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.
South Africa will launch its own development aid agency in 2011 in a move likely to boost the country's status as an emerging economic power and champion of the African continent. The South African Development Partnership Agency is expected to become operational before mid-2011 and will work with other donor agencies to coordinate development programmes, mainly on the continent. Although the government is hoping for contributions from the private sector, most of the funding will come from public money, said Dr Ayanda Ntsaluba, Director-General of the Department of International Relations and Cooperation. "South Africa is in a unique position - we're recipients of development assistance, and we're anxious that that status be preserved. At the same time ... we're in the African continent and in that context we occupy a relatively privileged position," Ntsaluba told IRIN.
Pfizer, the world's largest drug company, has agreed to pay up to $632 million to Theraclone Sciences in a research collaboration on antibody drugs for cancer and infectious disease, the companies said Tuesday. Pfizer, based in New York, is trying to keep up with its pharmaceutical rivals that are increasingly relying on biotechnology for products and profits. "This fits in the big picture of us wanting to be on the leading edge of biotherapeutics and antibody discovery, and this is one company we are very excited to work with," Jose-Carlos Gutierrez-Ramos, Pfizer's senior vice president and head of biotherapeutics research, said in an interview Tuesday...
... Theraclone has received other investments in its antibody work previously. That included financing from the International AIDS Vaccine Initiative, partly financed by the Bill & Melinda Gates Foundation, for an experimental antibody to AIDS, and money from the Tokyo-based drug maker Zenyaku Kogyo for an antibody to influenza.
For the third month running, men and women seeking condoms at local health centres in some northern Ugandan districts have found empty dispensers. Health workers warn that the continuing shortage could affect regional HIV prevention efforts. HIV/AIDS focal persons for Gulu, Kitgum and Nwoya districts say health facilities have no condoms in stock for free distribution and commercially available condoms are too expensive for many people in northern Uganda, which is still emerging from a two-decades-long conflict. "As I speak now we have no condoms for distribution," said Charles Luwa, HIV focal point for the Ministry of Health in Gulu district. "We do not know what to do to solve this problem; we made a request to the health ministry but there is no condom delivery yet."
The condom shortage in the north follows a similar scarcity reported in several districts in mid-2010. At the time, the government blamed a long procurement process and irregular delivery of condoms to the country. According to Zainab Akol, in charge of HIV programming at the Ministry of Health, the problem lay with district health officials who did not order condoms well in advance. "They need to order - the problem is that people from the district do not place their orders in time," she said.
The Ethiopian government has unveiled an HIV policy for its transport sector, which has grown significantly in recent years alongside the rapidly expanding road network. "Various national studies have shown that those working across the transport sector - especially drivers and their assistants - are vulnerable to HIV infection as they spend considerable time away from their families," said Ethiopia's transport authority director Kassahun Hailemariam. The country's Federal Transport Authority (FTA) and commercial transporters jointly issued the policy in December. It sets up a national taskforce to raise funds from state and non-state actors to finance projects, including condom distribution, and helping transport staff and family members living with the virus. The government has earmarked 2 percent of the FTA's annual budget to work towards an HIV-free transport sector. Although exact figures for the number of transport workers - from drivers to drivers' assistants and loaders - are hard to come by, an FTA official said the figure was "in the tens of thousands".
Avoidable medicine waste is a drain on resources and can lead to poorer health outcomes. As such, the UK National Health Service (NHS), and other healthcare providers, regard it as a significant problem and are seeking systems, such as novel packaging, to tackle the issue. To stimulate innovation the UK NHS has issued seven challenges, one of which is focused on reducing medicine waste. The NHS is aiming to cut avoidable medicines waste by 50 per cent and increase adherence to high cost and critical treatments by 30 per cent.
Applications are being sought from: private sector organisations partnered with someone or some organisation within the NHS; universities and other academic groups; charities and social enterprises; and individuals, groups and organisations within the NHS. Submissions will be reviewed by an expert panel made up of independent consultants, NHS directors and people from the private sector. Following review the expert panel will recommend an overall winner and a number of runners up the Secretary of State for Health. The expert panel will also recommend prize values on a case by case basis. "In every case the added value of the innovation to the NHS will be many times more than the prize value", says the initiative's website.
Women in the United States suffer from HIV-related illnesses more than twice as much as men according to a new study in The Journal of Infectious Diseases. The study also found minorities and people living in the South shoulder a much higher burden of HIV/AIDS related disease than anyone else in the country. Minority women have worse outcomes, according to the study. During a ten-year period starting in 1997, researchers followed more than 2,000 patients within a year of diagnosis. Patients were tracked an average of four years. Researchers say they were surprised to find that women had the worst outcomes even though after diagnosis they had lower viral loads and higher CD4+ T cell counts than the men. Viral load is the concentration of the virus in the blood. T cells help the immune system in fight infections. Most of the men in the study were white; the majority of women were minorities. Half of these women were from the South. The study found 64% of minority women had HIV-related illness and 22% suffered from AIDS-related illnesses. By comparison patients from other race and sex groups had 21% HIV-related and 6% AIDS-related events. 78% of non-whites in the South had at least one HIV/AIDS-related illness versus 17% in other regions. "To me that's just incredible," said Dr. Amie Meditz, University of Colorado-Denver and lead author. "We have to figure out why this group had poor outcomes and we have to develop strategies on how to fix this."
