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.

Recent blog posts

This was an oral abstract session focusing on some novel approaches to HIV treatment and modifying treatment in special risk groups.

Jean-Michel Molina presented some switch data from the EMERALD study, a randomized (2:1), open-label, international, multicenter, parallel-group, non-inferiority, 48-week study.  Virologically suppressed individuals were switched from boosted-protease inhibitors (PI/r)+emtricitabine/TDF to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (TAF).  This showed good virologic efficacy and better bone and renal profile at the wk24 interim analysis.

Jose Gatell presented data from an elegant study focused on virologically suppressed individuals with high cardiovascular risk.  They were aged 50 years or older and had Framingham cardiovascular risk greater than or equal to 10 percent.  They switched from PI/r-based to dolutegravir-based regimen and showed non-inferior virologic efficacy with improvements in lipid profile at wk48.  Other outcomes from this ongoing trial are awaited.

Laura Ciaffi showed data from a switching study.  After viral suppression with second-line PI/r+NRTIs, maintenance with PI/r+lamivudine showed virologic efficacy at wk 96 despite the presence of the M184V mutation.   This study was conducted in Africa.  This is an example of the increasing number of dual therapy studies presented at IAS this year.

Kathleen Squires presented data comparing a fixed dose combination of doravirine/lamivudine/TDF to efavirenz/emtricitabine/TDF in treatment-naïve adults with HIV-1 infection.  It showed non-inferiority at week 48 regardless of the baseline HIV RNA.  Doravirine also showed superior neuropsychiatric and lipid profile in these results of the Phase 3 DRIVE-AHEAD study.  A useful extension of this study would be a co-formulation of doravirine with FTC/TAF to reduce the renal and bone effects well known with TDF.

Micheal Aboud presented week 24 interim data from the DAWNING study.  This looked at individuals with first-line NNRTI-based regimen failure.  The superior efficacy of dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) compared with lopinavir/ritonavir (LPV/RTV) plus 2 NRTIs in second-line treatment was demonstrated.

Finally, Trevor Crowell presented data from a study using one of the newer approaches to HIV treatment, broadly neutralising antibodies.  In virologically suppressed individuals who initiated ART during acute HIV infection, VRC01 was well-tolerated.  However, VRC01 monotherapy was insufficient to maintain viral suppression.  This is an early setback but this will benefit future research in this area.  Broadly neutralising antibodies are being used in a growing area of research to assess alternative approaches to therapy besides daily oral therapy.  On a more reflective note, another theme from the conference this year was to start treatment as soon as possible to reduce the potential viral reservoir which we know is concentrated in lymphoid tissues.  This is likely to enhance prospects of cure or functional cure when future therapies become available.

 

Tagged in: 2017 IAS Conference

From HIV and the Liver: Co- infection and Complications  

Nikoloz Chkhartishvilli presented an overview of the co-infection care cascade from Georgia, a country which has a high disease burden of HIV/HCV co-infection. Despite the differences in our countries political and presumably health care systems, the roll out of their HCV elimination program recalled similar population priorities to the Australian model.

During 2011- 2015, the Global Fund supported Georgia to reduce the disease burden of HCV by offering PEG/RBV to people living with HCV. From 2015, in partnership with Gilead Sciences and U.S. CDC to launch their National HCV Elimination Program and DAAs became available. Similar to the Australian model, there was no cost to the patients and current injection drug use was not a barrier to accessing treatment.

The care cascade is described as follows: 1) HIV/HCV co-infected; 2) Diagnosed for both HIV & HCV, 3) Treated for HCV, 4) Achieve SVR . Data were obtained from the national AIDS health information system

Results: Among 3300 co-infected individuals, 2201 (67%) were not aware of their HIV status, 1099 (33%) were diagnosed with both HIV/HCV, and of those 1099 (33%) persons, 697 (63%) were treated with either PEG/RBV or DAAs. 480 (69%) of those treated attained SVR with 44% for PEG/RBV and 89% with DAAs. So of the 697 (21% of the original cohort) individuals treated, approx. 480 achieved SVR, this being 69% of the treated cohort and 15% of the original co-infected cohort.

A gap in care was identified from time of diagnosis to time of treatment as the major contributor to the low uptake and completion of treatment, calling for tighter systems to support the elimination plan. Highlighted that it’s not just free or subsidised treatment availability, but also the systems and infrastructure required to support programs such as this.

 

Nadine Kronfli presented on trends in cause- specific mortality in HIV/HCV co- infected patients in Canada 2003- 2016 and the impact of early HCV treatment.

Liver related deaths (ESLD & viral hepatitis) account for 20-25% of deaths in Canadian co-infected population. Mortality rates have decreased since introduction of DAAs achieving SVR>85% and opportunity to reverse fibrosis, decrease sequelae.

Looking at which modifiable risk factors may contribute to excess mortality in co-infected population to help prevent potentially preventable deaths in an already high risk population (lifestyle, exposures related to IDU in co-infected pop).

They used the Canadian Co-infection Cohort which is a prospective multicentre cohort of 1695 co-infected patients from 19 sites in Canada (resulting in 6675 person- years follow up from 1477 eligible patients). Deaths were classified using a ‘coding of cause of death in HIV’ protocol. Event rates per 1000 person- years before (2003- 2009) and after (2010- 2016) the availability of widespread effective treatment stratified by age 20-50, 50-80 yrs were calculated.  

75% of the cohort were current smokers at baseline, 84% taking ART, 64% HV VL <50 copies/ml, 81% HCV treatment naïve, 21% APRI > 1.5, 9% prior ESLD dx.

Overall and cause specific mortality, with cause of death divided into 5 categories: ESLD (20%), smoking related (17%), drug OD (16%), other- including AIDS/infections/ cancer/ trauma/ suicide (22%), unknown (25%).

