CLINICAL HIV RESEARCH UNIT (CHRU)
South Africa is at the epicentre of the HIV and tuberculosis (TB) epidemics. In a country of 51.7 million people, adult HIV prevalence is 17.9%, with nearly 6 million people living with HIV, the largest number in any country worldwide. The TB epidemic also continues unabated, with an estimated 948 new cases of TB annually per 100,000 population. The Clinical HIV Research Unit (CHRU) which was founded in August 1997, is today an established, highly successful and internationally recognised multi-disciplinary research group. CHRU’s activities comprise a wide variety of academic research and technical assistance pursuits ranging from Phase I to IV clinical Trials, to implementation sciences, and epidemiology and health economics. The Unit, based in Johannesburg, continues to grow from strength to strength, increasing the grant funded support, publication output and post-graduate research output.
CHRU is a division of the Wits Health Consortium, www.witshealth.co.za, which is a wholly owned company of the University of the Witwatersrand (www.wits.ac.za) Johannesburg, South Africa, under its faculty of Health Services. WHC is a not-for-profit organisation.
Prof Ian Sanne – Divisional Head and Principal Investigator : Prof Ian Sanne is a National Research Foundation (NRF) B-2 rated South African born and educated scientist with a strong track-record of over fifteen years of Phase I - III clinical trial research. Prof Sanne has demonstrated outstanding research leadership domestically and internationally, with over 160 publications, and over 320 publications from the University recognised research unit. He is the Founding Director of the Non-Profit Organization Right to Care, which has grown exponentially to become one of the largest non-profit organisations in South Africa. Prof Sanne was elected International Vice-Chair of the NIH funded ACTG in 2011, considered one of the most influential international research positions in HIV/AIDS and Tuberculosis. Over the last fourteen years Prof Sanne has served on numerous South African and international guideline committees for the World Health Organization, SA Clinicians Society, National ART and HIV Drug Resistance Guidelines.
Prof Cynthia S Firnhaber is a US trained internal medicine physician dedicated to the care of HIV patients. She has been involved in the care of HIV patient’s intermittently in Southern Africa since 1990 and has given most of her professional life to the clinical care of these patients and help establish over 20 cervical cancer screening sites in HIV clinics. Approximately 15 years ago she became involved in clinical studies as a route to obtaining better treatment and care for HIV-positive patients She has also been very involved in training other doctors both medical students, residents and primary health care doctors, both in the USA and Johannesburg. With the advent of donor and government funding of antiretroviral medication, this care and research expanded into research and care of co-morbidities in HIV infected patients with strong interests in hepatitis B, TB and Human Papillomavirus. She has published over 50 articles in these fields and are seen as a leader in her field of interest and has been invited to speak at several international conferences, including CROI (Conference on Retrovirals and Opportunistic Infections) and Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC). She has been part of the Pink Ribbon Red Ribbon initiative, an innovative partnership to leverage public and private investment in global health to combat cervical and breast cancer set up by the George Bush Institute. She is also the current CHAIRMAN of the ACTG Women’s Health Inter-network Scientific Committee (WHISC) and a member of the Scientific Committee for the first five International Workshops on HIV & Women. She was the recipient of the University of the Witwatersrand Research Award in 2011 and 2013. In 2012 the recipient of the international Constance B Wofsy Women’s Research Award for the advancement of care and knowledge of women with HIV infection.
Dr Sharlaa Badal-Faesen is a senior medical officer. She holds a joint appointment with the University of the Witwatersrand in the Faculty of Health Science, Department of Medicine as a Senior Researcher with 8 years of research experience, as either site leader or sub-investigator in 20 clinical studies.
CRS Coordinator – Pauline Vunandlala is a qualified nursing sister with a Bachelor of Science Nursing degree and a specialisation in infection control. She has been the CRS Coordinator since 2003, and has been involved in clinical research as a study coordinator for 13 years
Pharmacist of Record – Coreen Barker is currently the Responsible Pharmacist of the onsite research pharmacy RightMed™. She has a Bachelor of Pharmacy Degree and a nine year record as Pharmacist of Record in numerous clinical trials.
Quality Manager – Teia Neil-Boss has been involved as an Internal Monitor in the quality Assurance Department of a clinical research site involved in numerous clinical trials.
CTU and CRS Data Manager – Vuyokazi Jezile has a BSc in Biological Science and has been Data Manager for the CRS ACTG site for 5 years.
CRS Community Liaison Officer – Tembi Kubheka is an auxiliary Social Worker who has been involved in clinical research at our site since 2005.
Regulatory Compliance Manager – Marlene Naidoo has been the Regulatory Manager for the CRS since 2004.
CTU and CRS Grant Manager – Simone Thomson has been with the organisation for more than ten years, of which 7 have been as Grants Manager, with responsibilities for multiple NIH/USAID/EU funded grants.
Investigators : Investigators have to oversee study protocol regulatory submission, site preparedness and implementation, as well as training of all staff.
Pauline Vunandlala talks about the reprieve study
German Federal Ministry of Education and Research
Following a joint application by the Clinicial HIV Unit, Wits Health Consortium, and the University of Munich LMU, a grant of €7 million was granted through the German Federal Ministry of Education and Research, to conduct this investigation.
The title of the investigation is TB-Sequel :Pathogenesis and risk factors of long term pulmonary sequelae defining the individual outcome and public health impact of TB disease.
This will be a multi-country, multi-centre observational cohort study, conducted at four recruiting sites in four African countries.
Key to this investigation in South Africa is the CHRU, Wits Health Consortium, represented by Professor Ian Sanne as Site Director, Dr Mohammed Rassool as Site Principle Investigator and overall project manager, and Dr Denise Evans who will be the co-ordinator of the research task : Socio-economic costs and impact of TB.
