Delaying ART in Patients with HIV Reduces Likelihood of Restoring CD4 Counts

A larger percentage of patients with human immunodeficiency virus (HIV) achieved normalization of CD4+ T-cell counts when they started antiretroviral therapy (ART) within 12 months of the estimated dates of seroconversion (EDS) rather than later, according to a report published online by JAMA Internal Medicine.

The goal of ART has been focused primarily on achieving an undetectable HIV viral load (VL) because not doing so has been associated with impaired immune recovery. However, a specific CD4+T-cell count as a target for optimal immunologic health has not been validated nor has an interval from infection to ART initiation that promotes this goal been established.

Jason F. Okulicz, M.D., of the Uniformed Services University of Health Sciences, Bethesda, Md., and colleagues examined the timing of ART relative to HIV infection on the normalization of CD4+ T-cell counts, risk of AIDS development, and immune function. The authors evaluated participants in the U.S. Military HIV Natural History Study with documented EDS who achieved virologic suppression with ART. Normalization of CD4+ T-cell counts was to 900 cells/μL or higher.

HIV
Photo credit: Flickr

Results show that among 1,119 HIV-infected patients, 38.4 percent achieved CD4+ normalization after initiating ART within 12 months of the EDS vs. 28.3 percent of patients who initiated ART after 12 months. Patients with CD4+ counts of 500 cells/μL or higher when they entered the study or started ART had increased CD4+ normalization rates compared with other patients with HIV. However, even among patients with CD4+ counts of 500 cells/μL or higher at both entry to the study and before ART, the odds of CD4+ normalization were lower in those patients who initiated ART after 12 months from the EDS and study entry.

Researchers also found that starting ART within 12 months of EDS instead of later was associated with a lower risk of AIDS (7.8 percent vs. 15.3 percent), reduced T-cell activation and increased responsiveness to the hepatitis B virus (HBV) vaccine.

“Achieving CD4+ normalization is an imminently feasible therapeutic goal, provided ART is started within 12 months of the EDS at higher CD4+ counts (greater than or equal to 500 cells/μL). The importance of a public health strategy that includes frequent HIV testing in persons at risk and prompt initiation of ART after diagnosis is underscored by two findings: the rate of unwitnessed CD4+ count decline that occurs in the interval between HIV acquisition and diagnosis cannot be predicted, and the duration of the infection cannot be predicted by the CD4+ count. This strategy may offer the best chance for rapidly terminating the progressive immune damage (eg. lymphoid tissue fibrosis) that constrains optimal immune reconstitution with ART,” the study concludes.

Reference:

JAMA Intern Med. Published online November 24, 2014. doi:10.1001/jamainternmed.2014.4010.

Editor’s Note:

Authors made conflict of interest disclosures. This work was supported by the Veterans Affairs (VA) Research Center for AIDS and HIV Infection and other sources. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Commentary: Defining Success with Antiretroviral Therapy

In a related commentary, Timothy W. Schacker, M.D., of the University of Minnesota, Minneapolis, writes: “This important study reminds us that the goal of HIV therapy should be full restoration of immune function and not just suppression of viral replication. Okulicz and colleagues have provided the clearest signal to date that we will not restore immunity with the drugs we have available. Under ideal conditions only approximately one-third of the patients who receive treatment could achieve this goal. Most of the 35 million people infected with HIV live in conditions where only a few will have the opportunity to start therapy within 12 months of seroconversion. We need better formulations of antiretroviral drugs that fully suppress virus replication in tissues. However, we also need adjunctive therapies that eliminate the causes of persistent immune activation and restore lymphoid tissues to their normal anatomy and function.”

Reference:

JAMA Intern Med. Published online November 24, 2014. doi:10.1001/jamainternmed.2014.4004.

Editor’s Note:

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Efavirenz-Free Regimens Prove Effective For Initial Treatment Of HIV

Bottom Line:

Patients who cannot take efavirenz for initial treatment of HIV have effective options, according to an article being published in Annals of Internal Medicine.