20- 50 yrs: 2003- 2009: 26.04 (13.91, 48.75); 2010- 2016: 19.29 (11.59, 32.11)

50- 80 yrs: 2003- 2009: 56.61 (28.09, 114.1); 41.97 (28.2, 62.46)

Key point from deaths- most had poorly treated HIV and did not achieve SVR as higher deaths on ‘non- ideal’ patient population (CD4 <350, APRI > 1.5, HIVRNA>50).

Concluded that all cause mortality decreased in both age groups over time, explained by a reduction in mortality from a variety of competing causes, no significant decrease in ESLD deaths overall however ESLD appears to be declining in 50-80 year olds, or those who have been successfully treated; immediate impact of HCV therapy most profound among those with fibrosis, and targeting modifiable risk factors such as smoking may confer the highest benefit.

 

Maud Lemoine presented ‘metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV monoinfected patients: results of the METAFIB study’

Metabolic syndrome and its hepatic manifestation, NAFLD, have emerged as new concerns for PLHIV (prevalence 25% and 35% respectively).

METAFIB study proposed to assess the impact of metabolic syndrome on the proportion and severity of liver fibrosis and analyse association between met syndrome, liver fibrosis, markers of adipose tissue and macrophage activation.

METAFIB is a single centre exposed- non exposed cohort of HIV monoinfected individuals without excessive alcohol consumption, viral hepatitis, or other causes of CLD.

Fibroscan used to measure liver stiffness.

Results from 405 participants (203 with metabolic syndrome, 202 without). Patients with met syndrome were older and 49% had insulin resistance, risk factors for fibrosis: Obesity with BMI >30, T2DM, elevated GGT and leptin.

Liver transaminase levels, ART exposure or HIV parameter levels were not associated with liver fibrosis.

Take home message was that HIV monoinfected patients with metabolic syndrome are at risk of liver fibrosis irrespective of transaminase levels and should be systematically screened. Mass fat measured by BMI and circulating leptin is strongly associated with fibrosis independent of HIV parameters or ART exposure. Adipose tissue, insulin resistance and macrophage activation are likely key players in the development of fibrosis.

There was an audience question regarding impact of some ART in regards tocausing/ association with insulin resistance. Answered that the cohort was older, and treatment experienced, however patients with good virological control were selected so didn’t feel the results could answer that question.

Recommendation to screen all PLHIV with metabolic syndrome regardless of LFTs for fibrosis using fibroscan cheap, easy, non-invasive.

 

Hugo Perazzo Pedroso Barbosa presented data from the PROSPEC- HIV study looking at predictor factors associated with liver fibrosis and steatosis in a monoinfected population.

Cross sectional study from a cohort of 4000 patients who have been followed from 1990. Exclusion was viral hepatitis co-infection and ART naïve.

 

Heavily pre- treated population inc. AZT and other early ART.

Clinical evaluation including alcohol assessment, fasting bloods and fibroscan was used.

 A total of 348 HIV mono-infected patients [61% female, median (IQR) age=44 (34-52) years, BMI=25.4 (23.0-29.3) kg/m²] were included. Median (IQR) time under c-ART and under the current c-ART regimen were 7.3 (4.1-12.8) and 4.3 (1.9-7.5) years, respectively. LSM and CAP were unreliable in 6% and 12%. Liver fibrosis and steatosis prevalence were 9% (n=30/326) and 33% (n=102/305). In age and gender adjusted multivariate analysis, factors associated [OR (95%CI)] with liver fibrosis were: age > 45 years [2.91 (1.19-7.15); p=0.020]; CD4 count < 200 cells [5.00 (1.38-18.21); p=0.014] and type-2 diabetes [3.04 (0.97-9.55); p=0.056]. Male gender [5.69 (2.68-12.04); p< 0.001]; dyslipidemia [2.86 (1.46-5.60); p=0.002]; type 2 diabetes [6.00 (2.08-17.28); p=0.001] and central obesity [10.24 (4.11-25.50); p< 0.001] were independently associated with liver steatosis.

Concluded that low CD4 count was independently associated with presence of liver fibrosis, metabolic syndrome features were independently associated with steatosis by CAP, higher duration of ART especially AZT as a backbone was associated with steatosis independently of metabolic factors.

 

 

Take home message from session: Importance of reducing modifiable risk factors to improve patient’s health outcome, especially smoking and factors contributing to development of metabolic syndrome. 

Tagged in: 2017 IAS Conference

Summary of the Report from the IAS HIV Cure and Cancer Forum

In its 15th year, the IAS initiative Cure Towards an HIV Cure, held its forum prior to the IAS conference. This year the forum expanded its attention to Cancer given the similarities between the fields and limited formal collaboration. Many immunological therapies used for Cancer treatment may also have a role in HIV Cure. As our HIV patients age with suppressed HIV viremia they are experiencing more cancer. Cancer and Persistence of HIV share many features and goals of treatment so that a shared approach to research will only enhance outcomes for both groups and especially for HIV patients with cancer. This latter group are currently serving as an “observational cohort” as we try to understand the effects of immune checkpoint blockers – both efficacy and adverse effects, short and long term – in people living with HIV and its associated additional immune dysfunction. Cell surface marker CD32a on CD4 cells has now been recognised as a potential marker for HIV DNA levels. The concept of measurement of residual disease burden after treatment is being borrowed from oncology to aid in the understanding of achieving durable remission. Focus on the change in approach to treatment of cancer from drugs targeting cancer cells to the approach now of targeting the host’s own immune cells to kill the cancer cells. Understanding of how anti-cancer drugs affect the HIV reservoir was progressed, as was comparisons of the effects of immunotherapy for cancer and in HIV. The class and availability of different “immune checkpoint inhibitors” is exploding in cancer treatment, and as HIV patients with cancer start to receive these drugs for their cancer, the effects on latency reversal of HIV are being carefully documented. Interferons are being revisited, effects of stem cell transplants and gene therapy to improve the immune response to cancer are also being explored – but all early days and case reports in the main. One of the most important sessions was a round table discussion on clinical trial design once the safest better candidates have been identified – protocols with a common trial design, agreed endpoints (most likely composite) and biomarker measurement, need to be established. Access has been identified as a major consideration, community engagement vital, understanding of how analytical treatment interruptions will be used and viewed by participants and the financial “toxicity” of HIV Cure were identified. We continue to make strides towards our ultimate goal.