Professor Ian Sanne
Dr Mohammed Rassool
Dr Denise Evans
Also involved in Africa are NIMR – Mbeya Medical Research Centre, Tanzania; Instituto Nacional de Saúde, Mocambique; Medical Research Council Unit, Gambia.
Playing a key role are the German Centre for Infection Research and the AURUM Institute, with the Chief Investigators being Professor Michael Hoelscher, University of Munich, and Professor Gavin Churchyard, AURUM Institute.
Summary of the proposed research
The African continent today is emblematic of TB as a global health emergency with little known about the long-term sequelae. It is likely that TB patients from resource-constrained settings, who present with more extensive disease, are left with greater lung impairment.
This project aims :
• to advance the understanding of the clinical, microbiologic, and host immune factors affecting the long-term sequelae of pulmonary tuberculosis;
• to identify the most important factors that contribute to lung impairment, including the immunological response and genetic predisposition of the host and differences in the biology of the pathogen;
• to determine occurrence of reversible and irreversible costs and socio-economic consequences for patients;
• to facilitate novel interventions to restore and preserve overall health, well-being and financial protection in patients with TB.
The core of the current project is a prospective cohort of up to 1600 patients across four countries (Mozambique, Tanzania, South Africa and The Gambia), enrolled at the time of TB diagnosis, and followed until the end of the project.
The overall goal of the cohort is to describe and analyse the basis of the long-term clinical consequences of pulmonary TB, with a particular focus on lung injury. Patients will be enrolled during two years and followed up until the end of the project.
The project also includes a number of sub-studies:
• Pathogen and
General laboratory tests and TB specific tests, X-ray, physical examination and cardio-pulmonary assessment will be performed and the obtained clinical data will be recorded in study questionnaires. Biological specimens (blood, urine and sputum) will be collected and analysed longitudinally during the period of observation and after all specimens have been stored. In-depth analysis of the host immune response, focusing on potential mechanisms of lung damage, and molecular analysis of mycobacterial dynamics and markers in relation to pulmonary and microbiological treatment outcomes, including success, failure, relapse, reinfection and death will be carried out.
Socio-economic data, including patient costs, will be collected at the time of TB diagnosis, during treatment, at the end of treatment and during the follow up period, and analysed to determine how the risk of TB sequelae is linked with the socio-economic position of the patient, to establish the occurrence of catastrophic costs due to TB and the proportion of patients that resort to potentially irreversible socio-economic coping strategies.
Accurate data source will be maintained and confidentiality will be guaranteed. Data will be analysed according to the statistical plan. Results of the study will be disseminated to all relevant stakeholders through meetings, reports and publications.
September – Cervical Cancer Awareness Month
EFFECTIVENESS AND SAFETY OF THE HPV VACCINE IN HIV-1 POSITIVE WOMEN
Ongoing infection with Human Papillomavirus (HPV) can cause cervical and anal cancer. HIV-infected women are much more prone to HPV related genital disease, than HIV-uninfected women. The prevalence of genital HPV infections remains high in spite of the use of combination antiretroviral therapy (cART). Current cervical cancer prevention strategies are aimed at secondary preventions with early detection and treatment of symptoms due to HPV infection. However, these measures may not be accessible to women living in countries with limited medical resources and which thus experience disproportionate mortalities from cervical cancer. It is therefore critical to have primary prevention strategies.
The quadrivalent HPV vaccine was designed to prevent 4 types of HPV infection. Types 16 and 18 are the cause of most cervical and anal cancers, while types 6 and 11 cause most anogenital warts. The vaccine has been proven to be very effective in HIV-uninfected women, but to our knowledge no studies have been published to date on HIV-infected persons.
HIV-infected persons have been documented to have poor response to standard vaccinations such as hepatitis A and B. In this paper we presented data on the first 28 weeks on study to assess the effectiveness and safety of the quadrivalent HPV Vaccine among HIV-infected women aged 13-45 years.
The quadrivalent HPV vaccine was found to be safe and effective among HIV infected women aged 13-45 years who were seropositive for the HPV types included in the vaccine. For women seropositive for the given HPV types prior to the vaccination series, the vaccine induced a significant increase in antibody levels. This is a new finding for the HPV vaccine.
In conclusion, this study shows that the quadrivalent HPV vaccine directed against HPV types 6, 11, 16 and 18 is safe and effective in HIV infected women supporting the recommendations of the Advisory Committee on Immunization Practice and the World Health Organisation to vaccinate HIV-infected persons.
Publication : Oxford Journals / Oxford University Press on behalf of Infectious Diseases Society of America
Research Team :
Department of Infectious Disease, Brown University, Providence, RI – Erna Milunka Kojic, Susan Cu-Uvin
Centre for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA – Minhee Kang, Triin Umbleja
Division of Infectious Diseases, Icahn, School of Medicine at Mount Sinai, NY – Michelle S Cespedes, Judith A Aberg
HIV Research Branch, TRP, DAIDS, NIAID, NIH, Bethesda, MD – Catherine Godfrey
ACTG Network Co-ordinating Centre, Silver Spring, MD – Reena T Allen
Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand, South Africa – Cynthia Firnhaber
Infectious Diseases Department, Instituto de Pesquisa Clinica Evandro Chagas Fiocruz, Rio de Janeiro, Brazil – Beatriz Grinsztejn
Department of Medicine, University of California at San Francisco, CA – Joel M Palefsky
OHARA Virology, Microbiology and Immunology Dental Ecology, University of North Carolina, Chapel Hill, NC – Jennifer Y Webster-Cyriaque
Merck Research Labs, North Wales, PA – Alfred Saah
CERVICAL CANCER AND HIV
Edit of publication from HIV Nursing Matters
By : Dr Nomtha Mayisela-Mcuba, Sister Maureen Siminya – Right to Care Cervical Cancer Division, Johannesburg, South Africa; Prof Cindy Firnhaber – Faculty of Health Sciences, Department of Medicine, Clinical HIV Research Unit, University of Witwatersrand, Johannesburg, and Right to Care Cervical Cancer Division
In Africa cervical cancer comprises 23.3% of all cancers in women. Human Papillomavirus (HPV) is the main cause of cervical cancer and the reduced immunity caused by HIV is associated with a higher number of HPV infection and thus cervical cancer cases in HIV positive women. HPV infection is a common sexually transmitted infection.
