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.
At Merck's "automated biotechnology facility" here, robot arms adapted from automobile factories deftly shuttle plates containing human cells. Assisted by the robots and other complex machinery, scientists are studying what happens to the cells as each of the roughly 22,000 human genes is turned off. They hope to find the genes involved in different diseases, the starting point for creating a drug.
It is a merger of sophisticated biology and brute force made possible only because the Human Genome Project provided the identity of all the human genes. But as with so much else that has spun off from the genome project, it is also an expensive gamble, with success far from assured.
"Can I point to a single drug right now that this has facilitated?" said Michele Cleary, Merck's senior director for automated biotechnology. "No, because we are in the early stages of this. There's information feeding into the early stages of the pipeline that we'll see the fruits of in years to come."
Ten years after President Bill Clinton announced completion of the first draft of the Human Genome Project, in June 2000, its application to drug development is still, at best, a work in progress. But while many genetics scientists outside the drug industry say the project has had few medical benefits, industry researchers urge a wait-and-see patience.
For those looking for fresh evidence that companies and physicians are pushing cancer treatment into new frontiers, look no further than last week's annual American Society of Clinical Oncology meeting in Chicago. A new treatment designed to attack genetic abnormalities in a subset of lung cancer patients shrank or stabilized tumors in about 90 percent of patients in one study. Another clinical trial for a drug designed to boost the immune system extended survival for patients with melanoma, a deadly form of skin cancer that -- unless it's caught early -- is quickly fatal. Without a doubt, enormous public and private investments into the genetic causes of chronic disease are producing effective new treatments. But by the time promising treatments like those presented at ASCO actually gain FDA approval and reach patients, far too many patients will have died waiting. New discoveries move from the lab to patients only as fast as the FDA can certify that they're safe and effective, and it's taking the FDA too long to do so.
One reason why is money: the amount spent on improving regulatory science at the FDA is a pittance-just $18 million for the FDA's Critical Path Initiative (the agency's national strategy for modernizing how new medical products are developed and evaluated) in 2010, including for the veterinary and food centers at the agency -- compared to the over $30 billion we spend on basic research at the National Institutes of Health, and the $65 billion drug companies annually spend on R&D. This is the equivalent of building a state-of-the-art racecar, fitting it with a Model T engine, and expecting it to break the sound barrier.
If the FDA doesn't have the scientific base to create flexible regulations that keep up with the pace with of new research, some vital discoveries will languish or be lost entirely. Prioritizing new cures--and accelerating patient access to innovative therapies -- means recognizing that the FDA is not just a regulatory agency, but a scientific agency that plays a critical role in medical innovation. On average, it already takes drug companies over a decade, conducting tests and clinical trials, to bring a single new treatment to market. The FDA's drug-development regulations must be streamlined and modernized to help bring more innovative products to market faster.
European drugmakers still outrank their U.S. counterparts in making medicines available to poor people, but the lead they established two years ago is starting to shrink, according an analysis published on Monday. The Access to Medicines Index (AMI) -- released this week for the second time since its launch in 2008 -- is produced by a Dutch-based foundation and backed by 22 institutional investors and fund managers, who together manage $3.1 trillion in assets.
It put Britain's GlaxoSmithKline at the top of its list of 20 of the world's largest pharmaceutical companies, ranked on the efforts to make sure medicines are made for, and reach, people in developing countries. The index is designed to offer investors a way to compare drugmakers' social responsibility records. Behind GSK, which lead the field in improving access to drugs and vaccines, came the U.S. drugs giant Merck & Co., Switzerland's Novartis, U.S.-based Gilead Sciences, and France's Sanofi-Aventis.
In the 2010 index, six of the ten highest-ranking companies are based in Europe, while four are based in the U.S. This compares with two years ago, when seven European and three U.S. firms got a top 10 ranking. The analysis found big differences between the world's largest pharmaceutical companies in their efforts to provide millions of people in low-income countries with affordable drugs and vaccines.
Governments, employers and workers meeting at the annual conference of the United Nations International Labour Organization (ILO) today adopted a new international standard on HIV and AIDS -- the first international human rights instrument to focus specifically on the pandemic as a workplace issue. Among its provisions, the new instrument stresses that measures to address HIV and AIDS in the workplace should be part of national development policies and programmes. It rejects discrimination against workers, job-seekers and applicants on the grounds of real or perceived HIV status, and accords "fundamental priority" to preventing all modes of HIV transmission.
The standard states that workers, their families and their dependents should enjoy protection of their privacy, including confidentiality related to HIV and AIDS, and that no workers should be required to undertake an HIV test or disclose their HIV status. The workplace is expected to facilitate the access, by workers, their families and dependants, to prevention, treatment, care and support.
The fight to save hundreds of thousands of childrens' lives in poorer countries over the next few years by launching new vaccination projects is under threat amid the international economic downturn. Subsidies to extend the use of vaccines against rubella, HPV to tackle cervical cancer, cholera and Japanese encephalitis in the developing world are among those likely to be cancelled or delayed, the head of the UN-backed Global Alliance on Vaccines and Immunisation warned.
The board of Gavi -- which has disbursed $3.5bn since 2000 -- meets this week to discuss scaling back its plans against what it estimates to be a shortfall of $2.6bn over the next five years. The agency needs a total $4.3bn between now and 2015 to sustain all existing and planned programmes, including $2.6bn to introduce new vaccination projects.
The crisis has stoked concern among some donors that Gavi's board did not sufficiently anticipate future funding needs, "front-loading" expensive new vaccine programmes while failing to think about the long-term consequences or introduce greater efficiency measures to tackle them. "The board was large, and probably not historically very effective in dealing with these complex issues," said one funder. "We're treating the shortfall like a crisis."
Dr. Jerome Kabakyenga has just walked a pair of visitors through a pair of vividly different Ugandan hospital laboratories -- one ultramodern, the other an outdated relic. In the first, highly trained technicians investigate blood samples using a battery of high-throughput computerized systems. The brightly lit, air-conditioned facility is spotless. In the second lab on Kabakyenga's tour, there's little equipment beyond a clutter of microscopes, a pair of old refrigerators and a few centrifuges. The technicians here depend on daylight from a set of dusty windows, one of which is cracked. As he completes the tour, Kabakyenga, who is the dean of medicine at the Mbarara University of Science and Technology in western Uganda, does his best not to say what's on his mind. He knows the contrast between the two facilities -- both of which serve a population of about 1 million Ugandans in the region around the city of Mbarara -- tells a startling story about medicine right across Africa. But today, Kabakyenga wants to let the labs do the talking.
In this tale of two labs, the state-of-the-art facility is one that provides HIV/AIDS testing; it was paid for by wealthy foreign donors. The other facility is the Mbarara regional hospital's antiquated general diagnostic laboratory, which operates on a shoestring budget provided partly by Kabakyenga's university department. The disparity between the two labs means that, while many HIV/AIDS patients can get reasonable care, vastly larger numbers of patients -- in an area long stricken with numerous other killer diseases besides AIDS -- cannot. In a hospital where up to 20 percent of patients have HIV, investment in an HIV/AIDS lab is critically important. But the lack of resources for testing and treating diseases other than HIV/AIDS is disastrous: "We can do rapid and comprehensive viral load analyses for HIV patients," Kabakyenga says, using the careful cadences of a scholarly man who risks straying into a political minefield. "But we can't always manage a timely malaria test."