Tagged in: 2017 IAS Conference

Is “on-demand” PrEP a suitable tool for MSM who participate in Chemsex?  From ANRS-Ipergay.

This was in an IPERGAY sub-study of 331 participants during the open-label extension (OLE) phase of the study who reported drug use during at least one sexual encounter.

 2 monthly data was collected regarding drug and alcohol use, sexual behaviors and PrEP adherence during the participant’s most recent sexual encounter(s) and analyzed with a multivariate regression model. PrEP use was self-reported by participants.

Among the MSM participants, 29% reported Chemsex at least once during the follow up period and16% reported chemsex at all visits.

Socio-demographics between those labeled chemsexers were not different from those labeled non-chemsexers, other than a higher use of anxiolytics in chemsexers.

 After adjustment, chemsexers were found to be more likely to use PrEP (OR (95% CI = 2.18 (1.04; 4.49)) and less likely to use condoms (p< 0.001)

Of note, when MSM reported chemsex during their most recent sexual encounter there was a grater likelihood of receptive anal sex, hardcore sexual practices, casual sexual partnerships and a higher perception of risk. All p-values <0.001

This important and interesting sub-study suggests that PrEP may therefore be a suitable tool for HIV prevention people practicing chemsex.

 

Tagged in: 2017 IAS Conference

Day 3 of the conference and PrEP of course has been the 'hot topic'

This oral abstract session was a reminder that there is more to prevention than antiretrovirals however.

First up, Kelly Kilburn gave evidence from the HPTN 068 study in South Africa where a third of women experienced physical violence by a partner. And there are direct correlations between this and HIV transmission.

The experiment involved 2,533 women between the ages of 13 to 20 years. They were randomly assigned to one of two groups where one group of girls (or their parents) received approximately $10 USD if they attended at least 80% of school days in the past month. Participants then completed a self interview and HIV and HSV-2 test each visit and at 12, 24 and 36 months following. The questionnaire was able to distinguish between sexual and physical intimate partner violence (IPV). 

The conclusion was that the conditional cash transfers had no significant effect on sexual IPV, HIV or HSV-2 acquisition. There was however a significant risk reduction for physical IPV by 34%. It was interesting to note that there was 95% attendance in both arms of the study and that the cash payment had no effect at all on school attendance but may have given the young person the independence from a violent intimate partner. 

I took a few interesting points from Shona Dalal of the World Health organisation that will be useful to my practice. She presented a systematic review of HIV partner notification services. Assisted versus passive notification where there were varying types of active notification - contract, provider or dual referral approaches. Contract is where the HIV positive client enters into a contract to disclose their status within a certain time frame and advise their partner to have HIV testing. Provider is where the provider confidentially contacts the HIV positive clients partner and offers voluntary testing. Dual referral is where the provider accompanies the HIV positive client to assist whilst they disclose their status and voluntarily offer HIV testing services.

With all types of notification if it didn't occur within a week it was less likely to occur. There were very few reports of harm and there was increased linkage to care and treatment among partners.

There was a talk from Sean Allen regarding a change in the policy of syringe distribution in Baltimore, MD from 1 syringe given for 1 returned to as many given as required. The number of syringes distributed doubled but the average number of HIV infections per month reduced. 

Also covered in this session were male circumcision and its effect on transmissions to women of sexually transmitted diseases. And also community based distribution of oral HIV testing kits aiding the early diagnosis and treatment of men in Zambia. 

Phew - what a session!

 

Tagged in: 2017 IAS Conference

IAS2017 Tuesday 11 am 25/7/2017

 

This session provided updates from various oral, topical and long-acting injectable PrEP clinical trials.

Sheena McCormack presented long-term PROUD study data from 2-4 years post enrolment.  This indicated that reduction in HIV incidence was sustained, and confirmed high adherence and durable effectiveness of PrEP in the study population.  However, as suspected rectal chlamydia and gonorrhoea and syphilis diagnoses remained high re-iterating the need for structured regular followup of these high risk patients.

A qualitative analysis exploring PrEP perceptions among PROUD participants, found that most viewed PrEP as a temporary HIV prevention option. Participants described psychosocial benefits in terms of reducing fear and providing relief when taking PrEP.  They didn’t discuss some of the stigma that still persists in the community about people who take oral PrEP however.  Acceptability seems to be increasing however.

Guillemette Antoni presented data from a double-blind, randomised sub-study of IPERGAY which found a significant reduction in HIV infection risk with on-demand TDF/FTC vs. placebo, in MSM having infrequent sex.  Oral PrEP with tenofovir/emtricitabine is now subsidised in France.

Sharon Hillier presented data from the completed FAME study.  This study found that FGT and plasma drug levels of dapirivine were not affected by Lactobacillus or G. vaginalis microbiome.  Tenofovir levels in FGT and plasma however are adversely affected by vaginal disbiosis (bacterial vaginosis). The potential influence of vaginal microbiome on topical and plasma PrEP drug levels emphasises the need for HIV prevention products that work in women with vaginal dysbiosis.

Ian McGowan from the USA presented data from the MWRI-01 multi-dose Phase I study.  They found long-acting IM rilpivirine to be safe. Drug accumulation was significant in plasma, rectal, and female genital tract (FGT) tissue.

Finally, Raphael Landovitz presented data from HPTN077, a double-blind, randomised, placebo-controlled tolerability and pharmacokinetics trial.  They found LA cabotegravir was well tolerated at 800mg/600mg doses in HIV-uninfected low-risk males and females.

Updated safety, acceptability and pharmacokinetic data on LA IM rilpivirine and cabotegravir provides hope for the viability of long-acting injectable PrEP formulations and circumvention of the adherence challenges associated with oral or topical PrEP.

