The Opening Ceremony: First, a rant…there is a history to AIDS and Sunday night in Washington that history was reconstructed. It was reconstructed as one of common cause and compassion, driven by our collective faiths and heritage and the deluded notion that we have all been in this together, fighting the good fight, supporting each other in some sort of quasi evangelical quest for social justice, wherein we are blind to difference and saved by science and gods.
Every International AIDS Conference has its own local flavour, and that is appropriate; I know I am in America, a land far less cynical and irreligious than my own. But I am here, I was told, because of the fight. And I am here, I was told, because of my faith. Fighting together, fighting AIDS, fighting discrimination, fighting the naysayers who don't think treatment is prevention, who don't think we are all the same in some god's eyes. Fight on brothers and sisters! I am accompanied, I was told, by my brothers and sisters of faith, walking into the light of an AIDS free generation. An Elder of the local indigenous people waved a feather at me and a preacher called me a crusader; call me ungrateful but I resent having my motivations, my reasons for why I work in this field, presumed and attributed to someone else's idea of what makes this meaningful.
Again, I was told that I am "standing at a unique point in history", "at a defining moment". Oh, really? ... Still? ... These people have been telling me that I am standing at a unique point, 'facing a (perpetually) closing window of opportunity' for over twenty years now. When exactly is that window of opportunity going to shut? The mood of this conference would not be one of diminishing opportunity; quite the opposite, there would be more optimism of 'cure' and truly achieving an AIDS free generation than ever before. But this does not, it seems, suit the drama and theatrics of an opening night ceremony, devoted to the drama of AIDS.
The Mayor of this fair town assured me that 'AIDS knows no boundaries and crosses borders at will'. Well, yes sir, it does but the fact is it stays where it likes, stays where it meets least resistance and while it might occasionally cross into the leafy streets of Georgetown or Dupont Circle, it actually has taken up residence in your beltway and Black neighbourhoods with a vengeance that should shame you. Fact is, you have a better chance of accessing testing, getting into care and onto treatment and staying in care and on treatment in the Highlands of Papua New Guinea than you do if you are Black and gay, Black and injecting, Black and selling sex, Black and transgender, Black and any or all of the above, and you live in this city. Several presentations at this conference would show us data demonstrating this. But I digress, turns out the Mayor is "personally committed to finding a cure".
ASHM Report Back
Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.
The Opening Ceremony: First, a rant…there is a history to AIDS and Sunday night in Washington that history was reconstructed. It was reconstructed as one of common cause and compassion, driven by our collective faiths and heritage and the deluded notion that we have all been in this together, fighting the good fight, supporting each other in some sort of quasi evangelical quest for social justice, wherein we are blind to difference and saved by science and gods.
Building Bridges and adios DC Featured
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.
Late breakers Featured
Yesterday afternoon climaxed with some exciting late breaker oral presentations.
CONSORT study- This study showed that isoniazid prophylaxis (vs placebo) reduced active Tuberculosis over a 4 year period. 1369 patients were given 12 months of INH. Participants were all HIV positive, and 50 on cART. Most benefit seemed to be in the first year, although an effect was seen over the full study course. The HR was 0.63 for active TB (95% CI 0.41-0.94) p=0.03. They didn’t screen for latent T, unlike in Australia, because the Cape Town setting of this study meant that TB is exposure is the norm, indeed 40% had a history of prior TB. Interestingly 70% of the participants were already on cART, and 30% started cART at the commencement of the study. Resistance to INH in the 95 who did manifest TB remains to be determined. In such a high exposure environment, is this prophylaxis of latent TB or prophylaxis against new acquisition?
SPRING-2- Double blind double dummy RCT of 2 NRTIs plus dolutegravir or raltegravir in 800 treatment naives. VL 50 in 88% and 85% at 48 weeks respectively, proving non-inferiority. Both drugs were really well tolerated, andthere was little to choose between them. No treatment emergent II resistance was seen in the dolutegravir arm, and just one case in the raltegravir arm. There was no difference for VL 100,000 nor between truvada and kivexa as the backbone. Dolutegravir inhibits creatinine tubular secretion, so the eGFR appeared to drop by 15mls/min, but this was not a true reflection of renal function.. it muddies the waters a bit though when trying to interpret creatinines on people on tenofovir.
