Long-acting PrEP; Fem and VOICE PrEP sing same sorrowful song; PrEP not associated with increased risk of future HIV seroconversion

The provision of HIV antiretroviral pre-exposure prophylaxis (PrEP) is one of the four key action items of the ‘Action on HIV- Melbourne Declaration 2012’.  PrEP was discussed in several different sessions at CROI 2013. Here are some of the highlights:

In Session 8, ‘HIV prevention: ARV, Counseling, Contraception and Condoms’, Chasity Andrews from David Ho’s group at the Aaron Diamond AIDS Research centre gave an excellent talk on GSK744 which is a new, potent integrase inhibitor (abstract 24LB).  GSK744 exists both in an oral and a long acting parenteral formulation. The oral formulation has been evaluated as monotherapy and affords a 2-2.5 log₁₀ decrease in plasma HIV-1 viral load.  It’s half-life is approximately 3.71 weeks when given intramuscularly at 800mg.

In Ho’s study 8 Rhesus Macaques were injected with GSK744 twice, at week -1 and week 3+. All animals were intra-rectally challenged from week zero with SHIV 162P3 and received a total of 8 challenges, or until SHIV infection was confirmed.

None of the 8 Macaques receiving GSK744 became infected during the challenge, or during the 10-week follow-up phase whilst all Macaques receiving placebo GSK744 became infected.  In follow-up, there was no evidence of DNA in PBMCs nor an antibody response to SHIV in any of the actively treated Macaques.

Further work to be done with GSK744 includes (1) postmortem of the Macaques receiving active GSK744 to determine if there was contained local infection, (2) determining the minimum protective dose for rectal challenge, (3) determining its capacity to protect again HIV vaginal challenge in female macaques.

This drug has the potential to be given monthly or quarterly. 

Clinical trials, in addition to determining drug efficacy will need to carefully monitor for both short and longterm toxicity (including for a period of time after injections have ceased). If efficacious, this possible shift in the formulation of PrEP drugs could be remarkably beneficial for people at risk of HIV infection, but will still require appropriate ‘effectiveness’ studies to determine adherence, risk compensation and any informal use of PrEP as an injection.  Also in different countries, monthly or quarterly PrEP injections could potentially lead to infringement of human rights for some, including sex workers and people who inject drugs.

In the next talk of session 8, James Smith from the CDC provided further encouraging trial results that showed that a Tenofovir Disoproxil Fumarate (TDF) intravaginal polyurethane ring was able to completely protect 8 female macaques from SHIV vaginal challenge on 16 occasions over 4 months and using 4 ring changes during that time (abstract 25LB). There was no toxicity, no microflora change and Phase 1 Clinical trials will commence in Q3 2013. Very interesting presentation in terms of the machinations of developing the ring so that it effectively delivers the more potent form, TDF which is 500 times more potent than tenofovir and also has activity against HSV-2.

(Note-these two talks complement another session held later on that day “New approaches to HIV drug delivery”, Session 13).

In session 8 Jeanne Marazzo next presented the findings of the VOICE study (Abstract 26LB).

VOICE was a randomised, 5-arm, double-blind, placebo-control trial of PrEP that enrolled5,029 HIV negative women from Zimbabwe, South Africa and Uganda. Most participants were enrolled in South Africa (4,077).  Eligible participants had to have had sex in the previous 3 months, be willing to use oral contraception and not be pregnant, or breastfeeding. Participants were randomised to oral tenofovir, oral tenofovir- emtricitabine, oral placebo, 1% tenofovir gel or gel placebo. 

An interim DMSB in September 2011 ceased the oral TDF arm because it was safe but not effective.  In November 2011 the TFV vaginal gel arm was stopped because it was safe but not effective.  In August 2012 follow up of TDF-FTC arm was possible.

The mean age of the participants was 25.3 year. Most women were using injectable contraception. 17% reported anal sex at baseline. 85% reported use of a condom at last vaginal sex. Study retention was excellent with an overall 91% retention rate at study end

Adherence was assessed using monthly count of unused study products (pills or applicators) and quarterly audio-computer assisted self interview (A-CASI). Product return suggested 89% adherence and self-report by A-CASI found an adherence of 90% or above.