Efavirenz:

Efavirenz is a component of many effective antiretroviral regimens used to treat people with HIV.  However, women who are considering becoming pregnant or patients with a history of severe psychiatric disorders are not good candidates for treatments that include efavirenz because it can cause birth defects and suicidal thoughts.

Efavirenz
Efavirenz

 

Finding efavirenz-free regimens with equivalent virologic efficacy and tolerability is important for these patients. Researchers randomly assigned more than 1,800 patients with HIV to receive one of three efavirenz-free treatment regimens for 96 weeks: 300 mg/d of atazanavir with 100 mg/d of ritonavir; 800 mg/d of darunavir with 100 mg/d of ritonavir; or 400 mg/bid of raltegravir.

All participants received 200 mg/d of emtricitabine and 300 mg/d of tenofovir disoproxil fumarate in addition to the assigned regimen.  The authors found that the three regimens similarly suppressed HIV in the blood and restored function of the immune system; however, the tolerability differed among the tested regimens.

Conclusion:

The study authors concluded that the drugs tested are good options for initial HIV antiretroviral therapy that do not contain efavirenz.

Media Advisory:

To interview the lead author, please contact Holly Korschun at hkorsch@emory.edu or 404-727-3990, or Juliette Merchant at juliette.merchant@emory.edu or 404-778-1503.

Second Case Of Apparent HIV “Cure” in a Baby Followed By Reappearance Of Virus

Bottom Line:

Researchers today report the case of a baby, born HIV-positive, who appeared to have been cured of HIV after being given early antiretroviral treatment (ART) to combat the virus, but ultimately exhibited detectable HIV infection. 

The case report, published in The Lancet, is the second report of apparent viral remission followed by rebound in a baby given early ART treatment, after the case of the ‘Mississippi baby’ received widespread attention in 201314.

Methodology:

A team of researchers, including Professor Mario Clerici at the University of Milan and the Don Gnocchi Foundation in Milan, Italy, report that the babyborn to an HIV-positive mother in December 2009appeared to have been cured of HIV at age three years, after intensive ART treatment was begun shortly after birth. 

Results and Discussion:

Tests to measure the amount of HIV in the child’s blood (viral load) indicated that the virus had been eradicated.  Notably, even antibodies to HIV had disappeared, showing that the baby was no longer seropositive and, with the agreement of the child’s mother, ART was stopped. 

However, two weeks later, the child’s HIV tests came back positive, leading the researchers to conclude that the viral reservoirs had not been eliminated by ART, despite the virus being undetectable for more than 3 years. 

"HIV Virus"
HIV Virus (Photo credit: Sculpture HIV Virus | Flickr)

There are differences between this case, and that of the Mississippi baby (as well as the ‘Berlin patient’ Timothy Ray Brown, thought to be the only adult to be cured of HIV); importantly, the child’s immune system continued to show multiple signs of responding to HIV infection even after the viral load became undetectable, which was not the case for either the Mississippi baby or the Berlin patient. 

The authors also suggest that the child’s high viral load at birth, as well as an infection while in the womb, and low birthweight, may have also precluded long-lasting viral remission. 

The case report concludes that, “The availability of many classes of potent antiretroviral drugs has substantially decreased HIV morbidity and mortality, but these drugs cannot eradicate the virus because they do not eliminate viral reservoirs. The search for an HIV cure continues”.

Contact:

For interviews, please contact Professor Mario Clerici, Department of Physiopathology and Transplantation, University of Milan, Italy.  T) +39 331 651 0447  E) mario.clerici@unimi.it

Reference:

Giacomet Vania. No cure of HIV infection in a child despite early treatment and apparent viral clearance. Lancet 2014; 384: 1320

High Rates Of Recreational Drug Use Among HIV-Positive Gay And Bisexual Men in The UK Strongly Linked With Condomless Sex

Bottom Line:

New research published in The Lancet HIV shows that polydrug use is common among HIV-positive men who have sex with men (MSM) [1] and is strongly linked to sex without a condom (condomless sex).