HPTN 052- this analysis of the treatment as prevention study analysed clinic events in those starting immediately, or waiting to CD4 of 250. A combined endpoint of nonAIDS and AIDS did not show a difference, but there was a statistically significant reduction in AIDS evets. Questions from the audience focussed on the fact that this was all driven by diagnoses of extrapulmonary TB from just one clinical site, and that the average CD4 at commencement in the delayed arm was about 220-230, so much lower than we would ever wait in Australia.
It has been a wonderful yet wearing conference attended by over 23,000 people. We now look forward to the AIDS 2014 conference in our own Melbourne, Australia.
A key cross-cutting theme for me, wearing my hat as a general practitioner, has been the challenges current and in the future in managing the intersection caused by aging, HIV and non-communicable diseases (NCDs).
Australia continues to struggle with its approach to chronic and complex disease care. Does it increase verticalisation and place extra burdens on hospital based services? Many patients find the work of multiple presentations to specialists to be overwhelming and unachievable. Or can we continue to build comprehensive primary care level teams comprising general practitioners, practice nurses and community nurses along with various allied health professionals?
Will Australia be able to embrace the opportunities and challenges of task shifting? Can different tasks be reallocated? The appropriate balance between self management, primary, secondary and tertiary services is a question of great importance. This is both a challenge in Australia and even more so in low and middle income countries where the only part of their system oriented to chronic care is that modeled by HIV services. There are many opportunities in operational level research ahead.
The day held many highlights. There was ongoing discussion on the importance of the international community continuing to partner in the continuing challenges related to the epidemic. This is a time where national governments will be expected to continue to increase local contributions to local programs, however external assistance is a valuable and essential element in continuing to turn the tide. A great deal has been achieved. Yet there is much more to do. A way of contributing to this process is by signing the DC declaration.
Please could you consider signing this document. This is an important contribution you can make. Consider sharing it also with other friends and colleagues.
Some of the world's leading HIV researchers have signed the D.C. Declaration. Community advocates have signed. Have you?
The possibility of beginning to end the AIDS epidemic in our lifetimes is now a reality, but it requires a scale up of resources and efforts using the tools we have today to curb new infections and improve the health of tens of millions of people with HIV/AIDS. Turning the tide will take concerted leadership at all levels of government, health systems, and academic and non-governmental organizations. The Washington, D.C. Declaration calls for:
- An increase in targeted new investments
- Access for all to evidence-based HIV prevention, treatment and care
- An end to stigma, discrimination, legal sanctions and human rights abuses against those living with and at risk for HIV
- Marked increases in HIV testing, counselling and linkages to services
- Treatment for all pregnant and nursing women living with HIV and an end to peri-natal transmission
- Access to antiretroviral treatment for all in need
- Identification, diagnosis and treatment of TB
- Accelerated research on new HIV prevention and treatment tools
- Mobilization and meaningful involvement of affected communities.
- Sign the declaration online at www.dcdeclaration.org or www.2endaids.org
- You too can lend your name before the final number of endorsements is announced at the Closing Session!
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.
Fabulous plenary session in more way than one this morning. The first three speakers spoke passionately about the inclusion of marginalised populations in the response to HIV, reminding us that strategies that are developed without the full participation of affected communities are likely to fail.
Dr Paul Semugoma from Uganda highlighted how many countries are failing to provide adequate access to prevention and care for men who have sex with men, resulting in higher rates of HIV among most MSM populations, particularly in the developing world. Prejudice and homophobia remain major barriers to effectively working with MSM, and Semugoma argued we need to "fight stigma with data" to counter misinformation. Dr Semugoma argued that donors should insist that countries' HIV strategies address MSM and paid tribute to activists who have suffered and died trying to achieve rights for MSM, including the late David Kato.