To read the study abstract, see "Sex, race, and geographic region influence clinical outcomes following primary HIV-1 infection" in the "Published Research" section of this NewsDigest.
Male circumcision, which has been shown to decrease a man's risk of contracting the virus that causes AIDS, also appears to help protect his sexual partners against cervical cancer. In an offshoot of a landmark study of 1,200 heterosexual couples in Uganda involving circumcision and AIDS, researchers reported in The Lancet this month that having a circumcised partner reduced a woman's risk of catching human papillomaviruses by about 25 percent. Such viruses lead to genital warts and cervical cancer. The study, led by researchers from Johns Hopkins University, did not last long enough to see how many women actually developed cancer; that can take years or decades.
Back then, most people died in six to 12 months from horrible diseases like Kaposi's sarcoma, a skin cancer normally found in older men of Semitic descent; pneunocystis carinii pneumonia, a fungal infection in the lungs; cryptococcal meningitis, which causes the lining of your brain to swell; or toxoplasmosis: You got that from cat feces, and it turned your brain to Swiss cheese.
There were no treatments, really. A "long-time survivor" was someone who lived 18 months. I was 24 then. In April, I will celebrate my 54th birthday. I almost didn't make it. In 1996, my doctor at Kaiser Permanente in Los Angeles called my mother in Chicago to tell her that if she wanted to see me alive again, she should fly to Los Angeles immediately. They had given me less than 24 hours to live. I was in a coma in the ICU. I eventually came out of that crisis, and my doctor prescribed something brand new: a three-drug regimen, commonly referred to as "the cocktail." I recovered from that crisis and went on to found the Black AIDS Institute, an organization I still lead.
What a difference three decades can make. We have gone from no drugs to a few very toxic drugs that didn't really work to more than 25 antiretroviral drugs used to treat HIV. The new drugs are highly effective, and the side effects are much reduced. And the breakthroughs continue. Last year, scientists identified three new HIV antibodies that might contribute to the development of a vaccine. A gel that women can apply before sex, known as a vaginal microbicide, demonstrated efficacy in a clinical trial in South Africa, and research released last month indicates that some antiretrovirals, when taken as prophylactics, can prevent HIV infection.
Also last year, Congress passed and President Obama signed health care reform legislation that protects people with HIV from being discriminated against in getting health insurance, eliminates lifetime caps on health insurance coverage and expands access to prescription drugs. And finally, we have a national AIDS strategy that if properly implemented could dramatically reduce new infections, increase the number of people who know their HIV status and increase the number of people in appropriate care and treatment.
Since the November elections and after his compromise over the extension of the Bush-era tax cuts, some Democrats have suggested that President Obama doesn't have the guts to go mano a mano with the Republicans. Others have intimated that if Obama can't stand up for what they see as traditional Democratic values, perhaps the party needs to find another champion in 2012. As a loyal Democrat, I find that remarkable. As an AIDS activist, I find the proposition hard to believe for a personal reason, one that some may find surprising. I know that the president is willing to engage in political combat: He has castigated us at every turn for criticizing his policies on global health and HIV/AIDS.
A total of 1,158 men in various Lake Victoria islands have been circumcised in the four weeks as part of efforts to curb the spread of HIV in Kagera Region. The International Centre for Aids Care and Treatment Programmes (ICAP-Tanzania) in collaboration with the Ministry of Health and Social Welfare are conducting a male circumcision drive at two designated government hospitals in the region. As of June 2010, over 1,000 males aged between 10 and 55 had been circumcised at Rubya and Kagera regional hospitals while 1,158 others were circumcised in the four weeks preceding the official launch of the male circumcision campaign on Saturday. The campaign is being supported by the American people through the US President's Emergency Plan for Aids Relief (Pepfar).
In many parts of the world, the standard for preventing mother-to-child transmission of HIV is a short course of a single anti-retroviral drug. But a large randomized trial in Africa showed that full-scale anti-retroviral therapy with three drugs reduces the risk of passing on the virus even further, researchers reported online in The Lancet. A year after birth, children born to mothers given triple-drug therapy were 43% less likely to have HIV than children of women given standard prophylaxis, according to Timothy Farley, PhD, of the World Health Organization, and colleagues in the Kesho Bora Study Group. The results of the study (and others) were the basis of a 2009 decision by the WHO to revise its international guidelines for anti-retroviral use by pregnant and breast-feeding women. The agency now recommends maternal triple prophylaxis -- starting from the second trimester of pregnancy until all exposure to breast milk has ended -- even if the woman is not yet eligible for the therapy for her own health.
