17 SEPTEMBER 2010, VOLUME 11, ISSUE 34

Health enterprises in the emerging economies, particularly in China, India and Brazil, have made significant contributions to local and global health needs through low-cost manufacturing of health products. Moreover, a key policy objective for these countries is to foster a strong and innovative health biotech/pharmaceutical sector. The health biotech companies in this sector are innovating close to the 'coalface' of global health problems, making appropriateness, translation, uptake and affordability of the resulting solutions more likely. Even so, the shift from imitation to innovation in these countries--a trend largely stimulated by the adoption of the World Trade Organization's (WTO; Geneva) Trade-Related Aspects of Intellectual Property Systems (TRIPS)--is raising questions about the future market trajectory of the sector.

A basic question is whether this movement toward innovative products would mean movement away from poorer market segments, both at home and abroad. Stated differently, as enterprises in the emerging markets take on more costly innovative projects, would they be compelled to choose between global health and global wealth? Alternatively, is it possible for health entrepreneurs in the emerging economies, as their firms become more sophisticated technologically and financially, to address the needs of the poor while simultaneously taking advantage of more lucrative markets?

Almost 30 years after the Centers for Disease Control first identified the acquired immunodeficiency syndrome (AIDS) and its cause, the human immunodeficiency virus (HIV), the story of AIDS has largely devolved into one of sterile numbers and cold statistics. About 1.1 million Americans are living with HIV. More than 56,000 people are infected each year in the United States, and more than 575,000 Americans have lost their lives since the onset of the epidemic.

But while these statistics are horrifying and should never be minimized, the real story of HIV/AIDS in this country has largely been forgotten -- that of the individual's struggle against this terrible disease.

The New York office director of UNAIDS, Bertil Lindblad, is worried about the one region of the world where HIV infections are increasing, even as rates in the rest of the world level off. It's not in Africa or Asia, or even Latin America. It's Eastern Europe -- countries like Russia and Ukraine -- where a recent UNICEF report notes that increases in infection rates of as high as 700 percent have been seen since 2006.

"There is an urgent need for the whole Eastern European and Central Asian region to act quickly," Lindblad said this morning. "This is really quite scary given the fact that there is denial, and so much stigma and homophobia [in that region.] This could really create huge problems if HIV continues to spread from smaller groups in the population to wider."

It's HIV/AIDS's silent crisis, one that has been underway for the last decade. The region is home to a quarter of all injection drug users in the world (3.7 million), and this is where the epidemic is believed to have begun. These users are young -- most of them teenagers. But from there, HIV spread to sex workers (the majority of whom are also under 30), and now has fully moved into the everyday lives of men and women in the region, married and unmarried. A mark of the epidemic's progression -- from specific populations into the majority -- is the new incidence of HIV among women, who account for 40 percent of all new infections (that's up from only 24 percent at the turn of the century.)

HIV-positive patients about to start antiretroviral treatment are warned not to skip even the occasional dose of their medication because of the virus' ability to mutate rapidly and become drug resistant; but what about patients who have never taken treatment and already have a drug-resistant strain of the virus?

In Africa the extent of "primary", or transmitted HIV drug resistance in treatment-naive (never treated) patients is largely unknown, but a recent study at three clinics in Lusaka, Zambia, found that nearly 6 percent of patients about to start HIV treatment for the first time already had resistance to standard first-line antiretroviral (ARV) drugs.

The study was part of a programme to monitor transmitted HIV drug resistance, as well as "secondary" drug resistance (acquired during treatment), coordinated by the PharmAccess African Studies to Evaluate Resistance (PASER) - a project of the PharmAccess Foundation, a Dutch health NGO - and part of a broader initiative to track HIV drug resistance in Africa and Asia.

The Botswana government has passed an amendment to its Employment Act that will bring an end to dismissal based on an individual's sexual orientation or HIV status, but rights groups believe the legislation needs to go further. Civil society organizations in Botswana welcomed the move but said legislation to protect the rights of people living with HIV in the workplace was necessary.

In a 30 August statement, the Botswana Network on Ethics, Law and HIV/AIDS (BONELA) said that it had evidence that some employers had been using HIV status as grounds for dismissal, and welcomed the amended Employment Act as "a progressive move on the part of government, which is likely to uproot stigma and discrimination within the workplace".

For the past five years Musa* and his wife have known that their HIV status was different [discordant]. Now the father of two healthy, HIV-negative children, he spoke to IRIN/PlusNews about how he and his wife - like many couples - did not know discordancy existed, and had trouble finding the answers and services they needed.

