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Implementation research

Failed PrEP trial (VOICE) participants give reasons for their poor adherence

13 Nov, 14 | by Leslie Goode, Blogmaster

Despite indications of the acceptability of Pre-Exposure Prophylaxis (PrEP) among certain populations (MSM in London (STI/Aghaizu & Nardone) 2013, and Australia (STI/Holt & De Wit) 2012), the extremely varied results that have emanated from large studies seeking to determine its efficacy and effectiveness as a preventative intervention remain a concern.  To name the most important examples, levels of risk-reduction were estimated as follows: CAPRISA 004 – 39%; iPrEX – 44%; CDC TDF2 – 62%; Partners-PrEP – 75%; FEM-PrEP – 0%; VOICE– 0%.  The reasons for this variation have been the topic of a number of contributions to this blog (especially: STI/blogs/Hendrix & Bumpus; STI/blogs/Haberer & Bangsberg), with consensus tending towards the poor adherence of study participants.

Last week in Cape Town results were briefly reported from a sub-study (VOICE D) of one of the less successful of these trials (VOICE). Microbicide Trials Network’s (MTN) VOICE study, discontinued in 2011, trialled daily tenofovir, in the form of vaginal gel or tablet, in 5,029 (mostly young) women from a representative range of sub-Saharan countries – S. Africa, Zimbabwe and Uganda. On the basis of self-reporting measures in the original VOICE trial, levels of adherence to the tenofovir regime had been estimated at 90%.  However, blood samples taken from participants found evidence of the drug in less of a third of the participants in the tablet arm, and less of a quarter of the participants in the gel arm, of the study.

After the closure of the VOICE study itself, the sub-study, VOICE D, engaged 127 former VOICE participants in in-depth interviews at which they were challenged with evidence of their poor adherence – with a view to stimulating frank discussion. When confronted with the evidence of blood tests, poor adherers initially expressed surprise and disbelief. Yet, according to the report, the aim of engaging frank discussion would seem to have been met.  The reason most frequently given was fear of the side effects of the drug, fuelled by peer participants and relatives and by the negative attitudes of community members.

Current trials of PrEP have re-evaluated and strengthened efforts to enhance adherence in the light of previous failures.  These include: the Follow-on African Consortium for Tenofovir Studies’ FACTS 001 (tenofovir gel before and after sex), the MTN’s ASPIRE and the International Microbial Partnership’s Ring Study (both the latter of vaginal ring releasing the ARV drug dapivirine) (MTN Trials). It is interesting that the Partners-PrEP study incorporated intensive “adherence interventions” for participants whose adherence levels fell below 80% (STI/blogs/Haberer & Bangsberg).

However, the VOICE D results may have implications for the usefulness of PrEP interventions more generally. At the very least, they discredit any idea that PrEP is able to offer a panacea. The value of PrEP, relative to other preventative interventions, is a contentious issue.  STI/Mukandavire & Vickerman (2013), for example, conclude that a scale-up of condom use is in most circumstances likely to be more effective than PrEP, but that PrEP could have a specific application in the case of female sex workers. STI/Verguet & Walsh (2012) see a future for PrEP in sub-Saharan countries with high HIV prevalence and without circumcision practice, such as S. Africa.  STI/Ying & Barnabas (2013) see targeted PrEP as a cost-effective addition to ARV.

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Cultural constraints on the uptake of voluntary medical male circumcision in Eastern and Southern Africa

23 Jun, 14 | by Leslie Goode, Blogmaster

My previous blog spoke of the recent PLoS-Medicine Collection on the progress of a UNAIDS initiative for a five-year scale-up of Voluntary Male Medical Circumcision (VMMC) for HIV prevention in 14 high priority Eastern and Southern African countries.  Among the papers, Ashengo & Njeuhmeli (A&N) and Macintyre & Bertrand (M&B) deal with what the authors of the Collection Review identify as one of the two major obstacles to deployment of the initiative: the insufficiency of demand, especially amongst older (aged 25+) men.  They consider the cultural and social constraints on demand, as these are reflected in the very different cultural contexts of Zimbabwe and Tanzania/Iringa Province (A&N) and Kenya/Turkana County (M&B).

In Tanzania, where circumcision as a cultural practice is widespread, A&N’s figures show a proportion of older men presenting for VMMC through to 2013 of c.6%.  Very few of these were reached through campaigns, as opposed to routine services.  In Zimbabwe, by contrast, where circumcision is not widely practised, the proportion of aged 25+ circumcised through the program was c.33%.  There was much less difference in the age profiles of those accessed by campaign and routine service modalities.  Whereas, in Tanzania there is a cultural perception “that male circumcision is most appropriate before or during puberty” (and older men do not come to VMMC services in a setting that includes mostly adolescent clients) – in Zimbabwe there is less difference between age groups, either in respect to numbers circumcised or preferred mode of access.  Intriguingly, this suggests that the existence of a cultural norm of circumcision may be more of an obstacle than an asset where older clients are concerned.  Of course, this contrast has to be set in the context of the overall advantage in terms of HIV/AIDS prevention conferred on countries like Tanzania by the existence of the cultural norm.  On difficulties of demand in Zimbabwe specifically, see STI/Kaufman & Ross.