To read the study abstract, see "Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial" in the "Published Research" section of this NewsDigest.
They look like addicts anywhere in the world: tattered and vacant-eyed, they circle Moscow pharmacies known to sell prescription drugs illicitly, looking for something to inject for a quick high. Though public examples of Russia's problem with heroin are not new and seldom bring even raised eyebrows among locals, the issue has recently come to symbolize a broader failure. The country has become one of the world's low points in the effort to fight the spread of H.I.V., and unchecked intravenous drug use is the biggest cause, international health officials say.
The epidemic here has defied worldwide trends, expanding more rapidly year by year than almost anywhere else. Nearly 60,000 new cases of H.I.V., the virus that causes AIDS, were documented in Russia in 2009, an 8 percent increase from 2008, according to Unaids, the United Nations H.I.V./AIDS program. Of those new cases, more than 60 percent were believed to have been caused by intravenous drug use, and many of the others were believed to have been infected through sex with addicts. Though South Africa, with more infections than any other country, far outstripped that total number, with an estimated 390,000 new infections in 2009, the rate of new infections annually has decreased there by nearly half since its peak in the late 1990s. "I've been researching the problem of H.I.V. infection for 25 years, and I must say that the situation has become significantly worse" in Russia, said Dr. Vadim V. Pokrovsky, the head of the country's Federal AIDS Center.
Scientists have reported findings showing new evidence about broadly-reactive neutralizing antibodies, which block HIV infection. Leo Stamatatos of the Seattle Biomedical Research Institute said the major stumbling block in the development of an effective vaccine against HIV is the inability to elicit, by immunisation, broadly reactive neutralising antibodies (NAbs). These antibodies bind to the surface of HIV and prevent it from attaching itself to a cell and infecting it. However, a fraction of people infected with HIV develop broadly neutralising antibodies (bNAbs) capable of preventing cell-infection by diverse HIV isolates, which are the type of antibodies researchers wish to elicit by vaccination.
"We've found that the people who develop broadly-reactive neutralising antibodies-which are about 30 percent of those infected-tend to have a healthier immune system that differs from others who don't develop those antibodies," explained Stamatatos. He said these antibodies target only a few regions of HIV, which is good from the standpoint of vaccine development. In addition, the new findings have shown that these antibodies are generated much sooner than previously thought, in some cases as soon as a year after infection.
To read the study abstract, see "Characteristics of the earliest cross-neutralizing antibody response to HIV-1" in the "Published Research" section of this NewsDigest.
Background The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule.
Methods and Findings We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%).
Conclusions Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.
Background Male circumcision reduces human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2) acquisition, and HSV-2 infection is associated with an increased risk of HIV acquisition. To assess the cellular basis for these associations, we estimated immunologic cellular densities in foreskin tissue.
Methods Immunostained CD1a+ dendritic cell and CD4+ and CD8+ T cell densities were quantified in foreskin samples obtained from medical circumcision in Rakai, Uganda (35 HIV-infected, HSV-2-infected men; 5 HIV-infected, HSV-2-uninfected men; 22 HIV-uninfected, HSV-2-infected men; and 29 HIV-uninfected, HSV-2-uninfected men.
Results CD1A+ dendritic cell densities did not vary by HIV or HSV-2 status. Compared with densities in HIV-uninfected, HSV-2-uninfected men (mean, 26.8 cells/mm2), CD4+ T cell densities were similar in the HIV-infected, HSV-2-infected group (mean, 28.7 cells/mm2), were significantly decreased in the HIV-infected, HSV-2-uninfected group (mean, 11.2; P < .05), and were increased in the HIV-uninfected, HSV-2-infected group (mean, 68.7; P < .05). Dermal CD8+ T cell densities were higher in the HIV and HSV-2-coinfected group (mean, 102.9) than in the HIV-uninfected, HSV-2-uninfected group (mean, 10.0; P < .001), the HIV-infected, HSV-2-uninfected group (mean, 27.3; P < .001), and the HIV-uninfected, HSV-2-infected group (mean, 25.3; P < .005).
Discussion The increased CD4+ cellular density in the HIV-uninfected, HSV-2-infected men may help to explain why HSV-2–infected men are at increased risk of HIV acquisition. The absence of this increase in men coinfected with both HIV and HSV-2 is likely in part the result of the progressive loss of CD4+ cells in HIV infection. Conversely, HIV and HSV-2 coinfection appears to synergistically increase CD8+ T cell densities.
The promising and biomedically grounded "test and treat" HIV prevention strategy has empowered a growing movement to desocialize the field of HIV prevention. Mayer and Venkatesh provide a rigorous and balanced evaluation of this prevention approach, which would involve universal, voluntary HIV screening and initiation of antiretroviral treatment for all persons infected with HIV. If empirically feasible, the "test and treat" strategy would vastly increase access to life-saving...