Full Study: 

This is the largest questionnaire study of people living with HIV in the UK, accounting for about 5% of all HIV-diagnosed MSM in the UK. The findings show that half of MSM surveyed had used recreational drugs at least once in the previous 3 months [2]. About half of those who used drugs took three or more different types of drugs, while roughly a fifth said they had used five or more different drugs in the past 3 months. Condom use was markedly lower with increasing polydrug use. For example, over three-quarters of participants who said they had used five drugs or more in the past 3 months also reported condomless sex, compared with less than a quarter of those who reported no recent drug use.

 “Our findings show that polydrug use and condomless sex are closely linked in HIV-positive MSM in the UK, and that polydrug users are likely to be a group at increased risk of transmission of HIV and other sexually transmitted infections (STIs)”, explains lead author Ms Marina Daskalopoulou from University College London in the UK. [3]

 “The majority of these men would not consider or self-refer to traditional harm reduction services. Our findings highlight the need for cross-agency collaboration between HIV treatment and drug support organisations to provide tailored services for HIV-positive MSM who use recreational drugs, and with national HIV and STI prevention programmes to address recreational drug use.” [3]

 Methodology:

The study collected self-reported data on the drug use and sexual behaviour of 2248 MSM with HIV during 2011–2012 who were enrolled as part of the ASTRA study. All men were aged 18 years or older and attending eight HIV outpatient clinics in the UK.

Increasing number of drugs used was linked to increasing prevalence of sex that could pose a risk of transmission of HIV or other STIs.

"HIV (AIDS)"

Results and Discussion:

For example, recent users of five or more drugs were far more likely than those with no recent drug use to have sex without a condom (78% vs 24%); to have condomless sex with a partner of HIV-negative or HIV-unknown status (25%vs 10%); and to have sex with a higher risk of transmitting HIV (16% vs 4%; having condomless sex with a partner of HIV-negative or HIV-unknown status if the participant is not on antiretroviral treatment, has detectable viral load, or  another recent STI).

However, the authors point out that only a minority (15%) of HIV positive MSM reported condomless sex with a partner of HIV-unknown or HIV-negative status, and fewer (7%) reported higher-HIV-risk condom-less sex.

Comments: 

Writing in a linked Comment, Associate Professor Martin Holt, from the Centre for Social Research in Health at The University of New South Wales in Australia points out that, “Only (7%) of the 2248 MSM included in the analysis reported such high-HIV-risk sex. This finding is heartening, and suggests that most HIV-positive MSM take care to prevent HIV transmission. Only a small proportion, it seems, need assistance in negotiating sex, drugs, and HIV treatment A culturally appropriate evidence-based response is needed to help reduce harm in the UK without further sensationalising the issue.

Reference:

Marina Daskalopoulou, Alison Rodger, Andrew N Phillips, Lorraine Sherr, Andrew Speakman, Simon Collins, Jonathan Elford, Margaret A Johnson, Richard Gilson, Martin Fisher, Ed Wilkins, Jane Anderson, Jeffrey McDonnell, Simon Edwards, Nicky Perry, Rebecca O’Connell, Monica Lascar, Martin Jones, Anne M Johnson, Graham Hart, Alec Miners, Anna-Maria Geretti, William J Burman, Fiona C Lampe. Recreational drug use, polydrug use, and sexual behaviour in HIV-diagnosed men who have sex with men in the UK: results from the cross-sectional ASTRA study. Lancet HIV 2014. doi.org/10.1016/S2352-3018(14)70001-3

Lancet HIV:

The Lancet HIV is a new journal launched in September 2014 and will build on The Lancet journals’ rich history of publishing HIV/AIDS research to provide a reliable foundation for advocacy and for programmatic and political change. The journal publishes research articles, linked commentary, and correspondence related to previous content. The journal accepts clinical, epidemiological, operational, and implementation research submissions, unifying these disciplines across a single vision for the health of those living with HIV. Seehttp://www.thelancet.com/hiv for more details.

 

Notes to Editors:

This study was funded by the National Institute for Health Research.

[1] MSM includes gay and bisexual men as well as those who have sex with men but do not identify themselves as gay or bisexual.

