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World AIDS Day Picture Mixed

World AIDS Day Picture Mixed

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On World AIDS Day 2017, the picture of the pandemic is somewhat brighter — but with some ominous shadows.

On the bright side, more people than ever are on anti-HIV therapy and work continues apace on improving medications and developing new preventive methods, including two important vaccine trials. In the U.S. the CDC reported this week that delays in HIV diagnosis — an important factor in propagation of the virus — are shrinking.

In the shadows, new data suggests that HIV resistance to some drugs is rising rapidly in low- and middle-income countries, which might affect the success of therapy. In many countries, men with HIV are less likely than women to be diagnosed, on therapy, and in control of their virus. And in one developed country, the Russian Federation, the epidemic is expanding, rather than contracting.

The theme of this year’s World AIDS Day is “Let’s End it” but that’s easier said than done, according to three well-known researchers.

“The aspirational slogan … suggests that the goal of ending the epidemic is in our grasp and hinges only on our collective commitment to do so,” argued Steven Deeks, MD, of the University of California San Francisco, Sharon Lewin, MD, of the Peter Doherty Institute of Infection and Immunity in Melbourne, Australia, and Linda-Gail Bekker, MBChB, PhD, of the Desmond Tutu HIV Centre in Cape Town, South Africa.

“However, the remarkable progress, activism, resources, ingenuity, and sheer fortitude that have brought us this far will be needed in at least equal measure to take us to the end,” they concluded in a special HIV issue of PLoS Medicine.

That “remarkable progress” includes the largest-ever number of people with HIV who have access to therapy — some 20.9 million people in July, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS). That’s about 53% of the estimated 36.7 million people living with HIV around the world.

The latest data from UNAIDS also suggests that the rate of new infections is down and — a reflection, perhaps, of the increasing numbers on treatment — so is AIDS-related mortality.

“The significance of these achievements cannot be overstated,” Deeks, Lewin, and Bekker wrote. “In the past three decades, global biomedical and public health programs not only discovered how HIV causes disease and developed effective strategies to prevent and treat the infection, but also built a global public health response that is unprecedented in its scale and effectiveness.”

But many gaps remain, including an important “blind spot,” according to UNAIDS Executive Director Michel Sidibé, speaking in Ottawa today. “Men are not using services to prevent HIV or to test for HIV and are not accessing treatment on the scale that women are,” he said in a statement.

In a report released on World AIDS Day — dubbed “The Blind Spot” — the UN agency said that fewer than half the men living with HIV are on treatment, compared to 60% of women, and there is evidence that they are more likely than women to start therapy late, to interrupt treatment, and to be lost to follow-up.

Health officials have found ways to reach women at risk of HIV — in antenatal clinics, for instance — but have struggled to find similar ways of reaching men, the report says. Some results of that gap:

  • Men and boys accounted for about 58% of the estimated 1.0 million AIDS-related deaths in 2016. The imbalance was worse in sub-Saharan Africa, where men and boys accounted for 41% of people living with HIV and 53% of AIDS-related deaths.
  • Outside of eastern and southern Africa, 60% of all new HIV infections among adults are among men.
  • Men who have sex with men (MSM) are 24 times more likely to catch HIV than men in the general population; HIV prevalence among MSM is 15% or higher in some two dozen countries.
  • Some 80% of injection drug users are men and in several countries HIV prevalence among people who inject drugs exceeds 25%.
  • In prisons, HIV prevalence is estimated at between 3% and 8%; some 90% of inmates are men.

In general, HIV epidemics grow in marginalized and vulnerable groups that lack society’s attention and are often denied access to important healthcare interventions. A current case in point is the Russian Federation, according to Chris Beyrer, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues.

While it’s difficult to pin down the numbers, the Russian Federation is thought to have the largest number of HIV infected citizens of any country in Europe, Beyrer and colleagues reported in PLoS Medicine.

“Actual infections, including those that remain undiagnosed and/or unreported, are doubtless substantially higher,” they wrote, and the epidemic in Russia “continues to expand significantly.” More than 103,000 new HIV diagnoses were reported in 2016, up 5% from the previous year and AIDS deaths are also rising: 14,631 were reported from January to June 2017, up 13.5% over the previous six months.