"We were actually married in 2003, but in 2005 we were supposed to have a baby. At that moment in my career, I was [very successful] ... I thought my life was made until she went for antenatal [services]. "At that time, in Kenya [health workers at antenatal clinics] used ... to tell the women, 'Make sure you come with your [HIV test] results, and that of your partner, at your next visit.' "To cut a long story short, she [his wife] kept on pestering me, saying, 'We need to go for the [HIV] test because we need [to take] the results ... to the antenatal clinic.'
* Not his real name

Johnson & Johnson has pledged grant money, drugs and research funding for new HIV and tuberculosis medications as part of a five-year, private sector effort to improve the health of up to 120 million women and children in developing nations each year. The announcement on Wednesday by the drug, medical device and consumer products company supports the United Nations' call this year for a renewed push to meet the Millennium Development Goals of preventing premature deaths in women and children by 2015.

The US government has boosted its assistance to Uganda's AIDS programme with an emergency supply of antiretroviral (ARV) drugs worth more than US$5.5 million to begin to put an estimated 72,000 HIV-infected people on the treatment over the next two years. But it has also served notice that Uganda must find new sources of funding if its HIV programmes are to be sustainable.

"This donation by the American people will help bridge the gap in the availability of ARV drugs in Uganda and prevent stock-outs of the life-saving HIV/AIDS medications," said the US ambassador to Uganda, Jerry Lanier.

The donation is part of an increase in funding recently announced by the US President's Emergency Plan for AIDS Relief (PEPFAR) following appeals from Ugandan AIDS activists and health providers struggling to put patients on ARVs.

Could the aggressive strategies used in gaming come to the rescue of the biomedical research community? The Myelin Repair Foundation thinks so. The non-profit medical research organization is hosting a special "gaming event" this fall for R&D experts and biotech players designed to get them to shed their carefully laid plans in favor of forging a breakthrough approach to drug research.

"Those who play games have a sense of urgency and abandon when they are engaged in a game scenario," says Jane McGonigal, game designer and producer of the BreakthroughstoCures events. "We have seen these behaviors in corporate strategic game play where there are real stakes. The game we are building for the MRF is designed to generate that sort of urgency and unleash creative ideas for finding ways to speed medical research."

Anyone who's seen gamers performing at their top level know the way they can throw themselves into the action, shedding restraint in favor of a go-for-the-throat plan for victory. That's the kind of thinking the organizers want to see in biopharma execs and researchers--two groups not known for wild risk taking. The foundation has its own approach to accelerated drug development for MS and hopes to find some new collaborators in the process.

Freer trade could harm India's generic drug business, which supplies the bulk of the AIDS medicines sent to developing countries, a study backed by the drug-purchasing body UNITAID said on Tuesday. The report, written by a UNITAID official along with experts from Boston University and Harvard, warns that India's generics could cost more and be harder to access if the country has to adhere to stricter intellectual property rules. It said trade deals India already signed up to, such as the World Trade Organisation intellectual property accord known as TRIPS, have already begun to complicate efforts to get cheap, life-saving drugs to poorer countries.

"The introduction of product patents in India is severely constraining generic competition and supply, particularly for newer medicines," the report found. "Many free trade agreements that have been concluded or are being negotiated between industrialized and developing countries contain measures that restrict access to medicines."

To read the abstract in the Journal of the International AIDS Society, see "A lifeline to treatment: the role of Indian generic manufacturers in supplying antiretroviral medicines to developing countries" in the "Published Research" section of this issue of the NewsDigest.

Doctors and AIDS activists on Friday urged African governments to fulfill a decade-old pledge to spend more of their own money on health if they want international help in fighting AIDS. Graca Machel, a longtime advocate for children in her homeland of Mozambique and around the world, told reporters Friday that African governments need to honor pledges made at an African Union summit in 2001 to devote at least 15 percent of national budgets to health. To date, only a half dozen countries have done so. Machel blamed a lack of political will. "We have to prove ourselves if we are to have the courage to look into the eyes of our children and say, `We do care,'" she said.

Strengthened health systems will mean more pregnant women will get prenatal care and be tested for HIV, the virus that causes AIDS. Those who test positive can take drugs that will prevent HIV from being transmitted to infants. Dr. Avertino Barreto, Mozambique's deputy director of health, said foreigners cannot be expected to help if Africans don't help themselves. "I believe that donors will come," Barreto said. "But African governments ... must take the first decision."

Thanks to a $4.1 million grant from the National Cancer Institute (NCI), researchers at the Albert Einstein College of Medicine of Yeshiva University will begin studying the microbicide Carraguard(R) and its activity against HPV. Specifically, the research will include a clinical trial and translational work to evaluate the efficacy of the microbicide in preventing new HPV infections in women. It is a clear gel made from the seaweed derivative carrageenan.