Tagged in: 2017 IAS Conference

 

Presented as part of the mixed bag "Co-chair's Choice" session this study aimed to assess dolutegravir (DTG) in pregnancy. There are many benefits to DTG as treatment, highly effective, well tolerated, once daily with high barriers to resistance.  However, despite being a drug with many desirable qualities, the lack of data in pregnancy have resulted in DTG not being recommended in pregnancy by the WHO.  This study addresses some of the research shortfalls and compared pregnancy outcomes from patients who used EFV/TDF/FTC between August 2014 and August 2016 and those who used DTG/TDF/FTC from November 2016 to April 2017 

 

Much of the groundwork for this study was laid out by the Tsempano study, which demonstrated that EFV/TDF/FTC was associated with lower rates of any adverse birth outcomes as well as lower rates of severe adverse birth outcomes compared with other ART regimens (NVP/TDF/FTC, NVP/ZDV/3TC, LPV/r/TDF/FTC, LPV/r/ZDV/3TC).  A similar framework was adopted for the comparison of DTG/TDF/FTC with EFV/TDF/FTC in women who commence ART pregnancy.

 

Maternal demographics were well matched in both groups for age, employment, parity, gestational age at presentation, previous pregnancy losses and smoking and alcohol consumption.  They were also well matched with regards to the gestational age at which ART was commenced as well as their CD4 counts.

 

Outcomes were startlingly similar as listed below:

 

Total and severe adverse birth outcomes 34% in the DTG/TDF/FTC group, with 11% being a severe adverse birth outcome.

 

Total and severe adverse birth outcomes 35% in the EFV/TDF/FTC group, with 11% being a severe adverse birth outcome.

 

 

 

Birth at less than 37 weeks gestation 18% and less than 32 weeks gestation 4% in the DTG/TDF/FTC group

 

Birth at less than 37 weeks gestation 19% and less than 32 weeks gestation 4% in the EFV/TDF/FTC group

 

 

 

19% small for gestational age and 6% very small for gestational age in the DTG/TDF/FTC group

 

19% small for gestational age and 7% very small for gestational age in the EFV/TDF/FTC group

 

 

 

2.1% stillbirth in the DTG/TDF/FTC group

 

2.3% stillbirth in the EFV/TDF/FTC group

 

 

 

1 major congenital abnormality in the form of skeletal dysplasia in the EFV/TDF/FTC group

 

This preliminary data suggests that DTG may well be considered safe in pregnancy at some point but further research is needed in the following areas:

 

Birth outcomes associated with exposure to DTG from conception

 

Combination with other backbones eg ABC/3TC

 

Maternal viral load at delivery

 

Tagged in: 2017 IAS Conference

An important group of presentations today on STIs, a somewhat neglected area of discussion in HIV, despite evidence that people with higher rates of STIs are at increased risk of HIV and vice versa.

 

First presenter was Darren Russell from Australia presenting some background on the epidemiology of STIs.  First and foremost, the point was made that, if you do not test for it, you will not find it and then you cannot treat it (much like the first 90 with HIV!)  and that in contrast to HIV, testing, reporting and surveillance of STIs is inconsistent throughout the world, making STIs the “poor cousins“ of HIV. Given the international nature of the conference, epidemiological data from around the world was presented for STIs.  One slide demonstrated that in the early 20th century, as many people died from syphilis as did from HIV/AIDS at the height of the epidemic in the USA.  The incidence of syphilis from late last decade throughout the USA, Canada, Germany, Sweden, France, The United Kingdom and Australia was noted to have risen significantly in all countries and a special mention was made of the syphilis epidemic in Aboriginal and Torres Strait Islanders, a group in which we must try to do better if we are to close the gap.  This presentation ended on a high note with a success – the roll out of the HPV vaccine and the dramatic decrease of genital warts in vaccinated Australian women and eventually men.  I thought that ending on this information really served to demonstrate to the sexual health community what is really needed to stop epidemics – vaccine development.

 

Next Presenter was Scott McLelland from the United States who presented on STIs and susceptibility to infection.  We have known for some time that STIs place people at risk of HIV and vice versa but elucidating exact mechanisms has been challenging and interventions have not been as successful as previously hypothesised.  Yet more recent data has demonstrated significantly increased risk of HIV acquisition with HSV2, vaginal dysbiosis (bacterial vaginosis) and HPV due to the immune response.  For example, the site of HSV lesions has been shown to have high numbers of CD4 T cells and dendritic cells as does HPV infected mucosa, providing increased target cells for HIV virus.  How we use this information as a basis for further research, treatment and ultimately health policy remains to be seen.

 

Next was Connie Celum, also from the United States who presented on STIs in the era of TasP and PrEP.  One of the first and very important points made was that there is no evidence to indicate decreased efficacy of PrEP in users who have an STI – demonstrated in both iPrEx and Partners PrEP studies.  One caveat was that bacterial vaginosis may impact the efficacy of topical vaginal tenofovir.  The possibility of PrEP programs actually leading to a long-term reduction in STIs was brought up and the role of regular STI screens as part of PrEP use as well as the potential for STI PEP using doxycycline, presented as part of the ipergay study at CROI in early 2017 were both put forward as mechanisms to reduce the burden of STIs in PrEP users.  The model of STI testing, treatment and follow up was also addressed with reference to the Dean Street Express clinic in London with changes in service delivery proving effective in testing and treating more people in a shorter space of time and as mentioned previously – if you don’t test for it, you can’t treat it!

