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UNAIDS 2016 Report: How a ‘life-cycle’ approach can help the world ‘get on the fast track’ to HIV prevention

7 Dec, 16 | by Leslie Goode, Blogmaster

‘Get on the Fast Track: a Life-cycle Approach to HIV’ is the latest UNAIDS report, following on from the UN Assembly’s 2016 declaration of commitment to ‘Fast Track’ goals for ending the HIV/AIDS epidemic. The major theme of the ‘life-cycle’ appears to owe much to the findings of the South African CAPRISA study – above all, the idea of a transmission cycle between younger (25 year-old) women and older (>25 year-old) men.  Broadly, phylogenetic analysis reveals that the prevailing pattern of transmission is as follows.  Younger women appear to get infected through casual relationships with considerably older men, who have, in turn, been infected by their longer-term partners; in time, the younger women grow up and form longer-term relationships – and the cycle is repeated.  The former group – younger (≤25 year-old) women – appear to be more vulnerable to infection than men of the equivalent age due to complex social factors, and have recently seen only c. 6% declines in annual incidence; older (>25 year-old) men have incidence rates that have remained obstinately high despite all recent efforts to reduce them.  These are best explained by poor rates of testing, integration into treatment, and viral suppression making them a potential risk to non-HIV-infected partners.

Diagnosing a problem is one thing; framing the solution quite another.  In case of the younger women, the dominant factors appear to be structural and societal – e.g. gender inequalities.  These are difficult to address without major social and political change.  The authors suggest a number of prevention tools, including sexual education in schools, the introduction of pre-exposure prophylaxis (PrEP), and social transfers.  However, recent trials of PrEP in sub-Saharan Africa do not bode well for this intervention (STI/blogs/’Failed PrEP trial’; STI/blogs/‘Another failed PrEP trial’); while the evidence for the effectiveness of sexuality education and ‘social transfers’ is far from conclusive (School-based Sexuality Programmes/STI/blogs; STI/Galarraga & Sosa-Rubi; STI/Minnis & Padian; STI/Khan & Khan).  However, in the case of the other group – i.e. older men – the obstacles to HIV prevention (poor rates of testing and viral suppression) may be less intractable, and the report proposes a number of very practical measures that could help, including: distribution of self-test kits through female partners attending ante-natal clinics (STI/blogs/’Partner-delivered STI testing’); simplifying ART regimens so individuals have to take just one tablet a day; shifting from CD4 count testing to viral load testing.

The report also has much to say about other phases of the life-cycle, as well as about ‘key populations’ (estimated 45% of new infections).  Regarding the latter, the authors report the stability, or even rise, in new infections amongst sex-workers, drug-users and MSM. They emphasize the negative impact of criminalization of key populations and same-sex relations (73 countries) (see STI/blog/’HIV criminalization’/; STI/blog/’Health workers violate human rights’), the very low levels of domestic funding (on average, only 12% of total spending on MSM prevention), and the relatively young age of many in the ‘key populations’.  The authors recommend ‘comprehensive’ programmes for these populations incorporating access to a range of health care programmes, such as the Red Umbrella programme for sex workers in South African, and the ‘Targeted Strategy Plan’ for the transgender population in Lima, Peru.

 

School-based sexuality programmes fail to demonstrate an influence on STI and pregnancy outcomes

7 Dec, 16 | by Leslie Goode, Blogmaster

The 2016 UNAIDS Report – Get on the Fast Track: a Life-Cycle Approach to STI Prevention/STI/blogs – underlines the particular vulnerability to infection of women at a relatively early phase of the life-cycle, especially in limited resource settings such as sub-Saharan Africa as a result of structural factors .  These can seem intractable, but the authors of the report propose a number of practical measures for this group that include sexuality education in schools, social transfers and PrEP.  So the recent publication of a Cochrane Review of studies assessing the effectiveness of two of these interventions – sexuality education in schools and social transfers in the form of material incentives for girls to remain in school – is very timely – especially as five of the eight studies included in the analysis are based in the limited resource settings of sub-Saharan Africa that are the focus of the UNAIDS report.

A number of both European and non-European countries have incorporated some form of sexuality education into their school syllabuses, and there have been attempts to investigate their effectiveness in a number of places, including the UK (Stephenson & Johnson/STIs; Stephenson & Oakley; Henderson & Hart).  Unfortunately many of these trials rely on self-reported data, a tendency that has been shown to be problematic in this area (Langhaug & Cowan/STIs; Plummer & Hayes/STIs). The importance of the recent Cochrane Review is that it focuses largely on biological outcomes: namely, rates of STIs and pregnancy at follow-up.  The studies of sexuality education that are based on these outcomes have been undertaken in sub-Saharan Africa: Ross & Hayes (R&H,Tanzania); Cowan & Pascoe (C&P, Zimbabwe); Duflo & Kremer (D&K, Kenya). The same applies to studies of social transfers based on biological outcomes (Baird & Oezler (B&O) and Duflo & Kremer (D&K)).  (The non-African studies in the analysis use pregnancy prevalence as their preferred outcome (Cabezon & Garcia (C&G, Chile); Stephenson & Oakley (S&O, England); Henderson & Hart) (H&H, Scotland)).)

