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.

Danielle Collins

Danielle Collins

Danielle Collins is a registered nurse undertaking her final year of her Nurse Practitioner candidacy, specialising in HIV medicine, through the Alfred Hospitals Victorian HIV Service.


Danielle has previously worked for the Victorian AIDS Council and has a strong interest in HIV treatment and prevention.

This 1 hour lunch time poster session presented an overview of different studies presenting STI epidemiology amongst MSM & heterosexual populations. 

 

  1. Florence Lot: STI co- infections at HIV diagnosis in France

Aim was to analyse the frequency of STIs in new HIV infections between 2012- 2015, using the mandatory HIV surveillance system which has, since 2012, collected data on bacterial STIs (CT, NG, LGV, syphilis). These had to be reported if detected at time of or in the 12 months prior to HIV diagnosis. 

Analysis by transmission group and trends. Reported as ‘HIV/STI co-infection’.

Result 1: 

Frequency of STI/HIV co-infections in adults by HIV transmission group & sex:  14.6% globally (26.4% MSM; 11.3% male & 5.8% females born in France; 5.1% male & 2.5% females born abroad; 7.2% male & 8.7% female IDU).

Result 2:

Frequency of STI/HIV co-infections in adults by HIV transmission group & year of HIV diagnosis: Significantly increased over time with 12.6% in 2012 to 18.3% in 2016. By transmission group, this increase was only significant for MSM from 22.1% in 2012 to 31.9% in 2016.

Result 3:

 Frequency of STI/HIV co-infections in adults by HIV transmission group and bacterial STI: Syphilis on the rise especially in MSM, heterosexual men were more often co-infected with syphilis and NG than heterosexual women who were more frequently infected with CT. Rectal LGV dx only in MSM. 

Conclusion:

HIV & STI co- infection has increased over time and affect almost 1/3 of MSM newly dx with HIV. Highlight importance of testing, treating index + partner. 

There was a question around testing frequency in France- was once per year and is now 3 monthly, including viral hepatitis screen (not sure if this had increased from yearly..). Another Q around high syphilis prevalence- confirmed that asymptomatic people are screened. 

A comment from a clinician from the UK regarding HCV, they are seeing a significant increase in acute HCV infections not associated with IDU amongst HIV negative MSM population, same in France? A- don’t have the data. 

 

  1. Flavia Kiweewa Matovu: STI acquisition among women using a variety of contraceptive options in Uganda

LARCs are being widely promoted, not much data on STIs in LARC use. High risk female population in in Uganda, established STI increases risk of HIV transmission.

Prospective cohort study- ASPIRE study.

Results:

Analysis population: 2264 women (50.2% from Sth Africa). 817 cases of STIs detected over 3,440 person years of follow up.

CT: 408 cases/ incidence of 11.86/100 person years

NG: 196 cases/ incidence 5.70/100 person years

T.vaginalis: 213 cases/ incidence 6.19/100 person years

(No mention of HIV, syphilis etc).

Conclusion: 

Incidence of CT & NG were not different across contraceptive methods.

Incidence of T.vaginalis was significantly lower for DMPA (medroxyprogesterone acetate injectable contraceptive), implant and NET-EN (norethisterone enanthate injectable contraceptive) users compared to IUD. 

Significantly lower rates of T.vaginalis among users of progestin- based methods, likely due to hypoestrogenic states. 

Limited by lack of randomisation to contraception method. 

Question around extra- genital sites being tested- yes, serology and genital swabs. 

Another question around relative risks being adjusted for baseline sexual risk- yes, adjusted for baseline age, sexual risk. 

 

3) Jeffrey Parsons: Differences in biological and behavioural HIV risks before, during and after PrEP use among a national sample of GBM in the USA

PrEP & STIs- Does going on PrEP lead to increased condomless sex (CAS) and thus higher rates of STIs OR are the increases seen in STI rates due to the required quarterly testing…?

Limitations to these data: Predominately Caucasian, employed and well educated population. Half were in a relationship, half were single. The sample were also early PrEP adopters.

Results: 

Cross sectional between group analysis: the 823 PrEP naïve men had significantly lower STI infection rate (4.2%) than those 77 currently (10.4%) or 17 formerly (11.8%) on PrEP (p < 0.02), with men on PrEP also reporting more acts of CAS (p <0.001). 

Within- person longitudinal analyses of 181 men reporting PrEP use indicated a non- significant increase in the odds on an STI diagnosis while on PrEP  and after discontinuing (OR= 1.25, p= 0.55; OR= 1.43, p= 0.53 respectively), compared to before starting PrEP. There were also no significant changes in CAS while on PrEP (OR = 1.09, p = 0.76) or after PrEP discontinuation (OR = 0.48, p = 0.10) compared to pre-uptake levels.

Discussion:

Using between- subjects comparisons of all participants, some evidence was found that GBM on PrEP have higher levels of both behavioural and biological risks, though findings were mixed when examining multiple time points. 

Using within- subjects comparison over time among only those who had been on PrEP during at least one of the three visits, the rates of CAS increased while on PrEP but returned to pre- PrEP levels after discontinuation. They did not see a statistically significant increase in odds of STI infection. 