Cervical cancer is one of the most common cancers among women globally and comprises approximately 12% of all cancers in developing countries. The most recent data indicates that an estimated 490 000 new cases of cervical cancer occur annually among women worldwide, of which nearly 80% are in developing countries where screen programmes are not well established and are poorly organised. In Africa cervical cancer comprises 23.3% of all cancers in women.
South Africa has the highest number of people estimated to be living with HIV/AIDS in the world and is one of the countries hardest hit by the epidemic. The prevalence of HIV among South African women attending antenatal visits in 2010 was 30.2%.
HPV is the main cause of cervical cancer, and the reduced immunity caused by HIV is associated with higher prevalence, incidence and persistence of HPV infection. HPV infection is a common sexually transmitted infection. Most affected women are infected shortly after their first sexual experience, with those under 25 years of age being the most prevalent.
Invasive cervical cancer (ICC) develops relatively slowly typically over a period of at least 10 years. However, studies have shown that HIV seropositive women tend to present 10-15 years earlier in age (35 years instead of 45 -50 years of age) than their counterparts, this being due to lower immunity.
Screening and Treatment of Cervical Dysplasia
The Pap smear has been the standard of care screening method throughout the world for decades and has been shown to reduce the severity and death rate of cervical cancer even in middle and lower income countries.
Pap smear results are interpreted in the following categories (Bethesda classification) :
1. Negative for intraepithelial lesion or malignancy;
2. Squamous cell abnormality;
3. Glandular cell abnormality.
The adequacy or suitability of the Pap smear results is crucial in order for the results to be considered satisfactory by the cytologist. Unsatisfactory results are often due to incomplete sampling of both key areas of the cervix. It is important, in order to achieve satisfactory results, that patients do not have blood or vaginal discharge, and women should be told not to have a Pap smear if they are menstruating. Sexually transmitted diseases should also be cleared before performing a Pap smear.
The reproductive history of a woman also provides key information to assist in the interpretation of results. As such women will be asked their age, dates of last menstrual cycle, any hormonal therapy (including birth control) and if they have been treated before for dysplasia (abnormal cells)
All HIV positive women should have a baseline Pap smear at the time of diagnosis of HIV.
After an abnormal Pap smear, a patient should be referred for a colposcopy, which allows abnormalities of the cervix to be seen and a biopsy is taken and sent to the laboratory.
Cervical intraepithelial neoplasia (CIN) or Cervical dysplasia is graded according to its pathologic process seen on the biopsy specimen – from CIN1 to CIN3. This represents the depth of disease found on biopsy, from CIN1 (where 1/3 of the cervical specimen shows dysplasia) to CIN3 in which the entire specimen shows dysplasia. There is an outpatient surgical procedure called LLETZ (Large Loop Excision of the Transformation Zone) which recommended for managing CIN2 and CIN3. In HIV positive women, untreated CIN1 is likely to persist, so screening and follow-up of these patients is very important.
Published: 25 August 2015 in “MEDICAL BRIEF”, africa’s medical media digest
Cervical cancer in Northern Cape ‘alarming’
Cervical cancer is wreaking havoc in many rural communities in John Taolo Gaetsewe region in Kuruman, Northern Cape. SABC News report that this alarming discovery was made through a cervical cancer awareness initiative in 2012 by a local doctor.
Through a pap smear, 3 300 women were tested for cervical cancer – 200 were diagnosed with cervical cancer and 64 cases were found to be at a critical stage. Doctor Tshegofatso Gopane says she embarked on the initiative after realising that not enough preventative care was done, especially in rural areas.
While cervical cancer is often spread during unprotected sex, poor health facilities and lack of knowledge have also contributed to the scourge and the report says, Gopane has called on government to intervene before it spirals completely out of control.
According to Gopane, cervical cancer is twice as prevalent in the John Taolo Gaetsewe District, as it is elsewhere in the world. “We have a general prevalence in South Africa which is about 26.6 per 100 000 women and the world average is about 15.3. So we are way above the world average. So clearly it means we have to be doing far more in terms of screening to prevent cervical cancer. In our project we found approximately 200 cervical cancer sufferers over a period of three years…”
The Department of Health says they are unable to comment at the stage as they still have to go and assess the matter.
FROM MAIL & GUARDIAN AFRICA :
Sex initiation camps, child marriages and polygamy, the lesser-known side of cervical cancer in Africa
Malawi has the highest rate of cervical cancer in the world, affecting about 3,684 women, with only about 500 of them surviving.
SINCE 2007 Africa’s First Ladies have put their weight behind the “Forum of African First Ladies against Breast, Cervical and Prostate Cancer” - and with good reason.