Previous studies of Carraguard(R), including a recent phase 3 trial, did not demonstrate effectiveness against HIV. However, it was shown to be safe. Recent laboratory tests now indicate that carrageenan is about 1,000 times more effective against HPV than against HIV. Einstein researchers will enroll 200 women in their clinical trial. They will be assigned to use either Carraguard(R) or a placebo gel. At the end of 1 year, the women will be examined to determine if the microbicide protected them from acquiring HPV infections. Assays will also be performed to assess its activity and to develop a predictive test for efficacy. Samples will also be taken to look for signs that the gel alters the body's natural defenses against HPV. If so, this would point to potential problems with efficacy and safety in clinical use.

June 2013 -- that's the 'realistic' date by which vulnerable South African women can expect to begin using an officially approved vaginal microbicide gel that would provide them with an unprecedented tool to protect themselves from HIV infection. This is the belief of biochemist and epidemiologist, Dr Quarraisha Abdool Karim, who, together with her clinician and fellow epidemiologist husband, Professor Salim Abdool Karim, led the now world-renowned 'proof of concept' trial of tenofovir vaginal gel to prevent HIV infection in women.

In a 3-year study of 889 women in both rural and urban KwaZulu-Natal, they demonstrated a 39% reduction in HIV infection and a 51% reduction in genital herpes infection among women who used the gel (containing 1% of the antiretroviral (ARV), tenofovir). The trial results dominated the XVIIIth International AIDS Conference in Vienna, Austria, in July and led to a clamour for confirmatory studies and fast-tracking of the gel, of which the efficacy increases with use. (Women who used the gel in more than 80% of their sex acts had a 54% reduction in HIV infections.) Unlike other HIV prophylactic trials that use available tablets, the tenofovir gel was manufactured only for the trial, run by the Durban-based Centre for AIDS Programme Research in South Africa (CAPRISA), of which the research couple are directors.

THE University of York is opening its 5 million (British Pounds) Centre for Immunology and Infection (CII) today as part of its Heslington Campus expansion plans. The joint research centre created by the Hull York Medical School (HYMS) and the Department of Biology at the University of York will develop drugs and vaccines to combat chronic diseases, such as Crohn's Disease, diabetes and HIV/AIDS. The building is being officially opened today by Dr Robert Ridley, director of TDR, the World Health Organisation's special programme for research and training in tropical diseases, following a conference on immunity and infection featuring speakers from across the world.

Opinion Piece
Global HIV surveillance among MSM: is risk behavior seriously underestimated?
Bengtsson L, et al.
 
Basic Science
CXCR4-using viruses in plasma and peripheral blood mononuclear cells during primary HIV-1 infection and impact on disease progression
Raymond S, et al.
Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals
Fourati S, et al.
Distinct differentiation profiles of HIV-Gag and Nef-specific central memory CD8+ T cells associated with HLA-B57/5801 and virus control
Xie J, et al.
 
Clinical Science
A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod
Fox PA, e t al.
Prospective study of bone mineral density changes in aging men with or at risk for HIV infection
Sharma A, et al.
Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir
Gutmann C, et al.
Episomal and integrated human papillomavirus type 16 loads and anal intraepithelial neoplasia in HIV-seropositive men
Alvarez J, et al.
Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136
Katlama C, et al.
Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation
Tosini W, et al.
Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome
Meintjes G, et al.
Time course of total HIV-1 DNA and 2-long-terminal repeat circles in patients with controlled plasma viremia switching to a raltegravir-containing regimen
Delaugerre C, et al.
 
Epidemiology and Social Science
Epidemiology of non-B clade forms of HIV-1 in men who have sex with men in the UK
Fox J, et al.
 
Research Letters
Lower arterial stiffness and Framingham score after switching abacavir to tenofovir in men at high cardiovascular risk
Sinn K, et al.
HIV-1 Gag evolution in recently infected human leukocyte antigen-B*57 patients with low-level viremia
Durand CM, et al.
Detrimental clinical interaction between ritonavir-boosted protease inhibitors and vinblastine in HIV-infected patients with Hodgkin's lymphoma
Cingolani A, et al.
HIV genetic diversity between plasma and cerebrospinal fluid in patients with HIV encephalitis
Soulie C, et al.
 