Comment:

Important not to lump all GBM into one category. Differences in behaviour, risk and motivation for accessing and using PrEP. 

Early adopters- so more study required to determine the behavioural differences in early and late PrEP adopters. 

Question from the audience regarding the sites tested for STIs- in NYC, only 50% of participants had completed a rectal swab which could affect the data. 

88% completed urine and serology test.. pharyngeal swab around 60% (sorry missed that comment). 

Highlights the importance of a complete STI screen to ensure both a public health and epidemiological perspective. 

 

 

4) Marie Suzan- Monti: Partner notification (PN) of STIs among MSM on PrEP: s sub- study of the ANRS- IPERGAY trial

In France, there are no PN specific guidelines, and scarce PN information. Data on 275 HIV negative men from the ANRS- IPERGAY PrEP trial who reported an STI were used. 

Results:

Out of 275, 250 reported at least one previous STI. Of the 250, 172 had informed their partner (138 their occasional partner and 83 their main partner). 

No significant socio-demographic difference between this who did and did not notify their partner. 

Less likely to notify their main partner when most recent sexual contact was through condomless sex with an occasional partner (aOR(95%CI) 0.31 (0.14; 0.68), p=0.03).

Older MSM less likely to inform occasional partners (aOR(95%CI) 0.44(0.21;0.94), p=0.03).

Those participating in chemsex at most recent sexual encounter were more likely to inform sexual partners (aOR(95%CI) 2.56(1.07;6.09), p=0.03). 

Discussion:

Condomless sex with occasional partners was identified as a barrier to PN, and chemsex a motivator for PN. 

Not measures if health care workers were notifying partners. 

Hopefully these data support the need for systematic PN services, support and information in France- highlights how well Australia (speaking from a Victorian perspective) undertake PN form a top down approach. 

 

 

5)  Kristin Wall: Predictors of genital ulceration in HIV negative sero-discordant couples in Lusaka, Zambia.

Genital ulcers are a known risk factor for HIV transmission, and little is known about the risk factors for genital ulcers, limiting early detection and treatment. 

Exposure data were taken from HIV serodiscordant heterosexual couples every 3 months at ART uptake or HIV transmission. Associations were evaluated between exposures measured during the visit prior to the presentation with an ulcer. 18 year longitudinal cohort study (1994- 2012).

Results:

1393 M+F- couples were followed for 2756 couple- years, and 1656 M-F+ couples were followed for 3216 couple- years.

Risk for genital ulcer in HIV- women was associated (p<0.05) with bilateral inguinal adenopathy (BIA) (aHR=1.9), genital inflammation (GI) (aHR=1.5-1.9), male partners non- STI GI (aHR=2.9) and increasing number of previous pregnancies (aHR=1.1).

Risk for genital ulcer in HIV+ women was as above (BIA- aHR=1.5; GI- aHR=1.5-2.0; male non- STI GI- aHR=2.0), as well as late HIV vs early HIV (aHR=1.5) and being pregnant (aHR=0.7).

Risk in HIV- men was associated with BIA (aHR=1.8), STI GI (aHR=2.9) and non- STI GI (aHR=1.4), female partners ulcer (aHR=1.7), and being uncircumcised (aHR=1.7). Being uncircumcised with foreskin smegma was independently predictive (aHR=3.2). 

Risk in HIV+ men was associated with STI GI (aHR=2.8), HSV-2 positivity (aHR=2.5), late HIV  vs early (aHR=1.7) and being uncircumcised with foreskin smegma was independently predictive (aHR=2.4). 

Discussion:

Ulcers were also tested for syphilis, prevalence of chancre 2-3%  

BIA & GI may be early indicators/ risk factors for genital ulceration. Uncircumcised men with foreskin smegma either HIV +/- were at increased risk of ulceration. 

HSV-2 positivity not a predictor once controlled for genital ulcers and only a predictor in HIV+ men. 

Suggest: Targeted screening amongst those with advanced HIV infection. 

 

 

 6) Cari van Schalkwyk: Are associations between HIV & HPV transmission due to behavioural confounding factors or biological effects? 

This presentation was a mathematical modelling study to assess whether confounding for behavioural factors and network effects sufficiently explain associations between HPV & HIV infection. 

MicroCOSM is a dynamic individual- based network model and was used to simulate epidemics of HIV & 13 oncogenic HPV types.

Results: 

The mean unadjusted hazard ratio of HIV acquisition after detection of an oncogenic HPV type is 3.2 (95% CI 2.6, 3.8); and the mean unadjusted hazard ratio for the effect of HIV on newly detected HPV is 3.7 (95% CI 3.4, 4.1).

Discussion:

The study results are similar to observational study unadjusted results, suggesting that observed associations between HPV & HIV transmission could be attributed to confounding by behavioural factors and network- level effects. The author concluded that primary prevention with the HPV vaccine may therefore not be beneficial in HIV prevention. 

There was also no further increased risk in the presence of cervical lesions. 

 

The study group have a proposal for a clinical trial using the HPV vaccine to determine if this decreases HIV transmission although no funding as yet. 

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