Cervical cancer is a major issue in Africa: it is the most common cancer in women in eastern and central Africa and there are 80,419 incidents every year with approximately 53,334 deaths. This makes it the region with the highest rate in the world. In fact in 2014, of the countries with the top 20 highest incidences of cervical cancer, 16 were African.
Malawi has the highest rate of cervical cancer in the world, affecting about 3,684 women, with only about 500 of them surviving. Next in line were Mozambique and Comoros.
Whilst there are plenty of challenges in preventing and curing cervical cancer - most notably late detection due to a lack of screening and treatment policy, strategies and programmes - there are also particularly worrying social circumstances which could be perpetuating the high rates of cervical cancer in Africa’s women and which also need to be addressed.
Sex initiation camp
In Malawi for example, despite the high rates of cancer incidents and low survival rates, in some parts of the country there exists a disturbing coming of age tradition that could be contributing to these high figures.
Young girls, some as young as eight, are taken to a type of “initiation camp” during their holidays by an older woman known as a an “anamkungwi” or “key leader”. Here they are taught about how to engage in sexual acts so that “when they return to their villages they should cook and clean—and have sex.”
Whilst all women are potentially at risk of developing cervical cancer at some point in their lifetime, according to the World Health Organisation, one of the most common risk factors for it include an early age of first intercourse.
This is because early age at first sexual intercourse has been associated with an increased risk of high-risk human papillomavirus (HPV) infection, a sexually transmitted infection, that in susceptible women is responsible for virtually all cases of invasive cervical cancer. According to the WHO, the prevalence of the cancer-causing HPV (strains 16/18) in women with cervical cancer in Africa is 69.7%.
Young girls are largely unaware of the risks and are being told to have unprotected sex making their chances of contracting HPV even higher. To make matters worse, many countries that have high rates of cervical cancer mortality and morbidity are also burdened with high rates of HIV.
Recent findings are showing that HPV infection doubles the risk of acquiring HIV in women and also, that HIV significantly increases risk of persistent HPV infections, which can lead to cervical cancer. This is particularly worrying in countries like Malawi where 10% of the population, aged between 15 - 49 (therefore more likely to be sexually active), is HIV-positive.
This is also particularly concerning on a continent where estimates show that child brides could rise to 15 million by 2030.
In Tanzania for example the youngest legal age for marriage for girls is 15 and the country is ranked 6th in Africa in terms of cervical cancer incidents. The age these child brides first have sex though could be far younger because even though the law dictates that a girl of 15 years and above is considered an adult, the Penal Code provides that persons of “African or Asiatic descent” may marry or permit marriage of a girl under 12 in accordance with their custom or religion if marriage is not intended to be consummated before she is 12.
Another country with high rates of child marriages is Mozambique, and once again this country has one of the highest incidences of cervical cancer in the world - coming in second behind Malawi. Here, 21% of girls are married by the age of 15 and 56% by the age of 18 - the 7th highest rate of child marriage in the world - and about 65 cases of cervical cancer per 100,000.
Multiple partners and polygamy
In an interview with Evan Sequeira, a specialist on obstetrics & gynaecology based in Kenya, he said that “even more than just the young age, it’s the multiplicity of partners that increases the risk of cervical cancer”. This because that increases the chances of contracting HPV and which is why doctors “suggest that girls between the ages of 9 - 26 have the vaccination against HPV, before their sexual debut”.
This is a particular problem for Africa since multiple partners, even in marriage, is more the norm than the exception. Polygamy is explicitly abolished in law just a handful of countries: Ethiopia, Guinea, Cote d’Ivoire, Ghana, Benin, Angola, Rwanda, Burundi and Tunisia. Polygamy is reported to increase the risk of cervical cancer two-fold, and the risk increases with an increasing number of wives.
So whilst the challenges related to high cost of immunisation, treatment, early detection and access remain, without addressing some of these root social situations, there will be little progress in effectively and sustainably combatting this silent killer.
August – NATIONAL WOMEN’S MONTH
WE INTERVIEW PROF CINDY FIRNHABER, A CHAMPION FOR WOMEN’S HEALTH
By Nora-Jean Freeman
August is National Women’s Month, and who better to chat to about afflictions suffered by women in South Africa than a doctor passionate about medicine in the field of infectious diseases, Prof Cindy Firnhaber. Prof Firnhaber is the Technical Director of the Clinical HIV Research Unit (CHRU) in Johannesburg, and is the Manager of Right to Care, another non-profit organisation which is involved in the implementation and improvement of care for HIV patients in South Africa.
Prof Firnhaber has been involved with HIV care for many years, with her passion being the improvement of health for women. “Women with HIV are more susceptible to cervical cancer, and from a younger age,” says Firnhaber. “The problem in the past has been a lack of accessibility for screening for cervical cancer, as most HIV centres did not have facilities to conduct pap smears. A real obstruction to treatment is the follow-up evaluations where there is an abnormal pap”. It has been thanks to Prof Firnhaber that this accessibility has increased and there are now an additional 25 centres in government and NGO clinics around the country able to provide this service.
In 2014 CHRU was awarded a grant by Merck, manufacturers of the vaccine, Gardasil, which is a three dose injection that guards against the strains of papillomavirus that can lead to cervical, and other cancers. The vaccine only helps as a preventative treatment, not if the patient already has (dysplasia)pre-cancer or cancer, but if administered after the dysplasia (pre-cancer) has been cut out, it is hoped that it will prevent reoccurrence. The Merck grant is to study the effects of this vaccine, to see if it will reduce the persistence or recurrence of the cancer after it has been cut out. The study has been running for ten months under Prof Firnhaber’s leadership, and so far a cohort of 65 HIV positive women have been recruited to participate in the study – 180 HIV women are needed to complete the study cohort. This is the first study of its kind in the world, and the reason for the importance of this study is that, if it is found that the vaccine will reduce persistence or reoccurrence, it is simple to administer (as opposed to vaginal treatment), and would therefore greatly reduce the number of women suffering from HIV related cervical cancer. “The problem with HIV positive patients with cervical cancer is that they require frequent follow-up, and we need to find a way to reduce the follow-up required.” Firnhaber says. Hopefully the study will reveal that the vaccine will fulfil this role.
