Community calls for improved ethical practices in research

COMMUNITY CALLS FOR IMPROVED ETHICAL PRACTICES IN RESEARCH

At the just concluded project organised by the New HIV Vaccine and
Microbicides Advocacy Society (NHVMAS) in collaboration with The
Initiative for Equal Rights (TIER), Christ against Drug Abuse Ministry
(CADAM), Safehaven Development Initiative and International Rectal
Microbicides Advocacy (IRMA) Nigeria, and with funding support from
Sidaction, France, participants specifically requested that the
outcome of the meeting should be widely.

The meeting conveyed members of the community resident in Lagos,Ilesa,
Osogbo, Ife, Ifon in Ogin State, Ibarapa in Ibadan, Jos and members of
vulnerable communities (FSWs,MSM, IDUs, PLHIV) to discuss about
research and how to improve research conducts within these
communities. Also, two  roundtable dialogues that facilitated
discussions between research stakeholders (researchers, bioethicists,
research sponsors, policy makers, journalists, and community members)
were conveyed in June and September 2012 in Lagos and Abuja
respectively also.

The following were the objectives of the meeting:
(i) to identify priorities considerations by research communities when
HIV research is conducted in their community
(ii) identify considerations that should be of concern to ethics
committees during protocol review
(iii) identify measures to take to empower communities to become more
directly engaged with HIV treatment and prevention research conducted
within their communities.

The community made several observations with respect to informed
consent process, community engagement in research and standard of care
in research. Please find attached the summary of the outcome of the
meetings. Some of the findings and recommendations are enumerated
below:

1.0 Informed consent and other ethical considerations in research
•      Ethics committees do not provide proper oversight function for
the researches they approve.
•      Negotiation of research reimbursements often takes place at
the time of research implementation.
•      Poor information dissemination about the research to the
research community and individuals involved with a research.

2.0. Community engagement in research
•      There is little research literacy efforts on the field.
Communities therefore only respond to what researchers share with
them.
•      CSO engagement is often mistaken for community engagement.
•      Ethics committees do not monitor researches they approve to
ensure that community engagement happens in the field.

3.0.    Concern on standard of care
•      Some research participants in hospital based research are made
to bear the cost of research related investigations.
•      Study participants may be asked to defray the cost of
managingchronic illnesses that develop during the course of
implementing
researches with long duration the onset of which researchers consider
not to study related.

4.0.    Other concerns
•      There is minimal government investment in HIV research
conducted in Nigeria.
•      A number of HIV researches are repeated due to poor
coordination of the field.
•      Often, researches do not inform intervention and policy formulation

B. RECOMMENDATION
• Informed consent form should be available in local languages for
easy understanding. Verbal translation of English to local language is
not acceptable.

• Ethics committees should monitor all the researches they approve
including monitoring of the informed consent process. The community
considers it unethical not to do so. The current level of research
monitoring is extremely low and very unacceptable. This gives room for
research participants’ abuse. Unfortunately the vulnerable – including
those that do not understand their rights when it comes to research –
are preys to multiple unethical practices including paying for
research related investigations in disguise for treatment.

• Community engagement should happen throughout the lifecycle of
research – from the design to the dissemination stage in line with the
requirements of national ethics code and national HIV research policy.

• NGOs need to be funded to actively support community research
literacy so as to promote informed community engagement with research.
Researchers are encouraged to engage CSOs in all community based
research as community educators. This would encourage mutual trust for
the research and sustained community education on the subject matter
even after the project is concluded.

• CSO engagement should not be considered as community engagement.
Researchers should work with CSO as gatekeepers only: discussion and
recruitment of research participants should be done directly from the
community after duly providing information to the community.

• All research should make effort to promote research literacy. Ethics
committees should see that the information sheet for all the research
they approve should have an educational component. This way, at the
minimum, research participants get to learn something about the
research subject.

• The  standard of care package for research participants should align
with global standards.