There were 334 HIV acquisition events for the intention-to-treat analysis. 22 women were HIV+ by PCR at enrolment. Hence there were 312 HIV acquisitions in the primary analysis, giving an overall HIV incidence of 5.7%. None of the three studied PrEP modalities afforded protection from HIV. The incidence of HIV was highest in women who were less than 25 years old and unmarried. The HIV incidence per 100 person-years in South African women < 25 years of age was 8.7 [7,6-10], > 25 years of age 4.7 [3.8, 5.8], married 0.9 [0.2-2.7] and unmarried 7.5 [6.6, 8,4].

Adherence appears to be the key factor in the observed failure of the study drug as at least 50% of women tested had no TFV found in sampling across the three study arms. These results are consistent with the Fem-PrEP study (Van Damme et al, NEJM 2012), which showed that oral TDF-FTC did not significantly reduce HIV infection compared to placebo and that adherence appeared to be very low in the study.

The disappointing conclusions that the VOICE study team drew were that we need to consider PrEP agents and delivery systems that are long acting and require minimal daily adherence and that a greater understanding of HIV risk perception and biomedical, social and cultural determinants of adherence in these high-risk populations is urgently needed.

In follow-up questions we learned that very few women in the VOICE study reported that they were CSWs and that the study team are doing a separate study, VOICE-D, to explore via in-depth qualitative interviews the issues around risk perception and PrEP adherence.

Finally, to end on a more positive note we learnt from Bob Grant of the iPrEx study team (abstract 27) that during a gap phase that occurred between the iPrEx study ending and an open-label extension of the iPrEx study beginning (where gap times ranged from 7-19 months across the study sites and during which no PrEP was available), that there was no excess incidence of HIV infection observed. Here the theoretical concern was that the use of PrEP during the iPrEx study had simply delayed HIV infection and that when PrEP was ceased during the gap phase that an excess in HIV seroconversions would be observed. This speaks to the notions of biological and behavioural prevention futility where an intervention like PrEP may fail ultimately if it does not alter the conditions that allow transmission.  An excellent talk to catch on the webcast.

Dear readers, if you have not already done so please sign the Melbourne Declaration at http://www.melbournedeclaration.com/ as Australia, Asia and the Pacific Region gear up to host World AIDS 2014 next year in Melbourne. Act now and be part of this endeavour!

HIV Testing and Monitoring the Epidemic: New Tools for Patients and Populations. Session 51 Symposium

This was one of the conference’s last sessions and was very well attended.

HIV self-testing: Opportunities and Challenges. Abstract 162

Dr Julie Myers, New York City Department of Health

This was an important talk given that increased access to HIV point-of-care testing is one of the key aims of the Melbourne Declaration. It is worth watching on the CROI webcast.

Last year the FDA approved the Alere Determine HIV Combo home self-testing kit, also known as Orasure.

Dr Myers provided the results from a recent 5,000+ patient trial of the Orasure rapid HIV home testing kit, which was conducted across 20 sites in the USA.

These data were given to the FDA Advisory Committee last year by the product sponsor but have not yet been published.

In this study they found that 82% of people using the test were from high HIV prevalence areas.

5,055 patients were evaluable for test results. The overall prevalence was 2.12%. See slide below from Dr Myer’s talk for further results of this study.

Note that the sensitivity is only 91.67%. Of note when trained professionals use this test its sensitivity is over 98%. 

As we know this product went on to become licensed in the USA. Of note, people who use the kit have 24-hour phone access for support and for referral to sites for confirmatory testing.

There are few post marketing data available but there have been some published data to indicate that users of the test find it is ‘easy to use’.