[2] Recreational drugs included: acid (lysergic acid diethylamide, LSD), magic mushrooms, anabolic steroids, cannabis (marijuana), cocaine (coke), crack, codeine, methamphetamine (crystal meth), ecstasy (E), GHB (liquid ecstasy) or GBL, heroin, ketamine (K), Khat (chat), mephedrone, morphine, opium, amyl nitrites (poppers), amphetamine (speed), and erectile dysfunction drugs sildenafil (Viagra) and tadalafil (Cialis).

[3] Quotes direct from author and cannot be found in text of Article.

Contact:

 

Article: Ms Marina Daskalopoulou, University College London, London, UK. T) +44(0) 794 0500 ext. 34657   E) m.daskalopoulou@ucl.ac.uk

 

Comment: Associate Professor Martin Holt, Centre for Social Research in Health, The University of New South Wales, Australia. T) +61 2 9385 6410 E) m.holt@unsw.edu.au

Barriers to HIV Testing in Older Children

Bottom Line:

 Concerns about guardianship and privacy can discourage clinics from testing children for HIV, according to new research from Zimbabwe published this week in PLOS Medicine.  The results of the study, by Rashida A. Ferrand of the London School of Hygiene & Tropical Medicine and colleagues, provide much-needed information on how to improve care of this vulnerable population.

Background Information:

More than three million children globally are living with HIV (90% in sub-Saharan Africa) and in 2011 an estimated 1000 infant infections occurred every day. HIV acquired through mother-to-child transmission around the time of birth is often unsuspected in older children, and the benefits of treatment are diminished in children who develop symptoms of immune system failure before infection is discovered.

Methodology:

Provider-initiated HIV testing and counseling (PITC) involves health care providers routinely recommending HIV testing and counseling when people attend health care facilities. To investigate the provision and uptake of PITC among children between 6 and 15 years old, the researchers collected and analyzed data from staff at 6 clinics in Harare, Zimbabwe.

Among 2,831 eligible children, about three-quarters were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The researchers diagnosed HIV infection in about 1 in 20 (5.3%) of the children tested, highlighting the need for more effective PITC. HIV infection was also found in 1 out of 5 guardians who tested with a child.

HIV

Results and Discussion:

The main reasons that health-care workers gave for not offering PITC were perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child, and lack of availability of staff or HIV testing kits.  Children who were asymptomatic, older, or attending with a male or a younger guardian were less likely to be offered HIV testing. Male guardians were less likely to consent to their child being tested.

 In interviews, health-care workers raised concerns that a child might experience maltreatment if he or she tested positive, and showed uncertainty around whether testing of the guardian was mandatory and whether only a parent (if one was living) could legally provide consent.  When parents were alive but not present, seeking consent from another adult raised ethical concerns that a positive HIV test in a child would disclose the HIV status of a parent who hadn’t provided consent.

 The study, which was funded by the Wellcome Trust, did not explore the reasons for refusal of HIV testing by clients. Also, because the relationship of the child to the accompanying adult was not available, the appropriateness of the guardian could not be independently ascertained.

 Lead author Dr. Rashida Ferrand from the London School of Hygiene & Tropical Medicine said: “The fear of the stigma faced by the child and their family seems to be discouraging caregivers from testing children for HIV. However, with improved clarity of guidelines, engagement with staff, and organisational adjustments within clinics, it should be possible to harness the commitment of health-care workers and properly implement HIV testing and counseling.”

 In an accompanying Perspective, Mary-Ann Davies and Emma Kalk of the University of Cape Town, who were uninvolved in the study, point out that “The fact that >90% of infected children had a previous missed opportunity for testing indicates suboptimal pediatric PITC coverage in most routine settings,” and call for “clear HIV testing policies for children and guidance on guardianship, together with training of [health-care workers] on such policies.”

Funding:

The study was funded by the Wellcome Trust through an Intermediate Fellowship to RAF (Grant No: 095878/Z/11Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

The authors have declared that no competing interests exist.

