Simon Collins, HIV i-Base
The 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention that opened today in Kuala Lumpur and running to 3 July 2013 has a strong programme that will have lots to report.
In returning to South-East Asia, the meeting in Malaysia will refocus attention on issues relating to care and treatment of people who inject drugs (PWID) – similar to when the International AIDS Society (IAS) came to Bangkok in 2004.
The global focus on this region is likely to have contributed to social changes that allowed expansion of evidence based needle-exchange programmes and reducing use of the death penalty for drug offences.
This meeting is smaller than the biennial World AIDS Conferences with which it alternates – attracting approximately 5,000 compared to 25,000 delegates – also organised by the IAS. Although more focussed on science relating to HIV treatment and prevention the meeting will retain a strong human rights focus. Adeeba Kamarulzaman, the co-chair of this meeting, has led a radial and humanised approach to the HIV epidemic in Malaysia where PWID are disproportionally affected. Her work includes establishing the first needle-exchange programmes in Asia and has influenced may other countries in the region. An oral session on Monday is on evidence-based drug policies.
With many important sessions programmed at the same time, webcasts will be essential, even to people fortunate enough to be able to attend the meeting. The programme for the meeting is already online.
Weblinks for oral abstracts are expected to be accessible after the session has been presented. Web casts from oral sessions usually are usually available the day after the presentation but some sessions may take a couple of day to go live. All plenary and oral presentations being held in session rooms 1-4 are due to be web cast.
Highlights for the conference
WHO guidelines and global access
The new and consolidated WHO guidelines were launched on Sunday, after having to switch to a larger conference room due to the overwhelming interest they have generated. In the previous WHO satelitte meeting, a focus on current access highlighted that close to 10 million people in low- and middle-income countries are now taking HIV treatment.
The WHO guidelines though are likely to generate some of the most controversial discussions due to the shift to recommend a higher CD4 threshold for starting HIV treatment. The increase from 350 to 500, will be based on hoped for merger of clinical and prevention benefits. The recommendation to treat below 500 is supported by a grading of a “strong recommendation”, and by a “moderate” level of evidence. How the panel arrived at this decision is less clear as the panel had only two randomised clinical trials (SMART and HPTN052) to base their decision on. Importantly, these were sub-analyses rather than primary endpoints and neither study was designed to look at when to start treatment.
The guidelines then are based on supportive results from cohort studies and a very heavy sway from the impact treatment has on reducing transmission. This are aspirational and political guidelines and it would be helpful if this was stated clearly. Also, the evidence base for the guidelines will not be published until August and so in interpreting the WHO recommendations will involve distinguishing the likely clinical benefits from treatment from the population based prevention benefits.
Where resources limit access, people with CD4 counts <350 should be prioritised for treatment. Triple therapy is recommended during pregnancy for all HIV positive women and for all children less than five years old, irrespective of CD4 count.
This is a bold and political move by the WHO that establishes the importance of guidelines as aspiration goals, and that that the global urgency for broader access to treatment warrants this new profile above the practical difficulties and limitations of operational problems. Already the top line results that WHO recommends earlier treatment are probably a good thing if they result in earlier testing and access to treatment.
The guidelines also suggest a strong US influence. US guidelines were the first to swing back to 500 and now recommend treatment irrespective of CD4 count. Whether what is proposed for the US will work in very different settings, with different access to drugs and different medical infrastructures will be the long-term test. In practice most people in the US start treatment far later than 500.
Other aspects of the guidelines include:
- Consolidating several guidelines into one document: adult, paediatric, pregnancy and operational guidelines are now in a single document.
- That triple therapy should be the standard of care for HIV positive women who are pregnant, irrespective of CD4 count (strong recommendation, moderate evidence).
- That triple therapy should be the standard of care and initiated in all children with HIV who are five years or younger. Older children should start treatment, irrespective of age, at a CD4 threshold of 500.
- Recommending that treatment should be offered to all HIV positive people (ie at CD4 counts >500) if they have a sexual relationship with an HIV negative partner (this was carried forward from the 2012 recommendations).
- Recommendations for choice of treatment: which drugs to use in first, second and third line combinations. These raise some of the most difficult limitations for the guidelines. The disconnect between continued use of d4T and the thought of early treatment without access to latest treatment is one of the most important omissions.
The i-Base/TAG 2013 pipleine report reviews upcoming drugs for HIV, HCV and TB includes one of the first responses to these WHO guideline changes, including these recommendations for drug choice.
WHO: Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection
WHO guidelines press release
Global update on HIV treatment 2013: Results, impact and opportunities
Other highlights at IAS 2013
Children and HIV
The programme includes a wealth of studies including new drugs and formulations, discussion about optimal time for starting treatment and the transition from adolescent to adult care is highlighted in a plenary on Monday morning.
HIV prevention: TasP and PrEP
Several sessions are scheduled to present new results on ways to reduce HIV transmission, including using treatment as prevention and Pre-Exposure Prophylaxis (PrEP).
After a lean few years, this year the conference looks like it includes an increase in the number of studies on ART. These include updates on integrase inhibitors including Quad (Stribild) and dolutegravir in standard combinations with RTI (nuke) – based combinations but also a number of comparative “nuke-sparing” studies.
Basic science studies include cure research – leading with IAS pre-conference workshop on Saturday and Sunday – with an abstract-driven programme taken from studies submitted to the main conference, supported by lectures from prominent cure-based researchers on key themes.
But there are also interesting studies on the pathogenesis of HIV including the development and implications of drug resistance and the role of HIV tropism. Research into early treatment – on diagnosis and in primary infection – and on he role of immune activation and the roles for targeting this in clinical interventions.
Highlight links to important presentations, webcasts and reports will be posted to the i-Base facebook page.
Although i-Base doesn’t post same day reports from the conference, early articles for HIV Treatment Bulletin will be posted as published ahead of print articles when they become available.
- WHO 2013 guidelines: what about the missing formulations?
- WHO 2013 guidelines: when the risk:benefit may not favour starting at CD4 count of 500 cells/mm3
- Efavirenz at 400 mg compared to standard 600 mg dose has similar efficacy with fewer side effects
- Dolutegravir update: treatment experienced patients and drug resistance
- Elvitegravir/cobicisat/tenofovir/FTC: Stribild studies at IAS 2013
- Non-standard combinations: NRTI-sparing combinations
- ARVs and bone health: the role of NRTIs in second-line therapy
- No viral load rebound off-ART following stem cell transplant: two “cure” cases using reduced intensity conditioning chemotherapy and CCR5 d-32 negative donors
- HIV cure research: further capsules at IAS 2013
- Partner-dependent immune differences may protect against HIV infection
- Pipeline oral HCV drugs and generic global access: need to mirror ARV programmes