Scientists record major HIV breakthroughs

11% sufferers in poor countries risk becoming resistant to AIDS-prevention drugs, dying from condition
Hope for vaccine as two American-funded clinical trials launch in Africa, discovery puts brakes on virus’ ability to infect
Cancer drug triggers decrease in patient’s viral load as vagina ring provides protection for women with cheating partners

Two United States (U.S.)-funded trials for Human Immuno-deficiency Virus (HIV) vaccine launched in Africa, bringing us closer than ever to widespread protection against the virus that causes Acquired Immune Deficiency Syndrome (AIDS).

The start of the three-year vaccine trial involving 2,600 women in southern Africa means that for the first time in more than a decade there are now two big HIV vaccine clinical trials taking place at the same time.

Although modern HIV drugs have turned the disease from a death sentence into a chronic condition and preventative drug treatment can help, a vaccine is still seen as critical in rolling back the pandemic.

Meanwhile, up to 11 per cent of HIV sufferers in poor countries risk becoming resistant to AIDS-prevention drugs, which could cause hundreds of thousands to die from the condition, new research reveals.

The findings were published in the journal The Lancet Infectious Diseases.

Some 11.1 per cent of HIV-positive people in southern Africa carry a mutation that could cause them to become resistant to recommended AIDS-prevention drugs, known as non-nucleoside reverse transcriptase inhibitors (NNRTI), which control the virus’ replication, a UK study found today.

Those who have previously taken drugs that block viruses from reproducing after entering cells are more likely to carry such mutations, which in some regions is up to 30 per cent of the population, the research adds.

Without action, such resistance could result in 890,000 more AIDS deaths and 450,000 more HIV infections in Sub-Saharan Africa alone before 2030, according to the researchers.

The World Health Organization (WHO) recommends countries switch to more reliable first-line AIDS treatments to combat drug resistance.

Meanwhile, the latest vaccine experiments aim to build on the modest success of a trial in Thailand in 2009, when an earlier vaccine showed a 31 percent reduction in infections.

The new study is testing a two-vaccine combination developed by Johnson & Johnson (J&J) with the US National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation.

The first vaccine, also backed by NIH, began a trial last November.

At the same time, GlaxoSmithKline’s majority-owned ViiV Healthcare unit is starting another study enrolling 3,200 women in sub-Saharan Africa to evaluate the benefit of giving injections every two months of its experimental drug cabotegravir.

The ViiV initiative, which is expected to run until May 2022, also has funding from the NIH and the Gates Foundation.

ViiV is also running another large study with its long-acting injection in HIV-uninfected men and transgender women who have sex with men.

That study started in December 2016.

The new vaccines require one dose to prime the immune system and a second shot to boost the body’s response.

Significantly, J&J’s latest vaccine uses so-called mosaic technology to combine immune-stimulating proteins from different HIV strains, representing different types of virus from around the world, which should produce a ‘global’ vaccine.

One reason why making an HIV vaccine has proved so difficult in the past is the variability of the virus.

Initial clinical results reported at an AIDS conference in Paris in July showed the mosaic vaccine was safe and elicited a good immune response in healthy volunteers.

Also, in a study led by the University of Delaware and the University of Pittsburgh School of Medicine, US, researchers discovered a “brake” that interferes with HIV’s development into an infectious agent. This mechanism prevents the capsid–the protein shell covering the virus — from forming.

The finding, which was published in Nature Communications, are based on seven years of excruciatingly detailed studies of the structure and dynamics of HIV early and late in its life cycle. The movements of the virus molecules were measured experimentally and simulated in quadrillionths of a second–that’s much faster than the blink of an eye or the flutter of a hummingbird’s wings.

Also, doctors in France have found the first evidence that a drug normally used to treat lung, kidney or skin cancer may be able to eradicate HIV-infected cells in people with the AIDS virus.

A 51-year-old man with AIDS and lung cancer was given nivolumab – sold as Opdivo -which is used to treat lung, kidney or skin cancer.

In an unexpected turn of events, the man’s doctors in Paris noted a ‘drastic and persistent decrease’ in the reservoirs of cells where HIV normally hides away and evades standard treatments.

Experts have hailed the case as exciting, and called for urgent investigation into whether this could work for others.

Also, women in Malawi have adopted a secret preventive measure against HIV infection from their partners who they suspect of cheating or who refuse to wear a condom.