Reference:

Kranzer K, Meghji J, Bandason T, Dauya E, Mungofa S, et al. (2014) Barriers to Provider-Initiated Testing and Counselling for Children in a High HIV Prevalence Setting: A Mixed Methods Study. PLoS Med 11(5): e1001649. doi:10.1371/journal.pmed.1001649

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001649

Author Affiliations:

  • London School of Hygiene and Tropical Medicine, United Kingdom
  • Biomedical Research and Training Institute, Zimbabwe
  • Harare City Health Department, Zimbabwe
  • Population Services International, Zimbabwe
  • University of Zimbabwe, Zimbabwe

Contact:

Press Office at the London School of Hygiene & Tropical Medicine, UNITED KINGDOM, +44 (0) 207 927 2802, press@lshtm.ac.uk

Perspective Article

 Funding:

MAD receives funding from the National Institutes of Allergy and Infectious Diseases (Grant 2U01AI069924) and both authors receive funding from the National Institute of Child Health and Human Development (R01HD075156). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

The authors have declared that no competing interests exist.

Reference:

Davies M-A, Kalk E (2014) Provider-Initiated HIV Testing and Counselling for Children. PLoS Med 11(5):e1001650. doi:10.1371/journal.pmed.1001650

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001650

Author Affiliations:

University of Cape Town, South Africa

 Contact:

Mary-Ann Davies

Infectious Disease Epidemiology Unit

School of Public Health

University of Cape Town

3 Buxton Ave.

Cape Town, Western Cape 8001

SOUTH AFRICA

27 21 406 6487

Mary-ann.Davies@uct.ac.za

Patients in Most Need of Protection Against Shingles Cannot Currently Receive Vaccine

Bottom Line:

People at the highest risk of shingles are those with immunosuppressive conditions (such as HIV) but they are not entitled to vaccination due to safety concerns, suggests a paper published on bmj.com today.

Researchers say alternative strategies are needed to reduce the risk of shingles among these patient groups.

Shingles:

Shingles is a common disease among older individuals which causes an acute painful rash and can lead to a complication (called postherpetic neuralgia) resulting in pain lasting from months to years that can significantly impair a person’s quality of life.

Methodology:

Researchers from the London School of Hygiene & Tropical Medicine used data from over 144,000  UK adults diagnosed with shingles between 2000 and 2011, and compared this with a group of patients without shingles, to explore whether patients with certain medical conditions may be at increased risk of developing shingles.

Vaccination
Photo: PA/telegraph

Results and Discussion:

The median age at shingles diagnosis was found to be 62 years and around 60% of patients were female.

A number of relatively common conditions were associated with an increased risk of shingles. People with rheumatoid arthritis, chronic obstructive pulmonary disease, or inflammatory bowel disease were 30-50% more likely to have a shingles diagnosis, than individuals without these conditions. Other common medical conditions which were associated with a smaller increase in shingles risk were asthma, chronic kidney disease, type 1 diabetes and depression.

Among those with some of these medical conditions the increased risk of shingles appeared to be greater among younger individuals. But because shingles is less common in younger individuals their absolute risk of developing shingles remains low.

Shingles Vaccine:

A shingles vaccine is currently available and licensed among individuals aged over 50. Further research would be required to establish whether vaccination is warranted in patients with these medical conditions, particularly those in younger age groups not currently targeted to receive the vaccine; these individuals are less likely to develop long-term pain and complications from shingles.

However the researchers emphasise that those at the highest risk of shingles remain patients with conditions causing severe immunosuppression (such as HIV and leukaemia); for example patients with HIV were five times as likely to develop shingles compared to individuals without HIV. Such patients are currently not eligible for vaccination due to safety concerns. The researchers therefore say this study highlights the need to identify strategies to reduce the risk of shingles among patients with severe immunosuppression.

Reference:

Harriet J Forbes, Krishnan Bhaskaran, Sara L Thomas, Liam Smeeth, Tim Clayton, Sinéad M Langan. Quantification of risk factors for herpes zoster: population based case-control study. BMJ 2014;348:g2911 doi: 10.1136/bmj.g2911

Link:

You can access this research article by using this link. http://www.bmj.com/cgi/doi/10.1136/bmj.g2911

Note to Editors:

As described in the paper, we used a case control study design. The risk increases were calculated using conditional logistic regression to derive odds ratios for the conditions of interest, by comparing exposures in cases and their matched controls.