A further insight into the potentially negative impact of existing cultural practice is cast by M&B.  Focus group discussions and in-depth interviews in the rural, traditionally non-circumcising area of Turkana County, Kenya, draw attention to perceptions of circumcision amongst older men that are not favourable to their widespread up-take, especially by the older age-group.  The first is the identification of circumcision with the cultural values of other (potentially hostile) groups.  Interestingly, the negative impact of the perception of the practice as imposed from outside, or else non-traditional, has been demonstrated in other non-circumcising cultures (STI/David; STI/Madhivanan & Klausner). The second is the understandable perception that HIV/AIDS is a “new” problem among young urban dwellers (most Turkana sufferers belong in this category) and that circumcision, as a response to this “new” problem, is appropriate for the young, not for older, rural people (see also responses in a study on the acceptability of VMMC in Rwanda: STI/Mbabazi).

The impression that emerges from both studies is that the existence of a cultural practice of circumcision amongst certain groups in a region does not always confer an advantage where potential clients for VMMC are in the older age groups (25+).  In particular, good uptake of VMMC services by adolescents may actually prove an obstacle for older men, reinforcing the cultural perception of VMMC as primarily for younger men.  In this situation service providers may face a choice between strategies that yield the greatest number of circumcisions through an exclusive focus on the younger age-group, and strategies designed to attract a wider diversity of age-groups.

 

The roll-out of UNAIDS voluntary medical male circumcision programmes in sub-Saharan Africa: Is it working?

18 Jun, 14 | by Leslie Goode, Blogmaster

Voluntary medical male circumcision (VMMC) has been demonstrated to reduce HIV acquisition by 60% or more.  WHO and UNAIDS have recommended that VMMC form a part of comprehensive HIV prevention programming in regions of high prevalence, such as sub-Saharan Africa.  Mathematical modelling suggests that the achievement of 80% VMMC coverage within 5 years in 14 countries in Eastern and Southern Africa would avert 3.36m new HIV infections. In the light of this the UNAIDS Joint Strategic Action Framework (JSAF) has set out the goal of circumcising 20.2 million men in five years across these countries. The challenges this represents on both the supply and the demand side are comprehensively discussed by STI/Gray & Kigozi.

A recent PLoS – Medicine Collection considers the progress thus far, and through to 2016, of this initiative.  The Collection Review (Sgaier & Njeuhmeli (S&G)) offers a useful survey. The year preceding the JSAF and the first two years of the initiative have seen yearly VMMC of 0.88m, 1.7m, and 2.9m respectively. If we assume current rates of growth, this would give a cumulative total of 17.5m circumcisions by 2016 – about 3m short of the 20.2m target; if we assume no growth, the cumulative total for this period would be 13.7m.  The scale-up of VMMC over the last three years has been impressive. Still, rates of year-on-year growth have fallen from 109% (2011) to 72% (2013).  S&G identify two factors impeding the achievement of the JSAF goal: first, insufficient funding, largely as a result of the failure of international donors to step in alongside the US President’s Emergency Plan for AIDS Relief (PEPFAR) (which currently bears 80% of the cost); second, the lack of – or failure to create – sufficient demand for VMMC in the targeted countries, especially amongst the older element (i.e. aged 25+) of the population.

The 13 papers in the collection deal with issues around supply of VMMC – such as maintaining quality of service during scale-up (Jennings & Njeuhmeli; Rech & Bertrand; Rech & Njeuhmeli) and optimizing efficiency in service delivery (Rech & Njeuhmeli;  Mahvu & Bertrand; Perry & Bertrand).  But, more interestingly, they also deal with the problem that S&G identify as one of the two main obstacles to achieving the JSAF goal – that of creation of demand (Macintyre & Bertrand; Ashengo & Njeuhmeli).  This important issue will be covered in my next blog.

Responding appropriately to differentials in HIV care outcomes – are local answers needed?

12 May, 14 | by Leslie Goode, Blogmaster

The recent discovery of the preventative potential of anti-retroviral therapy (ART) (STIs/blog/modelling ART impact)  throws into sharp relief the challenge represented for the US by the very inadequate proportion of its 1.2 million HIV+ citizens (<30%) who are virally suppressed.  Nunn & Mayer  use new geographical mapping tools to bring home forcibly the epidemiological dimension of the problem by visualizing the association which HIV+ incidence/mortality show with social status and ethnicity as reflected in residence.  The picture that emerges is of an enormous concentration of the problem in certain very circumscribed neighbourhoods.  To give just one example of what is best conveyed in the diagrams (figures 1 & 2), age-adjusted death rates rise from <11.2 per 1000 people living with AIDS (PLWHA) to 19.4-32.5 per 1000 PLWHA as one passes from a predominantly white neighbourhood with large gay population and high rates of HIV/AIDS (≥2142 per 100,000 population) to the predominantly Afro-Caribbean neighbourhood of Harlem.