 

Last but not least was Cecile Bebear from France who gave a presentation called “should we fear antibiotic resistance for STIs?” with a focus on 4 bacterial STIs – Chlamydia trachomatis, Neisseria gonorrhoea, Treponema pallidum and Mycoplasma genitalium. For Chlamydia trachomatis, the concern for antimicrobial resistance (AMR) is low with the organism remaining sensitive to tetracyclines, macrolides and quinolones and only very rare cases of macrolide resistance being reported, so as Chlamydia trachomatis remains the most common bacterial STI, it also remains very easy to treat. Neisseria gonorrhoea is the complete opposite however, with resistance to almost every agent ever used against it since about the 1930s.  First line treatment with combined antibiotics of two classes has held Neisseria gonorrhoea at bay, but for how long?  Extended cephalosporin resistance rates in this organism, where there is resistance monitoring range from 0.1% to 30 % in various parts of the world (up to 5% in Australia).  Azithromycin resistance ranges from 2-8% across the world, fluoroquinolone resistance 30%- 50% and tetracycline resistance more than 50%.  New treatments are in development pipelines but the ideal way to tackle this organism would be through a vaccine.  Syphilis remains relatively easy to treat with penicillin or doxycycline but does have a high prevalence of azithromycin resistance (84% in Australia).  Finally, the new kid on the block, somewhat of a problem child, Mycoplasma genitalium, tetracyclines demonstrate poor levels of eradication but no resistance characterised, macrolide resistance is widespread, between 43% and 63% in Australia and there is acquired resistance to the agreed upon second line treatment moxifloxacin, ranging from 4.5% in the UK to 47% in Japan.  Unfortunately, this problematic organism did not generate much discussion nor were potential third line agents for consensus discussed.  Certainly more research needs to be done in regards to this organism and consistent guidelines on management are required.

 

Tagged in: 2017 IAS Conference

Transactional sex in MSM: How common is it? Who does it? What are the risk factors?

This presentation looked a cohort of MSM from Vancouver. Canada, to examine prevalence, trends and risk factors of transactional sex and ultimately if transactional sex constitutes an increased risk of HIV transmission.

The study design was a prospective cohort study with respondent driven sampling of approximately 700 MSM aged over 16 years. 201 participants were HIV positive. Participants used a computer assisted questionnaire with the main outcome was an exchange of money/drugs/goods or services for sex. The data was analyzed with a multivariate logistic regression model.

Transactional sex was found to be rare in this cohort (between 1-3%).

Transactional sex was more likely with the following factors:

1) partner was met online

2) a lower incomes

3) a lower level of education

4) identification as bisexual

5) having an older sexual partner and

6) having a partner who uses either crystal methamphetamine, GBL or GBH

Partner substance use was most strongly associated with transactional sex, No significant associations with HIV risk behaviour.

Tagged in: 2017 IAS Conference

A late breaker poster was presented Tuesday showing the 48 weeks data comparing Bictegravir co-formulated with FTC/TDF in a fixed dose combination (B/F/TAF) vs. DTG/F/TAF in treatment naïve HIV-1 positive adults. The study is phase 3 multi-centered RCT with a primary endpoint of HIV-1 RNA < 50 copies /mL at 48 weeks, powered for non-inferiority.

 

B/F/TAF was safe, well tolerated and non-inferior to DTG/F/TAF in treatment naïve adults. Discontinuations due to adverse events were uncommon in both arms . There was no evidence of treatment-emergent resistance to study medication. Interestingly there was less of a decrease in the e GFR observed in the B/F/TAF participants. No difference observed in lipids.  

Tagged in: 2017 IAS Conference

IAS2017 11 am Monday 14/7/2017

 

This session was about emerging therapies for HIV and new approaches to specific patient populations.  The topics covered in this session included immunodeficiency at the time of ART initiation and the use of various ART combinations in different settings such as advanced immunodeficiency, second-line ART resistance and the use of novel 2 and 3 drugs combinations in ART-naive individuals.

The first speaker, Nanina Anderegg showed that median CD4 count at ART initiation was <350 cells/µL, with >25% of individuals at CD4 count <200 cells/µL, in low, middle and high income countries in 2015.They analysed data from the International epidemiology Databases to Evaluate AIDS (IeDEA) in sub-Saharan Africa, Latin America, Asia-Pacific and North America regions and from the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). They included all HIV-positive adults (≥16 years) initiating cART between 2002 and 2015.  This demonstrated that a substantial number of individuals still initiated ART at advanced immunodeficiency. Additional efforts and resources are needed to improve testing coverage, linkage to care, and ART initiation globally.  There was a general trend to start ART at higher CD4 counts in the later years of the study though, which is encouraging.

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Lelièvre found that the addition of maraviroc (MVC) to standard ART in advanced HIV infection had no impact on the risk of occurrence of infections, serious events and mortality, virological control or CD4 count recovery.  However, post hoc analysis showed a trend for a beneficial effect of the addition of MVC in the first 24 weeks in CD4 count recovery that disappeared thereafter.  Therefore miraviroc may be of some benefit in immune system reconstitution in early stages of therapy.

 Moh reported that in individuals failing second-line PI-based regimens, a phase of intense adherence reinforcement with HIV-RNA monitoring may help determine whether switching to a third-line regimen is required. 

 Joel Gallant showed that bictegravir/emtricitabine/tenofovir alafenamide was non-inferior to dolutegravir/abacavir/lamivudine in terms of virologic efficacy and was well tolerated. This was in treatment naïve subjects and their data extends to 48 weeks.  The single-tablet formulation bictegravir/emtricitabine/tenofovir alafenamide is potentially suited to the setting of same day/rapid ART initiation as it can be safe to start pending hepatitis B screening results, has high virological efficacy and favourable safety profile.  This study is ongoing.

In other treatment-naïve individuals, simplified combinations such as ritonavir-boosted darunavir/lamivudine was shown to be non-inferior to ritonavir-boosted darunavir/lamividuine/tenofovir in achieving HIV-RNA <400 copies/mL at week 24 as presented by Pedro Cahn.  Dolutegravir/lamivudine also demonstrated potent virologic efficacy at week 24 in individuals with entry HIV-RNA <500,000 copies/mL thanks to data presented by Babafemi Taiwo.  Early data suggest that simplified regimens consisting of ART with a high resistance barrier and lamivudine may be non-inferior in virologic control in treatment-naïve individuals. Data with larger sample sizes and longer follow-up are needed to confirm these findings.