The sexual transmission of HIV is very inefficient, presumably because mucosal immune defences prevent infection after most exposures. Since numerous genital immune factors have antiviral effects in vitro, their elucidation might greatly inform the microbicide and HIV prevention fields, particularly in the context of HIV-exposed but persistently seronegative (ESN) individuals. However, several important confounders must be considered in such research. First, sound epidemiological criteria are needed to define individuals as ESN. Then, since high-risk sexual activity is commonly one of these criteria, its potential impact on genital immunology must be carefully considered, both the direct effects of sex and the secondary immune effects of genital co-infections. This means that it may be very difficult to determine whether differences in genital immunology between ESN and control groups are responsible for HIV protection, or are a consequence of high-risk sexual activity. To overcome this confounding, the demographics and epidemiology of ESN cohorts must be described very carefully, thorough co-infection diagnostics must be performed and, if possible, prospective studies with an endpoint of HIV acquisition should be performed to define the direction of causality.
Objectives We conducted a randomized clinical trial to test an integrated behavioral intervention designed to enhance using HIV treatment as prevention by improving medication adherence, reducing risks for other sexually transmitted infections, and minimizing risk compensation beliefs.
Methods Individuals living with HIV/AIDS (n=436) participated in a randomized clinical trial testing an intensive behavioral intervention aimed at reducing HIV transmission risks compared with an attention control condition. We used unannounced pill counts to monitor antiretroviral therapy adherence and computerized interviews to measure risk behaviors.
Results The integrated transmission risk reduction intervention demonstrated increased antiretroviral therapy adherence and less unprotected intercourse with nonseroconcordant partners at 3- and 6-month follow-ups as well as fewer new sexually transmitted infections diagnosed over the 9-month follow-up period (adjusted odds ratio=3.0; P<.05; 95% confidence interval=1.01, 9.04). The integrated intervention also reduced behavioral risk compensation beliefs.
Conclusions A theory-based integrated behavioral intervention can improve HIV treatment adherence and reduce HIV transmission risks. HIV treatment as prevention should be bundled with behavioral interventions to maximize effectiveness.
Background Human immunodeficiency virus (HIV)-infected individuals maintaining plasma HIV RNA levels <75 copies/mL in the absence of therapy ("HIV controllers") often maintain high HIV-specific T cell responses, which likely contribute to the control of viral replication. Despite robust immune responses, these individuals never eradicate HIV infection. We hypothesized that HIV-specific CD4+ T cells might serve as target cells for HIV, contributing to viral persistence in this setting.
Methods We measured frequencies of activated (CD38+ HLA-DR+) and HIV Gag-specific CD4+ and CD8+ T cells and plasma- and cell-associated levels of HIV RNA and DNA in a cohort of 38 HIV controllers.
Results Although there was no evidence of a relationship between the extent of low-level viremia and the frequency of either activated or HIV-specific CD4+ T cells, controllers with higher HIV-specific CD4+ T cell frequencies had higher cell-associated HIV DNA levels (p = 0.53; P = .019). Higher activated CD4+ T cell frequencies were also associated with higher levels of cell-associated DNA (P = .027) and RNA (P = .0096). However, there was no evidence of a relationship between cell-associated HIV RNA or DNA levels and HIV-specific CD8+ T cell frequencies.
Conclusions These data support a model in which strong HIV-specific CD4+ T cell responses in HIV controllers, while contributing to a potent adaptive immune response, may also contribute to viral persistence, preventing the natural eradication of HIV infection.
Objectives As a result of the impact of HIV among men who have sex with men (MSM), multiple strategies for reducing HIV risks have emerged from within the gay community. One common HIV risk reduction strategy limits unprotected sex partners to those who are of the same HIV status (serosorting). We tested a novel, brief, one-on-one intervention, based on informed decision-making and delivered by peer counselors, designed to address the limitations of serosorting (e.g., risk for HIV transmission).
Methods In 2009, we recruited a group of 149 at-risk men living in Atlanta, Georgia, and randomly assigned them to an intervention condition addressing serosorting or a standard-of-care control condition.
Results Men in the serosorting intervention reported fewer sexual partners (Wald c2=8.79, P<.01) at the study follow-ups. Behavioral results were also consistent with changes in psychosocial variables, including condom use self-efficacy and perceptions of risk for HIV transmission.
Conclusions With the current intervention, service providers can offer risk reduction for men arguably at the highest risk for HIV infection in the United States. Addressing risks associated with serosorting in a feasible, low-cost intervention has the potential to significantly affect the HIV epidemic.
Background It is estimated that there are up to 1.1 million injection drug users (IDUs) in India; the majority are likely married. We characterize HIV, hepatitis B (HBV) and hepatitis C (HCV) prevalence and the risk environment of a sample of spouses of IDUs.
Methods A cohort of 1158 IDUs (99% male) was recruited in Chennai, India from 2005-06. A convenience sample of 400 spouses of the male IDUs in this cohort was recruited in 2009. A risk assessment questionnaire was administered and a blood sample collected. Logistic regression was used to identify factors associated with prevalent HIV.