Correspondence
Incorrect attribution of cerebrospinal fluid HIV-1 virological escape and lymphocytic meningitis to lopinavir/ritonavir monotherapy
Perez-Valero I, et al.
High neonatal concentrations of raltegravir following transplacental transfer in HIV-1 positive pregnant women
Mckeown DA, et al.
Infectiousness of HIV-infected homosexual men in the era of highly active antiretroviral therapy
Baggaley RF, et al.

Purpose We assessed U.S. physicians' attitudes and perceptions regarding potential human papillomavirus (HPV) vaccination of males.

Methods We surveyed a random sample of 2,714 pediatricians and family practitioners identified in administrative claims of a U.S. health plan as HPV vaccinators of females; 595 pediatricians and 499 family practitioners participated.

Results Most physicians would recommend HPV vaccination to males aged 11-12 (63.9%), 13-18 (93.4%), and 19-26 (92.7%) years. Physicians agreed that males should be vaccinated to prevent them from getting genital and anal warts (52.9% strongly and 36.0% somewhat) and to protect females from cervical cancer (75.3% strongly and 20.8% somewhat). Physicians agreed that an HPV vaccine recommendation for males would increase opportunities to discuss sexual health with adolescent male patients (58.7% strongly, 35.3% somewhat). Most did not strongly agree (15.4% strongly, 45.4% somewhat) that parents of adolescent male patients would be interested in HPV vaccination for males, that a gender-neutral HPV vaccine recommendation would increase acceptance by adolescent females and their parents (19.6% strongly, 42.0% somewhat), or that a gender-neutral recommendation would improve current female vaccination rates (10.4% strongly, 26.0% somewhat).

Conclusions Physicians who currently vaccinate females against HPV supported the concept of vaccinating males for its benefits for both sexes. They agreed that a gender-neutral HPV vaccination recommendation would be appropriate with regard to public health and believed that it would increase opportunities for sexual health discussions, but were less sure that such a recommendation would change patient or parental attitudes toward HPV vaccination or improve current HPV vaccination efforts.

Background Routine national incidence testing with enzyme immunoassay for recent HIV-1 infections (EIA-RI) has been done in France since January, 2003. From the reported number of HIV infections diagnosed as recent, and accounting for testing patterns and under-reporting, we aimed to estimate the incidence of HIV infection in France in 2003-08.

Methods We analysed reports from the French National Institute for Public Health Surveillance for patients who were newly diagnosed with HIV between January, 2003, and December, 2008. Missing data were imputed with multiple imputation. Patients were classified with non-recent or recent infection on the basis of an EIA-RI test, which was calibrated with serial measurements from HIV seroconverters from the French ANRS-PRIMO cohort. We used an adapted stratified extrapolation approach to calculate the number of new HIV infections in men who have sex with men (MSM), injecting drug users (IDUs), and heterosexual men and women by nationality. Population sizes were obtained from the national census and national behavioural studies.

Findings After accounting for under-reporting, there were 6480 (95% CI 6190-6780) new diagnoses of HIV infection in France in 2008. We estimate that there were 6940 (6200-7690) new HIV infections in 2008, suggesting an HIV incidence of 17 per 100 000 person-years. In 2008, there were 3550 (3040-4050) new infections in heterosexuals (incidence of 9 per 100 000 person-years), 3320 (2830-3810) in MSM (incidence of 1006 per 100 000 person-years), and 70 (0-190) in IDUs (incidence of 86 per 100 000 person-years). Overall HIV incidence decreased between 2003 and 2008 (p<0.0001), but remained comparatively high and stable in MSM.

Interpretation In France, HIV transmission disproportionately affects certain risk groups and seems to be out of control in the MSM population. Incidence should be tracked to monitor transmission dynamics in the various population risk groups and to help to target and assess prevention strategies.

Background Sexual health promotion is a major public health challenge; there is huge potential for health promotion via technology such as the Internet.

Objectives To determine effects of interactive computer-based interventions (ICBI) for sexual health promotion, considering cognitive, behavioural, biological and economic outcomes.

Search strategy We searched more than thirty databases for randomised controlled trials (RCTs) on ICBI and sexual health, including CENTRAL, DARE, MEDLINE, EMBASE, CINAHL, British Nursing Index, and PsycINFO. We also searched reference lists of published studies and contacted authors. All databases were searched from start date to November 2007, with no language restriction.

Selection criteria RCTs of interactive computer-based interventions for sexual health promotion, involving participants of any age, gender, sexual orientation, ethnicity or nationality. 'Interactive' was defined as packages that require contributions from users to produce tailored material and feedback that is personally relevant.