Tagged in: 2017 IAS Conference

On-demand oral TDF/FTC for PrEP: is it an option? 4 speakers put forward their argument for (and perhaps against) on demand PrEP. On-demand PrEP is an attractive and cost saving was of delivering PrEP but has only a limited number of studies to demonstrate its efficacy.

 

The first speaker presented strong evidence that both daily and multiple non-daily oral TDF/FTC were highly protective against the rectal and vaginal acquisition of SHIV in macaques. Various pre and post dose models were examined with “double” pre and post event dosing showing increased efficacy.

 

A pharmacologist followed up with a presentation demonstrating pharmacokinetic data that TDF/FTC reaches mucosal sites quickly, at appropriate concentrations and with a long enough “residence” to cover residual virus.

 

Bob Grant spoke following this about clinical experience of non-daily PrEP. Worldwide. Various non-daily PrEP studies (e.g. Holland, Montreal) show a significant cost saving as well as high patient satisfaction and preference. However, data from HPTN 067 showed fewer sex events were covered by non-daily PrEP use when compared with daily PrEP use.

 

The final speaker elaborated on the HPTN067 study. Non-daily PrEP regimens in this study were found to me more appropriate in participants who could adhere, had fewer sexual exposures and who could plan for sex.

Tagged in: 2017 IAS Conference

There was a flavor of dual therapy around Mondays Plenary. An interesting study for Australian audience was the ACTG A5353 study which is a pilot study of Dolutegravir  + lamivudine for the initial treatment of HIV-1 infected individuals with viral loads of less than 500,000 copies/mL.  The 24 weeks data was presented using the FDA snapshot definition. There were 120 participants with no baseline resistance identified. There were no discontinuations. This regimen demonstrated potent virilogical efficacy at 24 weeks. 3 patients met the criteria for a protocol defined virilogical failure (PDVF), one had emergent M184V.

 

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The other interesting update was the 48 week data for Bictegravir(B)/F/TAF vs. ABC/DTG/3TC. This is a phase 3 RCT for treatment naïve adults. The primary endpoint HIV-1 RNA < 50 copies, powered for non-inferiority. B/F/TAF was non-inferior at 48 weeks. It was well tolerated and there were no adverse events leading to discontinuation. Nausea was significantly greater in patients taking ABC/DTG/3TC.  Gastrointestinal, Neuropsychiatric and sleep related problems were also more common in the ABC/DTG/3TC patients. Changes in BMD and renal function were comparable. The speaker felt that B/F/TAF was an “attractive” option for rapid commencement of antiretroviral therapy as no HLA status is needed and it could likely be commenced irrespective of Hepatitis B status and renal function.

Tagged in: 2017 IAS Conference

This was an interesting presentation in that it gave the perspective of what is happening with wider access to PrEP throughout the world, which I think is highly relevant given the recent submission for PrEP to be listed on the PBS in Australia.  It started off with a taste of the WHO's PrEP implementation tool that will be officially launched at IAS 2017 and aims to provide a framework for implementation of PrEP on current evidence to a number of stakeholders, including clinicians, pharmacists, consumers and regulatory officials.

 

The talk then moved on to what is happening in France, home of the ipergay study which demonstrated that on demand PrEP was efficacious.  France has been successful in implementing access to PrEP within their state funded health system and as of early 2017 had almost 3,000 people on PrEP.  The main PrEP users in France are men who have sex with men (MSM), however a strong campaign is underway to ensure other target groups within France, namely migrant and transgender women are aware of PrEP and their access to it.

 

Moving on to South Africa and their implementation which has focussed on two main priority groups within their context – commercial sex workers (CSW) and MSM.  Between June 2016 to June 2017, over 30,000 CSW had HIV tests and almost 2,000 were initiated on PrEP.  For the same time period, over 1,000 MSM had HIV tests and over 200 were initiated on PrEP.  Both these groups demonstrated a fairly low overall uptake with CSW uptake around 7% and MSM uptake around 21%.  The uptake within the transgender community was reported to be very low.  Possible reasons for low uptake included stigma of ART medications, even if used as PrEP and inconvenience of clinic setting and to address the latter issue, the model of care has evolved into a nurse or peer led service with more convenient hours, locations and mobility.  What is great to see is in South Africa, of the people who do commence PrEP, about 75% are women and about 75% are between the ages of 19-34, which means that PrEP is getting to the groups that need it most, as in Africa the highest growing incidence is in women and young people.  Another great outcome is the sheer number of HIV tests that are being done – a step towards addressing the first 90.

 

Next stop on our world tour -  England, home of the PROUD study, famously interrupted due to the high 9% incidence of HIV in the delayed PrEP group.   There are currently an estimated 6,000 people on PrEP in England, the main source is via personal importation as the NHS were not willing to fund the addition of PrEP onto the national formulary, despite two court cases to compel them to do so.  Some funding for limited places has been made available recently.  Further compelling evidence for PrEP was presented in a 42% reduction of new HIV cases between 2015 and 2016, demonstrating that PrEP is benefiting both the individual and the greater MSM community. What is interesting is that the incidence of Chlamydia has been reported as stable when compared to the number of increased tests and that cases of Gonorrhoea have indeed decreased by 24% between 2015 and 2016.  No data for syphilis was presented at this talk.  The data for the bacterial STIs is encouraging as opponents of PrEP may use the rise in these STIs as an argument against widespread implementation.

 

Over to Australia and the achievement of the 90, 90, 90 targets was highlighted yet despite this, stable notifications of new infections and a significant proportion of new infections (70-80%) in MSM demonstrated that in the Australian context, meeting 90, 90, 90 is just not enough to make a population impact. Small PrEP demonstration projects in 2014 in New South Wales, Victoria and Queensland with combined numbers of around 500 participants demonstrated that high risk MSM (demonstrated by high rates of other STIs on enrolment) were willing to enrol and uptake PrEP with good adherence. The taxpayer funded health system in Australia calls for a cost effective and high impact upscaling and as such, high risk MSM remain the target population.  This upscaling was implemented in the EPIC trial in NSW which has over 6,000 paticipants in that state alone (other state trials only got a brief mention but an estimated further 6,000 places combined are available).  Data presented from EPIC demonstrates that the target group of MSM is being reached, that those under 20 years of age are under represented and that Gonorrhoea notifications are continuing an upwards trend, one that was already underway before the implementation of wider use of PrEP. It appears that new HIV infections have decreased with a reported 29% reduction in all diagnoses and a 43%reduction in early diagnoses in the first quarter of 2017, compared with the previous five year average, however more data over more time is required to ascertain if this is a significant trend as a result of PrEP.  Given these figures, there is great hope that PrEP will be PBS listed and the outcome of recent submissions to the PBAC will be known late August 2017.

