges) were reported for the proportions of patients retained in each stage. We identified 28 eligible studies. The median proportion retained in Stage 1 was 59% (35%-88%); Stage 2, 46% (31%-95%); and Stage 3, 68% (14%-84%). Most studies reported on only one stage; none followed a cohort of patients through all three stages. Enrollment criteria, terminology, end points, follow-up, and outcomes varied widely and were often poorly defined, making aggregation of results difficult. Synthesis of findings from multiple studies suggests that fewer than one-third of patients testing positive for HIV and not yet eligible for ART when diagnosed are retained continuously in care, though this estimate should be regarded with caution because of review limitations.

Conclusions: Studies of retention in pre-ART care report substantial loss of patients at every step, starting with patients who do not return for their initial CD4 count results and ending with those who do not initiate ART despite eligibility. Better health information systems that allow patients to be tracked between service delivery points are needed to properly evaluate pre-ART loss to care, and researchers should attempt to standardize the terminology, definitions, and time periods reported.

An issue of The Lancet released in conjunction with the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention offers articles on new HIV research, as well as essays on antiretroviral treatment as prevention and a WHO/UNAIDS plan to widen antiretroviral access. (Note to NewsDigest Readers: Some articles require payment.)

Rilpivirine: a step forward in tailored HIV treatment
Schrijvers R, Desimmie BA, Debyser Z

The concurrency debate: time to put it to rest
Padian NS, Manian S

Test and treat in HIV: success could depend on rapid detection
Cohen T, Corbett EL

Antiretrovirals for HIV prevention: translating promise into praxis
Mayer KH

Treatment as prevention--a double hat-trick
Montaner JSG

Treatment 2.0: catalysing the next phase of scale-up
Hirnschall G, Schwartlander B

Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial
Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, et al.

Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial
Molina JM, Cahn P, Grinsztejn B, Lazzarin A, et al.

Effect of concurrent sexual partnerships on rate of new HIV infections in a high-prevalence, rural South African population: a cohort study
Tanser F, Barnighausen T, Hund L, Garnett GP, et al.

The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study
Powers KA, Ghani AC, Miller WC, Hoffman IF, et al.

HIV prevention transformed: the new prevention research agenda
Padian NS, McCoy SI, Abdool Karim SS, Hasen N, et al.

Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women
Abdool Karim SS, Kashuba AD, Werner L, Abdool Karim Q

Prevention of mother-to-child transmission of HIV and the health-related Millennium Development Goals: time for a public health approach
Schouten EJ, Jahn A, Midiani D, Makombe SD, et al.

HIV/AIDS and the road to Rome
The Lancet

Quest for an effective AIDS vaccine takes a new tack
Maurice J

Battles with donors cloud Malawi's HIV prevention plan
Donnelly J

Building the momentum to prevent HIV in MSM
Coates TJ

Bertrand Audoin: promoting a global strategy for IAS
Samarasekera U

Kamiar and Arash Alaei: championing HIV/AIDS initiatives in Iran
Shetty P

Should health professionals play the global health security card?
Elbe S

HPTN 052 and the future of HIV treatment and prevention
Cates W

HPTN 052 and the future of HIV treatment and prevention
Epstein H, Morris M

HPTN 052 and the future of HIV treatment and prevention
Seale A, Lazarus JV, Grubb I, Fakoya A, et al.

A strategic revolution in HIV and global health
England R

Antiretroviral prophylaxis: a defining moment in HIV control
Abdool Karim SS, Abdool Karim Q

Preventing HIV is a wide-ranging and thoroughly researched compendium of the history and development of every method of preventing HIV via sexual transmission. NAM was the first community HIV treatment organisation to publish a resource specifically devoted to HIV prevention when the first edition of Preventing HIV came out as a printed directory in 2006. This, the third edition, appears as a newly-structured and formatted searchable section of the Aidsmap website.

Preventing HIV summarises key evidence on HIV prevention in an accessible way. The online hub reviews existing approaches and looks at technologies and innovations still being investigated such as microbicides and pre-exposure prophylaxis and others undergoing expansion and rollout such as male circumcision and female condoms. It has been updated to reflect the latest information on HIV treatment as prevention and the outcomes studies such as HPTN052, iPrEx and FEM-PrEP. Users of the resource can be confident that they are keeping up with the latest developments and discussions in a rapidly changing field.

Capitalizing on Scientific Progress: Investment in HIV Prevention R&D in 2010 is the seventh annual report from the HIV Vaccines and Microbicides Resource Tracking Working Group documenting investments in biomedical HIV prevention research from the public, philanthropic and commercial sectors. This year's report argues that capitalizing on recent promising scientific breakthroughs will require substantial additional and sustained investment from a broader set of donors. The major, and surprising finding of the report, given the global funding environment, is that overall investment in HIV prevention R&D had actually increased, with the modest exception of a 1 percent decline in vaccine R&D.