• Researchers should make significant efforts to facilitate mechanisms
that will increase the translation of their research findings to
policies and programmes.

Cure for HIV: A prize to keep our eyes on

The call for a cure was launched in February 2011 by the president-elect of the International AIDS society and Nobel Prize winner Françoise Barré-Sinoussi. The article by Lewin et al (2011) provides an excellent overview of possible promising strategies for cure using an ‘infectious disease model’ (sterilising cure model), in which HIV and all HIV-infected cells would be eliminated, or a ‘cancer model’ (functional cure model), in which there would be long-term health in the absence of treatment accompanied perhaps by low levels of HIV in the blood.

The three challenges to finding such a cure are:  (i) viral latency in resting CD4 cells (HIV lying low with its genes turned off, unaffected by antiretroviral drugs or host immune responses), (ii) residual viral
replication (with low amounts of HIV reseeding the blood stream), and (iii) reservoirs (hiding places such as the gastrointestinal tract, the brain, and the genital tract). Latently infected cells are rare (1 in 100,000 to 1 in a million) so using promising strategies such as the histone deactylase inhibitors used in cancer that could turn HIV genes on or cytokines that could activate latently infected cells to replicate so that antiretroviral therapy could take effect, may haveindiscriminate effects on uninfected cells since these therapies will no select for only infected cells. The potentials for side effect will therefore be a challenge. Gene therapy with zinc finger nuclease to reduce CCR5 expression and block HIV docking is another possibility and is currently being explored in some ongoing studies.

The famous ‘Berlin’ HIV-positive patient who was treated twice for acute myeloid lymphoma with a pre-transplantation conditioning regimen, including total body irradiation, followed by transplantation of stem cells from a special donor is a point in time study of the possibility of a HIV cure (Allers et al, 2011). This patient had to undergo bone marrow transplantation twice due to leukemia. That bone marrow stem cell donor was homozygous for the CCR5Δ32 deletion (i.e. both genes coded for this deletion), meaning that his or her HIV target cells did not allow HIV to complete docking after linking with the gp120 receptor. Donor-derived memory CD4 cells replaced the recipient’s cells reaching the normal range over a 2-year period and HIV has remained undetectable in gut tissue, brain, bone marrow mononuclear cells, and peripheral blood cells (residual viral replication sites). The patient remains susceptible to HIV infection
if he is exposed to CXCR4-tropic HIV. It is impossible to analyse every cell in living humans so proving viral eradication is impossible. However, given that HIV has not reappeared after 3 years without antiretroviral therapy, the authors conclude that a cure has been achieved. With stem cell transplantation carrying a mortality of up to 30%, this procedure is not practical but this story does give hope that one day we will find a cure for HIV.

While we wait and hope for a cure in our lifetime, universal access to antiretroviral treatment remains top priority and an agenda for all nations in view of the evidence to show that treatment could also serve as a prevention tool. These are early days to be talking about a cure. But community engagement in this basic/clinical science challenge is key—this is one prize we need to keep our eye on.

(Adapted from the edits of Cate Hankins – Scientific Adviser for UNAIDS and Editor for HIV This week – Issue 91)

References:
1. Lewin SR, Evans VA, Elliott JH, Spire B, Chomont N. Finding a cure
for HIV: will it ever be achievable? J Int AIDS Soc. 2011 Jan 24;14:4.
2. Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E,
Schneider T. Evidence for the cure of HIV infection by CCR5Δ32/Δ32
stem cell transplantation. Blood. 2011 Mar 10;117(10):2791-9

Rethinking the risk factors for sexual risk among young persons: the evidence from analysis of South Africa and the USA

The evidence shown by the study by Pettifor AE et al throw up VERY important findings as we think about addressing the HIV risk of young people in Africa including Nigeria. As noted by Cate Hankins, the Scientific Adviser for UNAIDS, the comparison of two nationally representative surveys of young people by the authors of the study (see abstract below) starkly underscores that behaviour is not the sole determinant of HIV risk. South African young people had their first sex at a later age, have fewer sexual partners, and practise more safer sex than their American counterparts. How then can the more

than 10-fold difference in HIV prevalence be explained?

