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.

 

Dr Deborah Konopnicki from Belgium gave a fantastic overview of the current research in prevention and treatment of HPV-related malignancies in HIV positive men and women on Day 3 of the Glasgow Congress.

 

HPV-associated infections and lesions are more frequent and their outcome is more severe in persons living with HIV.  The prevalence and incidence of precancerous lesions of the cervix/vulva/vagina are 6 times higher, and of the anal region are 15 times higher than in HIV negative people.  Recurrence of these lesions is also twice as frequent after treatment. Rates of cancer of the cervix are three times higher than in the general population, and rates of anal cancer are 40-100 times higher.  Mortality rates from HPV-associated cancers are high, particularly in the case of anal cancer.

 

Antiretroviral therapy against HIV decreases HPV-associated infections and lesions after several years of optimal viral control and immuno-restoration of high magnitude.

 

A new preventative vaccine that targets 9 different strains of high risk HPV was approved by the FDA in 2014/5 (Gardasil9).  The newer vaccine is associated with a greater reduction in rates of squamous intraepithelial lesions in women (79% reduction versus <30% reduction) and AIN in men (89% versus 62%) than the vaccines targeting genotypes 16 and 18 alone.

 

Due to its high cost, it has been suggested that perhaps one or two, rather than three, doses of the vaccine could be administered, but there is no evidence for the effectiveness of fewer than three doses of the vaccine in the HIV positive population.  It has unequivocally been proven that HPV vaccination is beneficial for both primary and secondary prevention of HPV-related lesions in this population, although guidelines vary regarding the upper limit of age at which they should beneficially be administered as primary prevention.

 

Recent changes in cervical screening in the general female population in high resource settings are also application to HIV positive women:  under the age of 30, HPV prevalence is too high to warrant the use of HRHPV screening; after 30, HPV testing has good negative predictive value for women with CD4>500, so future screening may potentially be conducted at lower frequency than current guidelines in this population. 

 

A new approach to cervical screening studied in limited resource settings in South Africa, Botswana and India over the past few years has been the “screen and treat” intervention.  This involves visual inspection of the cervix and high risk HPV screening – the results are available within two hours and high grade CIN can be treated on the same day with cryotherapy of trichloracetic acid.  This approach has been shown to significantly decrease the incidence of HGCIN and cervical cancer at 3 years.

 

Another interesting development in this area has been the use of topical Lopinavir to treat CIN.  A single-arm, proof-of-concept trial was conducted by Lynne Hampson et al in Kenya, in which vaginal self-application of Lopimune (Lopinavir/Ritonavir) gel was used to treat high grade CIN in 23 HIV-negative women.  The intervention was well-tolerated and systemic absorption was weak; cytological response at month 3 was 82%, with 64% resolution of the CIN and 18% regression to a lower grade.  The effect of the gel was thought to be due to Lopinavir’s local anti-proliferative effect on cells, and similar cervical concentrations would not be achieved with oral Lopinavir treatment.

 

There are limitations to anal cancer screening – although high resolution anoscopy is the gold standard it is costly and time-consuming, and so far no RCTs have shown a reduction in mortality from anal cancer with any screening program. Results from two RCTs on the use of anoscopy that are currently underway are due in 2018 and 2022.  Dr Konopnicki stated that her clinic in Belgium incorporates both cervical screening and anoscopy as part of routine care for HIV positive patients, however.

 

Finally, therapeutic vaccines made of the E6 or E7 oncogenes (genotype-specific) or their DNA to induce cellular immune response against E6 or E7 are in development, and in the future they could contribute to less aggressive ablative therapy for HPV associated lesions.

 

 

 

One of the focuses of Day 3 of the HIV Drug Therapy Glasgow Congress was co-morbidities and HIV management, and how this affects patient care.

Dr Edouard Battegay from the University Hospital in Zurich presented in the morning on multimorbidity in HIV infected people as they age.  He stated that multimorbidity (the presence of multiple concurrent medical conditions) often occurs in clusters, and the complexity of managing the conditions, including potential drug-drug interactions, increases exponentially with each additional condition.  Common clusters in HIV–infected people include hypertension and dyslipidaemia, and pain and depression. 

 

The EACS guidelines for 2016 are one of the first sets of guidelines to systematically address comorbidities in DDIs in a specific disease.  Dr Battegay’s presentation prompted discussion of the relative and overlapping roles of HIV specialists, primary care physicians and specialists in managing these multiple conditions as the focus often shifts from the HIV infection, which is often stable, to management of the individual’s comorbidities.