 

Kenya presented next and identified their target populations as CSW, MSM and adolescent girls and young women (AGYW).  There have been significant milestones in Kenya’s upscaling since July 2016, including national guidelines, approval of generics and a national PrEP scale up launch in May 2017.  Further information presented revealed uptake in a number of groups beyond the initial three target groups, including partners of sex workers, men who have multiple female partners and serodiscordant couples.  A substantial media campaign was adopted to attempt to address the stigma with PrEP use in Kenya.

 

Last but not least was a presentation on the target group of adolescent girls and young women, an over represented group in Africa with some dramatic figures – 1000 young African women dying from HIV related illnesses every day in 2015, 90% of all new infections in 15-19 year olds in girls are in Southern Africa and only a 6% reduction in HIV in women 15-24 from 2010 to 2015.  HIV in pregnant women in South Africa was also startlingly high with an 11.5 % prevalence in women under 16 years attending for antenatal care all the way up to 51.9% in those over 25 years of age.  Given the high numbers in women and pregnancy, an assessment of PrEP in a sexual health and reproductive clinic seting has been commenced and between March 2016 and February 2017, 429 women were offered PrEP with a 61% uptake, a 67.8% retention rate with adherence being reported as 90% based on pill counts.  This demonstration project will hopefully inform how to roll out PrEP to South African women in sexual health and reproductive clinics in the very near future as it is desperately needed.

 

PrEP for adolescent girls and young women in Africa is NOT a luxury we can afford to withold 

 

 

 

Tagged in: 2017 IAS Conference

I attended this one hour punchy poster discussion session on Monday lunchtime. It covered a wide variety of topics including cardiovascular, renal, lipids and brain function, chronic pain and mental health in people living with HIV. It included an Australian presenter Dr Nicholas A. Medland who concluded that "Fanconi syndrome occurs at a late stage of antiretroviral treatment" and that it is "an uncommon but not rare" outcome. That "Ritonavir use increases the incidence by 5 times". And there was a memorable point to take away that monitoring is important and simple (once to twice a year urine dipstick test) even in long term patients who do not appear to be at increased risk.

Following this there was a talk by Dr Felicia Chow regarding higher HDL and improved brain function. There were 988 participants in the study and 80% were male. 27% were taking a statin medication and 36% an antihypertensive medication. I could relate to the frustration behind the questions from the audience regarding what can you actually do to increase HDL levels. As getting active, losing weight, healthy diet, reduce alcohol and stop smoking can be a slow process but it was a reminder once again to continue to encourage these lifestyle changes.

After this was an interesting talk regarding non pharmacological managment of chronic pain by Jordan E. Lake from the University of Texas. 55 participants who were aged fifty years or older and who were living with HIV. They had chronic pain for more than 3 months (mainly osteoarthritis and/ or peripheral neuropathy) and were randomly assigned to one of three twelve week treatment options. Either 1) Tai Chi (chosen for its ability to be used by even the frailest of patients) and Cognitive Behavioural Therapy and motivational mobile phone texts or 2) a support group or 3) no intervention. 

The conclusion was that substance use was reduced by both the support group and Tai Chi/CBT/SMS intervention and pain relief and physical function improved by the Tai Chi containing intervention. This reinforced the benefit of patients living with HIV having a chronic disease management plan and team care arrangement for easier access to an Exercise Physiologist and Psychologist from their General Practitioner.

 

Tagged in: 2017 IAS Conference
Mind the Gap: Filling knowledge gaps in Paediatric and Adolescent HIV for an AIDS free generation

I am reporting back from the IAS2017 session Mind the Gap: Filling knowledge gaps in Paediatric and Adolescent HIV for an AIDS free generation -- the first satellite session at 8 am on Sunday morning, well attended with standing room only.

This satellite, organised by the Elizabeth Glaser Pediatric AIDS Foundation will launch the research agendas and discuss considerations emerging from the process such as the use of observational data, optimising clinical trials design, the roles of basic and implementation science, and the role of community engagement, with a focus on the meaningful engagement of youth.

As a General Practitioner previously involved with youth sexual health screens in North Queensland where there is a relatively large proportion of teenage patients, I found this session quite useful. 

The most useful discussions were personal anecdotes by the speakers and from questions asked by the audience.

One question was asked to Carlo André Oliveras Rodriguez from Adolescent HIV Treatment Coalition (ATC), Puerto Rico, regarding the use of non-monetary incentives. He described using transport and internet access as alternatives.

I have myself seen the impact of using monetary incentives as impacting on future testing and treatment and it was great to get alternatives.

The delegate next to me, from the London School of Hygiene, said that ethics committees strongly restricted them to the use of food and drink or transport only for incentives. 

There was a flyer in my welcome pack for a program in the United States called the Undetectables which also touched on incentives for maintaining an undetectable viral load.

Visit the website: 
www.liveundetectable.org

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The discussions were mainly in the context of research but I would like to transfer this knowledge to youth engagement in primary care such as a youth drop in clinic.

They also discussed barriers such intellectually disabled youth and hearing impaired such as youth officers trained with this in mind.

They talked about some young people preferring twice daily smaller pills rather than once daily larger sized pills. But also that the options for treatment of younger people with low body weight were a barrier due to limited single pill combinations.