A silicon ring is inserted in the vagina which secretes an antiretroviral drug that prevents the virus being contracted.

A similar size to the contraceptive diaphragm, the device – that fits high up inside the vagina – is effective for a month after which time it should be replaced.

The advantages of it are that women can insert it themselves and men reportedly cannot feel it.

Those who regularly used it – coated with an experimental medication dapivirine –were up to 92 per cent less likely to get the deadly virus through unprotected sex, experts found.

Cultural practices in Malawi make safe sex difficult for women to negotiate. At least 10 percent of the country’s population has HIV.

Women in Malawi are increasingly becoming concerned about their sexual health as men in the country have many sexual partners, The BBC reports.

Research published last year found 27 per cent fewer women acquired HIV in the group using dapivirine compared to those using a placebo ring containing no active drug.

Developed by the International Partnership for Microbicide, the ring tested in the study contained 25 mg of dapivirine, about 4 mg of which gets released over 28 days.

More than 2,600 HIV-negative women between the ages of 18 and 45 from Malawi, Uganda, South Africa and Zimbabwe were analysed.

They were categorised into one of four groups depending on how often they used the ring, ranging from non-use to near perfect ring use – and, as expected, the ring appeared to be far more effective when used most or all the time.

The level of protection for those who used the ring most consistently ranged from 75 per cent in one analysis to 92 per cent in another.

First regulatory approvals for the vaginal ring could be granted in 2018.

In 2007, an American HIV and leukemia patient called Timothy Brown was cured of HIV.

Brown, known as the Berlin Patient since he was treated in Berlin, received a bone marrow transplant for his leukemia.

The stem cells he received contained a gene mutation that is known to be resistant to HIV.

After the operation, tests revealed he had been cured.

However, every attempt to replicate his cure resulted in crippling outcomes and even death of the patient.

Scientists are still trying to understand why it worked for Brown, now healthy and living in California 10 years on, and why it didn’t work for others.

Bone marrow transplants are always life-threatening since they replace a person’s immune system with another’s, and sometimes the body rejects the transplant.

As such, it is unlikely we would see such deadly outcomes if doctors tried to replicate the new French case. More likely, the worst case scenario is that it would simply not work as well.

The case, at the Pitie-Salpetriere Hospital AP-HP in Paris, was detailed in a report in the Annals of Oncology journal, where the same doctors also gave a case study of another patient treated with Opdivo who did not show any HIV benefit.

“We must remain careful, especially because this is only one case,” said Jean-Philippe Spano, a professor and head of the medical oncology department at the Paris hospital.

“This is the first case of such a drastic decrease of the HIV reservoir (but) we have…another case where there was no decrease.”

Some 37 million people worldwide have the human immunodeficiency virus (HIV) that causes AIDS. Scientists have for years been trying to find a way of clearing HIV reservoirs with a view to being able to eradicate the virus completely and cure AIDS.

These reservoirs of HIV-infected cells are found in the immune system in places like the brain, bone marrow and genital tract. They lie hidden and dormant, and can’t be reached with standard anti-retroviral therapy HIV treatments.

If standard treatment is stopped or interrupted, the reservoirs seize the chance and the virus starts to replicate and infect more cells, rendering the patient’s immune system too weak to fight back.

“Increasingly, researchers have been looking into the use of certain drugs that appear to re-activate the latent HIV-infected cells,” Spano said. “This could have the effect of making them visible to the immune system, which could then attack them.”

Opdivo, or nivolumab is a PD-1 inhibitor, designed to help the body’s own immune system fend off cancer by blocking a protein called PD-1. It is one of several cancer immunotherapy drugs made by drugmakers including Merck, Roche and AstraZeneca that work in similar way.

In this case, the 51-year-old man had received 31 injections of nivolumab every 14 days since December 2016. He was diagnosed HIV-positive in 1995 and diagnosed with non-small cell lung cancer in May 2015.

After his first injection, the man’s HIV infection load, which had been low, increased progressively up until day 45, then fell back again. At the same time, the doctors explained – the activity of his immune system increased.

By day 120, the treatment had “resulted in the drastic decrease in the HIV reservoir…leading to a sustained reduction of the HIV reservoirs,’ Spano said.

Andrew Freedman, an infectious diseases expert at Britain’s Cardiff University, said the case was ‘potentially exciting’. But like others, he advised caution.