Prof Firnhaber was born and raised in the USA, where she graduated at the University of Colorado. She has been married to Kurt Firnhaber, CEO of Right to Care, for 31 years and they have six adopted children. It was her stint volunteering as a medical officer at Musami Mission in Zimbabwe in 1990 that caused her to fall in love with, and settle in Africa.
PAMELA TSHANDU, A DRIVING FORCE IN THE CHRU COMMUNITY ADVISORY BOARD
The first thing that strikes me when I meet Pamela Tshandu, is her open, friendly face – I’m immediately drawn to her. August being Women’s Month I asked to interview a prominent female member of the Community Advisory Board (CAB) whose passion is women’s health. Pamela is just such a person, although her humility belies the fact.
Having been a member of the CAB since 2006, Pamela also holds a position on the Community Scientific Sub-committee, an international body whose policies are filtered down to the local CABs. Her involvement includes discussing protocols, and providing feedback to the communities. She advocates for cultural participation to ensure that clinical trials are efficient and timeous and that all populations are involved with none being marginalised.
Asked what drives her, Pamela says, “I am passionate about women issues, and believe that women do not have much of a voice, and we all know that much more women than men are infected with HIV. It is important that women are educated and empowered.” Pamela finds the women in the communities to be very open and receptive to the counselling offered by the CAB.
CAB members meet once a month and strategise what topic and which area should be focussed on in the following month. Outreach programmes are then planned accordingly. The CAB is made up of people from various backgrounds; teachers, social workers, health workers, traditional healers and trainers and each plays a role that suits their strengths. For example, in Youth Month, an educator will give talks on sexuality, HIV prevention etc at schools. Outreach programmes are made up of community visits, counselling, distribution of pamphlets, and provision of screening and health services.
Pamela is also a consultant to corporates where she offers HIV and Wellness Programmes for employees. She is a single mother of a 17 year old son … her biggest challenge!
June – MEN’S HEALTH MONTH
ETHICS AND MALE CIRCUMCISION
(Edited by Nora-Jean Freeman from presentation by Dr Khumbulani Moyo, Right To Care)
There are various reasons for circumcision, which is the surgical removal of the foreskin from the human penis – mainly religious or cultural, and obviously in some case, for medical reasons. There are several benefits of medical male circumcision (MMC) :
· Easier hygiene;
· Fewer urinary tract infections;
· Less risk of STDs including HIV (although practicing safe sex is still essential);
· Prevention of penile problems;
· Reduced risk of penile cancer;
· Reduced risk of cervical cancer in women.
Medical Male Circumcision and HIV
HIV can be transmitted through :
· Sexual contact;
· Pregnancy, childbirth, breastfeeding;
· Injection/drug abuse;
· Occupational exposure;
· Blood transfusion/organ transplant.
Risks associated with male circumcision :
· The frequency of severe adverse complications following neonatal, infant and child male circumcisions is 0%;
· The median frequency of any complication was 1.5%, with more occurrence in older children than in neonatal or infant cases;
· Complication rates in adult male circumcision are 2-8%, with the most common complications being pain, bleeding, infection, unsatisfactory appearance.
There are few well designed studies of sexual sensation following male circumcision, but most report either and improvement or no change.
· Governments need to ensure that safe, voluntary, informed, affordable male circumcision is available to all who seek it, without any discrimination.
· The male circumcision services must be respectful of medical ethics, offered and delivered in a culturally appropriate manner, and all necessary information on the risks and benefits must be provided.
· In the case of children, Government should consider the best interests of the children in designing and implementing male circumcision services.
· Health providers must obtain full and free informed consent from the patient before performing the male circumcision.
· Women should be involved as much as possible, without compromising men’s right to consent or privacy
· Health providers should ensure good quality, sanitised services are provided;
· Health providers must protect the privacy and confidentiality of individuals seeking male circumcision;
· Health providers should recommend HIV testing and counselling to all individuals seeking male circumcision services, but this should not be a prerequisite for performing the operation.
Men who have sex with men (exclusively)
· Available data do not indicate that male circumcision reduces the overall risk for HIV among SMS, but it is plausible, and some epidemiologic data suggests that there is partial protection from male circumcision during penile-anal sex. However, being circumcised no plausible HIV risk reduction benefit for the partner engaging in anal-receptive sex, which carries a higher risk for acquisition of HIV.
· MSM should be fully informed of these findings, and should be encouraged to continue to use other proven HIV and STD risk-reduction strategies.
· There is no evidence that male circumcision directly affects the risk of transmitting HIV from HIV positive men to women.
In summary …
· Male circumcision
Ø Reduces the risk that a man will acquire HIV from an infected female partner, and
Ø Also lowers the risk of other STD’s, penile cancer, and
Ø Infant urinary tract infection
Ø In female partners, it reduces the risk of cervical cancer, and several other conditions.
· Although male circumcision has risks including pain, bleeding and infection, more serious complications are rare;
· Uncircumcised, HIV-infected men and male adolescents are at increased risk for HIV acquisition through penile-vaginal sex should be counselled about the risks and benefits of male circumcision;
· Men to choose to be circumcised should be referred for surgical consultation and provided access to high quality, voluntary male circumcision surgical services.