Zambia on Wednesday played down fears of a looming health crisis after the Global Fund suspended more than $300 million in health assistance to the country citing corruption. The freeze, the latest graft scandal to hit President Rupiah Banda before an election due next year, is likely to affect the southern African country's fight against AIDS, tuberculosis and malaria.
Health Minister Kapembwa Simbao said the Global Fund would still continue supporting Zambia but the funding would now be made available through the United Nations Development Programme (UNDP). "It is just that the Ministry of Health will no longer be the principal recipient of the funding but all the programmes will continue under UNDP," Simbao told Reuters. "We hope that with the support of the UNDP, the Ministry of Health can build capacity to administer the funding in about one to two years."
The aid freeze comes a year after Sweden and the Netherlands suspended $33 million in Health Ministry aid due to a missing $5 million. Some officials were later charged with stealing the money. The European Union has also halted aid earmarked for road construction because of concerns about graft.
Thousands of South African protesters marched on the U.S. consulate Thursday to demand the U.S. increase its AIDS funding for Africa, weeks after U.S. officials said their biggest AIDS fund would not substantially rise. The protesters, clad in green T-shirts emblazoned with the words "HIV-Positive," marched before the consulate in a wealthy northern suburb of Johannesburg to demand that the U.S. government increase its contribution to the Global Fund on AIDS, TB and Malaria to $2.8 billion by 2013.
Protest organizers said the lack of a significant increase in the President's Emergency Plan for AIDS Relief -- a major funder of AIDS programs around the world -- has led clinics to run out of drugs and forced providers to ration treatment. Officials from the international program, known as PEPFAR, say this year's budget had increased only marginally, from $6.8 billion in 2010 to nearly $7 billion for 2011.
But in a statement, protesters said more funding was needed. "Over the years ahead, (lack of funding) will condemn millions of newly infected patients to death and threaten the health of those already on treatment," the statement said.
HIV patients in Tanzania are as hooked on the World Cup as the rest of the continent. My companion in front of a restaurant television, 35-year-old electrician Abasi Mkapa, was impressed by the German performance against Australia and had views on who might win the Cup. All very normal except that without modern drugs, and the largesse of U.S. and European taxpayers, Mr. Mkapa and two million other HIV-positive Africans would not be well enough to shout at their televisions for each missed goal opportunity.
Antiretroviral HIV drugs are still relatively expensive and most African patients very poor. The recession has added budgetary pressure to assistance programs, so fewer people will be treated this year and next than previously predicted. There are still disputes between drugmakers, and tensions between governments and donors. But by and large the situation has improved markedly.
The hope of today is a far cry from the despair of a decade ago, when GlaxoSmithKline (the world's second largest drug firm) and 41 other Western companies making HIV drugs sued the South African government for importing patent-breaking copies of their products from India. Fewer than 10,000 people were being treated on the continent at the time, and the pharmaceutical giants' corporate lawsuit was ill-advised -- a public-relations disaster ensued. But the plaintiffs did have a point in that many of the drugs being produced in India were of sub-standard quality.
Today the HIV drugs coming out of India not only pass the required quality controls set by agencies like the U.S. Food and Drug Administration, but are often nearly identical to originator brands. Improvements are due in part to the innovative licensing agreements arising between some Western and Indian drug companies. These agreements have held even though the governments of India, Thailand, and Brazil continue to threaten Western drug companies with loss of patent protection if they do not lower their prices. The best producers have found a way of moving beyond this confrontation, and are increasing . . .
The development of an effective anti-HIV topical microbicide, especially a female-controlled, vaginal microbicide, has been deemed an urgent global priority by numerous international agencies, including the World Health Organization, the U.S. Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and others. The present invention provides antiviral proteins (collectively referred to as cyanovirins), conjugates thereof, DNA sequences encoding such agents, host cells containing such DNA sequences, antibodies directed to such agents, compositions comprising such agents, and methods of obtaining and using such agents for the production of microbicides.
Cyanovirin-N (CV-N) potently and irreversibly inactivates diverse primary strains of HIV-1, including M-tropic forms involved in sexual transmission of HIV, as well as T-tropic and dual-tropic forms; CV-N also blocks cell-to-cell transmission of HIV infection. CV-N is directly virucidal, interacting in an unusual manner with the viral envelope, apparently binding with extremely high affinity to poorly immunogenic epitopes on gp120. Further, cyanovirin-N (CV-N) and homologous proteins and peptides potently inhibit diverse isolates of influenza viruses A and B, the two major types of influenza virus that infect humans.
The described technology includes glycosylation-resistant mutants of CV-N, which code sequences to enable ultra large-scale recombinant production of functional cyanovirins in non-bacterial (yeast or insect) host cells or in transgenic animals or plants. Therefore, these glycosylation-resistant mutants may allow industry to produce CV-Ns on a large scale and make CV-Ns cheap enough for developing countries to benefit from this invention.
South African Dr. Sonnet Ehlers was on call one night four decades ago when a devastated rape victim walked in. Her eyes were lifeless; she was like a breathing corpse. "She looked at me and said, 'If only I had teeth down there,'" recalled Ehlers, who was a 20-year-old medical researcher at the time. "I promised her I'd do something to help people like her one day."
Forty years later, Rape-aXe was born. Ehlers is distributing the female condoms in the various South African cities where the World Cup soccer games are taking place. The woman inserts the latex condom like a tampon. Jagged rows of teeth-like hooks line its inside and attach on a man's penis during penetration, Ehlers said. Once it lodges, only a doctor can remove it -- a procedure Ehlers hopes will be done with authorities on standby to make an arrest.
Ms Idah Munzele was elated at pronouncements that scientists were working tirelessly to develop a microbicide gel that would prevent women from contracting HIV/AIDS. She felt that such a development would go a long way in empowering women and in safe-guarding the lives of the girl-children who are most vulnerable to sexual abuse and contracting HIV. "This is the best news so far. If it works, that would be great for our women and girls," she said.
In Zambia, new HIV infections (incidence) in adults have decreased since 1990 and are estimated to be at a stable level, according to UNAIDS. This is consistently higher in women than in men. In 2009, an estimated 82,681 adults were newly infected with HIV - 59 per cent in women and 41 per cent in men. This is about 226 new adult infections per day. The adult HIV incidence rate in Zambia is currently estimated at 1.6 per cent, which is still considered too high to slow the epidemic.
The epidemic has also changed over time - it has matured, and has seen reductions in some provinces, increases in other provinces, reductions amongst urban men and young women. "Some of our efforts have been successful. The Government is mindful that if we do not carry out concrete actions, it will increase to 276 Zambians every day in the next five years," reads a UNAIDS report in part.
The government is set to launch the national policy on safe male circumcision to encourage men and boys to seek circumcision from health facilities. Reports show that the policy emphasises that safe male circumcision is an alternative HIV control measure. This is a very important strategy especially if we consider the HIV situation in Uganda today, where over 100,000 Ugandans get infected every year.
Mass male circumcision is indeed necessary considering the compelling evidence that male circumcision reduces the risk of heterosexually acquired HIV infection in men by about 60 per cent. Since very few Ugandan men are circumcised, and yet the scale of HIV is high (6.4 per cent), safe male circumcision is likely to help both men and women reduce their risk of infection. Moreover male circumcision is believed to guarantee various benefits ranging from lowering the possibilities of sexual related diseases like syphilis, gonorrhea, genital herpes, and penile or cervical cancers.