How homebased self-testing tests are being used

Dr Myer then discussed the way that the tests are being used including by those who are at risk and by potential sexual partners. Dr Myers reviewed some recent publications that showed that rapid tests are being used to test prospective sexual partners and acquaintances and that no sex occurred with partners who tested positive. The numbers in these studies were fairly small however.

Concerns noted by Dr Myers

1. Propensity for self-harm and violence

Similarly although there are no data to support ongoing concerns that HIV home self-testing kits will lead to an increased risk for self-harm and suicide and inter-partner violence Dr Myers noted that more work and study needs to be undertaken in this area.

2. Lost opportunities

In addition Dr Myers noted that home self-testing kits mean there is an increased chance for patients to lose the opportunity to have additional STI testing and to be referred for other appropriate services.

3. False reassurance

A major concern is that some people will be falsely reassured that they are HIV negative when they have false-negative results.

4.Cost

Cost is a real concern because the kit costs US$40 and those most at risk of HIV are those who are most financially disadvantaged. Only 17-18% of people in the US and Europe would be willing to pay this amount for a kit in studies cited by Dr Myers.

5. Risk compensation

There are not yet any data on whether home HIV self-testing kits are associated with risk compensation- meaning an increase in risk-taking.

Dr Myers noted an important study presented at CROI 2013 Abstract#1064 by Katz et al where modeling done around MSM in Seattle suggested that switching from clinic to home-based testing using Orasure would lead to an increase in HIV transmission.

6. Linkage to care

There are not data to show whether use of these tests will lead those people who test HIV positive to seek appropriate medical care. Although 88% of people in the self-test clinical trial presented to the FDA last year said that they would ‘definitely get follow-up’ this remains an important area to monitor and study.

7. Resource constrained settings

Limits of supply chain and also quality assurance.

 During question time Dr Myers got hammered by two audience members who were particularly concerned about how little data there are available about whether home-testing would improve linkage to care in the USA. However, as another audience member noted, the US linkage to care using clinic based testing is pretty poor! This is also an issue that Australia must address.

Point of care assays for immunological and virological monitoring of HIV disease. Abstract 163.

Dr Ilesh Jani, Mozambique

Dr Jani gave a fantastic talk and overview about point of care testing for HIV diagnosis and monitoring regarding POCT for CD4 cell counts and HIV viral load including for children.

Amongst other things he discussed implementation issues and noted:

1. POCT is not error proof. It IS error prone in all phases of testing

2. Implementation of point of care tests is not always done efficiently.

In Mozambique his team's data showed that despite having POCT CD4 instrument on site, they lost 24% of people BEFORE people got tested with the POCT CD4 test. They only managed to test 50% of people on the same day as their HIV diagnosis. Median time to get a CD4 count was 3 days (Jani et al 2011

One key point that I took home from him was that whole blood viral load testing is likely to become common in the future. In patients whose plasma HIV viral is undetectable they may still have a detectable HIV viral load in their whole blood test. He explained that we don’t really know what this means clinically and we don’t know the correlation between plasma and whole blood HIV viral load testing

Accurate cross-sectional incidence testing. Abstract 164

Dr Laeyendecker, NIAID and Johns Hopkins

Dr Laeyendecker gave a masterful talk on this subject, which was valuable for a naïf such as myself. It’s a must watch talk for those who wish to understand how to optimize testing algorithms to assess HIV incidence in populations

Key points include (1) that there is a difference between how HIV clade D versus clades A and C perform in these testing algorithms wherein the tests overcall the prevalence of clade D infections and (2) that multi-assay algorithms perform best for HIV incidence testing in stable, expanding and waning HIV epidemics.

Viral load measures: patients, populations and interpretations. Abstract 165

Dr Irene Hall, CDC

This talk was good. The main point I learnt was that community viral load refers to the viral load of those people who have been diagnosed with HIV. Population viral load refers to all people in a population who are HIV infected including those who are unaware of their diagnosis. This is an important distinction because community viral load does not accurately reflect HIV transmission potential in the community.