Results Median age was 31 years; thirteen percent were widowed and 7% were not currently living with their spouse. Only 4 (1%) reported ever injecting drugs; Twenty-two percent and 25% reported ever using non-injection drugs and alcohol, respectively. The majority had one lifetime sexual partner and 37(9%) reporting exchanging sex. Only 7% always used condoms with their regular partner. HIV, HBV and HCV prevalence were 2.5%, 3.8% and 0.5%, respectively; among spouses of HIV+ IDUs (n=78), HIV prevalence was 10.3%. The strongest predictor of HIV was spousal HIV status (OR: 17.9; p<0.001). Fifty-six percent of women had ever experienced intimate partner violence; Eight-six percent reported sexual violence.
Conclusions Our finding of a 10-fold higher HIV prevalence among spouses of IDUs compared with general population women indicates their vulnerability; prevalence is likely to increase given the context of low condom use and frequent sexual violence. Prevention efforts directed at IDUs should also include programs for spouses.
Background Despite the grave consequences of sexual violence, and its persistence both within and outside marriages, this subject has received relatively little attention from researchers, policy makers, and programme managers in Nepal. This paper explores the definition of sexual violence and its various forms and consequences as reported by young married women in Nepal. In addition, it describes the coping mechanisms used by young married women to avoid sexual violence perpetrated against them by their husbands.
Methods This paper analyzes data collected during the qualitative study on "Sexual violence among young couples in Nepal", conducted amongst two major ethnic groups - Brahmin/Chhetri and Tharu - between 2006 and 2007. The data is comprised of 39 free-lists and 15 in-depth case histories with married women aged 15-24 years. The average rank and Smith's Salience were calculated from the free-listing data. The thematic analysis approach was used for the analysis of information from the case histories.
Results Approximately three-quarters (74%) of the young women mentioned 'sex against one's wishes' as sexual violence within marriage (SVWM). Sixty-two percent of respondents described 'forced sex during illness' and 'forced sex after consumption of alcohol' as SVWM. About half of young women (48.7%) who participated in the free-listing exercise reported having experienced SVWM. The types of SVWM ranged from unwanted sexual touch to forced sex. Backache, headache, lower abdominal pain, vaginal bleeding and thoughts of suicide were the most commonly reported negative physical and psychological health consequences of SVWM. Women reported various coping strategies including 'trying to convince husbands', 'sleeping in a separate room', 'visiting maternal home', 'waking up the children', and 'using pretexts such as being ill or menstruating', to avoid SVWM. However, in most cases, women reported that these coping strategies were unsuccessful. Almost all women experiencing SVWM were socially isolated and did not turn to institutions, relatives or friends for advice and support.
Conclusions Sexual violence within marriage is common in Nepal. Findings provide circumstantial evidence of links between sexual violence and negative general and reproductive health outcomes for women. Various actions are required to prevent SVWM and provide immediate support to the victims.
Background Methamphetamine (MA) use continues to be a major public health concern in many urban settings. We sought to assess potential relationships between MA use and individual, social, and structural HIV vulnerabilities among sexual minority (lesbian, gay, bisexual or transgendered) drug users.
Methods Beginning in 2005 and ending in 2008, 2109 drug users were enroled into one of three cohort studies in Vancouver, Canada. We analysed longitudinal data from all self-identified sexual minority participants (n = 248). Logistic regression using generalized estimating equations (GEE) was used to examine the independent correlates of MA use over time. All analyses were stratified by biological sex at birth.
Results At baseline, 104 (7.5%) males and 144 (20.4%) females reported sexual minority status, among whom 64 (62.1%) and 58 (40.3%) reported MA use in the past six months, respectively. Compared to heterosexual participants, sexual minority males (odds ratio [OR] = 3.74, p < 0.001) and females (OR = 1.80, p = 0.003) were more likely to report recent MA use. In multivariate analysis, MA use among sexual minority males was associated with younger age (adjusted odds ratio [AOR] = 0.93 per year older, p = 0.011), Aboriginal ancestry (AOR = 2.59, p = 0.019), injection drug use (AOR = 3.98, p < 0.001), having a legal order or area restriction (i.e., "no-go zone") impact access to services or influence where drugs are used or purchased (AOR = 4.18, p = 0.008), unprotected intercourse (AOR = 1.62, p = 0.048), and increased depressive symptoms (AOR = 1.67, p = 0.044). Among females, MA use was associated with injection drug use (AOR = 2.49, p = 0.002), Downtown South residency (i.e., an area known for drug use) (AOR = 1.60, p = 0.047), and unprotected intercourse with sex trade clients (AOR = 2.62, p = 0.027).
Conclusions Methamphetamine use was more prevalent among sexual minority males and females and was associated with different sets of HIV risks and vulnerabilities. Our findings suggest that interventions addressing MA-related harms may need to be informed by more nuanced understandings of the intersection between drug use patterns, social and structural HIV vulnerabilities, and gender/sexual identities. In particular, MA-focused prevention and treatment programs tailored to disenfranchised male and female sexual minority youth are recommended.