Cheryl Overs (Monash), founder of the Global Network of Sex Work Projects, sounded a warning note about rolling out new prevention and testing technologies without adequate consultation with and protections for sex workers. She suggested that developments such as PrEP and rapid testing could be used to coerce sex workers into having unprotected sex, with the industry seeing a market opportunity to use new technologies to sell unprotected sex. Overs reminded the conference, to much applause, that although the US decision's to allow entry of HIV-positive people into the country is long overdue and welcome, people who admit to being current sex workers or injecting drug users remain barred from entry. This means that the conference is failing to represent affected populations, undermining the response.
This criticism, summed up in the slogan, "No drug users? No sex workers? No International AIDS Conference", was taken up by Debbie McMillan. As McMillan put it, as an African American transgender woman, former drug user and sex worker who has been incarcerated, her chances of avoiding HIV were slim - but that does not mean she could not or cannot address HIV, which she now does as a counsellor. McMillan criticised the continuing US ban on federal funding for needle and syringe programs, despite the overwhelming research showing their beneficial effects - as she put it, "I don't need the research to know this is true." Debbie's testimony of growing up in poverty, wrestling with her sexual identity, doing sex work, becoming drug addicted and being incarcerated was powerful, and starkly illustrated the inequities faced by many in the US. McMillan spoke convincingly about the value of non-judgmental drug treatment programs, specifically designed for LGBT people, that helped her manage her addiction, come to terms with being a transgender woman, and fire her enthusiasm for activism.
The final speaker, Gottfried Hirnschall (WHO), gave an overview of the achievements to date in promoting global treatment access for HIV, suggesting that while current targets are aiming for 15 million people on ART by 2015, we need to start thinking about bigger and bolder targets. Acknowledging the previous speakers, he noted the huge disparities in roll-out and access, particularly among stigmatised groups. For example, it is estimated globally no more than 10% of HIV-positive IDU have access to treatment. Hirnschall went on to discuss another hot topic - treatment guidelines and when to initiate treatment. He noted that even a compromise guideline to initiate treatment at ≤350CD4 with treatment as prevention for people in discordant couples (for example) would include 23 million people globally - which is why scale-up needs to be considered now. Hirnschall noted that none of this will work without universal access to HIV testing, and that it has become vital to broaden access to testing. He referred the audience to the WHO's new strategic policy framework for HIV testing and counselling, released today (download here). The framework emphasises that all countries trying to boost uptake of testing need to consider a range of approaches in addition to clinic-based testing, most notably community-based testing and self-testing. I think this framework will be a valuable tool as we plan for Australia to offer rapid testing in a range of settings, and consider the merits and risks of home-based testing.
The best posters of the day were invited to give a 5 minute speech. I thought these two might interest you as much as they did me.
1) Charpentier et al looked at outcomes of patients in France with a HIV VL 20 copies/ml (a level many labs are now using), to those with a VL 20-50copies/ml over a 12 months period. She found no statistical evidence of a greater likelihood of ultimately developing virological failure in the 20-50 copies/ml group. Although I did think the power was pretty limited to detect this... In fact 4% of the <20 groups developed virological failure, compared to 8% of the 20-50 group... So no p-value to speak of, but maybe something that merits repeating with bigger numbers.
2) Finally Gale et al presented a study looking at whether we need to bother measuring CD4 counts after viral suppression. This was actually done by Chilton et al in the UK some years ago, but this study was from the US. In short, if the VL as undetectable, if the CD4 was >300 then less than 1% of patients had a CD4 drop to below 200 cells over 4 yrs of follow-up. Further CD4 did not lead to any clinical management changes that could not have been foreseen by measuring only VL. The exceptions of course are those starting IFN therapy, chemotherapy or other medical reasons to expect a possible CD4 drop that might require prophylaxis of OIs.
You’re probably aware that 3 studies were published in the last few months linking, particularly injectable contraception, to HIV transmission and susceptibility (Wand et al, Sullivan et al and Heffron et al). Renee Heffron was able to provide more data on her study (partners in prevention HIV/HSV transmission study). Despite cutting the data several ways, including new variables around potential sexual confounders, and performing various sensitivity analyses, the adjusted Hazard ratio for injectable contraception and HIV acquisition was still about 2.0.