There was no significant difference in the risk of death if antiretroviral treatment was initiated within 2 months of beginning TB treatment or more after 2 months after beginning TB treatment, according to results of a South African cohort study presented earlier this month at the South African TB Conference in Durban. Nor was there any difference in rates of toxicity -- related treatment modifications, loss to follow up, hepatic toxicity, or poor immunologic and virologic response. However baseline CD4 cell count, body mass index (BMI) and haemoglobin level at the time of ARV initiation were the significant risk factors for mortality regardless of the time period of ARV initiation.
The prospective cohort study examined and compared clinical outcomes occurring within different groups of HIV/TB co-infected patients initiating ART after different durations of TB treatment, and was presented by Dr Simbarashe Takuva of the Clinical Research Unit at the University of Witwatersand
An ongoing randomised clinical trial, SAPIT, is examining whether there is any difference in outcomes according to whether antiretroviral treatment is initiated quickly after starting TB treatment -- within two weeks -- or delayed for two months in order to overcome potential problems of drug toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). One arm of the SAPIT study, in which patients were randomised to receive antiretroviral treatment after they had completed their course of TB treatment, was halted after an interim analysis showed that patients in this arm were more likely to die than those who started ART during their course of TB treatment.
Visitors expecting broken test tubes and threadbare carpets are often surprised by Kenya's Centre for Geographic Medicine Research in Kilifi. The gleaming white building, laden with top-notch equipment and perched atop a hill overlooking the azure Indian Ocean, is part of the Kenya Medical Research Institute (KEMRI), based in Nairobi, but would look at home in California or Singapore.
World-class laboratories are not common in Africa, but they are becoming less of an exception. There is a whiff of a scientific renaissance in the air, with new labs mushrooming in the capitals of Kenya and Uganda and local researchers taking the helm of formerly Western-run institutions.
The improved conditions carry a cost: continued dependence on foreigners, who foot most of the bills. "If you look at any of the researchers who carry out any significant research in Africa, 99.9% of their funding comes from outside," says Tom Egwang, a Ugandan immunologist and founding director of Uganda's Med Biotech Laboratories, headquartered in Kampala. "I really think that all these programmes are killing African science."
Others agree that the millions flowing from philanthropists, non-governmental organizations (NGOs), aid agencies and traditional research funders into African science are undermining efforts to convince African governments to spend money on research. "Governments don't assume their responsibilities in this area, simply because the NGOs spend money in their place," says Ahmadou Lamine Ndiaye, vice-president of the National Academy of Science and Technology of Senegal.
In an aging research building at the University of Southern California, a $14.5 million biomedical experiment is under way that until a few years ago would have made many AIDS researchers snicker at its ambition. Mice are the main research subjects (for now), and some 300 of them live in a room the size of a large walk-in closet. Signs plastered to the room's outer door include blaze-orange international biohazard symbols and a blunter warning that says, "This Room Contains: HIV-1 Infected Animals." Yet the hazard is accompanied by an astonishing hope. In some of the infected mice, the virus appears to have declined to such low levels that the animals need no further treatment.
This is a feat that medications have not accomplished in a single human, although daily doses of powerful anti-HIV drugs known as antiretrovirals can now control the virus and stave off AIDS for decades. Every person who stops taking the drugs sees levels of HIV skyrocket within weeks, and immune destruction follows inexorably. The lack of a cure -- a way to eliminate HIV from an infected person or render it harmless -- remains an intractable and perplexing problem.
"This doesn't look like a multimillion-dollar operation at all, does it?" jokes Paula Cannon, a lead researcher on the project, as she enters the ill-smelling room, which has shelves lined with mice living together in plastic cages that resemble large shoeboxes. As she leads a tour of the cramped space, Cannon wears a face mask, a hairnet, a gown over her clothes, latex gloves, and cloth shoe coverings over her stylish heeled boots. She takes these precautions not to protect herself but to ensure that she won't transmit a dangerous infection to this colony of mice -- which is worth somewhere around $100,000.
The future of Kenya's workforce is at risk as new HIV infections among the youth rise, a regional conference has been told. New infection trends reveal the youth, young children and married couples form the highest risk groups in the country. "These mixed epidemic groups now form the most critically affected groups in the country. There is need for HIV prevention programmes to target areas where these groups are most easily found," said Alloys Orago, the National Aids Control Council director.
Even though infection rates in Kenya have fallen significantly over the last 10 years, stakeholders are worried new infections are threatening the workers of tomorrow. Some 1,500 peer educators at the fourth National Organisation of Peer Educators (NOPE) conference in Nairobi were told the bulk of the over 166,000 new infections in the country daily affect the three groups most, raising concern about economic productivity.
The National Aids Secretariat in partnership with UNFPA on Monday 14th June 2010 commenced a five-day training of trainer's workshop on condom programming at the Hotel 5:10 in the east end of Freetown. Thirty participants from across the country and other stakeholders from different organizations were involved in the training, with focus on the popularization of female condoms. The purpose of the training, it was revealed, was centred on the use of condoms with particular reference to the female condom as lot of people do not know anything about female condoms and most people have never seen one.
The workshop was officially launched by the Information and Communication Officer, National Aids Secretariat Abubakarr Koroma. In his opening statement, he said "the training is one of the strategic plans the secretariat and development partners intend to use in the fight against aids", noting that "as a nation we are doing fine but there are challenges we face and that the training is part of some of the challenges stakeholders are facing, hence the "essence of the training is to get a proper coordination in condom programming."
Twenty South African boys have died following botched circumcisions in the Eastern Cape Province. "The deaths occurred over the past 12 days, with nine of them occurring over the past 24 hours," said a provincial health spokesperson. Some 60 boys have been rescued from 11 initiation schools which have since been closed.
Circumcision is seen as a rite of passage into manhood in some South African communities. The practice is common among the Xhosa and Ndebele communities. However, Zulu King Goodwill Zwelithini wants it reintroduced among the Zulu people because of reports that medical circumcision can reduce the chances of getting HIV.
A priority of AIDS prevention in Botswana is to reduce multiple concurrent sexual partnerships. We analysed data from interviews with people aged 16-60 years in a 2007 national stratified random cluster sample of communities across Botswana.
Among 768 male and 1784 female respondents, 10% reported multiple sexual partners in the month prior to the survey (MP1); 19% of men and 6% of women. In a multivariate analysis, men were more likely to report MP1 if they had not completed primary education (adjusted Odds Ratio (ORa) 2.13, 95% confidence intervals with adjustment for clustering (CIca) 1.19-3.85), if they were single (ORa 2.29, 95% CIca 1.28-4.11), if they had experienced intimate partner violence in the last year (ORa 2.59, 95% CIca 1.51-4.45) and if they reported acquiescence to high risk sex (ORa 8.32, 95% CIca 3.38-20.46). Women who said they earned more or the same as their partner were also more likely to report MP1 (ORa 1.76, 95% CIca 1.21-2.56).
The higher rate of MP1 among men with different forms of choice-disability shows an important potential multiplication of male risk factors. Women with higher income were more likely to have more partners, questioning the idea that multiple concurrent partners is mainly a question of male disposable income.
Diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitors (NNRTIs) have inherent flexibility, helping to maintain activity against a wide range of resistance mutations. Crystal structures were determined with wild-type and K103N HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278). These structures reveal a similar binding mode for TMC125 and TMC278, whether bound to wild-type or K103N RT. Comparison to previously published structures reveals differences in binding modes for TMC125 and differences in protein conformation for TMC278.
