NAM AIDS MAP – 9TH IAS SCIENTIFIC AIDS CONFERENCE – PARIS FRANCE JULY 2017

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Thursday 27 July 2017

Contents

PrEP for adolescents in southern Africa

Katherine Gill presenting at IAS 2017. Photo by Roger Pebody, aidsmap.com

Adolescent girls and young women aged 15 to 24 account for 23% of all new HIV infections in sub-Saharan Africa. Females are much more vulnerable to HIV than their male peers. Whereas 0.7% of adolescent boys aged 15 to 19 have HIV in South Africa, the equivalent figure for girls is 5.6%. In the 20 to 24 age group, 5.1% of men and 17.4% of women have HIV. In some parts of the country, prevalence is even higher.

New prevention options that are acceptable to young people, and especially to young women, are urgently needed in southern Africa. Pre-exposure prophylaxis (PrEP) for young people is being considered in several countries as a potential option.

One of the first studies to explore the acceptability, safety and use of PrEP with adolescents in an African context has found that PrEP was safe and tolerable, although PrEP usage and adherence did tail off during the 12 months of the programme.

Presenting the findings of the PlusPills project to the 9th International AIDS Society Conference on HIV Science (IAS 2017) in Paris this week, Katherine Gill of the Desmond Tutu HIV Foundation said that South African adolescents need access to PrEP with tailored adherence support and more frequent clinic visits. Less frequent dosing schedules, if validated, could be of interest to this population, she suggested.

Yogan Pillay of South Africa’s National Department of Health said that five demonstration studies had already provided preliminary data on how to target and deliver PrEP to adolescent girls and young women.

The uptake of PrEP varies considerably between different studies and in different social contexts, ranging from 36 to 98% of those approached. Retention and adherence also varies considerably, with between 40 and 70% of participants either reporting continued PrEP use or having sufficient levels of the drug in their blood.

The experience so far has underscored the need for flexibility and adaptability in providing oral PrEP to young women in South Africa. The diversity of settings in which young women live means that PrEP cannot be a one-size-fits-all prevention tool.

Concern about side-effects has been a recurrent challenge and a frequent reason for young people to discontinue PrEP. Other reasons for opting out of PrEP include dislike of the pill’s size or taste, and difficulties remembering to take it every day.

Pillay said that community education is critical to uptake and adherence. It needs to try to reduce the stigma of young people’s sexual activity and to legitimise PrEP as a form of prevention. Parents and caregivers are extremely influential in adolescent girls’ decision-making about PrEP.

The South African government is hoping to deliver PrEP through clinics in tertiary and vocational education colleges and universities, as well as in family planning services. Work is needed to ensure that staff are sensitive and do not stigmatise PrEP users, Pillay said.

Injectable PrEP

Raphael Landovitz at IAS 2017. Photo by Liz Highleyman, hivandhepatitis.com

A long-acting injectable formulation of cabotegravir given every 8 weeks produces high enough drug levels in both men and women to offer protection against HIV, according to results from the HPTN 077 study presented at the conference. But another injectable prevention candidate, long-acting rilpivirine, has been abandoned.

The effectiveness of antiretroviral drugs for HIV pre-exposure prophylaxis (PrEP) is heavily dependent on maintaining good adherence. Some people may find it easier to take PrEP consistently if they could have an injection every month or two, instead of taking pills every day or when they plan to have sex.

The HPTN 077 study is looking at the safety, tolerability and acceptability of long-acting injectable cabotegravir, an experimental integrase inhibitor. As a phase 2a trial, it is not designed to evaluate prevention efficacy. (The conference also heard promising data on long-acting cabotegravir for HIV treatment.)

Cabotegravir is being given every eight weeks as an intramuscular injection. The study found that injections were well tolerated – only one out of 199 participants left the study because of an injection-site reaction.

Although HPTN 077 was not intended to assess prevention efficacy, no participant acquired HIV while receiving regular injections. One participant seroconverted 48 weeks after their last cabotegravir injection, when levels of the drug were undetectable.

A larger study, HPTN 083, comparing the efficacy of injectable cabotegravir compared to oral Truvada (tenofovir/emtricitabine) for PrEP is now underway.

First-line treatments for HIV, viral hepatitis, TB don’t cost more than $90 to make – so why pay more?

Dzintars Gotham presenting at IAS 2017. Image credit: Enzo Poultreniez / http://aides.org

HIV, hepatitis B and C and tuberculosis can each be treated for less than $90 a year where generic drugs can be made available, Dzintars Gotham of Imperial College, London, reported at the conference.

The findings come from an analysis of prices paid for the raw materials used to make drugs for the treatment of each disease, and the costs of manufacturing each product.

The research showed that a year’s supply of the first-line antiretroviral combination of tenofovir, emtricitabine and efavirenz can be manufactured for US$78, and a course of treatment for hepatitis C for between $47 and $79.

Although the cost of antiretroviral treatment has fallen dramatically since generic manufacturers first began to manufacture versions of antiretroviral drugs in India in 2001, generic products have not been available in all countries due to patent restrictions. Over the next few years, it will begin to be possible to provide first-line treatment for HIV using generic drugs, as patents expire on some of the key drugs used in HIV treatment.