Data collection and analysis Two review authors screened abstracts, applied eligibility and quality criteria and extracted data. Results of RCTs were pooled using a random-effects model with standardised mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for binary outcomes. We assessed heterogeneity using the I2 statistic. Separate meta-analyses were conducted by type of comparator: 1) minimal intervention such as usual practice or leaflet, 2) face-to-face intervention or 3) a different design of ICBI; and by type of outcome (cognitive, behavioural, biological outcomes).

Main results We identified 15 RCTs of ICBI conducted in various settings and populations (3917 participants). Comparing ICBI to 'minimal interventions' such as usual practice, meta-analyses showed statistically significant effects as follows: moderate effect on sexual health knowledge (SMD 0.72, 95% CI 0.27 to 1.18); small effect on safer sex self-efficacy (SMD 0.17, 95% CI 0.05 to 0.29); small effect on safer-sex intentions (SMD 0.16, 95% CI 0.02 to 0.30); and also an effect on sexual behaviour (OR 1.75, 95% CI 1.18 to 2.59). Data were insufficient for meta-analysis of biological outcomes and analysis of cost-effectiveness. In comparison with face-to-face sexual health interventions, meta-analysis was only possible for sexual health knowledge, showing that ICBI were more effective (SMD 0.36, 95% CI 0.13 to 0.58). Two further trials reported no difference in knowledge between ICBI and face-to-face intervention, but data were not available for pooling. There were insufficient data to analyse other types of outcome. No studies measured potential harms (apart from reporting any deterioration in measured outcomes).

Authors' conclusions ICBI are effective tools for learning about sexual health, and they also show positive effects on self-efficacy, intention and sexual behaviour. More research is needed to establish whether ICBI can impact on biological outcomes, to understand how interventions might work, and whether they are cost-effective.

Context Protease inhibitor (PI)-based therapy is recommended for infants infected with human immunodeficiency virus (HIV) who were exposed to nevirapine for prevention of mother-to-child HIV transmission. However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages.

Objective To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy.

Design, Setting, and Patients Randomized trial conducted between April 2005 and May 2009 at a hospital in Johannesburg, South Africa, among 195 children who achieved viral suppression less than 400 copies/mL for 3 or more months from a cohort of 323 nevirapine-exposed children who initiated PI-based therapy before 24 months of age.

Interventions Control group children continued to receive ritonavir-boosted lopinavir, stavudine, and lamivudine (n = 99). Switch group children substituted nevirapine for ritonavir-boosted lopinavir (n = 96).

Main Outcome Measures Children were followed up for 52 weeks after randomization. Plasma HIV-1 RNA of greater than 50 copies/mL was the primary end point. Confirmed viremia greater than 1000 copies/mL was used as a criterion to consider regimen changes for children in either group (safety end point).

Results Plasma viremia greater than 50 copies/mL occurred less frequently in the switch group (Kaplan-Meier probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95% CI, 0.470-0.668) (P = .02). Confirmed viremia greater than 1000 copies/mL occurred more frequently in the switch group (0.201; 95% CI, 0.125-0.289) than in the control group (0.022; 95% CI, 0.004-0.069) (P < .001). CD4 cell response was better in the switch group (median CD4 percentage at 52 weeks, 34.7) vs the control group (CD4 percentage, 31.3) (P = .004). Older age (relative hazard [RH], 1.71; 95% CI, 1.08-2.72) was associated with viremia greater than 50 copies/mL in the control group. Inadequate adherence (RH, 4.14; 95% CI, 1.18-14.57) and drug resistance (RH, 4.04; 95% CI, 1.40-11.65) before treatment were associated with confirmed viremia greater than 1000 copies/mL in the switch group.

Conclusion Among HIV-infected children previously exposed to nevirapine, switching to nevirapine-based therapy after achieving viral suppression with a ritonavir-boosted lopinavir regimen resulted in lower rates of viremia greater than 50 copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen.

Editor's Note: Abstract unavailable. Article available as HTML full text and PDF with a subscription.