Unless optimal adherence in microbicide clinical trials is ensured, an efficacious microbicide may be rejected after trial completion, or development of a promising microbicide may be stopped, because low adherence rates create the illusion of poor efficacy. We provide a framework with which to conceptualize and improve microbicide adherence in clinical trials, supported by a critical review of the empirical literature. The information-motivation-behavioral skills (IMB) model of microbicide adherence conceptualizes microbicide adherence in clinical trials and highlights factors that can be addressed in behavioral interventions to increase adherence in such trials. This model asserts that microbicide adherence-related information, motivation, and behavioral skills are fundamental determinants of adherent microbicide utilization. Specifically, information consists of objective facts about microbicide use (e.g., administration and dosage) as well as heuristics that facilitate use (e.g., microbicides must be used with all partners). Motivation to adhere consists of attitudes toward personal use of microbicides (e.g., evaluating the consequences of using microbicides as good or pleasant) as well as social norms that support their use (e.g., beliefs that a sexual partner approves use of microbicides). Behavioral skills consist of objective skills necessary for microbicide adherence (e.g., the ability to apply the microbicide correctly and consistently). Empirical evidence concerning microbicide acceptability and adherence to spermicides, medication, and condom use regimens support the utility of this model for understanding and promoting microbicide adherence in clinical trials.
Give me your tired, your poor, your Phase II failures... Well, OK, to be honest, I'm not sure I want your tired or your poor, and besides, The Statue of Liberty has that pretty well covered. But I am sure that I want your Phase II failures. I REALLY want your Phase II failures.
Before I explain what I mean, I should review the progress in making drugs to treat serious human illnesses in the first decade of the 21st century - or, more accurately, the lack of progress. While it's been true for a long time that about the hardest thing human beings have ever tried to do is to make a drug, it seems as though lately it's got even harder. The number of new therapeutics approved for use on humans, per year, has been essentially flat for more than two decades. During this time, new technologies such as structure-based drug discovery have been created, pharmaceutical companies have merged to form giant entities, and hundreds of biotechnology companies have been launched to rival them, the research expenditure of the National Institutes of Health (NIH) has more than doubled, and the R&D budget of the drugs industry has shot up. Yet despite all that, we are not developing new drugs any faster than we did before. Why not?
One reason is that the diseases we are now trying to treat, such as cancer and Alzheimer's disease, are harder than many of the infectious diseases that dominated our efforts 50 years ago. But another reason lies in the nature of the drug development process itself.
Background HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells.
Results We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK. A panel of 10 microbicide candidates [T20, CADA, lectines HHA & GNA, PVAS, human lactoferrin, and monoclonal antibodies IgG1B12, 12G5, 2G12 and 2F5], were investigated using cell-free unopsonized or opsonized HIV-1 by complements. Only HHA and PVAS were able to inhibit HIV trancytosis. Upon opsonization, transcytosis was affected only by HHA, HIV-1 adsorption on iMDDC by four molecules (lactoferrin, IgG1B12, IgG2G5, IgG2G12), and replication in iMDDC of HIV-1BaL by five molecules (lactoferrin, CADA, T20, IgG1B12, IgG2F5) and of HIV-1NDK by two molecules (lactoferrin, IgG12G5).
Conclusion These observations demonstrate that HIV-1 opsonization by complements may modulate in vitro the efficiency of candidate microbicides to inhibit HIV-1 infection of mucosal target cells, as well as its crossing through mucosa.
Introduction This study compares client volume, demographics, testing results, and costs of 3 "mobile" HIV counseling and testing (HCT) approaches with existing "stand-alone" HCT in Kenya. A retrospective cohort of 62,173 individuals receiving HCT between May 2005 and April 2006 was analyzed. Mobile HCT approaches assessed were community-site mobile HCT, semimobile container HCT, and fully mobile truck HCT. Data were obtained from project monitoring data, project accounts, and personnel interviews.
Results Mobile HCT reported a higher proportion of clients with no prior HIV test than stand-alone (88% vs. 58%). Stand-alone HCT reported a higher proportion of couples than mobile HCT (18% vs. 2%) and a higher proportion of discordant couples (12% vs. 4%). The incremental cost-effectiveness of adding mobile HCT to stand-alone services was $14.91 per client tested (vs. $26.75 for stand-alone HCT); $16.58 per previously untested client (vs. $43.69 for stand-alone HCT); and $157.21 per HIV-positive individual identified (vs. $189.14 for stand-alone HCT).
Conclusions Adding mobile HCT to existing stand-alone HCT seems to be a cost-effective approach for expanding HCT coverage for reaching different target populations, including women and young people, and for identifying persons with newly diagnosed HIV infection for referral to treatment and care.
Objectives Assess population attributable fractions (PAFs) for late postnatal transmission (LPT) of HIV-1 in a cohort of HIV-1-exposed infants.
Methods We used data established from a risk factor analysis of LPT (negative HIV-1 results through the 4-6 week visit, but positive assays thereafter through the 12-month visit) from a perinatal clinical trial conducted in 3 sub-Saharan countries. PAFs were calculated as the proportions of excess LPTs attributed to identified risk factors.
Results For the cohort of 1317 infants, 206 (15.6%) had only low maternal CD4+ counts (<200 cells/mm3), 332 (25.2%) had only high maternal plasma viral loads (VLs) (>50,000 copies/mL), and 81 (6.2%) had both low CD4+ counts and high VLs. Their PAFs were 26.0% [95% confidence interval (CI): 12.0% to 36.0%], 37.0% (95% CI: 22.0% to 51.0%), and 16.0% (95% CI: 6.0% to 25.0%), respectively.
Conclusions Our PAF analysis illustrates the public health impact of the substantial proportion of LPTs accounted for by high-risk women with both low CD4+ counts and high VLs. In light of these results, access to and use of antiretroviral therapy by high-risk HIV-1-infected pregnant women is essential. Additional strategies to reduce LPT for those not meeting criteria for antiretroviral therapy should be implemented.
Background We evaluated the influence of type and timing of prophylaxis on perinatal HIV transmission in St. Petersburg, Russia.
Methods We linked surveillance data for 1498 HIV-infected mothers delivering from 2004 to 2007 with polymerase chain reaction data for 1159 infants to determine predictors of transmission.
Results The overall perinatal transmission rate was 6.3% [73 of 1159, 95% confidence interval (CI) 4.9% to 7.7%]. Among the 12.8% (n = 149) of mother-infant pairs receiving full course (antenatal, intrapartum, postnatal) dual/triple antiretroviral prophylaxis, the transmission rate was 2.7%. Among the 1010 receiving less complete regimens (full course zidovudine, single-dose nevirapine, or incomplete), transmission ranged from 4.1% to 12.2%. Among the 28.9% (330) of mothers initiating antiretroviral drugs <=20 weeks gestation, perinatal transmission was 1.8%, compared with 4.0%, 8.6%, and 11.3% for those initiating antiretrovirals at 21-28 weeks, 29-42 weeks, or during labor and delivery, respectively (P for trend <0.0001). Compared with those initiating antepartum prophylaxis <=20 weeks, those initiating antepartum prophylaxis >=29 weeks (or not at all) had increased transmission odds (adjusted odds ratio: 4.9, 95% CI: 1.8 to 12.9; odds ratio: 5.1, 95% CI: 2.0 to 13.1, respectively).