Cate’s first thought goes to larger age gaps between sexual partners for the two countries. In South Africa, it is evident that women have older sex partners when compared to what is observed in the US. This means sexual mixing with older partners who can act as a bridge population to younger cohorts…. but there has to be more to it than that.

Also, in South Africa, male circumcision levels are far lower, herpes simplex 2 infection levels are higher, genital tract inflammation is higher, co-infections (tuberculosis, helminths) that can increase viral set points are more common, and the prevalence of the CCR5Δ32 coreceptor is lower.

As Cate rightly notes, social determinants such as gender power imbalances, poverty, coerced sex and rape, lack of youth friendly services, and stigma are likely playing important roles in the observed higher HIV risk observed amongst young persons in South Africa. There are however need for further studies to pull together how all these factors truly increase the risk of young persons to HIV.

The study by Pettifor et al was based on surveys conducted in 2003 (South Africa) and 2001-2 (USA) using somewhat different methodologies. Yet the findings give South Africa something to work with: they gradually are better understanding their epidemic and learning how to use their limited resources cost effectively to address their epidemic. Lets take a cue from this study and pull the multiple data we have in the country together – the many, many sentinel survey reports including the upcoming NARHS 2011 study – to learn more about the true drivers of the Nigerian epidemic. Lets pay more attention to the youths as efforts at cubbing the epidemic at this level will significantly drive down our incidence. Secondary data
analysis like the one done by Pettifor et al may well be most welcome
for a country like Nigeria

Morenike Ukpong

 

The need to discuss a rectal microbicide agenda for Nigeria

I am in Ethiopia and I sat down through a 2 days session listening to data presentation about the HIV context and situation in Africa. Asusual, I was all out to hear and listen about what the data was saying

about Nigeria.

One key issue was the place and role of anal sex in driving the HIV epidemic in Nigeria. This can no longer be ignored. As per statistics, yes there are Statistics from Nigeria that shows that anal sex is
practiced by 12% of public secondary schools students (Bamidele et al, 2009). There was another presentation that showed that 12.1% of university students  and 15.2% in-school adolescents in Northern Nigeria practice anal sex.

What does this evidence mean? Anal sex is known to be the highest risk form of sexual transmission of HIV infection with approximately 14 (10 – 20) times higher risk of HIV transmission when compared to
penile-vagina sex. The probability of HIV infection transmission in penetrative anal sex is about 1.4% per sex act both in heterosexual and homosexual relationships.

There are evidence to show that about 10% of women and 14% of men in the general population practice anal sex with condom use being low during this sexual practice as a result of multiple erroneous believes including believes that anal sex is safer than vagina sex. Request for anal sex by clients of FSW is high (not a negligible proportion) with men paying higher to have anal sex with sex workers (male and female) for many reasons (more pleasurable, tighter, gets to ejaculate faster and for prevention of STIs, and it is cleaner as fewer people engage with this ‘hole’).

And you know what? For women, the risk is highest as they will always be the receptor in either vagina or anal sex. Maybe this be an unidentified driver of the HIV epidemic amongst females. Study do show
that many women engage in anal sex during pregnancy, menstruation, for pleasure and a whole host of other reasons. Yet evidence show that as receptors of sex (anal or vagina) their risk are increased.

What do we need to do? I personally think there is the need to discuss more openly about the risk of anal sex. Many times we discuss sex during our sex, sexuality and HIV education in a way that
unconsciously limit our verbal and non verbal communication about sex to vagina sex. Our discussion around sex must become broader to encourage public understanding of the multiple forms of sexual
practices (vagina, oral, anal) and the risk of HIV infection associated with all the forms of sex. I had personally been engaged in a public discuss with university students where a major player in the
HIV field actually noted in her discuss that anal sex was safe. Anal sex is associated with high risk and we need to get the public to understand this. Our family life education series need to identify
this and share this information in schools in view of the statistics that show that despite under-reporting, 12% -15% of adolescents practice anal sex.