 

Expanding on this exploration of the needs of the ageing HIV-positive population, Dr Charles Cazanave from France spoke about the results from a cross-sectional analysis of the ANRS CO3 Aquitane cohort.  He described the evolution of chronic non-HIV related disease and their risk factors in 2,138 patients included in this cohort between 2004 and 2014.  The mean age of the cohort increased from 42 to 52 years and the majority (71%) were male. 

 

He found that there was a significant improvement in HIV markers over the ten-year period, but also an increase in renal and cardiovascular risk scores, with rates of dyslipidaemia increasing by 40%, and rates of hypertension increasing by 37%.  There was also a high rate of smoking in this cohort (40%), reinforcing the importance of addressing lifestyle factors in comprehensive HIV management.  One of the limitations of this analysis was that there wasn’t a HIV-negative control group for comparison to see what happens to the rates of these conditions in the general population over a similar ten year period.

 

Is HIV-related lipodystrophy associated with an increase in the risk of morbidity and mortality?  Dr Estaban Martinez’s 20 year longitudinal cohort study asked this question and found that, contrary to their initial hypothesis, lipodystrophy or lipoatrophy (but not lipohypertrophy alone) was associated with a reduced risk of death in the group studied.  This was thought to be due to the fact that in the cohort studied, the presence of lipodystrophy is a proxy for effective viral suppression with antiretroviral medication.  LA, LD and LH were, however, all associated with an increased risk of hypertension and diabetes. 

 

Finally. Dr Davide de Francesco reported on results from the POPPY study in UK and Ireland, which showed that the HIV-positive people studied exhibit poorer cognitive scores when compared to controls, and there is a correlation with increased scores on depression-rating scales.  He concluded that reduced cognitive function may be mediated by depression or the two conditions may in fact be related to the same, as-yet unelucidated, pathophysiological process.   

 

 

Day 3 started with an excellent Symposium " Helping the Patients Stay on Course"

The session started with the importance of adherence to treatment and the barriers to this - the most common one being depression. 45% of cases of depression do unrecognised in HIV clinical care so if we are to look at the 90 90 90 target we need to make sure that we address the Mental Health needs of our patients to start to attempt to address this but more important is the fourth 90 - the quality of life.

Moises Agosto is a PLWHIV who is a Public health Physician and he gave a very personal account of the patient aspect and the doctor aspect. He also addressed the ageing of the HIV epidemic and the impact of comorbidities becoming more important after the age of 50 years.

The second session was  "Comorbidities and HIV management"and looked at the needs of HIV patients today and 10 years ago - particularly cognitive function and neuropsychiatric events - in particular looking at discontinuation of treatment due to adverse drug interactions and side effects.

During the lunch break there was a very interesting session on APPS and New technology in the Management of HIV infection and using social media to get the messages out to the target audience.

There was also discussion about medical APPS and privacy issues - should we be worried about confidentiality?? Should the medical APPS be developed by clinicians or IT gurus? 

Andri Rauch presented a very interesting session on HCV therapies and the remaining challenges - the take home message for me was that an SVR reduces the risk of HCC but does not eliminate it - do not forget the HCV treatment successes because they may not be a long term success.

 

Speaker: Edouard Battegay from the Centre for Competence Multi-morbidity (MM) at University Hospital Zurich.

Between 20–30% of the population and about 90% of inpatients hospitalised in General Internal Medicine have multiple concurrent acute or chronic diseases.

 He spoke about most prevalent triads seen at their out patient clinics such as combination of hypertension, dyslipidaemia, with chronic back pain/ osteoarthritis/diabetes mellitus or coronary heart disease, in people living with HIV. 

There are limited evidence-based guidelines for MM, be it without or with HIV, even for more prevalent forms of MM and frequent interacting combinations. This leaves MM care heavily reliant upon clinical guidelines intended for the treatment of single diseases.

He informed the audience about the new version of EACS guidelines (released 3-4 days ago) with new additions on managing MM.