The data though, is conflicting. Pollis presented a meta-analysis of the various studies in this field. Many of them were of too poor quality to provide firm data, and the studies were rarely purposefully designed with this endpoint in mind, but were often post-hoc analyses of other studies and unable to adequately control for all possible confounders. Nonetheless, the WHO still recommend particular counselling to young women using injectable contraception that they really do need to use condoms thoroughly to reduce their HIV risk.
Fichorova presented a complicated study trying to unravel the biological mechanism behind these findings. She looked at markers of inflammation or HIV susceptibility in the cervices of 800 women with and without and STI, and taking or not taking various forms of contraception. I got a bit stuck in the immunology and cytokine mire, but essentially she found that DMPA increased RANTES (some sort of marker of inflammation) in all women, and that DMPA also reduced protective mediators in the cervix. Not causal, but an initial attempt to provide biological plausibility to this theory.
The issue of breastfeeding for HIV positive mums was discussed in detail at a special session today. I tend to forget the legacy of previous advice to not breastfeed, combined with heavy marketing of formula feed. Would you have ever guessed that breastfeeding rates in some parts of South Africa are 6-8%! The WHO guidelines recommend exclusive breastfeeding for at least 6 months, since the mortality of HIV negative bottle-fed babies was increased 6 fold in resource poor settings. Plus the Mma Bana and Kisumu breastfeeding studies showed that cART could reduce the postnatal MTCT transmission rates.
How to tackle re-educate and change practice was discussed by Yogen Pillay from South Africa. They have taken both a top down (ministerial statements and the restriction of formula to prescription-only), and a bottom up approach (involvement of traditional healers and community peer workers), and are reaping slow but steady success. Ensuring time and space for women to breastfeed was key. Prof Tyllaskar from Norway’s group also showed that a focus on the whole community was crucial to changing breastfeeding practice, not just targeting HIV positive women. He doubled breastfeeding rates over a year with a program of peer-counsellors as part of the larger PROMISE study in South Africa, Burkina Faso and Uganda.
Not so relevant in the Australian context when safe, affordable, reliable and quality formulas are available if necessary for HIV positive mums, but a sobering insight into the impact the guidelines of the WHO and the advertising from formula companies can have on a vulnerable population who just want to protect their babies from HIV.
This conference is a marathon. Day 4 and I am exhausted. So many people, protests and presentations to attend - it's quite overwhelming. One of the highlights for me yesterday was a packed oral poster session on PEP, PrEP and HIV testing held over lunch. The presenters only had 5 minutes each to present their key findings, and there was spirited discussion from the audience. A presentation by Antonio Urbina (St Luke's Roosevelt Hospital) reviewed the delivery of non-occupational post-exposure-prophylaxis (PEP) in emergency departments in New York City. 216 cases were reviewed. While apparently very successful (94% completed the course and only one person seroconverted), the audience questioned the intensity and length of the PEP regime - a 4 week course based on Combivir, which often causes nausea. There was debate about whether a shorter and better tolerated regime could be used. One of the other presenters in the session, Kristen Underhill (Yale) picked up on how negative experiences of antiretroviral drugs from a course of PEP can have lasting consequences. Kristen had conducted group interviews with gay and bisexual men in Rhode Island to explore the acceptability of HIV pre-exposure prophylaxis (PrEP). She found that men who had had a previous bad experience with PEP found the idea of PrEP very unappealing.
The other standout presentation was from Alex Carballo-Diéguez (HIV Center for Clinical and Behavioral Studies, NYC). Alex was reporting the results of his study of home HIV testing among 'high risk' HIV-negative gay men in New York City. A small group of men (n=32) was enrolled and given OraQuick oral fluid rapid test kits to use at home (the test has just been approved by the US FDA for sale over-the-counter). The men were encouraged to test themselves and their casual sex partners. Around 100 tests were performed. Telephone support/counselling was offered but rarely used. Five sexual partners tested positive for HIV during the study. Very few adverse incidents were reported. When quizzed by a member of the audience who was concerned about relying on a test with a longer window period than a lab-based HIV test, Alex noted, "Sometimes when looking for the optimal, we overlook the good enough." While debate will undoubtedly continue about the merits of home-based testing, I think this research illustrates that home testing can function pretty well as a harm reduction tool and, as Alex noted, can give gay men a greater sense of control over their health and HIV status. It's certainly motivated me to work with my colleagues in Sydney and Melbourne to do a similar study of home-based HIV testing.