Do we discourage anal sex? People have choices. We need to promote safe practices. Anal sex and howbeit all sexual practices need to be made safe (use dental dams for oral sex, condom for vagina sex, and condom + lubricants for anal sex and vagina sex with the vagina is dry). These are existing tools and are effective. We need to advocate for increased distribution and access to lubricants in the same spaces as condoms can be accessed. And for the future, there is the rectalmicrobicide.

What is rectal microbicide? It is a product currently being developed. When developed, it will be available as a lubricant, gel, douche or an enema that can be used by women and men to reduce the risk of HIV transmission during anal sex. It would be able to offer some level of protection from HIV infection even in the absence of a condom. It would also serve as a backup protection if a condom breaks or slips
off during anal intercourse. For more information, visit www.rectalmicrobicides.org

Some Nigerian researchers are very much interested in conducting rectal microbicide research. Lets support this process. Lets speak up for rectal microbicide in Nigeria. Lets discuss about this during our
World AIDS day activities as we ensure a AIDS free generation.

Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study

Renee Heffron, Deborah Donnell, Prof Helen Rees, Connie Celum, Nelly Mugo, Edwin Were, Guy de Bruyn, Edith Nakku-Joloba, Kenneth Ngure, James Kiarie, Robert W Coombs, Jared M Baeten

Lancet Infect Dis. 2012 Jan;12(1):19-26. Epub 2011 Oct 3.

Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. Heffron and colleagues aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, they followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, they compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. Cox proportional hazards regression and marginal structural modelling were used to assess the effect of contraceptive use on HIV-1 risk. Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6–24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06–3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8–24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12–3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, andabout the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1.

For abstract access click herehttp://www.ncbi.nlm.nih.gov/pubmed/21975269

Use of injectible hormonal contraceptives and risk of HIV-1 transmission

There have been suggestions about the increased HIV infection risk with the use of  hormonal contraception. Prior to this study, observational studies have suggested a possible link with observed increased risk of HIV infection with the use of hormonal contraceptives. This study of HIV serodiscordant couples , while not specifically designed to examine this issue, further provides evidence to the possible link between the use of ijectable contraceptive and increased HIV risk. The study showed a doubling of the risk of HIV acquisition for HIV-negative women using injectable DMPA (depot-medroxyprogesterone acetate) and a doubling of the risk of HIV transmission from HIV-positive women using DMPA to their seronegative partners.

Cate Hankins, the Scientific Adviser for UNAIDS notes that ‘while contraception improves the health of women and children worldwide, and plays a crucial role in helping women with, or at risk of, HIV infection to prevent the adverse social and health consequences of unintended pregnancies, it is important to examine the meaning and implication of these evolving evidences. In view of this, WHO and partners are convening a technical consultation in early 2012 to re-examine the totality of evidence on the potential effects of hormonal contraception and of intrauterine devices on HIV acquisition, disease progression, and infectivity/transmission to sexual partners. The need to conduct randomized controlled trials to determine whether hormonal contraception increases the risk of HIV acquisition in women and/or of HIV transmission to men will be assessed.  In the meantime, we need to reinforce the importance of correct and consistent condom use, regardless of whether another method of contraception is being used. It is and has been for decades the ‘dual protection’ message’.

While we wait for the outcome of the WHO consultative meeting, it is important for those in the field to be aware of the evolving evidence and its potential implications in the design of HIV prevention services for serodiscordant couples at the least. Below is the abstract of the study. 

Implication for HIV prevention research protocol development and review: It may be important that when researchers plan HIV prevention studies, it will be important to factor the role that injectible hormonal contraceptives can plan in HIV acquisition during the data analysis process.