June – NATIONAL YOUTH MONTH
GETTING IN TOUCH WITH HIV AND SA ADOLESCENTS
Interview conducted by Nora-Jean Freeman
In line with June being National Youth Month, I touched base with Dr Marnie Vujovic, Adolescent Programme Manager, of Right To Care, about the effect of HIV in South African adolescents. Following are the questions and very interesting answers :
NJF : What are the statistics for HIV in adolescents?
MV : The World Health Organisation defines adolescence as those between the ages of 10-19. In this age group there are 320 000 young people infected with HIV in South Africa.
NJF : Has there been an increase/decrease?
MV : Incidence rates have declined and prevalence is stabilising. However controlling incidence in young girls is a high priority. They are a high risk group and we need to be particularly concerned with prevention efforts in this population. Nearly a third of all new HIV infections in South Africa occur in 15-24 year olds with young women in this age group being up to eight times more likely to be infected with HIV that their male counterparts. There are various reasons for this, including the physiological vulnerability of girls. However age disparate relationships are an important contributing factor. In all other age groups mortality due to AIDS is decreasing however in the adolescent population the mortality has doubled, with 120 000 adolescents dying from AIDS in 2013.
NJF : What are your objectives in tackling this matter?
MV : In light of the severe vulnerability of adolescent girls to HIV infection, we need to move beyond what has been called ‘single-problem’ thinking to focus on combination interventions that deal with the multiple causes of risk behaviours. We need to tailor programmes to local contexts and circumstances and take behavioural, biological and structural factors into account if we are to develop effective intervention frameworks.
A key objective is to support the implementation of a well-targeted package of interventions that can address some of the most pressing challenges we face, for example worrying levels of sexual coercion and violence, high rates of teen pregnancy and so forth. Ensuring that these issues are addressed effectively calls for a co-ordinated, multi-sectorial response which can help strengthen the support systems available to young women at various levels for example family, school, and healthcare facility, and which meet individual needs for knowledge and education around issues such as sexuality and HIV risk.
NJF : Are you successfully achieving your objectives
MV : Helping young women build skills to increase personal and social competence, and providing them with health knowledge that is age-appropriate and contributes to health promoting decision-making is an important component of our programme. A 20-session support group resource that addresses issues ranging from contraception, to teen pregnancy, gender relations, self-esteem, HIV and treatment adherence, provides facilitators of facility, community and school based support groups with a means of addressing key health issues in a manner that is age appropriate.
Feeling supported, heard and provided with an opportunity to share worries and concerns with others of the same age can help to foster healthier outcomes. Support groups and adolescent adherence clubs are a way of achieving this. An important step has therefore been to provide technical assistance and mentoring to those wanting to start and run groups. We have made great strides across the provinces in this area.
We will be growing this package in the coming months to provide parents and caregivers with the skills necessary for open and honest communications around sexual and reproductive health. We will also be providing technical assistance to support the needs of educators engaging with learners around sexual and reproductive health and other health related issues, and in building an appreciation amongst healthcare providers of the special health challenges faced by positive and non-positive adolescents. A core component is the strengthening of linkages, for example between school, clinic and community-based organisations to ensure that young people are supported at every level.
The support group resource and its value for use with young people is currently being evaluated. A combination prevention package – “Catch them Young” is to be piloted shortly. Monitoring and evaluation will provide valuable insight into the extent to which objectives are met and will inform opportunities for scale-up.
NJF : How do they deal with stigmatisation in their communities
MV : Great efforts have been made to address the problem of stigma and discrimination in our communities. The National Strategic Plan on HIV, STIs and TB (2012 – 2016) states as one of five key objectives, the need to reduce self-reported stigma related to HIV by at least 50%. On World AIDS Day 2014 the call was made for “Zero Stigma” and “Zero Discrimination’’. In this regard the recently announced SANAC HIV Stigma Survey Results are interesting. Over 10 000 people of 15 years and older were interviewed in the study which found that whilst external stigma has decreased in South Africa, levels of internal stigma are still high. Over 40% of the study participant’s experienced internalised stigma with women and young people aged 15-24 years reporting the highest levels.
Adolescents find different ways of coping, one of the most common strategies being to avoid the possibility of stigma by keeping their status a secret and not disclosing beyond the immediate family. Concealment of status is generally regarded as a maladaptive coping mechanism, however the extent to which it is employed suggests that stigma is still a significant factor in determining how young people deal with HIV infection.
Having said this however, adolescents confront the reality of infection in different ways. Whilst some may not wish to disclose, others cope by educating their peers and through activism, for example speaking out against stigma at public gatherings.
Adolescents who access support structures, such as support groups or clubs that have enabled them to build a strong sense of self-worth are in a better position to deflect stigma. Apart from building coping skills that assist in dealing with stigmatisation in their communities, they benefit from supportive networks that foster interpersonal and communication skills.
NJF : What are the challenges that you face?
MV : There are a number of challenges, one of which is the capacitation of healthcare providers and educators to work with young people in a way that is sensitive to their needs, and which does not reflect their own personal values and attitudes regarding adolescent sexuality. An appreciation of adolescent development issues is important. However whilst many of us have a good understanding of adult and paediatric treatment, care and support, the same understanding is not always evident when it comes to the adolescent population.
Other challenges include difficulties experienced in getting groups started and ensuring sustainability. For example there are challenges around space, accessibility and the transport costs involved in regular attendance. In response to this we have put together a trouble-shooting guide that provides guidance on how to overcome some of these issues.
