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.

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A brief blog reviewing the Bernard Fields Lecture. Monday 22nd Feb.

T Cells Control of HIV: Implications for Vaccines and Cure.

Speaker: Dr Bruce D Walker (Harvard, MA, USA)

In summary CD8 T cell immunity is still undergoing vital research in assessing how it impacts on overall immunity specifically relating to HIV. Can it help us in a cure or vaccine development? 

Known that CD8 T Cells can kill infected cells before progeny virions are produced. Yang 1997 showed that In vitro CD8 cells can kill HIV infected cells.

In order to assess T Cell response in initial pre peak viremia infection they are studying HIV infected babies in Durban, South Africa. FRESH program was implemented. It was noted within these patients that the rate of increase in viral load was similar across all new infection babies, but the actual peak viral load number and time to reach that in an individual varied. http://ragoninstitute.org/international/fresh/

 From current findings they have found that CD8 cells increase their activity within the human body just after initial exposure to HIV, a substance known as PD-1 is expressed and the more of this that is expressed over time there appears to be some correlation with the immune system getting turned down in regards to response. This was apparently similar to what has been noticed with cancer modulating cells and immune response impact.

They have been able to show that HIV some how activates CD8 activity –they hypothesize that perhaps active CD8 T cells are HIV specific. It was noted that an increased level of CD8 cell activated initial stages of infection was linked with a lower viral load set point.

Two other markers noted to be of relevant were, BCL-2 and perforin. As BCL-2 was activated CD8 cells underwent increased apoptosis, and similarly as there was a loss in perforin there was a progressive decline in CD8 functionality.

Overall early treatment does impact the overall quality of the immune response. To further hypothesis but if CD8 cell functions were maintained by commencing treatment in the pre-viremia stages of infection exposure could this help in the development of a cure and it’s effectiveness.

At the conclusion of the talk, despite being moderately confused with the biochem aspects, I got the impression that for now in order to help the development of future effectiveness of a potential cure we need to maintain baseline immunity of newly diagnosed HIV positive patients as much as possible, and prevent the exhaustion or destruction of CD8 cells after peak viremia.

I’m not sure if I would use this particular pitch to promote early commencement of ARVs in patients or for increased testing programs to detect earlier, but it’s food for thought as to why there is a possible other reason to suppress viral loads as early as possible.

 

This paper reviewed the increase in viral suppression and sustained viral suppression in USA adults on ART between 2009 and 2013.

Viral suppression increased in a linear fashion from 72 - 80% a significant 2% rise year on year. Sustained virological response followed a similar trajectory from 58% - 68% over the same time. This was not explained simply by an increase in number of people on therapy.

Women, 18-29 year old's, 30-39 year old's, African Americans all had a greater benefit than the overall. MSM were higher than the average at all time points.  There were two Guidelines introduced during the study period which actively promoted treatment and barriers and delays to accessing AIDS drugs. All suggesting that policy change is having impacts.

This is Oral paper number 53, in session O-5, if you want to have a look when the presentations go on-line. http://www.croiconference.org/

HIV and Women's Health was the topic of Wednesday morning's stream. Much interesting and varied work was presented. I will attempt to summarise below.

Damian Jeremia presented his work entitled Prevalence and Factors Associated with Modern Contraceptive use among HIV-positive women aged 15-49 years in Kilimanjaro region, Northern Tanzania.

Women's responses to a questionnaire and interview in Swahili language were aggregated. Results showed that only 54% of these women were using a form of modern contraception. Male condoms were the most common contraceptive method (25.4%). He cited lack of contraception information and lack of combined reproductive health and HIV services being the main barriers in contraception use. 

Dr Lisa Noguchi presented on some complex findings from women participating in the S African-based VOICE trial. The VOICE trial is a Phase 2B trial of women using tenofavir as HIV prevention, and one of the eligibilty criteria required having effective contraception.  Lisa's secondary analysis of the data looked at injectable Progestin contraception and acquisition of HSV2 Infection. Injectable progestins are the most common contraceptives used in S Africa. Whilst some data suggests hormonal contraception may increase HIV-1 risk for women, recent studies have suggested there are differences in this risk between the 2 commonly available progestin injectables - DMPA and NET-EN. Retrospective analysis of the VOICE data showed HIV-1 was higher for users of DMPA vs. NET-EN (aHR 1.41, 95% CI 1.06-1.89) p=0.02.   However, the risk of HSV-2 acquisition  between the 2 types of injectables turned out to be not significantly different.     She noted that the data was extracted from the VOICE study retrospectively, which was originally designed to demonstrate different data and results could therefore be prone to bias.

 

Shaun Barnabas presented longditudinal cohort data on genital symptoms and STIs in just under 300 women aged 16-22 years in different cities of S Africa. The Cape Town cohort was more risky in behaviour with a high prevalence in STIs vs. Johannesburg, specifically a higher prevalence of chlamdyia, gonorrhoea and HSV-2. There were low rates of symptoms reported across the board,with "normal vaginal discharge" being the most common symptom (58%) and "abnormal discharge" 8% at baseline.There was little correlation between symptoms and STIs. This is an issue as S African guidelines are based on syndromic management, thus potential for under treatment is significant. 

His final question was "Is it time for the SA government to move away from syndromic management?"  The resounding answer from the audience response was "Yes!".

 

Alison Norris educated us about the gender differences in HIV testing and knowledge in Rural Malawi, one of the poorest per capita countries in the world. There were encouragingly very high rates of HIV testing in both sexes. Most powerful predictor in whether someone of either sex had ever had an HIV test was knowing the partner had received a test. Ultimately their prediction that there would be significant differences between testing and knowledge between men and women was unfounded.

 

A/Prof Sheona Mitchell talked on uptake of cervical cancer screening among HIV positive women participating in a pilot RCT in Uganda: the ASPIRE project (a collaborative study between Canada and Uganda).  The aim of the ASPIRE project is to inform policy makers about cervical screening programs in resource poor areas.

They studied 500 women in an urban community in Kampala. Usual cervical screening involves visual pelvic speculum exam with acetic acid application.ie invasive. The potential for a less invasive test such as a self-collected swab detecting high-risk HPV strains is a novel, attractive approach for low-resource settings. HIV positive and negative women were randomised to speculum visual exam or self-collected swab. 

Self collection of swabs had a high uptake in both HIV pos and neg women. It was found to highly acceptable, improved access and had high rates of retention going forward to further exam and treatment (compared to visual exam alone).  She was hopeful of future POCT for the HPV swab to further reduce barriers to cervical screening uptake. 

 

Elizabeth Fearon then finished up the session by presenting interesting data on a method to estimate the national prevalence of HIV among female sex workers in Zimbabwe by pooling data from Multiple Sampling Surveys and Programme Consultations.

My take home message from all of the above presentations is that there is much great innovative research going on in some of the most resource-stretched places on Earth.   Many small steps are being made towards improving access to screening, testing, support and treatment for women (both HIV positive and negative) from these difficult to reach populations and places.  But there is still a long way to go.