Dr Hall noted an excellent oral presentation given at CROI 2013 Abstract 96 which reported on the first study in Swaziland of their HIV population viral load. This household-based counseling and testing study evaluated 18,169 individuals. 5802 individuals were identified as being HIV+ and, of these, only 67% knew that they were HIV+ and, of these, only 50% reported current ART use. A high viral load, defined as >50,000 copies/ml was found in 35% of the total population, (cue heartsink feeling here).

Overall an excellent session.

Opportunities and Threats to ART success (session 36) and related CROI abstracts

Greetings from Atlanta, home to CDC, CNN and Coca Cola of which I have ingested output from all three during this visit.

For those interested in the obstacles to ART implementation and its therapeutic success including new antiretroviral drugs and formulations, there was a terrific symposium held yesterday that addressed these issues.

Jennifer Kates from Kaiser Family Foundation outlined issues arising from Obama’s Affordable Care Act (ACA) as they pertain to HIV care and treatment access. Like Australia, the US Federal- State divisions and discords can be disconcerting. In the US states have the choice of accepting the expansion of the public health fund Medicaid or not. For those states that accept it, people living with HIV will have greater access and financial support for their HIV care. Currently 68% of people living with HIV in the USA live in states that will support Medicaid’s expansion but this leaves the potential for disparate levels of care for people living in the remaining states who decline Medicaid expansion. A good talk for those who seek to better understand the ACA.

Sharon Lewin from Alfred/Burnet/Monash gave an outstanding talk on the impact of the residual inflammation experienced by virologically suppressed HIV positive people on ART.  Sharon addressed the impact of residual inflammation upon risk for mortality and non-AIDS diseases. She addressed the drivers of this inflammation and the current (largely theoretical) therapeutic approaches we could take to decrease inflammation. A must-watch talk on CROI’s webcast.

Raph Hamers from Academic Med Ctr of the University of Amsterdam gave a very good talk on ARV drug resistance. He discussed in detail transmitted drug resistance, which is a key issue for populations living in eastern and southern Africa where transmitted NNRTI resistance predominates. Also he addressed the recently published observation that K65R resistance appears to occur more rapidly in clade C infected patients whose first-line therapy included tenofovir. K65R is also selected in patients who have been treated previously with stavudine (d4t). He highlighted the importance of switch studies from first to second line therapy.

Of note ASHM President-elect Mark Boyd and his colleagues’ SECOND-LINE study’s 48-week results were presented as a late breaker poster (180LB).  The study results support switching to a boosted lopinavir + raltegravir, NRTI-sparing regimen for individuals failing their first-line NNRTI with 2N(t)RTIs regimens. This approach was non-inferior to switching to boosted lopinavir +2-3N(t)RTI regimens and was associated with a significantly higher CD4 cell recovery.

Joe Eron from the University of North Carolina gave Trip Gulick’s talk on new ARVs, which was, thankfully optimistic. There are a number of new ARV formulations in the pipeline including atazanavir/cobicistat, darunavir/cobicistat which precludes use of ritonavir as a boosting agent. Rilpivirine is also being studied in a nanoparticle form and as a long-acting intramuscular injection. Efavirenz and atazanavir are also being considered for nanoparticle formulation. Antiretroviral agents can be formulated as solid or liquid suspension nanoparticles. Theoretically nanoparticles could afford better bioavailability and higher tissue concentrations as they are taken up and then released into tissues by mononuclear phagocytes. Abstract 513 reported on successful in vitro studies of Efavirenz formulated as solid drug nanoparticles.   

The talk provided an excellent table of all the up and coming drugs- check out this talk via the CROI webcast site to view the table.

Importantly Joe Eron mentioned the new tenofovir pro-drug tenofovir alafenamide (TAF). TAF is notable because its plasma levels are 90% lower than those of tenofovir but it has a 5-fold increase in intracellular TFV diphosphate compared to tenofovir, which affords it the potential for lower toxicity. Indeed significantly lower bone and renal toxicity was observed in the TAF arm of a phase 2 randomised, double blind trial presented as a late breaker oral presentation (abstract 99LB). Here elvitegravir/ cobicistat/ emtricitabine/tenofovir was compared to elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide. The two regimens had comparable efficacy at week 24 and the findings support scaling up to a phase 3 study. All points bulletin to bones and kidneys: watch this space!