NJF : How do you convince youth that they are not immortal and that HIV isn’t discriminatory?
MV : Adolescence is a time of transition which is best appreciated by understanding what happens to young people physically, cognitively and socially at this stage of development. For example, in order to understand why adolescents may believe that they are invincible, it is important to recognise that a young person’s brain is still developing and is much less mature than the adult brain. The “personal fable” which reflects an “It can’t happen to me” orientation is an example of an immature brain structure that gives rise to feelings of invulnerability. This is not to say that adolescents cannot and do not develop new skills and behaviours. Cognitive functioning can be greatly improved when young people are encouraged and supported towards the development of skills such as decision-making and problem solving. The resource that Right to Care has developed for use in adolescent support groups is a good example of how a psycho-educational tool can help young people to evaluate their decision making.
CHRU COMMUNITY ADVISORY
The enthusiasm emanating from the CHRU Head of Counselling Department, Tshidi Lelaka and CAB Executive Secretary and Community Health Worker, Isaac Sedumedi, is contagious, and leaves me with a ‘warm fuzzy’ feeling about the work these individuals, along with the rest of the CHRU CAB members, are doing in their community.
The CHRU CAB’s focus is on educating the community about diseases in general, but specifically the most prevalent cancers (e.g. breast, skin, cervical), tuberculosis (TB) and of course, HIV/AIDS. Education methods are varied according to the reception received in the community. Educational flyers are produced and distributed, with recipients invited to ask questions, either immediately, or at a later stage, in which case they’re told where they can find the CAB representatives. In some cases, the strategy of doing door-to-door visits, or even engaging with a group of individuals playing board games outside a shebeen, has been found to be successful, with several taking up the invitation to visit the CAB base to ask questions.
The stigma that participants in Clinical Trials are ‘guinea pigs’ is a challenge that needs to be overcome. There are many benefits to participating in Clinical Trials, not least of which is the feeling of self-worth for having played a part in the positive outcome of research into a particular disease. Added benefits are medical care, and the difference made to family, friends and the community as a whole. The CAB representatives are tireless in their efforts to recruit more clinical trial participants – there are no risks, only benefits.
The CHRU CAB meets for a six-monthly strategy session, where they look at the monthly ‘theme’s coming up e.g. Cancer Awareness Month; the statistics of the various diseases, e.g. a rise in incidence of HIV in a certain area, etc, around which they shape their activities. For instance, in June, Youth Month, the CAB is concentrating on education at schools, with emphasis on HIV/AIDS awareness and prevention, although the outreach will only take place early in July owing to June being school examination month.
The CAB measures the success of its campaigns by the number of pamphlets distributed as a percentage of the size of the community, and increased questions and interest shown by the community. An important success would be an increase in willing clinical trial participants. In some communities there is a request for more services, such as TB screening, which the CHRU CAB facilitates on a regular, ongoing basis.
The CHRU CAB has three sites, the main one being based at the Helen Joseph Hospital, covering the Johannesburg city area, with the other two being at Witkoppen Hospital (covering Diepsloot), and Sizwe Hospital (covering Alexandra).
Asked how his role as Community Health Worker made him feel, Isaac responded, “It makes me feel I am needed, and an important person to the community. I believe I am making a difference in terms of education and growth in my community. People look up to me and show me respect. People can testify that I am doing a good job, and are proud of what I’m doing.”
March – (Press Release) High-dose rifampicin demonstrates an improvement in TB response rates
(South African scientists and patients involved)
Nijmegen, Netherlands / Munich, Germany 2 March 2015: At the annual Conference on Retroviruses and Opportunistic Infections (CROI), the Pan-African Consortium for the Evaluation of Antituberculosis Antibiotics (PanACEA), presented the results of its most recent phase IIb study (MAMS-TB-01). The most exciting finding from the study is that high-dose rifampicin results in faster killing of TB bacilli during treatment, compared to the current standard treatment.
The standard WHO-recommended TB treatment regimen (2 months of daily ethambutol, isoniazid, rifampicin and pyrazinamide followed by 4 months of daily isoniazid and rifampicin (2EHRZ/4HR)) involves taking the drugs daily for 6 months. This can make adherence to treatment hard, and has substantial costs to the health system and patients. Shortening the length of time treatment needs to be taken for, may help to reduce the burden on health systems, the costs of treatment, and make treatment easier for patients. PanACEA MAMS-TB-01 was set up to address this.
High-dose (35mg/kg) rifampicin, in combination with standard dose of isoniazid, pyrazinamide and ethambutol, showed a significant shortening of time to culture conversion with a covariate-adjusted hazard ratio of 1.75, 95% confidence interval (1.21-2.55) over the 12 weeks of experimental treatment. For comparison to previous TB trials, covariate-adjusted hazard ratios compared to control over 8 weeks were 1.99, 95% confidence interval (1.21-3.29). It was not possible to culture TB bacilli in sputum by 8 weeks in 56% of patients on the 35mg/kg arm compared to 42% of patients on the standard of care arm. These proportions were 80% and 70% respectively after 12 weeks. Culture on solid media, which was a secondary endpoint, showed a similar although less marked result.
Chief Investigator Martin Boeree (Radboud University Nijmegen) says: “This is the largest reduction in time to culture conversion seen in any previous TB trial, to our knowledge. High doses of rifampicin may be an important component in shorter TB regimens in the future.”
The arm containing moxifloxacin with rifampicin 20mg/kg, pyrazinamide and ethambutol showed a borderline significance, hazard ratio 1.42 (95% confidence interval, 0.98-2.05) for improvement over control.