Conclusions In St. Petersburg, the potential for further reductions in perinatal transmission is evident, given low transmission among women receiving early combination prophylaxis.
Background As second-line antiretroviral therapy (ART) availability increases in resource-limited settings, questions about the value of laboratory monitoring remain. We assessed the outcomes and cost-effectiveness (CE) of laboratory monitoring to guide switching ART.
Methods We used a computer model to project life expectancy and costs of different strategies to guide ART switching in patients in Cote d'Ivoire. Strategies included clinical assessment, CD4 count, and HIV RNA testing. Data were from clinical trials and cohort studies from Cote d'Ivoire and the literature. Outcomes were compared using the incremental CE ratio. We conducted multiple sensitivity analyses to assess uncertainty in model parameters.
Results Compared with first-line ART only, second-line ART increased life expectancy by 24% with clinical monitoring only, 46% with CD4 monitoring, and 61% with HIV RNA monitoring. The incremental CE ratio of switching based on clinical monitoring was $1670 per year of life gained (YLS) compared with first-line ART only; biannual CD4 monitoring was $2120 per YLS. The CE ratio of biannual HIV RNA testing ranged from $2920 ($87/test) to $1990 per YLS ($25/test). If second-line ART costs were reduced, the CE of HIV RNA monitoring improved.
Conclusions In resource-limited settings, CD4 count and HIV RNA monitoring to guide switching to second-line ART improve survival and, under most conditions, are cost-effective.
The issue of human rights for men who have sex with men and how national and local attitudes can affect the spread of HIV and AIDS was highlighted last month when Steven Monjeza and Tiwonge Chimbalanga, a male couple in Malawi, were sentenced to 14 years hard labour for sodomy, after they held the country's first known same-sex commitment ceremony. International outcry followed, and after pressure from UN Secretary General Ban Ki-moon during a visit to the country, Malawi's president, Bingu wa Mutharika, granted an unexpected pardon. "This was a very courageous decision by President Mutharika. I highly applaud the President's leadership. Distinguished members of the Parliament, I am confident that you will take appropriate steps to update laws discriminating based on sexual orientation in line with international standards", Ban announced at a press conference shortly afterwards.
In the 20 years since homosexuality was removed from the list of mental health disorders by the World Health Assembly, there has been substantial progress in North America, western Europe, and more recently in Latin America, towards greater public acceptance and legal protection for men who have sex with men. In many parts of the world, however, denial of health care, stigmatisation by health-care workers, and the continued "pathologisation" of homosexuality is still a reality. Highly publicised cases of arrests and imprisonment of gay men in Egypt, Senegal, and Malawi often required doctors to carry out examinations and provide evidence confirming homosexual conduct for prosecutors on the basis of spurious scientific knowledge. "Many serious cases of human rights abuses against men who have sex with men, such as killings, torture, violence, harassment, and sexual abuse, are also reported every year in many countries", reported Cheikh Traore, Senior Adviser on Sexual Diversity at UN Development Programme (UNDP), New York, USA.
Background Nucleic acid testing (NAT) in routine HIV testing programs can increase the detection of infected individuals, but the most effective implementation of NAT remains unclear.
Objective To determine how many HIV cases can be identified with NAT and how many persons can be contacted, to identify predictors of acute and early HIV infection cases, and to test reporting of negative results by automated Internet and voicemail systems.
Measurements Rates and predictors of HIV infection by stage, notification of positive NAT results, use of automated Internet or voicemail systems to access negative NAT results, and estimated HIV infections prevented.
Results Of 3151 persons tested, 79 had newly diagnosed cases of HIV: 64 had positive results from rapid HIV test, and 15 had positive results only by NAT (that is, NAT increased the HIV detection yield by 23%). Of all HIV infections, 44% (in 35 persons) were in the acute and early stages. Most participants (56%) and persons with HIV (91%) were men who have sex with men (MSM). All persons with NAT-positive results were notified within 1 week. Of all 3070 uninfected patients, 2105 (69%) retrieved their negative NAT results, with 1358 using the Internet system. After adjustment for covariates, persons reporting MSM behavior, higher incomes, younger ages, no testing at substance abuse rehabilitation centers, no recent syphilis, and no methamphetamine use were more likely to access negative NAT results by either Internet or voicemail systems.
Limitation Findings may not be generalizable to other populations and testing programs.
Conclusion Nucleic acid testing programs that include automated systems for result reporting can increase case yield, especially in settings that cater to MSM.
Background Expanded access to combination antiretroviral therapy (ART) in resource-poor settings is dependent on task shifting from doctors to other health-care providers. We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients.
Methods This randomised non-inferiority trial was undertaken at two South African primary-care clinics. HIV-positive individuals with a CD4 cell count of less than 350 cells per [micro]L or WHO stage 3 or 4 disease were randomly assigned to nurse-monitored or doctor-monitored ART care. Patients were randomly assigned by stratified permuted block randomisation, and neither the patients nor those analysing the data were masked to assignment. The primary objective was a composite endpoint of treatment-limiting events, incorporating mortality, viral failure, treatment-limiting toxic effects, and adherence to visit schedule. Analysis was by intention to treat. Non-inferiority of the nurse versus doctor group for cumulative treatment failure was prespecified as an upper 95% CI for the hazard ratio that was less than 1.40. This study is registered with ClinicalTrials.gov, number NCT00255840.
Findings 408 patients were assigned to doctor-monitored ART care and 404 to nurse-monitored ART care; all participants were analysed. 371 (46%) patients reached an endpoint of treatment failure: 192 (48%) in the nurse group and 179 (44%) in the doctor group. The hazard ratio for composite failure was 1.09 (95% CI 0.89-1.33), which was within the limits for non-inferiority. After a median follow-up of 120 weeks (IQR 60-144), deaths (ten vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66), and programme losses (70 vs 63) were similar in nurse and doctor groups, respectively.
Interpretation Nurse-monitored ART is non-inferior to doctor-monitored therapy. Findings from this study lend support to task shifting to appropriately trained nurses for monitoring of ART.
Background Cross-sectional studies have shown that intimate partner violence and gender inequity in relationships are associated with increased prevalence of HIV in women. Yet temporal sequence and causality have been questioned, and few HIV prevention programmes address these issues. We assessed whether intimate partner violence and relationship power inequity increase risk of incident HIV infection in South African women.
Methods We did a longitudinal analysis of data from a previously published cluster-randomised controlled trial undertaken in the Eastern Cape province of South Africa in 2002-06. 1099 women aged 15-26 years who were HIV negative at baseline and had at least one additional HIV test over 2 years of follow-up were included in the analysis. Gender power equity and intimate partner violence were measured by a sexual relationship power scale and the WHO violence against women instrument, respectively. Incidence rate ratios (IRRs) of HIV acquisition at 2 years were derived from Poisson models, adjusted for study design and herpes simplex virus type 2 infection, and used to calculate population attributable fractions.
Findings 128 women acquired HIV during 2076 person-years of follow-up (incidence 6.2 per 100 person-years). 51 of 325 women with low relationship power equity at baseline acquired HIV (8.5 per 100 person-years) compared with 73 of 704 women with medium or high relationship power equity (5.5 per 100 person-years); adjusted multivariable Poisson model IRR 1.51, 95% CI 1.05-2.17, p=0.027. 45 of 253 women who reported more than one episode of intimate partner violence at baseline acquired HIV (9.6 per 100 person-years) compared with 83 of 846 who reported one or no episodes (5.2 per 100 person-years); adjusted multivariable Poisson model IRR 1.51, 1.04-2.21, p=0.032. The population attributable fractions were 13.9% (95% CI 2.0-22.2) for relationship power equity and 11.9% (1.4-19.3) for intimate partner violence.