The notion that concurrent sexual partnerships are especially common in sub-Saharan Africa and explain the region's high HIV prevalence is accepted by many as conventional wisdom. In this paper, we evaluate the quantitative and qualitative evidence offered by the principal proponents of the concurrency hypothesis and analyze the mathematical model they use to establish the plausibility of the hypothesis. We find that research seeking to establish a statistical correlation between concurrency and HIV prevalence either finds no correlation or has important limitations. Furthermore, in order to simulate rapid spread of HIV, mathematical models require unrealistic assumptions about frequency of sexual contact, gender symmetry, levels of concurrency, and per-act transmission rates. Moreover, quantitative evidence cited by proponents of the concurrency hypothesis is unconvincing since they exclude Demographic and Health Surveys and other data showing that concurrency in Africa is low, make broad statements about non-African concurrency based on very few surveys, report data incorrectly, report data from studies that have no information about concurrency as though they supported the hypothesis, report incomparable data and cite unpublished or unavailable studies. Qualitative evidence offered by proponents of the hypothesis is irrelevant since, among other reasons, there is no comparison of Africa with other regions. Promoters of the concurrency hypothesis have failed to establish that concurrency is unusually prevalent in Africa or that the kinds of concurrent partnerships found in Africa produce more rapid spread of HIV than other forms of sexual behaviour. Policy makers should turn attention to drivers of African HIV epidemics that are policy sensitive and for which there is substantial epidemiological evidence.

Background More than 90% of children living with HIV have been infected through mother to child transmission. The aims of our present study were to: (1) assess the utilization of the prevention of mother to child transmission (PMTCT) services in five reproductive and child health clinics in Moshi, northern Tanzania, after the implementation of routine counselling and testing; (2) explore the level of knowledge the postnatal mothers had about PMTCT; and (3) assess the quality of the counselling given.

Methods This study was conducted in 2007 and 2008 in rural and urban areas of Moshi in the Kilimanjaro region of Tanzania. Mixed methods were used. We interviewed 446 mothers when they brought their four-week-old infants to five reproductive and child health clinics for immunization. On average, the urban clinics included in the study had implemented the programme two years earlier than the rural clinics. We also conducted 13 in-depth interviews with mothers and nurses, four focus group discussions with mothers, and four observations of mothers receiving counselling.

Results Nearly all mothers (98%) were offered HIV testing, and all who were offered accepted. However, the counselling was hasty with little time for clarifications. Mothers attending urban antenatal clinics tended to be more knowledgeable about PMTCT than the rural attendees. Compared with previous studies in the area, our study found that PMTCT knowledge had increased and the counsellors had greater confidence in their counselling.

Conclusions Routine counselling and testing for HIV at the antenatal clinics was greatly accepted and included practically every mother in this time period. However, the counselling was suboptimal due to time and resource constraints. We interpret the higher level of PMTCT knowledge among the urban as opposed to the rural attendees as a result of differences in the start up of the PMTCT programme and, thus, programme maturation. After comparison with earlier studies conducted in this setting, we conclude that when the programme has had time to get established, both its acceptance and the understanding of the topics dealt with during the counselling increases.

Background Indian manufacturers of generic antiretroviral (ARV) medicines facilitated the rapid scale up of HIV/AIDS treatment in developing countries though provision of low-priced, quality-assured medicines. The legal framework in India that facilitated such production, however, is changing with implementation of the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights, and intellectual property measures being discussed in regional and bilateral free trade agreement negotiations. Reliable quantitative estimates of the Indian role in generic global ARV supply are needed to understand potential impacts of such measures on HIV/AIDS treatment in developing countries.

Methods We utilized transactional data containing 17,646 donor-funded purchases of ARV tablets made by 115 low- and middle-income countries from 2003 to 2008 to measure market share, purchase trends and prices of Indian-produced generic ARVs compared with those of non-Indian generic and brand ARVs.

Results Indian generic manufacturers dominate the ARV market, accounting for more than 80% of annual purchase volumes. Among paediatric ARV and adult nucleoside and non-nucleoside reverse transcriptase inhibitor markets, Indian-produced generics accounted for 91% and 89% of 2008 global purchase volumes, respectively. From 2003 to 2008, the number of Indian generic manufacturers supplying ARVs increased from four to 10 while the number of Indian-manufactured generic products increased from 14 to 53. Ninety-six of 100 countries purchased Indian generic ARVs in 2008, including high HIV-burden sub-Saharan African countries. Indian-produced generic ARVs used in first-line regimens were consistently and considerably less expensive than non-Indian generic and innovator ARVs. Key ARVs newly recommended by the World Health Organization are three to four times more expensive than older regimens.

Conclusions Indian generic producers supply the majority of ARVs in developing countries. Future scale up using newly recommended ARVs will likely be hampered until Indian generic producers can provide the dramatic price reductions and improved formulations observed in the past. Rather than agreeing to inappropriate intellectual property obligations through free trade agreements, India and its trade partners - plus international organizations, donors, civil society and pharmaceutical manufacturers - should ensure that there is sufficient policy space for Indian pharmaceutical manufacturers to continue their central role in supplying developing countries with low-priced, quality-assured generic medicines.

See also Reuters article, "Freer trade may hurt access to India generic drugs", in the "Media Coverage" section of this issue of the NewsDigest.