In an interim analysis conducted in early 2014, recruitment to both arms that included the new drug SQ109 were terminated, as it was clear that both regimens would not meet the predetermined hazard ratio of 1.8 using liquid culture and thus were unlikely to result in substantially improved regimen. Patients on these arms remained on treatment and in follow-up, and the now available data confirms the interim analysis decision.
Preliminary analysis of safety events showed no differences in side-effects in any of the arms as compared to control.
The MAMS-TB-01 trial enrolled 365 patients from 7 sites in Tanzania and South Africa in only 11 months. It used an innovative adaptive clinical trial design that allows several new regimens to be compared to the current standard, and incorporates interim analyses that allow for regimens that show little treatment shortening potential to be excluded from the trial at an early stage.
Data on treatment up to week 26 and post-treatment follow-up will be analyzed and reported together with the results mentioned above in the main publication.
“We would like to thank our main donor, the EDCTP, for its support of this African-European consortium,” said Michael Hoelscher, sponsor representative. “We are pleased to have optimized one potential component of a future treatment-shortening regimen. This is, however, only the beginning of a series of phase I and II studies that will evaluate in a systematic manner at least 5 novel and improved TB drugs. “
In South Africa contact:
Prof Ian Sanne, Divisional Director, Clinical HIV Research Unit, Wits Health Consortium T +27 82 457 5223 email@example.com or Michelle K Blumenau, Turquoise PR & Marketing Communications T +27 83 273 9891 firstname.lastname@example.org
Note to editor:
It is the mission of PanACEA (Pan African Consortium for the Evaluation of Antituberculosis Antibiotics) to develop TB regimens that significantly shorten treatment duration. The PanACEA consortium is a partnership of 11 African and 7 European institutions.
African institution partners are:
• University of Cape Town Lung Institute(Rodney Dawson);
• University of Stellenbosch (Andreas Diacon);
• University of the Witwatersrand (Ian Sanne);
• The Aurum Institute (Gavin Churchyard);
• University of Zambia, Lusaka, Zambia (Shabir Lakhi); NIMR–Mbeya Medical Research Centre, Mbeya, Tanzania (Nyanda Elias); Ifakara Health Institute– Bagamoyo Research and Training Centre, Bagamoyo, Tanzania (Lilian Tina Minja); Swiss Tropical and Public Health Institute (Klaus Reither); Kilimanjaro Clinical Research Institute, Moshi, Tanzania (Gibson Kibiki); Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon (Abraham Alabi); Kenya Medical Research Institute, Nairobi, Kenya (Evans Amukoye); Makerere University, Kampala, Uganda (Alphonse Okwera, Moses Joloba).
January – Skin Cancer Awareness Month
Kaposi Sarcoma (KS) is a skin lesion most commonly linked with HIV/AIDS. There are three other sub-types apart from AIDS related KS, namely Classic KS (affects men of Mediterranean descent); African endemic KS and KS in iatrogenically immunosuppressed (organ transplant) patients. The African endemic KS and AIDS related KS are the most aggressive forms, the latter of which quickly develops from a mild rash to plaques and nodules found mostly on the upper body, face and mouth.
KS is a cancer of the blood vessels, which usually manifests as skin lesions. But it can presentas lesions in other organs; including the gut, mouth cavity, lungs etc. Most people with KS dismiss it as a mild rash to start with, and therefore don’t seek medical assistance early. As such, most of those who do seek medical attention, do so at a more advanced stage of KS. There is limited knowledge of KS in the community and thus there is a need for education and awareness in this area. The CHRU has developed a pamphlet on KS to assist counsellors and the Community Advisory Board (CAB) to share the knowledge with the community.
KS is treatable and can be curable if found early enough. The AIDS Clinical Trials Group is looking at treatment options for people presenting with HIV related KS. One of the studies is A5264 under the guidance of Principle Investigator, Dr Noluthando Mwelase, of the CHRU. Dr Mwelase says that the main challenge presented to the unit is the recruitment of patients into this study. As mentioned earlier, the appearance of a rash or lesions is not taken seriously enough for patients to seek medical help early. And there is lack of knowledge in the community regarding this disease. The Unit works hard to proactively seek HIV patients with KS to include in the study.
Methods of recruitment:
• Counsellors visiting patients at HIV and Dermatology clinics to try to identify and recruit KS sufferers;
• Community Advisory Board (CAB) does healthcare awareness campaigns to educate the community regarding KS and encourage people to seek medical attention early.
on the study; they sign a letter of consent and are monitored on an ongoing basis. The group is split into two sub-groups. The first sub-group will receive Chemotherapy together with anti-retroviral (ARV) treatment from the start of study; the second sub-group starts only with
The recruited patients receive a full explanation of what the study is about, what to expect (benefits and potential risks) and study treatment. If the patient is agreeable to participate on the study; they sign a letter of consent and are monitored on an ongoing basis. The group is split into two sub-groups. The first sub-group will receive Chemotherapy together with anti-retroviral (ARV) treatment from the start of study; the second sub-group starts only with ARV treatment, with chemotherapy being introduced at a later stage if indicated. The aim is to compare the two subgroups to see which with treatment option works best in treating early KS. However, with the shortage of participants presenting with early stage KS to health care centres, this study is severely hampered.
Below are statistics from pre-screening KS participants from May 2012 to May 2014. In total all 95 KS patients were referred for the study many of whom could not be on the study due to different reasons.
|Reason for Failure
|Already on Art
||these patients were on ART for 2 months - 8yrs
|Less than 5 KS lesions
||other skin conditions e.g. PPE, folliculitis
||did not want to be part of study/ did not want medical treatment / did not want to do HIV test
||renal failure, thrombocytopenia