Official figures for 2016 suggest that injection drug use accounts for 48.8% of infections, followed by heterosexual sex at 48.7% and homosexual sex at 1.5%, with a handful of perinatal infections.

“These proportions are of uncertain validity, however,” Beyrer and colleagues noted. In particular, laws that ban the sharing of information related to homosexuality, as well as official support for stigma towards MSM, are “highly likely to affect these results,” they wrote.

The range of interventions that have been shown to reduce the spread of HIV includes opioid agonist substitution therapy (such as methadone), needle and syringe exchanges, HIV treatment as prevention, and pre-exposure prophylaxis (PrEP), among others, they wrote.

But in Russia, “all of these interventions are either not available or are unavailable at the scale necessary to control HIV,” they concluded, adding that the Russian epidemic is “a true public health crisis and one that could largely have been avoided.”

Another issue that has experts concerned is HIV drug resistance.

Anti-HIV medications attempt to prevent viral replication but the virus, which is highly adaptable, can quickly evolve ways around the drugs unless they are consistently taken as directed — so-called acquired resistance.

Especially worrisome is what is called pretreatment resistance, meaning a new HIV infection is already resistant to some drugs even before the patient has begun therapy.

In an analysis of data from low- and middle-income countries, researchers found that pretreatment resistance to one class of drugs — the non-nucleoside reverse transcriptase inhibitors (NNRTIs) — has been rising sharply.

The issue is particularly important because the NNRTIs are part of most first-line anti-HIV regimens in those countries, according to investigators led by Ravindra Gupta, MD, of University College London in England.

In a systematic review and meta-regression analysis of 358 datasets, representing 56,044 adults in 63 countries, Gupta and colleagues estimate pretreatment NNRTI resistance in 2016 at about 10% in most regions — 11% in southern Africa, 10.1% in eastern Africa, 7.2% in western and central Africa, and 9.4% in Latin America and the Caribbean.

Importantly, they reported online in The Lancet Infectious Diseases, the yearly odds of pretreatment resistance have been rising: 23% in southern Africa, 17% in eastern Africa, 17% in western and central Africa, 11% in Latin America and the Caribbean, and 11% in Asia.

“Treatment resistance indicators have turned to red in several countries,” increasing the risk that first-line therapy with NNRTIs will no longer be effective, commented Sabine Yerly, PhD, and Alexandra Calmy, MD, PhD, both of Geneva University Hospitals and Faculty of Medicine in Switzerland.

Changing the guidelines for first-line therapy will likely reduce the rates of pre-treatment resistance, but by itself will not be enough to prevent its recurrence, they argued in an accompanying commentary.

They argued that different drugs must be used and health authorities must ensure treatment for all people who need it, including those now excluded or disengaged from care, to prevent the emergence of resistance in the first place.

Meanwhile, the National Institute of Allergy and Infectious Diseases reported, just in time for World AIDS Day, that a new vaccine candidate is under test in Africa — the second major trial looking for what is regarded as the keystone of HIV prevention.

The so-called Imbokodo trial, a phase IIb proof-of-concept study, will enroll 2,600 HIV-negative women in sub-Saharan Africa to evaluate both safety and efficacy of the vaccine candidate. Earlier studies have shown it is safe in healthy volunteers.

The vaccine candidate being tested in Imbokodo is based on “mosaic” immunogens — vaccine components designed to induce immune responses against a wide variety of HIV strains.

That’s different from the so-called HVTN 072 efficacy trial, which is currently testing a tweaked version of the vaccine regimen tested in the RV144 Thai trial — the only candidate HIV vaccine ever shown to provide some protection against the virus.

That candidate is actually two vaccines — a modified canarypox virus called ALVAC carries the HIV gag, env, and pro genes, while a second vaccine targets the HIV gp120 protein. In its first iteration, that vaccine reduced the risk of HIV infection by about 30%, although with wide confidence intervals; the HVTN investigators are hoping the changes they’ve made, including an adjuvant and an extra shot, will increase its efficacy.

While all this is going on, other investigators are investigating the potential of what are called “broadly neutralizing antibodies” to prevent HIV, although that work is in the early stages.

Adding an effective vaccine to current prevention strategies would have “potentially transformative benefits” in the fight against HIV, Deeks and colleagues argued.


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