As efficacy trials of antiretroviral pre-exposure prophylaxis (PrEP) continue, a growing literature has begun anticipating the potential challenges of implementing PrEP for HIV prevention. These efforts coincide with a shift toward combination interventions for preventing HIV, which integrate biomedical, behavioral, and structural components. The optimal implementation of PrEP would exemplify this combination model, incorporating not only PrEP drugs, but also HIV testing, safety screening, behavioral interventions addressing adherence and risk behavior, and long-term monitoring. Efforts to plan for PrEP implementation therefore present an opportunity to advance the science of implementation and delivery in HIV prevention, in order to better address the challenges of scaling up combination approaches. We review the published and unpublished literature on PrEP implementation, organizing themes into five categories: scientific groundwork, regulatory and policy groundwork, stakeholder and infrastructure groundwork, delivery, and long-term monitoring. The lessons from PrEP planning can benefit the scale-up of future combination interventions.

Semen was recently shown to contain amyloid fibrils formed from a self-assembling peptide fragment of the protein prostatic acid phosphatase. These amyloid fibrils, termed semen-derived enhancer of virus infection, or SEVI, have been shown to strongly enhance HIV infectivity and may play an important role in sexual transmission of HIV - making them a potential microbicide target. One novel approach to target these fibrils is the use of small molecules known to intercalate into the structure of amyloid fibrils, such as derivatives of thioflavin-T. Here, we show that the amyloid binding small molecule BTA-EG6 is able to bind SEVI fibrils and effectively inhibit both SEVI and semen-mediated enhancement of HIV infection. BTA-EG6 also blocks the interactions of SEVI with HIV-1 virions and HIV-1 target cells, but does not cause any inflammation or toxicity to cervical epithelial cells. These results suggest that an amyloid-binding small molecule may have utility as a microbicide, or microbicidal supplement, for HIV-1.

The Food and Drug Administration's (FDA or agency) Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) are announcing a public meeting to solicit comments and concerns of industry, other government agencies, and interested parties on the regulatory and scientific challenges as addressed in the draft document entitled "Guidance for Industry: Animal Models--Essential Elements to Address Efficacy Under the Animal Rule" dated January 2009 (Draft Guidance), and as related to the development of medical countermeasures under the "Animal Rule" with respect to chemical, biological, radiological, or nuclear (CBRN) threats. Comments on these issues will be considered in connection with the development of a final version of the Draft Guidance:.
Date November 5, 2010
Time 8:00 a.m. to 5:30 p.m.
Location FDA White Oak Complex, 10903 New Hampshire Avenue, Bldg. 31, Room 1503, Silver Spring, Maryland, 20993-0002

On September 10, 2010, the Food and Drug Administration granted tentative approval for a fixed dose combination formulation of lamivudine, nevirapine, and stavudine tablets, 150 mg/200 mg/30 mg indicated for use alone or in combination with other antiretrovirals for the treatment of HIV-1 infection. This fixed-dose combination is manufactured by Hetero Drugs Limited of Hyderabad, India.

FDA's tentative approval means that although a product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., existing patents and/or proprietary issues currently prevent marketing of the product in the United States. Tentative approval, however, does qualify the product for consideration for purchase under the President's Emergency Plan for AIDS Relief, or PEPFAR program.

A complete list of all Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan is available on the FDA web site.

From Anthony S. Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases; Richard J. Hodes, M.D., Director, National Institute on Aging; Jack Whitescarver, Ph.D., Director, NIH Office of AIDS Research

Older HIV-infected adults face unique health challenges stemming from age-related changes to the body accelerated by HIV infection, the side effects of long-term treatment for HIV, the infection itself and often, treatments for age-associated illnesses. Sept. 18 marks the third annual National HIV/AIDS and Aging Awareness Day, an opportunity to highlight these challenges and the research under way to improve the health and quality of life of older people infected with HIV.

Many HIV-infected individuals are living into their 50s and well beyond as a result of the powerful combinations of antiretroviral drugs that suppress the replication of the virus. In 2006, an estimated 25 percent of people living with HIV in the United States were age 50 years and older. In those with long-term HIV infection, the persistent activation of immune cells by the virus likely increases the susceptibility of these individuals to inflammation-induced diseases and diminishes their capacity to fight certain diseases. Coupled with the aging process, the extended exposure of these adults to both HIV and antiretroviral drugs appears to increase their risk of illness and death from cardiovascular, bone, kidney, liver and lung disease, as well as many cancers not associated directly with HIV infection.