Gender and racial differences in CD4+ T cell counts and human immunodeficiency virus (HIV)-1 RNA levels among chronically HIV-infected persons have been shown to exist in multiple studies, and although women have significantly lower plasma HIV-1 RNA levels than men, the rate of progression to AIDS is similar among men and women . Similarly, several studies have suggested that blacks and Latinos have lower CD4+ T cell counts and higher viral loads at presentation, but this is likely due to delays in diagnosis and, thus, more advanced disease at presentation. The study by Meditz et al in this issue of the Journal confirms and extends these findings by demonstrating that gender and racial differences are present in the earliest stages of infection -- in those with acute and recent HIV infection. Among untreated patients in their cohort, however, this difference disappeared after 24 weeks, and by week 104 of follow-up, women had higher viral loads than men. Their data also suggest that women report fewer symptoms associated with the acute retroviral syndrome, which may delay or complicate early diagnosis in this population. These biologic differences between races and genders remain unexplained; however, there is little indication that these findings have major clinical significance. Nevertheless, a better understanding of the biologic factors leading to these differences may give insight into HIV pathogenesis. Although the lessons to be learned may be important, the likelihood is low that these will lead to interventions that will change disease course in the near future.
Background It is unknown whether sex and race influence clinical outcomes following primary human immunodeficiency virus type 1 (HIV-1) infection.
Methods Data were evaluated from an observational, multicenter, primarily North American cohort of HIV-1 seroconverters.
Results Of 2277 seroconverters, 5.4% were women. At enrollment, women averaged .40 log10 fewer copies/mL of HIV-1 RNA (P < .001) and 66 more CD4+ T cells/microL (P = .006) than men, controlling for age and race. Antiretroviral therapy (ART) was less likely to be initiated at any time point by nonwhite women and men compared to white men (P < .005), and by individuals from the southern United States compared to others (P = .047). Sex and race did not affect responses to ART after 6 months (P > .73). Women were 2.17-fold more likely than men to experience >1 HIV/AIDS-related event (P < .001). Nonwhite women were most likely to experience an HIV/AIDS-related event compared to all others (P = .035), after adjusting for intravenous drug use and ART. Eight years after diagnosis, >1 HIV/AIDS-related event had occurred in 78% of nonwhites and 37% of whites from the southern United States, and 24% of whites and 17% of nonwhites from other regions (P < .001).
Conclusions Despite more favorable clinical parameters initially, female HIV-1-seroconverters had worse outcomes than did male seroconverters. Elevated morbidity was associated with being nonwhite and residing in the southern United States.
See related article in the "Media Coverage" section of this NewsDigest: "Study: Sex, race and location may influence HIV outcomes".
Recent cross-sectional analyses of HIV-1+ plasmas have indicated that broadly cross-reactive neutralizing antibody responses are developed by 10%-30% of HIV-1+ subjects. The timing of the initial development of such anti-viral responses is unknown. It is also unknown whether the emergence of these responses coincides with the appearance of antibody specificities to a single or multiple regions of the viral envelope glycoprotein (Env). Here we analyzed the cross-neutralizing antibody responses in longitudinal plasmas collected soon after and up to seven years after HIV-1 infection. We find that anti-HIV-1 cross-neutralizing antibody responses first become evident on average at 2.5 years and, in rare cases, as early as 1 year following infection. If cross-neutralizing antibody responses do not develop during the first 2-3 years of infection, they most likely will not do so subsequently. Our results indicate a potential link between the development of cross-neutralizing antibody responses and specific activation markers on T cells, and with plasma viremia levels. The earliest cross-neutralizing antibody response targets a limited number of Env regions, primarily the CD4-binding site and epitopes that are not present on monomeric Env, but on the virion-associated trimeric Env form. In contrast, the neutralizing activities of plasmas from subjects that did not develop cross-neutralizing antibody responses target epitopes on monomeric gp120 other than the CD4-BS. Our study provides information that is not only relevant to better understanding the interaction of the human immune system with HIV but may guide the development of effective immunization protocols. Since antibodies to complex epitopes that are present on the virion-associated envelope spike appear to be key components of earliest cross-neutralizing activities of HIV-1+ plasmas, then emphasis should be made to elicit similar antibodies by vaccination.
See related article in the "Media Coverage" section of this NewsDigest: "New findings bring scientists closer to an effective HIV vaccine".
This paper studies how increased access to antiretroviral therapy effects sexual behavior using data collected in Mozambique in 2007 and 2008. The survey sampled both HIV-positive individuals and households from the general population. The findings support the hypothesis of disinhibition behaviors, where individuals are more likely to engage in risky sexual behavior when they believe that they will have greater access to better healthcare, such as antiretroviral therapy. The findings suggest that scaling up access to antiretroviral therapy without prevention programs may lead to more risky sexual behavior and ultimately more infections. The study concludes that during this era of increased antiretroviral availability, prevention programs need to include educational messages so that individuals know that risky sexual behavior is still dangerous.
Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial
Background Breastfeeding is essential for child health and development in low-resource settings but carries a significant risk of transmission of HIV-1, especially in late stages of maternal disease. We aimed to assess the efficacy and safety of triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis in pregnant women infected with HIV.
Methods Pregnant women with WHO stage 1, 2, or 3 HIV-1 infection who had CD4 cell counts of 200-500 cells per microL were enrolled at five study sites in Burkina Faso, Kenya, and South Africa to start study treatment at 28-36 weeks' gestation. Women were randomly assigned (1:1) by a computer generated random sequence to either triple antiretroviral prophylaxis (a combination of 300 mg zidovudine, 150 mg lamivudine, and 400 mg lopinavir plus 100 mg ritonavir twice daily until cessation of breastfeeding to a maximum of 6·5 months post partum) or zidovudine and single-dose nevirapine (300 mg zidovudine twice daily until delivery and a dose of 600 mg zidovudine plus 200 mg nevirapine at the onset of labour and, after a protocol amendment in December, 2006, 1 week post-partum zidovudine 300 mg twice daily and lamivudine 150 mg twice daily). All infants received a 0·6 mL dose of nevirapine at birth and, from December, 2006, 4 mg/kg twice daily of zidovudine for 1 week after birth. Patients and investigators were not masked to treatment. The primary endpoints were HIV-free infant survival at 6 weeks and 12 months; HIV-free survival at 12 months in infants who were ever breastfed; AIDS-free survival in mothers at 18 months; and serious adverse events in mothers and babies. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISRCTN71468401.
Findings From June, 2005, to August, 2008, 882 women were enrolled, 824 of whom were randomised and gave birth to 805 singleton or first, liveborn infants. The cumulative rate of HIV transmission at 6 weeks was 3.3% (95% CI 1.9-5.6%) in the triple antiretroviral group compared with 5.0% (3.3-7.7%) in the zidovudine and single-dose nevirapine group, and at 12 months was 5.4% (3.6-8.1%) in the triple antiretroviral group compared with 9.5% (7.0-12.9%) in the zidovudine and single-dose nevirapine group (p=0.029). The cumulative rate of HIV transmission or death at 12 months was 10.2% (95% CI 7.6-13.6%) in the triple antiretroviral group compared with 16.0% (12.7-20.0%) in the zidovudine and single-dose nevirapine group (p=0.017). In infants whose mothers declared they intended to breastfeed, the cumulative rate of HIV transmission at 12 months was 5.6% (95% CI 3.4-8.9%) in the triple antiretroviral group compared with 10.7% (7.6-14.8%) in the zidovudine and single-dose nevirapine group (p=0.02). AIDS-free survival in mothers at 18 months will be reported in a different publication. The incidence of laboratory and clinical serious adverse events in both mothers and their babies was similar between groups.
Interpretation Triple antiretroviral prophylaxis during pregnancy and breastfeeding is safe and reduces the risk of HIV transmission to infants. Revised WHO guidelines now recommend antiretroviral prophylaxis (either to the mother or to the baby) during breastfeeding if the mother is not already receiving antiretroviral treatment for her own health.
See related article in the "Media Coverage" section of this NewsDigest: "Three-drug ART reduces HIV transmission risk".
Each year, several million people become infected with HIV -- the agent responsible for AIDS. This formidable statistic highlights the need for drugs that could be given as a preventive measure to vulnerable populations. Such drugs would be as valuable as those currently used to prevent infection after recent possible exposure to the virus and to treat the symptoms of HIV infection. Two papers, one published in Science and the other in The New England Journal of Medicine, now report on a class of anti retroviral drug that can prevent HIV infection in a significant proportion of individuals. Although previous animal studies have shown evidence for such effects, the current trials provide the first proof of principle for the approach in humans.
The two studies used different modes of drug administration to achieve protection. In the first, a microbicide-based approach carried out in South Africa, Abdool Karim et al. asked roughly 450 women who were at risk of acquiring HIV to self-administer a vaginal gel impregnated with the drug tenofovir before sexual intercourse. The authors report a 39% reduction in HIV transmission in these women over 2.5 years compared with a similar number of women who received a placebo gel.
The recently published Caprisa 004 trial of tenofovir 1% gel used intravaginally to prevent HIV was an impressive success ("Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women," Q. Abdool Karim et al., Research Articles, 3 September 2010, p. 1168). The gel, when used once up to 12 hours before and once up to 12 hours after coitus with a maximum of two doses per 24 hours, was 50% effective at preventing HIV infection, based on a follow-up 12 months later. At 2.5 years, the protective effectiveness was lower (39%), likely due to lower adherence over time. Among those who were high (>80%) adherers, based on counting used and unused applicators, the effectiveness estimate was 54% at 2.5 years. No viral resistance in breakthrough infections was seen, a concern in ongoing oral pre-exposure prophylaxis trials such as iPrEX and PEM-PrEP.