Plummets in Vit D, increased kidney stones, increased fractures (more than half do not have osteoporosis, 13% vs 5%), direct cellular aging as measured by telomeres fraying, increased depression, these are some of changes associated with HIV and aging.
In 2015, over half of the HIV population in North America and Europe will be over fifty years of age.
We can now say to a young person who is recently diagnosed with HIV "Some day you will be old!".
In Uganda a 35 yr old Man starting ART with a CD4 greater than 100 has a life expectancy of more than 35 years. Life expectancy gains in sub Saharan Africa are similar to those in western settings. Aging adds chronic disease to the mix of issues to address in the list of HIV health challenges.
It was recognised the limits of a silo based approach - care needs communication and coordination. Disability, frailty - depletion in organ system reserve and functional status - are terms increasingly applicable to those ageing with HIV. Each is a consequence of a chronic disease burden.
Age is accentuated not accelerated for those with HIV. There is increased risk of various conditions at the usual ages. Polypharmacy (>5) increases risk of an adverse drug reaction, this increases by 10% with each additional drug. The principles and risks of polypharmacy are applicable here.
Falls are increased by a vast range of medicines.
Call for a patient centred approach. Risks are greatly increased after 65 yrs compared to those 50-64.
Over 60% of mortality is due to Noncommunicable diseases (NCDs) in the developed world and only a little less in developing countries. The challenge of NCDs are made more complicated by HIV. The workforce is being challenged to task shift, as part of these new situations. This is supported internationally but is less welcomed in Australia. There will be an increased demand for primary care service providers, especially GPs to better provide comprehensive, integrated team based care. The new ASHM Life Plans (led by Edwina Wright and others) will be an important contribution.
We do not yet have good baseline markers for many NCDs in many, many countries especially in the 50+ age group- lots of research opportunities ahead.
Also see JAIDS, Vol 60, Supplement 1, July 1, 2012 And AIDS, Vol 26 Supplement 1, 2012-07-25 Both of these supplements focus on HIV and Aging.
Drugs and therapeutic challenges were the themes of this morning’s session.
The plenary started with some excellent overview talks, especially one detailing the various attempts to induce activation of latently infected cells. Current strategies still in vogue are to use IL-7, (Eramune studies), or the HDACi inhibitor vorinostat. Studies using disulfiram or IFN-alpha have not been successful to date.
The next session was a series of important pharma-sponsored studies. First up Mills from Los Angeles presented 96 weeks data on maraviroc 150mg od with ritonavir boosted atazanavir, compared to truvada boosted atazanavir. It was a phase 2b study, so not many stats were presented. At 96 weeks 82% of the truvada arm were 50 copies/ml compared to 67.8% of the maraviroc arm. Most of the detectable VL in the maraviroc arm were in the 50-400 range, and the presenters focussed on this, and the lack of resistance and rather avoided discussing the primary outcome. I thought it was disappointing they appeared to gloss over this; surprisingly tese results have been taken as encouraging and a further study is planned, this time using ritonavir boosted darunavir and maraviroc.
Next up J Gallant presented the 48 weeks results of a ritonavir vs cobcistat booster comparison study. When used with truvada and atazanavir cobcicistat was non-inferior to ritonavir, in fact there was little to choose between them, except for the known rise in creatinine with cobicistat as it blocks creatinine active secretion in the tubules. Although non-significant, 5/6 who had renal dysfunction with cobicistat had proximal tubular disease, compared to 2/5 of renal dysfunction cases on ritonavir. Lipids were the same.
Pallela then presented the SPRIT study, which is a switch study from 2NRTIs plus a boosted PI to Eviplera. Patients were 50/ml prior to switching. Results showed switching did not compromise virological control, and lipids improved a bit. Thy did not stratify lipid changes by which PI was used. Interestingly, all 17 patients who were known to harbour the K103N mutation successfuly suppressed on a rilpivirine based regimen.