Building Bridges: HIV and non-communicable diseases.

My last day in Washington DC and although I am sorry to leave I am keen to return to Australia buoyed by the wonderful energy and optimism arising from both the conference findings and the attendees.  At our next conference in 2014 in Melbourne, we hope to hear a lot more from and about people who inject drugs, sex workers and transgender people.

Building Bridges was one of my favourite sessions at the conference (Session MOAE01). It addressed how best to link services for HIV testing and treatment to the diagnosis and management of non-communicable diseases (NCDs). The studies reported at the session were ambitious, well designed and showed promising results. It will be great to see similar studies coming out of the Asia Pacific region.

The first speaker was Miriam Rabkin from the Mailman School of Public Health at Columbia University. She gave an excellent overview on linking systems and services for HIV and chronic NCDs. She noted that 15% of patients at several ICAP sites are > 50 years of age. ICAP is the International Centre for AIDS Care and Treatment Programs http://www.columbia-icap.org/.

 Dr Rabkin posed the important questions:

• What are the best and most efficient ways to screen PLWH for NCD in resource-constrained     settings?
• Where should NCD prevention, care and treatment services for PLWH be delivered?
• Should they be integrated into the HIV clinic or provided elsewhere?
• Which health care providers should treat NCD in PLWH?

The second speaker was Dr Gabriele Chamie from UCSF and the UCSF- Makerere University Research Collaboration in Kampala who gave a superb presentation (MOAE0103) describing the results of a 5-day campaign undertaken in the Kakyere Parish, Uganda.

6,300 residents participated in the campaign, which represented 74% of the entire local community. The success of this study engagement was attributed to the fact that they partnered with local village leaders, designed and executed community mobile efforts through churches and mosques, put out posters and pamphlets and used radio announcements. Importantly the campaign focused on a number of illnesses for screening and did not focus solely on HIV, which they felt was important.

Each day they saw over 1,000 patients with a median waiting time of 90 minutes. Patients were offered comprehensive point-of-care screening for HIV, malaria, hypertension and diabetes. Patient diagnosed with HIV were offered immediate referral to on-site counselors and clinic staff.

30% of people had never been tested for HIV infection. The HIV prevalence in the study population was 8% and 46% of patients were unaware of their status prior to the campaign. The median CD4 cell count was 449 cells/uL, which is almost identical to the median CD4+ cell count at diagnosis in Australia.  Patients with CD4+ counts 100/uL were sent for intnsive counseling and rapid referral for ART. HIV+ patients were also tested with GeneXpert for TB screening.

Regarding hypertension, BP findings showed 23% had BP > 140/90 and 12% had BP > 150/100.  69% of patients were unaware that they were hypertensive before the campaign.  The prevalence of diabetes was 3.5 % and 23% of patients were newly diagnosed with diabetes.  Malaria was diagnosed in 10% of children.

The findings of linkage to care following diagnosis showed that with an active referral at 3 months only 59% of HIV+ patients had linked to follow-up care. However those patients with lower CD4 cell counts had received enhanced referral practices and 74% of patients linked up with care and started ART within a median of 2 days.

There were three other excellent presentations at this session and I would draw your attention to the presentation by Dr Elanore Mulenga on cervical cancer screening, ‘Integrating cervical cancer prevention services into mobile HIV counseling and testing services to reach more women with life-saving cancer interventions’ (MOAE0105).  This study was undertaken in Zambia and was an ambitious ‘screen and treat’ method for cervical cancer that was linked to HIV mobile testing and counseling units in 14 Zambian Defence Unit sites.  Cervical cancer remains a leading cause of death in women globally including within the Asia Pacific region in countries like Papua New Guinea.

Bye for now. 

An early morning blog spawned by a salty dash of guilt for not having reported back much this time around and a state of not-being-able-to sleep.