Contact:

Harriet Forbes, Research Fellow in Epidemiology via Press Office at the London School of Hygiene and Tropical Medicine, London, UK
Tel: +44 (0) 207 927 2802
Email: press@lshtm.ac.uk

Voluntary Medical Male Circumcision for HIV Prevention: Improving Quality, Efficiency, Cost Effectiveness, and Demand for Services during an Accelerated Scale-up

Bottom Line:

With new HIV infections in Sub-Saharan Africa occurring at a rate of 2.3 million each year, a new PLOS Collection, featuring original research published inPLOS Medicine and PLOS ONE, presents interim results from a public health campaign applying a longstanding method – voluntary medical male circumcision (VMMC) – performed by health care practitioners in low resource settings to prevent new infections in men ages 15-49. Since WHO and UNAIDS issued recommendations in 2007, this program has been scaled-up with an ongoing, largely US-funded program in 14 countries in Eastern and Southern Africa, the epicenter of the global epidemic with over 16 million people currently living with HIV and where new HIV infection rates are highest.

Full Study: 

In 2005, PLOS Medicine published the first randomized controlled intervention demonstrating a 60% reduction in HIV infections over a two-year period among a trial population of 3,274 young South African men who received a voluntary medical circumcision to assess the effectiveness of VMMC as a means of reducing the rate of sexual transmission from female sexual partners.

 This level of risk reduction against contracting the AIDS virus was considered to be equivalent to what a vaccine of high efficacy would have achieved. The new PLOS Collection, Voluntary Medical Male Circumcision for HIV Prevention: Improving Quality, Efficiency, Cost Effectiveness, and Demand for Services during an Accelerated Scale-up, documents the translation of this subsequently amplified evidence base into a program to circumcise 20.3 million Sub-Saharan men by 2016. Based on modelling studies, published by PLOS Medicine in 2011, if this number of circumcisions is achieved by 2016, authors predicted 3.4 million new HIV infections will be prevented, saving the lives of thousands of men, women and children, and averting approximately $16.5 billion in medical treatment costs over 15 years.

 “In 2008, when this program first started, there was skepticism about whether health systems could deliver a high volume of services and still keep the quality of services high,” said Emmanuel Njeuhmeli, Senior Biomedical HIV Prevention Advisor at the U.S. Agency for International Development (USAID). “This collection provides evidence from four African countries that safe, high-quality VMMC can be implemented and sustained at scale. No one could have imagined that a surgical intervention could be rolled out in this way; yet, as of today, countries have done more than six million medical male circumcisions, averting thousands of new HIV infections.”

 The 13 research papers and overview contained in this new PLOS Collection examine lessons learned from the scaled-up VMMC program since 2008. Research papers focus on programs in Kenya, South Africa, Tanzania, Zimbabwe and Lesotho, identifying strengths and challenges in key program areas, including demand creation, the quality of surgical services, operational efficiencies, data collection and cost controls. Of particular concern to researchers is the program’s relative lack of success reaching men over age 25, health-worker burnout and the outstanding need for substantial additional funding from other nations and sponsors to meet the VMMC program’s completion and long-term sustainability goals.

HIV
Image credti: Getty Images

 Dr Rhona MacDonald, Senior Editor and Collection Editor at PLOS Medicine says: “This Collection shows that at a time of constrained international resources to fight HIV/AIDS, voluntary medical male circumcision offers the advantage of its relatively low cost and one-time action to achieve continuous benefits over other prevention methods, such as pre-exposure prophylaxis and preventative Antiretroviral Therapy (ART).”

 The question of demand creation is addressed in several collection papers in which authors determine factors impacting uptake of VMMC by men over the age of 25 who live in countries with ongoing HIV epidemics and low levels of male circumcision. Researchers found that the most effective outreach was not the effectiveness of VMMC in decreasing an individual’s risk of contracting HIV (as well as HPV and other STDs) but rather alternative influential factors, such as hygiene, attractiveness to partners, peer group norms and modernity.