Finally Elion et al presented the 96 weeks data on study 145, a raltegravir versus elvitegravir double blind double dummy study in treatment experienced patients. I think all patients had a boosted PI in their regimen already, which makes interpreting differential lipid and GI toxicity difficult. Results were pretty equal between the arms with around 55-60% 50copies/ml, a CD4 rise of 200 cells, and about 40% discontinuations. Each arm developed resistance mutations to integrase inhibitors in 7% of cases. The resistance pattern was different however, with less N155H mutations in the elvitegravir arm, and a broader range of mutations seen. How this will impact on sequencing IIs and the role of dolutegravir aftr either raltegravir or elvitegravir failure was unfortunately not discussed.
It was the best of times, it was the worst of times (Charles Dickens, 1859, “The Tale of Two Cities”) ...
The incremental growth of HIV science year by year has accumulated many successes in many areas. This science has lead to a range of interventions, yet biological efficacy will not be effective without adherence, and adherence is situated in the domains of cultural, economic and gender realities.
I have heard today that the issues of adherence in a Washington clinic, in a Melbourne hospital, in a west African village, or in a Russian prison demonstrate a great diversity of challenges. Yet the discourse of human rights has been strengthened as the common basis for empowering, authorising and allowing people to be agents for the necessary changes in these settings. Though, of course, this does not diminish the difficulties in each setting.
A Ugandan colleague, Dr Musoke, has highlighted the key roles of political commitment, logistical problems such as stockouts, and the difference between capital city tertiary facilities and rural cities. There are still many difficulties. Concerns about long term resistance are real issues in many settings.
There is a move internationally to prioritise the disease burden due to non-communicable diseases (NCD). The NCD agenda is in one sense, I believe, rising to the top of the international health priorities. In this context, there were interesting studies from Uganda (Chamie et al) and from Nigeria (Gwarzo et al) indicating that HIV programs were also effectively integrating screening for non-communicable diseases, and also from Zambia (Mulanga et al) including cervical cancer services.
I learnt about the Gardner Treatment cascade which is an important new tool to allow us to picture the cascade of challenges of access and adherence that are now and future concerns. Let me share this example to illustrate how it works.
For every 100 individuals living with HIV in the United States, it is estimated that:
- 80 are aware of their HIV status.
- 62 have been linked to HIV care.
- 41 stay in HIV care.
- 36 get antiretroviral therapy (ART).
- 28 are able to adhere to their treatment and sustain undetectable viral loads.
In short, CDC estimated that only 28 percent of the more than 1 million individuals in the U.S. who are living with HIV/AIDS are getting the full benefits of the treatment they need to manage their disease and keep the virus under control. Put another way, nearly 3 out of 4 people living with HIV in the U.S. have failed to successfully navigate the treatment cascade. Since a picture “is worth a thousand words,” see the included image.
Earlier today I went to an oral abstract presentation (MOAC03) on Access to and retention of antiretroviral treatment.
Despite improved mortality, a study from the UK (M Kall et al) found that PWLHA were still at 2 fold risk of non-AIDS mortality compared to the general population, at all age ranges. This contrasts with data from the AHOD study which demonstrated that Standard mortality ratios, particularly for those undetectable for a few years, and of older age, were not particularly increased. A difference between these findings might be that the UK study was not able to take into account last CD4 count before death, a possible important factor.
Another interesting study, performed in part by a Melbourne study group (McMahon et al) looked at methods to improve retention in care; an important aspect if treatment is to be rolled out further. Specifically they performed a meta-analysis of physical patient tracing studies, in other words studies where patients were actively followed up in person (rather than by telephone call or not followed up), if they became lost to follow up. They found that of about 50 studies addressing this issue, on average lost to follow up rates were lower (7% vs 15%) if physical tracing occurred, and retention on cART was slightly better. The cost effectiveness of this approach is yet to be tested, and apparently a randomised controlled trial is planned to address this. Many Australian clinics have SMS based reminders or follow-up processes, but unfortunately this study could not include analysis of these techniques.
On a lighter note, I was served an entire half duck in a restaurant last night, and breakfast is so large I don’t need to eat any lunch all day! Might have to go for a quick jog to burn it all off.