Interpretation Relationship power inequity and intimate partner violence increase risk of incident HIV infection in young South African women. Policy, interventions, and programmes for HIV prevention must address both of these risk factors and allocate appropriate resources.
Background The viral load setpoint (VLS) is an important predictor of HIV disease progression, but there is a lack of information regarding the VLS and its possible determinants in African populations.
Methods Initially HIV-negative adults from 3 distinct groups (female bar workers, females, and males from the general population) were followed for up to 4 years. The VLS was calculated for 108 seroconverters and associations of the VLS with possible risk factors were analyzed using univariate and multivariate regression.
Results The median VLS for female bar workers, females, and males from the general population were 69,850, 28,600, and 158,000 RNA copies per milliliter, respectively. Significant associations with an elevated viral load were observed for male gender [risk ratio (RR) = 1.83, 95% confidence interval (95% CI) = 1.14 to 2.93], the expression of harmful HLA I alleles (RR = 1.73, 95% CI = 1.13 to 2.66) and multiple infection with different HIV-1 subtypes (RR = 1.65, 95% CI = 1.03 to 2.66). Bar workers were considerably more often infected with different HIV-1 subtypes than participants from the general population.
Conclusions Our study confirms that gender and the expression of different HLA class I alleles are important determinants of the viremia at VLS, and it also corroborates an earlier finding that multiple infection with different HIV-1 subtypes is associated with a higher VLS.
More than 90% of the 430,000 human immunodeficiency virus type 1 (HIV-1) infections in children each year occur in sub-Saharan Africa, where HIV-1 acquisition through breast milk accounts for more than 40% of infections. However, in Africa, breast-feeding is a cornerstone of child survival. Two randomized trials reported in this issue of the Journal show that antiretroviral regimens in breast-feeding infants or lactating mothers significantly decrease postnatal acquisition of HIV-1. It should be possible to eliminate new perinatal HIV-1 infections globally with the use of antiretroviral therapy when needed for maternal health and, when treatment is not otherwise required for . . .
Objectives We examined the association between unprotected anal intercourse and sexually transmitted diseases (STDs) among heterosexual women.
Methods In 2006 through 2007, women were recruited from high-risk areas in New York City through respondent-driven sampling as part of the National HIV Behavioral Surveillance study. We used multiple logistic regression to determine the relationship between unprotected anal intercourse and HIV infection and past-year STD diagnosis.
Results Of the 436 women studied, 38% had unprotected anal intercourse in the past year. Unprotected anal intercourse was more likely among those who were aged 30 to 39 years, were homeless, were frequent drug or binge alcohol users, had an incarcerated sexual partner, had sexual partners with whom they exchanged sex for money or drugs, or had more than 5 sexual partners in the past year. In the logistic regression, women who had unprotected anal intercourse were 2.6 times as likely as women who had only unprotected vaginal intercourse and 4.2 times as likely as women who had neither unprotected anal nor unprotected vaginal intercourse to report an STD diagnosis. We found no significant association between unprotected anal intercourse and HIV infection.
Conclusions Increased screening for history of unprotected anal intercourse and, for those who report recent unprotected anal intercourse, counseling and testing for HIV and STDs would likely reduce STD infections.
Background Three national HIV household surveys were conducted in South Africa, in 2002, 2005 and 2008. A novelty of the 2008 survey was the addition of serological testing to ascertain antiretroviral treatment (ART) use.
Methods and Principal Findings We used a validated mathematical method to estimate the rate of new HIV infections (HIV incidence) in South Africa using nationally representative HIV prevalence data collected in 2002, 2005 and 2008. The observed HIV prevalence levels in 2008 were adjusted for the effect of antiretroviral treatment on survival. The estimated "excess" HIV prevalence due to ART in 2008 was highest among women 25 years and older and among men 30 years and older. In the period 2002-2005, the HIV incidence rate among men and women aged 15-49 years was estimated to be 2.0 new infections each year per 100 susceptible individuals (/100pyar) (uncertainty range: 1.2-3.0/100pyar). The highest incidence rate was among 15-24 year-old women, at 5.5/100pyar (4.5-6.5). In the period 2005-2008, incidence among men and women aged 15-49 was estimated to be 1.3/100 (0.6-2.5/100pyar), although the change from 2002-2005 was not statistically significant. However, the incidence rate among young women aged 15-24 declined by 60% in the same period, to 2.2/100pyar, and this change was statistically significant. There is evidence from the surveys of significant increases in condom use and awareness of HIV status, especially among youth.
Conclusions Our analysis demonstrates how serial measures of HIV prevalence obtained in population-based surveys can be used to estimate national HIV incidence rates. We also show the need to determine the impact of ART on observed HIV prevalence levels. The estimation of HIV incidence and ART exposure is crucial to disentangle the concurrent impact of prevention and treatment programs on HIV prevalence.
Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding) B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8). Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.
The development of a topical microbicide blocking the sexual transmission of HIV-1 is urgently needed to control the global HIV/AIDS pandemic. The actinomycete-derived lectin actinohivin (AH) is highly specific to a cluster of high-mannose-type glycans uniquely found on the viral envelope (Env). Here, we evaluated AH's candidacy toward a microbicide in terms of in vitro anti-HIV-1 activity, potential side effects, and recombinant producibility. Two validated assay systems based on human peripheral blood mononuclear cell (hPBMC) infection with primary isolates and TZM-bl cell infection with Env-pseudotyped viruses were employed to characterize AH's anti-HIV-1 activity. In hPMBCs, AH exhibited nanomolar neutralizing activity against primary viruses with diverse cellular tropisms, but did not cause mitogenicity or cytotoxicity that are often associated with other anti-HIV lectins. In the TZM-bl-based assay, AH showed broad anti-HIV-1 activity against clinically-relevant, mucosally transmitting strains of clades B and C. By contrast, clade A viruses showed strong resistance to AH. Correlation analysis suggested that HIV-1's AH susceptibility is significantly linked to the N-glycans at the Env C2 and V4 regions. For recombinant (r)AH expression, we evaluated a tobacco mosaic virus-based system in Nicotiana benthamiana plants as a means to facilitate molecular engineering and cost-effective mass production. Biochemical analysis and an Env-mediated syncytium formation assay demonstrated high-level expression of functional rAH within six days. Taken together, our study revealed AH's cross-clade anti-HIV-1 activity, apparent lack of side effects common to lectins, and robust producibility using plant biotechnology. These findings justify further efforts to develop rAH toward a candidate HIV-1 microbicide.
A shocking number of women die or are disabled each year trying to give birth -- more than 10 million women, according to the WHO, 99% of whom are in developing countries . The maternal health Millennium Development Goals (MDGs) -- to reduce maternal mortality by three-quarters and to provide universal access to reproductive health by 2015 -- are long considered the most underachieving of the MDGs and have been chronically low on political priority lists. Recent international attention to maternal health, including its prominence at upcoming G8, Pacific Health, African Union, and UN General Assembly Summits, is therefore a welcome development and comes at a time when critical new data are available to guide action.