When September 21, 2010 - September 22, 2010 (9:00 AM)
Where Keck Center (Room 100), 500 Fifth St. NW, Washington, DC 20001

The neglected tropical diseases (NTDs) represent possibly the worst of all diseases in terms of their destabilizing effects and their relationship to conflict. The NTDs are the most common infections of the bottom billion, in whom they cause chronic, debilitating, disabling, and disfiguring effects. One of the most important features of the NTDs is their tendency not only to occur in the setting of poverty, but also to exacerbate poverty and to destabilize communities.

Although medically diverse, neglected tropical diseases share features that allow them to persist in conditions of poverty, where they cluster and frequently overlap. Approximately 1.4 billion people - one sixth of the world's population - suffer from one or more neglected tropical diseases. Conflict situations or natural disasters aggravate conditions that are conducive to the spread of these diseases.  Around half of the world's population is at risk of NTD infections.  The human NTDs are diseases of poverty, afflicting the world's poorest and trapping them in a cycle of poverty.  The global burden of the neglected tropical diseases is equivalent to at least half of the global burden of HIV/AIDS, TB, and malaria combined.

The Institute of Medicine's Forum on Microbial Threats will hold a 2-day public workshop in order to explore the scientific and policy dimensions of neglected tropical and zoonotic diseases.  Through presentations and discussions, this workshop will illuminate the evolutionary, genetic, and ecological origins of the neglected tropical and zoonotic diseases and their increasing impacts on human and animal health, economic productivity, and opportunities for medical diplomacy and global engagement.

The 2011 BIO International Convention is the forum where you'll want your thoughts, ideas and innovations to be seen and heard. Grab your chance to gain credibility with the industry's most influential audience by submitting a session proposal or apply to present a company presentation.

Inovio Pharmaceuticals, Inc., a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that it has achieved best-in-class immune responses in its Phase I dose escalation study of VGX-3100, its DNA vaccine to treat pre-cancerous cervical dysplasias and cervical cancers caused by human papillomavirus (HPV) types 16 and 18. This vaccine targets HPV E6 and E7 proteins and is delivered via in vivo electroporation. All dose groups developed significant antibody and T-cell immune responses; however, more notably, in the third and final dose group, five of six (83%) patients developed unprecedented T-cell responses not achieved by any other non-replicating vaccine platform in humans. Inovio is planning to start a Phase II clinical study in the first quarter of 2011.

Preliminary data from the trial indicate:

• Antigen-specific, dose-related T-cell responses across the three dose groups, averaging 1362 SFU per million cells in the high dose group responders
• Strong antigen-specific antibody responses in all three dose groups
• VGX-3100 delivered using Inovio's proprietary CELLECTRA(R) intramuscular electroporation delivery device was generally safe and well tolerated at all dose levels
• There were no vaccine-related serious adverse events. Reported adverse events and injection site reactions were mild to moderate and required no treatment.

Gilead Sciences, Inc. (Nasdaq:GILD) today announced Phase II clinical trial results showing that its investigational fixed-dose, single-tablet "Quad" regimen of elvitegravir, cobicistat and Truvada(R) (emtricitabine and tenofovir disoproxil fumarate) for the treatment of HIV infection maintained a high rate of virologic suppression through 48 weeks, exhibiting antiretroviral activity comparable to that of Atripla(R) (efavirenz 600 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg). At week 48, the proportion of patients who achieved HIV RNA (viral load) less than 50 copies/mL was 90 percent in the Quad arm and 83 percent in the Atripla arm (using an analysis where missing equals failure). These data are being featured in a late-breaker poster presentation today at the 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Boston (Abstract #H-938b).

The 48-week data from this Phase II study (Study 236-0104) extend the positive 24-week results announced in February 2010 at the Conference on Retroviruses and Opportunistic Infections (CROI). Safety, tolerability and discontinuation rates were similar between both arms of the study, but fewer central nervous system (CNS) adverse events, including abnormal dreams/nightmares, dizziness and anxiety were observed in patients receiving the Quad compared to those receiving Atripla.

Mymetics Corporation, a pioneer in the development of vaccines preventing mucosal transmission of human infectious diseases, announced today that its innovative HIV vaccine will enter a new preclinical trial at the University of California, Davis. The study will be led by Professor Christopher J. Miller of the California National Primate Research Center, a leader in immunodeficiency virus transmission in nonhuman primate models, and partially funded by the NIH (National Institutes of Health). It follows a recently completed smaller study at the Institute of Laboratory Animal Science (ILAS) in Beijing, China in which the vaccine provided an unprecedented 100% protection in macaque monkeys. The vaccine is also currently in a Phase I trial in human volunteers.