This is the final day of the conference.

Last night a symposium was held that was organised by ASHM and supported by the Victorian Government: ‘Working towards AIDS 2014 in Melbourne: a partnership approach- symposium on priority issues in HIV.’ The meeting was chaired by Sharon Lewin and speakers were Gary Quinlan, Australia’s Ambassador to the UN, Tony Fauci, Paul De Lay, Deputy Executive Director, Program UNAIDS, Myron Cohen who led HPTN052, Dede Oetomo, Trustee of GAYaNUSANTARA, from Indonesia and the President of ASHM. The symposium tightly focused upon what might be deliverable over the next few years leading up to World AIDS 2014.  Key messages included: 1. Paul De Lay: countries need to work quickly and efficiently to meet the targets set by UNAIDS in 2011; 2. Tony Fauci: we can have an AIDS-free generation using HIV prevention and treatment without necessarily having a cure and vice versa; also he cautioned against us conceptualizing that we have ended the scientific era and that we are now entering the implementation era as he believes that a number of important scientific discoveries lie ahead of us in HIV medicine; 3. Myron Cohen: new, promising agents for HIV prevention are in view including long-acting injectable drugs and cervical rings for PrEP and data on these should be available in 2014; 4. Dede Oetomo: we need to continue to use social science to understand the cultural and sociological/ anthropological aspects of human behaviour in order to make any roll out of HIV care and treatment effective. 5. ASHM President: future challenges for managing the HIV epidemic in the Asia Pacific region include increasing country ownership of the HIV response, ongoing decriminalization to end discrimination against MSM, people who inject drugs, sex workers and transgender people, the need for high quality home-based HIV testing and linkage of HIV care with diagnosis and management of non-AIDS illnesses.

We really look forward to a great World AIDS Asia Pacific regional conference in Melbourne 2014.

Greetings from Washington DC. Nice to be back. I used to live here and went to George Washington University as an undergraduate. I couldn’t understand why all the guys at University wore pink cashmere jumpers and tartan trousers until a friend from Australia sent me a book on ‘Preppies’.

Today we had a retrospective symposium on SMART: “Five Years after the SMART study, a Paradigm-shifting Trial” (SUSA56)

Some of the speakers’ points are outlined below

Tony Fauci opened the Symposium noting that SMART one of the most influential trials in HIV medicine, that it helped us understand the importance of chronic immune activation and coagulation in HIV disease and, finally, that it was the result of major collaborative efforts.

Wafaa El-Sadr reflected on HIV Treatment Research in 2002
She reflected on the background to the SMART study: the idea was conceived in her apartment in New York city one evening with Jim Neaton, Fred Gordin and Birgit Grund.

Wafaa noted:

• The impact of SMART was to immediately change guidelines such that treatment interruptions were not recommended at a guideline level
  - Objective evidence of SMART’s impact upon treatment patterns comes from an analysis of the Royal free database: after SMART the percentage of people using intermittent ART decreased from 5-6% to 2%-3%.
• A paradigm shift occurred as a result of SMART vis-a-vis a greater understanding of the pathogenesis of HIV disease.
• With all the bio specimens that were collected in SMART it created the opportunity to engage with non-HIV doctors who became interested and utilized the samples from SMART in collaboration with SMART investigators => excellent synergies from working with people outside of the HIV field

Wafaa’s final slide noted

• SMART challenged the status quo
• Getting an unexpected answer to a question is often more profound than getting the expected answer
• Seeking definitive answers to tough questions is not easy, requires patience and may be costly but is well worth it
• Other tough questions of the hour remain that will have to be answered

Andrew Wilson addressed HIV Treatment Research Post SMART
He noted:

• That SMART was the first trial that used serious non-AIDS events as a major trial endpoint
• That 92% of all deaths in SMART were serious non-AIDS events
• Clinical event risk at high CD4 count range are nearly all related to non-AIDS conditions - these events were not being collected in most HIV cohort studies at the time
• The key question is what is the ongoing excess risk of morbidity due to HIV in people with successful viral suppress on compared to HIV negative controls ART

Jens Lundgren addressed why the START trial is necessary and how it stands on the shoulders of SMART
He posited that one must consider the case that START may show early ART is harmful and he invoked the physician’s creed: Primum non nocere (first do no harm).