Just got back from a debate on “treatment as prevention”, although the speakers only really disagreed on how easy such a policy would be to achieve, rather than whether it is the right strategy. Julio Montaner from British Columbia pointed out the reductions in HIV diagnoses in his setting, which he attributes to increased use of HAART and Kenneth Mayer from the US discussed not losing focus on testing since 54% of infections are from the 21% of those living with HIV but untested.
It was left to the co-chair Sean Stub from the USA to question the ethics, coercion and autonomy issues that need to considered, and also the potential legal ramifications for those who do not accept treatment as prevention… are they now at risk of prosecution for transmission?
DC is hotting up. The opening plenary last night was long and impassioned, with various speakers exhorting the audience to 'end AIDS now'. Michel Sidibé (UNAIDS Executive Director) summed up the push to maintain international funding levels and deliver treatment to those who need it when he said, "The end of AIDS is not free, it is not too expensive, it is priceless."
I'm stepping back to earlier in the day to consider a different but no less important issue: HIV testing. The whole push for 'treatment as prevention' will, of course, fail if people do not present for testing and find out their HIV status. Françoise Barré-Sinoussi, President-elect of the IAS, introduced a satellite session by the French NGO, Sidaction, titled "Confronting the hidden epidemic: HIV testing science and implementation". Professor Barré-Sinoussi noted that internationally many at-risk groups have poor access to testing, and there is a need to diversify testing to engage people and make it more efficient, using a variety of methods such as community-based testing, self-testing and outreach. The session had a particular focus on undiagnosed infection and engaging hard-to-reach groups, particularly in France. I felt that many of the observations had relevance for Australia.
Virginie Supervie (U943 Inserm) presented a mathematical model of the French HIV epidemic and undiagnosed infection. For the statisticians among you, she used a modified back-calculation method based on the number of new HIV cases over time. No, I don't know what that means either. The model indicates that there are 29000 people with undiagnosed HIV in France, 9000 of whom are men who have sex with men (MSM) and 9800 are French-born heterosexual people. Because the MSM population is relatively small, their prevalence rate is the highest, at 314 per 10000. This means it is much easier to find undiagnosed MSM through testing; huge numbers of heterosexuals need to be tested to find undiagnosed people. The analysis suggested that median time from infection to diagnosis is ~2 years and that 59% of undiagnosed people have a CD4 count below 500 i.e. they are undiagnosed but already eligible for ART. Supervie went on to talk about the broader French epidemic and reported that, because there is good access to ART in France (once people are diagnosed), they estimate that 56% of PLHIV are virally suppressed (as opposed to only 28% in the US). It would be interesting to know the figure in Australia - hopefully closer to the French figure than the US one.
Sandrine Fournier (Sidaction) reported on an innovative community-based, outreach testing strategy to engage gay, bisexual and other MSM in the Paris area. The Flash Test program offered rapid HIV testing (using the INSTI test) to MSM at 39 gay venues, beats, NGOs, general practices and health centres during a one week period. Intensively publicised with the tagline, "Et toi, tu sais?" (And you, you know?), the aim was to engage men who had not tested for a long time (or ever) and to make testing easy and attractive. Over a hundred health care workers and activists were trained to work in the program. 556 tests were performed during the week, identifying 7 new HIV diagnoses. The locations that were rated as most attractive by MSM were gay venues (because it was convenient and social). Cruising areas were found to be difficult places to recruit. NGOs found they had increased attendance at their sites during the test period; GPs were not particularly proactive at offering tests, but it was difficult for them to offer appointments during the testing period. The success of the project means that Sidaction is considering promoting an Annual Testing Week in France. In Australia, we seem a long way off such a project - we don't even have one rapid test licenced yet!