This month PLoS Medicine releases new data on priority interventions for maternal health, part of a series on maternal, neonatal, and child health (MNCH) in Africa. The goal of the series, authored by a group of international collaborators, is to identify scientific interventions and accelerate actions that are tailored and specific to sub-Saharan Africa. Based upon consultations with 60 scientists and policy makers from nine countries and using local and national data, the series updates the current status of MNCH in the region, reviews evidence based solutions, and identifies high-impact opportunities for reducing maternal and child mortality.
A low-molecular-weight human immunodeficiency virus type 1 (HIV-1) inhibitor, PF-68742 (molecular weight, 573), has been identified in a high-throughput screen for compounds that block HIV-1 envelope glycoprotein (Env)-mediated fusion. The compound is shown to be potent against R5 and X4 isolates in both cell-cell fusion and antiviral assays (50% effective concentrations of ~0.1 to 1 [micro]M). Postfusion and HIV-1 pseudotyping control experiments confirm that PF-68742 is an entry inhibitor with Env as the specific target for antiviral action. PF-68742 was not able to block binding of monomeric gp120 to soluble CD4 or the binding of gp120:CD4 complexes to cell-associated CCR5, thus distinguishing PF-68742 from described gp120 antagonists and coreceptor binders. Escape variants of HIV-1NL4-3 were selected, and all resistant viruses were found to contain a common G514R (HxB2 numbering) mutation in Env, located proximal to the furin cleavage site in the fusion peptide of gp41. When introduced into wild-type NL4-3 gp41, G514R conferred resistance to PF-68742. Resistance via G514R is shown to be associated with enhancement of virion infectivity by PF-68742 that may result from altered properties of inhibitor-bound Env, rather than from a loss of compound binding. Wild-type viruses and those with substitutions in the disulfide loop (DSL) region of gp41 were also examined for PF-68742 sensitivity. Here, complete resistance to PF-68742 was found to occur through changes outside of position 514, including in the gp41 DSL region. The results highlight PF-68742 as a starting point for novel therapies against HIV-1 and provide new insights into models of Env-mediated fusion.
HIV epidemic has had greatest impact in sub-Saharan Africa (SSA) and mainly in East and Southern Africa with HIV prevalence in some parts going up to 30%. In the recent years, considerable HIV research on prevention, treatment and care, and vaccine has been conducted in many developing countries and provided evidence-based knowledge to control the epidemic. However, there have also been disappointing results in HIV prevention trials such as in HIV vaccine and microbicide trials. Despite these outcomes, important lessons have been learnt that help in designing future trials. This article examines the recent advances in HIV research in developing countries. The most recent HIV prevention research has demonstrated the effect of male circumcision on HIV acquisition, and lack of impact of HSV-2 treatment on HIV transmission and acquisition. Use of HIV antiretroviral drugs (ARVs) for HIV prevention is a new area that has attracted interest and a number of trials are examining the effect of oral Pre-Exposure Prophylaxis on HIV acquisition and also looking at the potential of ARVs in reducing infectiousness. Progress has been made in HIV treatment, monitoring treatment efficacy and toxicity as well as evaluation of different models of ART delivery. HIV vaccine research has, however, faced most challenges despite many efforts that have been put in. Looking into the future, there are ongoing trials that will hopefully generate important information to strengthen HIV policies in the next few years. There are, however, many other gaps in HIV research that need to be urgently addressed.
Prevention of mother to child transmission of HIV (PMTCT) programme in KwaZulu-Natal, South Africa: an evaluation of PMTCT implementation and integration into routine maternal, child and women's health services
Objectives To evaluate prevention of mother to child transmission of HIV (PMTCT) implementation and integration of PMTCT with routine maternal and child health services in two districts of KwaZulu-Natal; to report PMTCT coverage, to compare recorded and reported information, and to describe responsibilities of nurses and lay counsellors.
Methods Interviews were conducted with mothers in post-natal wards (PNW) and immunisation clinics; antenatal and child health records were reviewed. Interviews were conducted with nurses and lay counsellors in primary health care clinics.
Results Eight hundred and eighty-two interviews were conducted with mothers: 398 in PNWs and 484 immunisation clinics. During their recent pregnancy, 98.6% women attended antenatal care (ANC); 60.8% attended their first ANC in the third trimester, and 97.3% were tested for HIV. Of 312 mothers reporting themselves HIV positive during ANC, 91.3% received nevirapine, 78.2% had a CD4 count carried out, and 33.1% had a CD4 result recorded. In the immunisation clinic, 47.6% HIV-exposed babies had a PCR test, and 47.0% received co-trimoxazole. Of HIV-positive mothers, 42.1% received follow-up care, mainly from lay counsellors. In 12/26 clinics, there was a dedicated PMTCT nurse, PCR testing was not offered in 14/26 clinics, and co-trimoxazole was unavailable in 13/26 immunisation clinics. Nurses and lay counsellors disagreed about their roles and responsibilities, particularly in the post-natal period.
Conclusions There is high coverage of PMTCT interventions during pregnancy and delivery, but follow-up of mothers and infants is poor. Poor integration of PMTCT services into routine care, lack of clarity about health worker roles and poor record keeping create barriers to accessing services post-delivery.
DNA vaccines have undergone important enhancements in their design, formulation, and delivery process. Past literature supports that DNA vaccines are not as immunogenic in nonhuman primates as live vector systems. The most potent recombinant vector system for induction of cellular immune responses in macaques and humans is adenovirus serotype 5 (Ad5), an important benchmark for new vaccine development. Here, we performed a head-to-head evaluation of the Merck Ad5 SIV vaccine and an optimized electroporation (EP) delivered SIV DNA vaccine in macaques. Animals receiving the Ad5 vaccine were immunized three times, whereas the DNA-vaccinated animals were immunized up to four times based on optimized protocols. We observed significant differences in the quantity of IFN[gamma] responses by enzyme-linked immunosorbent spot (ELISpot), greater proliferative capacity of CD8+ T cells, and increased polyfunctionality of both CD4+ and CD8+ T cells in the DNA-vaccinated group. Importantly, Ad5 immunizations failed to boost following the first immunization, whereas DNA responses were continually boosted with all four immunizations demonstrating a major advantage of these improved DNA vaccines. These optimized DNA vaccines induce very different immune phenotypes than traditional Ad5 vaccines, suggesting that they could play an important role in vaccine research and development.
A combination gene therapy that endows human stem cells with three ways to resist HIV has passed its first safety test in humans. Four patients with AIDS who were infused with these cells tolerated the treatment, and the cells produced their anti-HIV weapons for up to two years. The study is published today in Science Translational Medicine. Not enough cells were transplanted in the trial to cure the patients or even reduce their viral load. But researchers hope that after further clinical trials, combination gene therapy may replace or complement anti-retroviral drugs as a way to treat people living with HIV. The trial piggybacked on a standard treatment, in which individuals with AIDS receive transplants of their own previously saved blood stem cells, in an attempt to prevent the development of lymphoma (blood cancer). In addition to normal blood stem cells, the patients were also given cells into which three types of RNA-based gene therapies were carried by a lentivirus.
Community engagement in research may enhance a community's ability to address its own health needs and health disparities issues while ensuring that researchers understand community priorities. However, there are researchers with limited understanding of and experience with effective methods of engaging communities. Furthermore, limited guidance is available for peer-review panels on evaluating proposals for research that engages communities.