 The VMMC program faces challenges at multiple levels that will have to be overcome to achieve the ambitious targets, such as maintaining quality of services while rapidly scaling up, generating demand for services, and resource and capacity constraints. In order to accelerate scale-up and impact the Collection authors recommend increasing program efficiency by identifying and prioritizing those most at risk of acquiring HIV, focusing on program efficiency and quality at all levels, matching supply with demand, and exploring the role that technologies, especially devices, can play in scale up, among other recommendations.

 What has been achieved in a relatively short period of time is remarkable and could hold lessons for other public health interventions as well.

 This Collection is a joint collaboration between PLOS and the U.S. President’s Emergency Plan for AIDS Relief (through the U.S. Agency for International Development, the Centers for Disease Control and Prevention, and the Department of Defense), the Bill & Melinda Gates Foundation, PEPFAR implementing partners, and the Ministries of Health in Kenya, Tanzania, Zimbabwe, and South Africa. 

KEY FINDINGS FROM THE COLLECTION

Quality of Services:

It is possible to maintain and even improve service quality, especially surgical performance, as VMMC is scaled up, but improved provider training is needed to strengthen quality of pre- and post-operative care and infection control.

Costs:

Personnel and consumables are the largest cost drivers, but costs may be reduced as programs scale up and economies of scale are achieved, as well as by improving service efficiency. Under utilization of service capacity increases unit costs more than any other variable, highlighting the importance of predictable demand and nimble service platforms so that sites are consistently performing as close to capacity as possible. Responsible public-sector pricing strategies for devices have the potential to reduce overall unit costs, and further discounts should be negotiated as procurement volumes increase.

Demand Generation:

Messaging must be tailored to different age groups and to the cultural norms of different communities. Men aged 25 and above are less motivated to undergo VMMC. Studies suggest that we need to go beyond simple HIV messaging and present VMMC in terms of hygiene, appearance, attractiveness to partners, peer group norms, and modernity.

Efficiencies:

Adoption of various elements of surgical efficiency is variable between countries studied. Task sharing, bundling of surgical instruments, and electrocautery are associated with surgical efficiency outcomes, and surgical quality need not be compromised by measures to reduce operating time.

Contact:

PLOS Collections Team (UK), collections@plos.org+44 (0)1223 442836.

Researchers Trace HIV Adaptation To Its Human Host

Bottom Line:

In a study published in PLOS Genetics, which traces the evolution of HIV in North America, the Brumme lab and colleagues at the BC Centre for Excellence in HIV/AIDS, Harvard University, the New York Blood Center, and The San Francisco Department of Public Health found evidence that the virus is slowly adapting over time to its human hosts. However, this change is so gradual that it is unlikely to have an impact on vaccine design.

HIV (AIDS):

  “HIV adapts to the immune response in reproducible ways. In theory, this could be bad news for host immunity – and vaccines – if such mutations were to spread in the population ” says Brumme.   “Just like transmitted drug resistance can compromise treatment success, transmitted immune escape mutations could erode our ability to naturally fight HIV”.

 Objective of Study:

“Much research has focused on how HIV adapts to antiviral drugs – we wanted to investigate how HIV adapts to us, its human host, over time,” says lead author Zabrina Brumme from Simon Fraser University.

Methodology:

Researchers characterized HIV sequences from patients dating from 1979, the beginning of the North American HIV epidemic, to the modern day. Data analysis – which required the painstaking recovery of viral RNA from historic specimens – was led by a trio of SFU graduate students.

 The team reconstructed the epidemic’s ancestral (“founder”) HIV sequence and from there they assessed the spread of immune escape mutations in the population.

AIDS
AIDS Virus

Results and Discussion:

“Overall, our results show that the virus is adapting very slowly in North America” said Brumme. “In parts of the world harder hit by HIV though, rates of adaptation could be higher.”

 The study ends with a message of hope. Says Brumme: “We already have the tools to curb HIV in the form of treatment – and, we continue to advance towards a vaccine and a cure. Together, we can stop HIV/AIDS before the virus subverts host immunity through population-level adaptation.”