To achieve global targets for HIV treatment and viral suppression, hepatitis C elimination and reducing the burden of tuberculosis and drug-resistant tuberculosis, large increases in the number of people treated for each disease will be necessary. Cutting the prices paid for medicines will be essential if countries are to afford large treatment programmes for HIV or viral hepatitis.

Treatment can become more affordable as patents expire and more countries are able to obtain generic versions of drugs to treat HIV and viral hepatitis, the researchers said. Even where patents are still in force, knowing the costs of production should enable governments to demand more affordable prices from pharmaceutical companies, speakers at a symposium on drug pricing agreed.

Male medical circumcision: benefits for women?

Carlos Toledo presenting at IAS 2017. Photo by Roger Pebody, aidsmap.com

It is well established that circumcision protects men against acquiring HIV, but until now there has been little evidence of benefit to women of men being circumcised. Almost a decade ago, a meta-analysis found no evidence to suggest that circumcision of men directly reduced the risk of women acquiring HIV.

However, a study presented to the conference found that South African women whose most recent sexual partner was circumcised are less likely to have HIV, suggesting that the voluntary medical male circumcision programmes do have benefits for women too.

Studies have shown a reduced risk of human papillomavirus, genital ulcers, herpes simplex virus type 2, syphilis, bacterial vaginosis, and T vaginalis in women whose partners are circumcised. This is likely due to changes in the male partner’s anatomy, making transmission of an infection less likely.

However, in the case of HIV, it is more likely that male circumcision can benefit women by reducing the prevalence of HIV in men who have been circumcised.

The new study involved men and women in KwaZulu-Natal, South Africa, and found that women whose most recent partner was circumcised had lower rates of HIV (42%) than women whose partner was not circumcised (54%). Controlling for other factors, an analysis of the results found that women with circumcised partners had a 30% lower likelihood of having HIV. They were also less likely to have herpes simplex virus type 2.

Side-effects of commonly used drugs

Tenofovir disoproxil is one of the most frequently used antiretroviral drugs in the world today. Rare but serious side-effects of the drug have the potential to affect a substantial number of people because of its widespread use.

Doctors need to monitor people regularly for kidney function if they are taking tenofovir, especially if combined with ritonavir, the conference heard this week.

Fanconi syndrome is an acute type of kidney failure caused by substances that would normally be reabsorbed being released out of the blood into the urine instead: phosphates (which help build bone), amino acids and bicarbonate, which raises the acidity of the blood to dangerous levels (acidosis).

Dr Nicholas Medland of Monash University in Melbourne, Australia, told delegates that Fanconi syndrome was “uncommon, but not rare”, with 1.25% (one in 80) of the people in his study developing it within a ten-year period. Importantly, it could appear unexpectedly, in people with no characteristics linked to kidney disease.

Tenofovir has also been linked to bone loss in some studies. However, Dominique Costagliola of the French national medical research agency INSERM told delegates she had found no association between tenofovir, or any other HIV drug, and the risk of bone fractures of the type associated with low bone mineral density.

New option for first-line treatment: doravirine

Kathleen Squires at IAS 2017. Photo by Liz Highleyman, hivandhepatitis.com

A single-tablet regimen containing the next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) doravirine, reduced HIV viral load as much as an efavirenz-based co-formulation, but it had a more favourable side-effect profile, according to results from the DRIVE-AHEAD study presented at the conference.

Current first-line antiretroviral therapy regimens are safe and highly effective. Integrase inhibitors have largely replaced NNRTIs for first-time treatment in recent years, but having multiple potent and well-tolerated drugs from different antiretroviral classes offers more options for individualised therapy.

Doravirine, an investigational NNRTI being developed by Merck, has a unique resistance profile and is active against HIV with common NNRTI-resistance mutations including K103N. It can be taken with or without food and has low potential for drug-drug interactions.

The DRIVE-AHEAD study showed that after 48 weeks on treatment, 84% of people in the doravirine arm of the study and 81% in the efavirenz arm had undetectable viral load, showing that the new co-formulation was non-inferior. People who received doravirine were less likely to experience central nervous system side-effects such as dizziness, sleep problems or depression.

Treatment for hepatitis C co-infection: a new pangenotypic option

Karine Lacombe at IAS 2017. Photo by Steve Forrest/Workers’ Photos/IAS

AbbVie’s new pangenotypic regimen combining glecaprevir and pibrentasvir cured hepatitis C virus (HCV) in almost all participants living with HIV and HCV co-infection in the EXPEDITION-2 study, according to a presentation at the conference.

Treatment was highly effective, with 98% having continued undetectable HCV RNA at 12 weeks post-treatment (SVR12).

Glecaprevir/pibrentasvir (Maviret) is expected to be approved by the US Food and Drug Administration in August. It has received a positive opinion from the scientific committee of the European Medicines Agency (the CHMP) and should receive European Union marketing approval within the next few months.

“These results suggest that the glecaprevir/pibrentasvir regimen could be the first 8-week, pangenotypic treatment option for HCV/HIV-1 coinfected patients without cirrhosis,” the researchers concluded.

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