A confirmatory trial is needed to empower licensure approval by regulatory bodies such as the U.S. Food and Drug Administration, the European Medicines Agency, and the South African Medicines Control Council. Confirming safety is especially important with a prevention method used by healthy women, given that there is a lower threshold for acceptable side effects compared with the use of antiviral products by HIV-infected persons.
Doctors, scientists, and other health professionals use biomarkers as tools to obtain information about a person's health status or response to interventions. Defined as characteristics that indicate biological processes, biomarkers are essential for monitoring the health of both individuals and communities. In 2008, the Food and Drug Administration (FDA) asked the IOM to conduct a study on the evaluation process for biomarkers, focusing on biomarkers and surrogate endpoints in chronic disease. In its report Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease, the IOM recommends that the FDA adopt a consistent scientific framework to evaluate biomarkers, consisting of three steps: analytical validation, evidentiary qualification, and utilization analysis.
The IOM held a workshop June 21-22, 2010, to provide stakeholders with an opportunity to learn about, react to, and discuss the report. Presenters provided perspectives on the report from the point of view of participants from the FDA, the National Institutes of Health, and from a diverse group of industry stakeholders. This document summarizes the workshop.
The scientific papers describing the CAPRISA 004 and iPrEx results are among the six papers chosen to compete for the Lancet paper of the year. Details (and a link to vote for your favorite) follow below.
Voting begins for paper of the year 2010 2010 has been an interesting year for elections: a republican-controlled House of Representatives in the USA resulted in a split between party control of the House and the Senate; a coalition government in the UK; and the first female President in Brazil. What surprises will voting bring to The Lancet's poll of the paper published in 2010 that is most likely to shape future research or health care?
In response to our call for nominations, six topical papers of wide interest to clinicians and policy makers were suggested. The candidate papers can be read on The Lancet's website, where votes can be cast. Two themes emerge. One is the extension of HIV control to pre-exposure prophylaxis with an oral preparation in men and a vaginal gel in women. The other is the role of dabigatran, a reversible direct thrombin inhibitor given orally in people with atrial fibrillation, which is discussed in three reports from the same trial. The sixth nomination studies the population benefit of vaccination against influenza for children and adolescents in rural communities.
The topics in this year's nominations -- HIV, atrial fibrillation, and influenza -- have been the subjects of excellent previous papers and will continue to attract research in the years ahead. Which nominated paper from 2010 is most likely to influence that research or care for these conditions? Readers of The Lancet will decide by casting votes online from now until Jan 31. The winning team -- because one goal of this competition is to emphasise the collaborative nature of good research -- will be announced in February.
Diener H-C, Connolly SJ, Ezekowitz MD, et al, for the RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol 2010; 9: 1157-63.
Ezekowitz MD, Wallentin L, Connolly SJ, et al, and the RE-LY Steering Committee and Investigators. Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation. Circulation 2010; 122: 2246-53.
Grant RM, Lama JR, Anderson PL, et al, for the iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363: 2587-59.
Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al, on behalf of the CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329: 1168-74.
Loeb M, Russell ML, Moss L, et al. Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. JAMA 2010; 303: 943-50.
Wallentin L, Yusuf S, Ezekowitz MD, et al, on behalf of the RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY investigators. Lancet 2010; 376: 975-83.
The National Institute of Nursing Research (NINR) invites interdisciplinary formative research projects attempting to explore HIV/AIDS risk avoidance decision-making among adolescents. Additional research is needed on HIV prevention interventions developed within social and gender constructs of adolescents that consider neurocognitive developmental stage and neurocognitive variables as they exist within those social and gender constructs. Prevention strategies that consider social, cultural, and gender constructs in combination with neurological and cognitive maturity may offer the best opportunity for prevention strategies to reduce HIV transmission in adolescents.
The objectives of this FOA are to explore decision-making in adolescents relative to the avoidance of risk for HIV/AIDS. A better understanding of the role of psychological predictors and neurological biomarkers of adolescent risk-taking within sociological constructs can lead to alternative developmentally and culturally appropriate interventions which successfully address the rise in HIV infections in adolescents. Foundational research at the intersections of sociology, psychology, and both developmental and functional neuroscience is needed in order to advance this area. As such, formative research projects attempting to explain the neurological basis of decision-making in adolescents relative to the avoidance of risk for HIV/AIDS are the focus of this initiative. Appropriate feasibility pilot data may be used to support proposed research projects. Interdisciplinary collaborations that include nurse scientists, neuroscientists, psychologists and sociologists are strongly encouraged. In addition, applicants are encouraged to draw on existing infrastructure resources such as CTSAs, existing research cores, networks, or other common institutional assets in the design of their projects.
Letter of Intent Due Date March 15, 2011 Application Due Date(s) April 15, 2011, by 5:00 PM local time of applicant organization.
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