A highly topical subject, and one that is sure to get more attention in Australia in the coming months, is home-based testing for HIV. Tim Greasen (EPS Maison Blanche) reported on a survey of over 9000 French MSM about attitudes to self-testing and the use of HIV home test kits ordered online. Greasen noted that the US has leapt ahead of other countries in liberalising access to testing with the recent FDA approval of the OraSure home test kit, but the US has had a version of home HIV testing for 16 years (!), using a system in which people send in dried finger prick specimens for testing at a lab, backed up with telephone results and counselling. As in Australia, home HIV testing is not legal in France, but there is suspicion that MSM in particular are ordering test kits over the internet. Greasen's survey of MSM found low numbers who had ordered home test kits (~1% of MSM), but a whopping 87% were interested in the idea, citing convenience, rapidity and anonymity as the main attractions. Men who more secretive about their same-sex activities and had never tested (or had not tested for a long time) were more interested in home testing. There was no association with suicidality (a concern of those who worry about men testing by themselves). Among the 69 men who had used a self-test, who tended to report more HIV risks, 62 tested negative, 3 tested positive (1 result was subsequently disconfirmed), and 4 were uncertain of the test result. Greasen noted that in France there is a perception that HIV testing is 'owned' by health professionals and there is resistance to citizens controlling their own health. However, he still thought (when quizzed by me) that home rapid tests are likely to become available in a year or so, backed up by telephone counselling (as in the US). It will be very interesting to see how this debate is taken up in Australia, in advance of Melbourne 2014.
Hello- and welcome to this conference report.
The conference formally opened last night, with speeches from, amongst others, Jim Kim, (the head of the world bank), Ban Ki-Moon, (the UN secretary general) and the mayor of Washington. However, despite rampant speculation, there was no sign of Barack Obama or George W Bush, who were both billed to speak, or at least if they were there I couldn’t see them for the swathes of people.
The theme of the speeches was one of optimism. It seemed they were saying that now we know how to stop HIV spreading through treating it, we must now aim for the eradication of transmission. The focus was certainly on treatment-as-prevention, although poverty, stigma and access to condoms were also given some attention. A website: www.2endAIDS.org has been launched to promote the Washington Declaration.
However, many of these scripted speeches repeated the same stuff, and more interesting were the smaller, more human stories presented. We got to hear from Florence, a women living with HIV in Nigeria, and her 13 year old HIV negative daughter, and how they wished that every mother and child had access to the prevention measures that had secured her daughter’s health. There were also some powerful and moving videos of community-based prevention programs from across the globe.
My favourite was the award (The Elizabeth Taylor award) given to two Iranian doctors recently released from prison, the Ayerai brothers, who had been jailed for several years for setting up an HIV, sexual health and drug use clinic in their country; apparently this amounted to treason. Whilst in prison they set about improving the health and wellbeing of other prisoners through needle education and smoking cessation. Remarkable guys. They were presented their award by the actor Sharon Stone, minus ice-pick. The venerable doctors seemed very excited about this. Perhaps they were thinking of the same scene in Basic Instinct that I was.
The conference proper starts this morning, so I’m off to breakfast to flick through the 430 page conference program book and the 100 page program supplement to decide what to attend.
You would never have known it was a World AIDS conference - the Opening Ceremony was a festschrift of US backslapping. While the US was congratulated on being the largest financial contributor to the global AIDS response (although it only gives 0.19% of GDP for foreign aid in general). According to Elly Katabira, President of the International AIDS Society (IAS) AIDS2012 is an important opportunity to thank the American people and highlight the millions of lives saved as a result of generous U.S. contributions to the global fight against AIDS and its leadership in HIV research.While the US was congratulated on being the largest financial contributor to the global AIDS response, it only gives 0.19% of GDP for foreign aid in general).
What was not mentioned in was the moral agenda that inhered in PEPFAR - the disastrous ABC (abstinence, be faithful, use a condom); no funding for HIV clinics that counselled women on abortion; no funding for sex worker programs and so forth.
An evangelical style rhetoric was prominent throughout the speeches. Surprisingly (or maybe not - this is America), for a secular conference, there were 2 prayers. There was also a highly moral tone to a number of speeches: the World Bank President stated, "I challenge you to join me in harnessing the moral power and practical lessons that the AIDS movement has produced to speed progress against that other global scourge, poverty". He did not however mention the HIV risk-effects of his Bank's own development policies.
African HIV-positive women left to give the ceremony some kind of 'human' face;
, There was a wonderful use of statistics - we can do anything with numbers to show how well we are doing.