The Elizabeth Glaser Pediatric AIDS Foundation host again another satellite session this afternoon with the goal of the satellite to raise awareness and facilitate discourse regarding adolescent-specific needs as a part of a comprehensive national HIV/AIDS care and treatment package.

See: Nonstop Journey: Delivering an Uninterrupted Continuum of HIV Services to Adolescents and Youth

Tagged in: 2017 IAS Conference

Dr Marcos Davi G. Sousa Specialist in Infectology, Federal Hospital of the Servants of the State of Rio de Janeiro presented a case history of a male, unfortunately he didn't state how long the patient had been HIV +.

* 51 years of age

* COPD

* alcohol dependant 

* very poor ARVT compliance

He had previously been treated for Tuberculosis, mycobacterium kansasii and mycobacterium avium, but continued to experience poor health, and poor compliance on ARVT.

He was tested and treated for M. intracellulare in Jan 2015, then tested positive for "atypical mycobacteria" in Sep. 2015.

In Nov 2015 a positive culture identified M. colombiense, the first isolate of this species in Brazil. It is a slow growing  type of  mycobacterium that infects both immunocompetent and immunocompromised people and was first isolated in Bogota, Columbia in 2006. Importantly, infection can mimic tuberculosis.

Treatment provided was the same for tuberculosis and should have continued for one year after the last negative test, but the patient continued to be non compliant with treatment and apppointments. Resistance testing was not yet available, and the outcome for the patient was not presented. 

 

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How do you summarise such a comprehensive and jam packed conference into one post?!

 I have been absolutely overwhelmed by the great presentations and seeing such wonderful colleagues from around the world share their research to everyone.

 Some of the main highlights for me were the Doxycycline as prevention plenary which had a great discussion post presentation from a lot of clinicians around the world, but overall good to see the willingness to possibly adopt a new strategy with condom-less STI prevention.

 I engaged in Twitter posts throughout this conference (NB: #stirio2017 was the second most trending tag in Brazil), which I noted was quite popular among a lot of speakers and presenters to share information back home. Even seeing some of my tweets liked or re-tweeted by people from BASH or the Lancet was great to see how quickly the sharing of information between colleagues can happen. This was an exciting approach to disseminating conference material for those who couldn’t attend.

 A common theme I found was discussions around the antibiotic resistance in Mycoplasma and Gonorrhoea, and how appropriate testing and prescribing practices, specifically around not using Azithromycin with rectal chlamydia are really important to bring inline uniformity to treating as based on the WHO treatment guidelines.

 PrEP implementations are varied worldwide, and you can see how much funding and stigma around getting TDF/FTC out to communities is quite difficult in different political landscapes. There were so many posters presented and some great questions were posed around PrEP in relation to STI’s and Hepatitis C.

 One of the final presentations from Tetyana Vasylyeva (Ukraine) was quite moving considering the research was based on changing opinions on HIV prevention in the landscape of countries facing war. With a high amount of IVDU and a cut on all methadone programs at the time of the civil unrest in Ukraine, larger numbers of migration changes into already high prevalence areas without primary health resources, are increasing risk of HIV transmission.

 Currently in Ukraine they have over 220 000 known HIV + people with only 28% ARV coverage. Post war data showed over 1.7million people are currently displaced and with migration patterns changing, and cuts to public health funding this is making ARV programs difficult to sustain.

 I had hoped to catch up with Tetyana after the talk to ask more questions but like others, most people were running between rooms to catch different talks.

I've also attached some of the posters I enjoyed reading as well.

 I am so humbled and honored to have been selected as a scholarship recipient for ASHM, it has enhanced my knowledge significantly and after seeing a large number of clinicians in Rio, I hope further sexual health nursing members are able to attend in the future to bring relevant information back to their colleagues.

 

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Findings from the national online HIV self-sampling service in England. (Luis Guerra).

I found this talk to be if interest because in NSW we have launched the Dried Blood Spot - Home HIV self testing.

In England - eligible participants go to a website - WWW.freetesting.hiv and answer a. Few questions and then get a box sent the address they register.

The person then follows the instructions in the kit and utilising a lancet leaves a blood spot which is then posted back for testing.

Results are then sent out within 3 days via the delivery method the participant chooses.

If the result shows Reactive - the participant is contacted via phone and notified of the Reactive result - explaining the possible outcomes of a reactive result (Explaining it doesn't mean its a positive test).

The participant is given the details of local clinics and services and offered an appointment or they are able to book themselves.

Of the 40726 kits sent out - 22085 were returned. That's a 54% return rate.

There were 239 reactive samples.

Of those that tested 30% had never had a test. And 32% last tested over 1 year ago.

 

I hope that the NSW Dried blood spot testing program has such a high return rate and that we are able to capture the amount of people that otherwise would not have tested.

 

 

This morning I attended the Oral presentations for HIV/STI testing and management, looking at different studies around HIV risk.

Brendan Harney from Melbourne presented his study: Risk of HIV following repeat sexually transmissible infections among men who have sex with men in Victoria, Australia. 

This presentation was a retrospective study questioning, if MSM have repeat positive STI diagnoses, are they at an increased risk of HIV transmission? 

Out of 8941 MSM (median age 29, Australian born) surveyed at a busy Melbourne Sexual Health Centres, 2.5% were diagnosed as HIV positive.

Although repeat Chlamydia and Syphilis notifications were common, Rectal gonorrhoea was found to be the highest, with 13.5% of those with a repeat positive gonorrhoea rectal infection becoming HIV positive.

Conclusion? Repeat Gonorrhoea infections are strongly associated with a HIV infection, and that this data is key to looking at PrEP inclusion criteria and why we target specific groups and behavioural activities for PrEP enrolment studies. 

 

The Multicultural HIV and Hepatitis Service (MHAHS) has launched a multilingual communication communication toolkit… https://t.co/eXa72MaSv2

ASHM ASHM

#ASHMResource HIV Management in Australasia is a ‘living resource’ for health practitioners managing people with HI… https://t.co/yKj1D4aCrE

ASHM ASHM