For Nunn & Mayer (N&M), these visualizations raise the question whether either (1.) the allocation of resources to metropolitan areas, or (2.) the nature of the strategies employed by public health interventions, reflects the very geographically focussed nature of the problem of HIV/AIDS incidence and mortality.  Their response to the epidemiological dimension of the problem revealed by their mapping tools is to urge the importance of implementation research as a vital component of HIV initiatives.

N&M’s emphasis on viraemia suppression, rather than just HIV incidence, accords well with their insistence of the epidemiological importance of the local dimension.  Retention in care is a factor that is presumably amenable to initiatives at local level – whereas HIV incidence may owe much to transmission through sexual contacts external to the community (STI/blog/Grabowski & Gray).

Their message is in line with increasing public health interest over recent years in “program impact evaluation methods that take account of the complex interactions among interventions and between intervention packages and the context into which they are introduced” (STIs/Aral & Blanchard).  There is surely a strong argument in favour of designing interventions to take place within an evaluative framework allowing a reflection on the kind of program mix likely to be most effective in a given context.  On the other hand, N&M may be in danger of undervaluing the potential of interventions of a non-localized character that act on the socio-economic determinants of the HIV problem, and especially non-retention in care – for example, the wider provision of medical insurance (STI/blogs/ObamaCare).  It would be interesting to see how far a geographical mapping of the incidence of other health problems in New York or Philadelpia coincided with N&M’s mapping of HIV/AIDS mortality.  How far is the effect of “micro-epidemics”, conjured up by epidemiological language, just a reflection of socio-economic determinants that produce identical results wherever they happen to be present?

 

 

Sustained health systems strengthening holds the key to prevention of mother-to-child transmission of syphilis

25 Jun, 12 | by Leslie Goode, Blogmaster

Half a million still-births annually are due to syphilis in pregnancy – deaths that could be averted by means of a single dose of penicillin.  An important project, reported in PLoS Medicine by Mabey, Peeling et al., to introduce point-of-care syphilis tests (POCTs) at ante-natal clinics (ANCs) in six countries, has resulted in all six countries adopting a policy to recommend POCTs; it has also influenced two of those countries, Brazil and China, to make syphilis testing for pregnant women a major public health priority (http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001233).

The past failure to address the problem of mother-to-child transmission is nothing to do with the efficacy of the intervention or its cost-effectiveness.  A recent systematic review, covered by this blog, indicates an odds ratio of 0.46 for reduced perinatal death and of 0.42 for reduced still birth (http://blogs.bmj.com/sti/2011/06/29/screening-for-syphilis-in-pregnancy-evidence-for-the-effectiveness-of-doing-something/?preview=true&preview_id=407&preview_nonce=8747e0989c).  The cost effectiveness of ante-natal screening is strongly endorsed by Terris-Prestholt, Ndeki et al. (2003) (http://sti.bmj.com/content/82/suppl_5/v38.abstract?sid=82a53292-0a5a-46d1-a01d-9cf6bbade9ae).  In the past an important obstacle to testing in low and middle income countries (LMICs) may have been the absence of a medical laboratory infrastructure.  But cheap and effective POCTs now offer a means to conduct screening in ANCs, which are attended by most pregnant women even in limited resource settings.  The relative merits of four POCT devices are compared by Mabey, Galban, et al. (2006) (http://sti.bmj.com/content/82/suppl_5/v26.abstract?sid=87c460fb-7f2f-49e6-b978-8720b427de3f).  You will find technical description of a POCT in this blog (http://blogs.bmj.com/sti/2011/10/02/what-fluidics-engineering-can-do-to-prevent-vertical-hivsyphilis-transmission-in-low-resource-settings/?preview=true&preview_id=495&preview_nonce=99cf925437).

So what are the obstacles to POCT deployment?

Mabey, Peeling et al. focus on the training and organizational challenges to deployment of POCTs in LMICs.  From the research angle, their project is a piece of “implementation research”.  What they set out to evaluate in their paper is the way in which the project meets the challenges of: 1. training the health care workers to implement the tests; 2. maintaining the quality of tests through a quality assurance program; 3. ensuring the continuity of supply chains for material and staff.  At the outset, design and location of the project were agreed with local authorities and stakeholders; next, training was offered not only to health-workers (HCWs) but to supervisors – and in the latter case the training included the assessment and training of HCWs, stock management etc.;  the project was then allowed to run.

What emerged in one area (Tanzania),was, interestingly, a 65% drop over the first six months in the percentage of ANCs passing the quality assurance controls due to high staff turn-over: but, subsequently, with the HWC training mechanism kicking in, there was a return to 100% levels of proficiency.  Also interesting was the initial resistance of laboratory staff in another area (Peru) to the idea of HWCs doing the work of laboratory technicians, though this was finally overcome.

In due course detailed papers will be published on the data from each of the countries involved: Brazil, China, Peru, Zambia, Uganda and Tanzania.  The published paper stresses the power and value of implementation research, and its potential application to other areas (e.g. HIV).  An implication of this approach is the significance of obstacles to improved health care delivery represented by the structural and organizational considerations.  The secret of obtaining better outcomes for prevention of mother-to-child transmission and other interventions may, therefore, lie in sustained health systems strengthening .

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