The National Institutes of Health Director's Council of Public Representatives developed a community engagement framework that includes values, strategies to operationalize each value, and potential outcomes of their use, as well as a peer review framework for evaluating research that engages communities. Use of these frameworks for educating researchers to create and sustain authentic community-academic partnerships will increase accountability and equality between the partners.
Background In 2006 the World Health Organization described the status of prevention of mother to child transmission (PMTCT) service implementation as unacceptable, with an urgent need for a renewed public health approach to improve access. For PMTCT to be effective it needs to be accessible, acceptable and affordable; however research in Africa into accessibility, uptake and acceptability of PMTCT services has been predominately urban based and usually focusing on women who deliver in hospitals. The importance of involving other community members to strengthen both PMTCT uptake and adherence, and to support women emotionally, has been advocated. Urban men's and rural traditional birth attendants' (TBAs) involvement have improved uptake of HIV testing and of nevirapine.
Methods A qualitative study was carried out in a rural district of Malawi's central region to explore the views about and perceptions of PMTCT antiretroviral treatment. Semi-structured interviews and focus group discussions were held with antenatal and postnatal women, fathers, grandmothers, TBAs, community leaders and PMTCT health workers.
Results Two broad themes of findings emerged: those that relate to the hospital PMTCT service, and those that relate to the community. Trust in the hospital was strong, but distance, transport costs and perceived harsh, threatening health worker attitudes were barriers to access. Grandmothers were perceived to have influence on the management of labour, unlike fathers, but both were suggested as key people to ensure that babies are brought to the hospital for nevirapine syrup. TBAs were seen as powerful, local, and important community members, but some as uneducated.
Conclusion PMTCT was seen as a community issue in which more than the mother alone can be involved. To support access to PMTCT, especially for rural women, there is need for further innovation and implementation research on involving TBAs in some aspects of PMTCT services, and in negotiating with women which community members, if any, they would like to support them in ensuring that newborn babies receive nevirapine.
Background HIV incidence estimates are crucial in understanding and predicting the HIV/AIDS epidemic and identifying sub-populations and regions most at risk for the epidemic. However, incidence estimation is a challenge due to the nature of the disease and type of data available. This paper aims to present a simple and creative HIV incidence estimation method for resource constrained settings with scarce data.
Methods The authors developed a simple user-friendly non-iterative spreadsheet estimation method, which can produce incidence estimates by age group using observed cross-sectional, age-specific HIV prevalence. Data from two prospective FHI microbicide Phase III clinical trials in Nigeria were used to validate the spreadsheet method. Since both the clinical trials involved condom use promotion to reduce HIV risk, the authors also used the AVERT software to estimate the extent of incidence reduction due to the intervention.
Results The spreadsheet incidence estimates after accounting for AVERT adjusted reductions, for age groups 18-20, 21-25 and 26-30 were: 1.69%, 0.96% and 1.12% in the SAVVY trial, and 2.11%, 1.47% and 1.28% in the CS trial respectively. The corresponding actual observed incidence rates were 1.62%, 2.39%, and 1.13% in the SAVVY trial and 1.93%, 1.78% and 1.40% in the CS trial.
ConclusionComparisons of the spreadsheet-estimated incidence with the actual incidence from the clinical trials demonstrated that the method is reasonably accurate in its estimation. Because of the method's limitations it should not be used to evaluate HIV/AIDS prevention interventions or without understanding the direction of the bias in the case of an evolving HIV epidemic.
Weigh in on NIAID's HIV/AIDS Prevention Research Agenda
Date: 21 June 2010 Source: National Institute of Allergy and Infectious Diseases (NIAID) http://blog.aids.gov/
NIAID is looking to expand the focus of its HIV/AIDS clinical trial networks and is seeking thoughtful input from the research and HIV/AIDS communities on how best to do that. Over the next several weeks, NIAID will be blogging on http://www.aids.gov/ on a series of topics related to the future direction of its HIV/AIDS networks. Each blog post will feature questions designed to spark feedback from the broader community.
On June 18, 2020, FDA approved a new, "4th generation" HIV diagnostic assay. The ARCHITECT HIV Ag/Ab Combo Assay is the first HIV diagnostic assay that simultaneously detects both antigen and antibodies for the Human Immunodeficiency Virus (HIV). The new test is also the first diagnostic test approved by FDA for use in children as young as 2 years of age, and pregnant women.
This single, automated test, known as the ARCHITECT HIV Ag/Ab Combo Assay, is a highly sensitive chemiluminescent microparticle immunoassay intended to be used as an aid in the diagnosis of HIV-1/HIV-2 infection, including acute or primary HIV-1 infection. It is specific for the detection of the HIV-1 p24 antigen (the substance found on the virus that triggers the production of antibodies), as well as antibodies to HIV-1 groups M and O, and as antibodies to HIV-2.
News on the progress of a new trial may give new hope to patients with HIV who are dependent on anti-HIV drugs. The AIDS Research Consortium of Atlanta (ARCA) has received approval to begin enrollment of the first therapeutic trial ever conducted using a promising HIV vaccine candidate from Atlanta-based, GeoVax Inc, a biotechnology company that creates, develops and tests innovative HIV/AIDS vaccines. Although the GeoVax vaccines are currently being studied for HIV prevention, this is the first study using the same products for treatment of persons who already have HIV infection. ARCA is the only site for this trial.
"ARCA is pleased to be conducting this important clinical trial," said Dr. Melanie Thompson, Principal Investigator for ARCA. "New approaches to HIV treatment are critically needed, and an effective therapeutic vaccine would be an important tool in our ongoing efforts to treat people with HIV infection. A vaccine that enhanced the body's ability to control HIV and delayed or decreased the dependence on anti-HIV drugs would be a major breakthrough for HIV treatment."
The U.S. government continues to lay the groundwork for efforts under the U.S. Global Health Initiative (GHI), announcing the first round of "GHI Plus" countries, as well as the program's governance structure. GHI is a six-year, $63 billion initiative to help partner countries improve measurable health outcomes by strengthening health systems and building upon proven results. It places a particular focus on improving the health of women, newborns and children. Pursuing a comprehensive approach, GHI includes programs addressing HIV/AIDS, malaria, tuberculosis, maternal and child health, nutrition, family planning and reproductive health, and neglected tropical diseases. These U.S. global health investments are an important component of our national security "smart power" strategy, critical to national security as well as our common security.
GHI activities are being implemented in the more than 80 countries where U.S. government global health dollars are already at work. Under GHI, the U.S. government will coordinate with partner country governments to ensure that investments align with national priorities and build capacity. Eight countries have been selected as the first set of "GHI Plus" countries. They are: Bangladesh, Ethiopia, Guatemala, Kenya, Malawi, Mali, Nepal, and Rwanda. These countries will receive additional technical and management resources to quickly implement GHI's approach, including integrated programs and investments across the spectrum of infectious diseases, maternal and child health, family planning, and health systems activities. GHI Plus countries will provide enhanced opportunities to build upon existing public health programs; improve program performance; and work in close collaboration with partner governments, across U.S. government agencies, and with global partners.
All India Institute of Medical Sciences Institute of Medical Sciences, New Delhi, India is organizing an International Conference on Opportunistic Pathogens from September 27-30, 2010. The conference will focus on several breakthroughs which have occurred recently in the field of HIV/AIDS such as co-pathogens of HIV, receptor attachment, neuropathology, tissue tropism, use of nanomedicine in HIV treatment, testing guidelines for diagnosis and blood safety, opt-out and universal testing strategies, drug resistance mechanisms and future vaccines against HIV.