 Reference:

Cotton LA, Kuang XT, Le AQ, Carlson JM, Chan B, et al. (2014) Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic. PLoS Genet 10(4): e1004295. doi:10.1371/journal.pgen.1004295

Contact:

zbrumme@sfu.ca

Men with HIV Have a Greater Risk and Extent of Coronary Artery Disease

Bottom Line:

Men with HIV have a greater risk for coronary artery disease (CAD) and have more severe disease than uninfected men, according to an article being published in Annals of Internal Medicine.

Full Study:

 

Patients with HIV are living longer and, as such, are experiencing more chronic noninfectious age-related diseases such as CAD. Data has suggested a connection between HIV infection or its treatment and CAD, but the data are inconsistent. Researchers used cardiac computed tomography (CT) to measure coronary artery calcium and coronary CT angiography to assess plaque extent and characteristics in HIV-infected men and a control group.

HIV

The control group consisted of uninfected men with similar demographics (age and race), CAD risk factors, and lifestyle (men who have sex with men) to the study patients. Even after adjusting for demographic variables and known risk factors for CAD, the men with HIV had a greater prevalence and extent of noncalcified plaque, the kind that is more prone to rupture, potentially leading to heart attacks.

Conclusion:

Men with more advance HIV infection and a greater number of years on antiretroviral therapy had a higher prevalence of clinically significant coronary stenosis greater than 50 percent.

Suggestions:

The authors suggest an effort to address and reduce traditional cardiovascular risk factors to improve long-term outcomes for HIV-infected men.

Reference:

W.S. Post, M. Budoff, L. Kingsley, F.J. Palella Jr., M.D. Witt, X. Li, R.T. George, T. Brown, and L.P.
Jacobson. Associations Between HIV Infection and Subclinical Coronary Atherosclerosis. Annals of Int Med (2014). 160, Issue 7, Page(s) 458-467

http://www.annals.org/article.aspx?doi=10.7326/M13-1705

Contact:

To interview the lead author, Dr. Wendy Post, please contact Stephanie Desmon at sdesmon1@jhmi.edu or 410-955-8665.

Patients Co-Infected with HIV and HCV More Likely to Suffer Liver Decompensation

Despite treatment with antiretroviral therapy (ART), patients co-infected with HIV and hepatitis C virus (HCV) have higher rates of liver decompensation than patients with HCV alone, according to an article being published in Annals of Internal Medicine.

Up to 30 percent of patients with HIV also are often co-infected with HCV and HCV-related liver complications are an important cause of morbidity in co-infected patients. It has been suggested that ART slows HCV-associated liver fibrosis. However, whether rates of hepatic decompensation and other severe liver events in co-infected patients receiving ART are similar to those with HCV only remains unclear.

"Liver decompensation in HIV and HCV patient"
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Veterans Affairs researchers compared health records for 4,280 patients co-infected with HIV and HCV who initiated ART with those of 6,079 veterans with HCV only to compare hepatic decompensation rates. Co-infected patients that had HIV RNA levels less than 1,000 copies/ML had a lower rate of hepatic decompensation than those with a lesser degree of HIV suppression.

However, the rate was still higher than that of patients with HCV alone. Higher rates of decompensation were seen in co-infected patients receiving ART who had baseline advanced liver fibrosis, severe anemia, diabetes, and were of nonblack race.

Reference: 

V. Lo Re, M.J. Kallan, J.P. Tate, A.R. Localio, J.K. Lim, M.B. Goetz, M.B. Klein, D. Rimland, M.C. Rodriguez-Barradas, A.A. Butt, C.L. Gibert, S.T. Brown, L. Park, R. Dubrow, K.R. Reddy, J.R. Kostman, B.L. Strom, and A.C. Justice. Hepatic Decompensation in Antiretroviral-Treated Patients Co-Infected With HIV and Hepatitis C Virus Compared With Hepatitis C Virus–Monoinfected Patients: A Cohort Study. Ann Intern Med. 2014;160(6):369-379