This argument runs as follows:

• Morbidly and mortality in early HIV in young persons are LOW
• ART may adversely effect a variety of organ functions
• If this scenario turns out to be correct we will know whether early ART is harmful within 3 years
• Jens also noted that only 3 RCTs had addressed early versus deferred ART: The Haiti trial (NEJM 2010), the SMART subgroup (JID 2008) and HPTN 052 (NEHM 2011) but none of these used the same CD4 criteria as START
• He also noted that 4 observational studies had addressed early versus deferred ART: When to start, NA ACCORD, Causal collaboration and CASCADE
  - However using the GRADE classification (see www.gradeworkinggroup.org) these studies would be graded as C whereupon a score of A is best

It was an excellent retrospective.

It's official: there has been an HIV Neurology spring uprising in Seattle. This conference saw over 60 posters, two themed discussions, an oral abstract session and a presentation on HIV neurology in the closing clinical session- all devoted to HIV neurology. Early CNS infection, screening for HAND, Aging and neurocognitive impairment, identifying biomarkers in plasma and CSF for HAND diagnosis, neuroimaging studies and HAND in longterm virologically suppressed populations were the key themes. The two leading topics in HIV neurology at the moment are (1) whether high CNS penetrating regimens are superior to low penetrating regimens for patients with HAND and (2) whether asymptomatic neurocognitive impairment (ANI) leads to more severe symptomatic HAND. The latter was in a presentation from the CHARTER group (Poster 77) wherein patients with ANI and the symptomatic minor neurocognitive disorder (MND) were likelier to have neurocognitive decline over 36 months than neurocognitively normal controls. Not all patients with ANI/MND were virologically suppressed. Given that ANI is the commonest form of HAND in our populations, if it is shown to lead to MND or HIV dementia this will be a finding of import at a patient and population health level. Abstracts came from a number of groups including Alan Winston's group at Imperial College London, Johns Hopkins, (Justin McArthur) the CHARTER group, the Belgian group led by Bernard Du Pasquier, Serena Spudich's group at Yale, Richard Price from UCSF, Magnus Gisslen from Gothenberg, Beau Ance's group from Washington University, Lucette Cysique and Bruce Brew from Sydney, UNSW, Victor Valcour (UCSF) and Brad Navia from Tufts. It was an enjoyable meeting but, as always, too much to take in at once- hence jump onto the CROI website and watch some of the presentations and search for the abstracts also. Signing off for now.

Today was a good day for HIV Neurology with a themed discussion on advances in diagnosis and management of cryptococcal meningitis (Session 15). This included a review by Rolfes et al of the concordance between a new point-of-care assay for plasma- the lateral flow assay- and serum /CSF cryptococcal antigen and CSF culture. Overall the concordance was high - hence important early findings for a test that should prove promising in resource limited settings (Abstract 953).

Another presentation by Chang et al revealed that achieving CSF sterility prior to commencement of cART was significantly associated with decreased risk of neurological deterioration and decreased risk of mycological persistence or relapse at 24 weeks of cART therapy (Abstract 955). These data are important because cryptococcal meningitis remains a common AIDS illness in resource poor settings and because cryptococcal IRIS is a relatively common sequelae when cART is introduced. Lots of excellent posters today also with an emphasis on findings in early HIV infection.

Tomorrow we see sessions on ageing and neurocognitive impairment and on the natural history, markers and treatment of HIV neurological disease. Goodnight!

Greetings from Seattle. Very much looking forward to this conference. There are a lot of presentations about HIV neurology and PrEP. There is a very positive atmosphere at the conference, buoyed I think by all the great HIV prevention work that is coming out. Goodnight for now.