The link to new edition of EACS guidelines;

http://www.eacsociety.org/files/guidelines_8.1-english.pdf  

CROI 2016: Intensive cervical cancer screening only needed in HIV positive women with low CD4

Intensive cervical cancer screening may be appropriate for HIV-positive women with a CD4 count below 500 and for immunosuppressed solid organ transplant recipients--but not for HIV-positive women with more CD4s or for women on immunosuppressive therapy [1]. Those conclusions arose from a 121,000-woman case-control study in the Kaiser Permanente healthcare system in northern California. Women with HIV had twice higher odds of advanced cervical intraepithelial neoplasia (CIN) or cervical cancer than women without HIV.

 

Kaiser investigators conducted this study to get a better fix on which HIV-positive and other immunosuppressed women need intensive cervical cancer screening. The researchers considered all women 18 to 70 years old in care between July 1996 and June 2014. Cases were women with incident (newly diagnosed) CIN 2, CIN3, or cervical cancer, designated CIN2+ or CIN3+. For every case the researchers identified 5 women without CIN2+ matched by age, diagnosis date of the case, years in the Kaiser system, and date of first Kaiser Pap test. They analyzed risk of CIN2+, CIN3+, and cancer in (1) all HIV-positive (versus negative) women, (2) HIV-positive (versus negative) women grouped by recent CD4 count below 200, 200 to 499, and 500 or higher, and (3) women with non-HIV immunosuppression, including immunosuppressive therapy (such as calcineurin inhibitors and corticosteroids) in the last 18 months (versus no therapy) and solid-organ transplant (versus no transplant).

Cases were 20,146 women with CIN2+, including 11,275 with CIN3+ and 646 with cervical cancer. Because of matching, cases and controls had the same average age (36) and similar numbers of years in the Kaiser system (6.4 and 6.6 years). Cases and controls were also similar in proportions of whites (54% and 49%), Hispanics (20% and 21%), and blacks (8% and 9%). Cases included a higher proportion of smokers (19% versus 13%). About 2% in each group had been vaccinated against HPV.

Cases included 36 women with HIV (0.18% of 20,146) and controls included 79 HIV-positive women (0.08% of 100,780). All of this percentage difference lay among women with a CD4 count below 500. The proportion of HIV-positive cases with a recent CD4 count above 500 was 0.04%, exactly the same proportion of HIV-positive controls with a recent CD4 count above 500. Numbers of cases and controls with recent immunosuppressive therapy were 1370 (6.8% of cases) and 6429 (6.4% of controls). Cases included 51 transplant recipients (0.25% of cases) and controls included 69 transplant recipients (0.07% of controls). 

In adjusted analyses, compared with HIV-negative women, HIV-positive women had 2.0-fold higher odds of CIN2+ and 2.3-fold higher odds of CIN3+. HIV-positive women with a recent CD4 count under 200 CD4s had 5.7-fold higher odds of CIN2+ and women with 200 to 499 CD4s had 3.0-fold higher odds. But risk of CIN2+ was not greater in HIV-positive women with 500 or more CD4s compared with HIV-negative women. The same held true for the CIN3+ analysis: Odds were 5.4-fold higher with a recent CD4 count under 200 CD4s and 3.6-fold higher with 200 to 499 CD4s, but risk was no greater in women with 500 or more CD4s.

Women with a solid-organ transplant had independently higher odds of CIN2+ (3.3-fold) and CIN3+ (2.9-fold). But women on immunosuppressive therapy did not have higher odds of CIN2+ or CIN3+. 

Among the 646 women in whom cancer developed, 2 (0.3%) had HIV compared with 0 of 3230 matched controls; 34 of 646 women with cancer (5.3%) had recent immunosuppressive therapy compared with 156 of the 3230 matched controls (4.8%); and no woman with cancer had a solid-organ transplant compared with 4 matched controls (0.1%). 

The Kaiser team concluded that HIV-positive women had 2-fold higher odds of CIN2+ and CIN3+, but these higher odds applied only to women with a recent CD4 count below 500. Solid-organ transplantation conferred 3-fold higher odds of CIN2+ and CIN3+, but recent immunosuppressive therapy did not affect CIN2+ risk. 

Take home message: more frequent cervical cancer screening may be needed only for subsets of women with HIV and non-HIV immunosuppression, including HIV-positive women with a CD4 count below 500 and solid-organ transplant recipients. They suggested that future studies addressing these issues "should take into account harms and costs anticipated with various screening strategies."

Reference

 

1. Silverberg MJ, Leyden W, Steven Gregorich S, et al. Is intensive cervical cancer screening justified in immunosuppressed women? Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 162.

Tagged in: CROI2016

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