So what biological evidence do we find of the effectiveness of school-based education interventions? Practically none, say the reviewers.  No difference was reported between intervention and control groups for HIV or for other STIs – except in the case of R&H for syphilis prevalence at the end of follow up (RR 0.81: CI 0.47-1.39).  Even the statistically significant aggregate outcome for long-term pregnancy prevalence (0.55: CI 0.34-0.91) (C&G, S&O, H&H, D&K) seems largely accounted for by the results of C&G, which were at particularly high risk of bias.  When the latter were excluded, differences in pregnancy prevalence dropped to 0.93.

When it came to the other element of this survey, social transfers (B&O and K&K), only B&O reported a significant effect for HIV prevalence and HSV-2 prevalence.  This evidence was considered weak because, in the former case, it concerned data for school ‘drop-outs’ which, say the reviewers, the B&O study was not powered to detect, and, in the latter, because there was no measurement of prevalence at baseline.  As for pregnancy outcomes, both studies reported a reduction in short-term prevalence (0.76).

The trials of educational interventions may simply have been underpowered to detect small, but clinically important effects (especially with HIV).  On the other hand, the authors of the review also point to a growing consensus among experts that the determinants of sexual health outcomes and sexual risk-taking are wider structural factors such as poverty and cultural gender norms that lie beyond the capacity of school-based education programmes to influence.  The evidence for the effectiveness of incentives to stay at school, though as yet very inadequate, seems more encouraging.  This is evidently a field that requires further research.

Criminalizing HIV transmission: Is imprisonment ever the right response?

28 Nov, 16 | by Leslie Goode, Blogmaster

This month sees the publication of a ‘Consensual Statement’  by Australian medical professionals on ‘Sexual Transmission and the Law’.  This draws on a similar Canadian ‘Consensus Statement’  issued in 2014.

The involvement of the law in this area remains a highly controversial matter.  It is easy to assume that UNAIDS policies underlining the public health disbenefits of “overly broad criminalization” largely concern those African nations which have recently adopted draconian legal previsions in response to the HIV crisis (Kpanake & Mullet/STIs; Stackpole-Moore/STIs).  Yet we should not forget that prosecution and imprisonment for transmission of HIV continues to occur in first-world countries as well (e.g. 16 custodial sentences in England over the period 2001-2012 (Phillips & Sukthankar/STIs)).  National jurisdictions differ in respect to whether, in order to be subject to prosecution, the transmission must be intentional or reckless.

Many in sexual health, I suspect, would reject the idea of involving the criminal law in such cases.  Stackpole-Moore/STIs, for example, argues that its use “in order to guide normative behaviour” is irreconcilable with the concern to avoid internalized stigma among at risk populations.  According to S, employing criminal sanctions in this area involves promoting just the kind of social stigma that health policy makers have found so counter-productive in fighting the epidemic.  However, this side-steps the question whether there might ever be a moral argument for legal sanctions regardless of their impact on behaviour.  Phillips & Sukthankar/STIs, in their theoretical examination of traditional justifications for sentencing to imprisonment, recognize the possibility that ‘retributive justice’ could provide some genuine justification for imprisonment for HIV transmission.  This might explain why those African legislators responsible for passing the recent severe previsions, tend, when asked about their motivations, to revert to the argument of retribution – even where that is not the ‘official’ justification (Stackpole-Moore/STIs and Kpanake & Mullet/STIs).

To come at last to the recent Australian and Canadian statements – these discourage, even if they don’t quite exclude, the involvement of the law.  However, they do so not on the grounds of a principled rejection of all justifications for criminalization (such as advocated by Stackpole-Moore/STIs), but on the grounds of the changing reality, and changing perceptions, of HIV.  They specify the risk of per sex-act transmission – in the case of penal-vaginal transmission, rated low (0.4%-1.4%) – and point to the effectiveness and tolerability of treatment.  If HIV is no longer a ‘death-sentence’, then transmitting HIV to a partner can hardly be considered ‘killing’.  Still more conclusively, perhaps, they point to the inadequacy of phylogenetic analysis as forensic evidence, which, they argue, “simply cannot determine beyond reasonable doubt that the reference samples are linked”.

Yet it should be remembered that the first two of these three considerations (unlike the claims of retributive justice) are context-dependent.  Whether or not HIV amounts to a ‘death sentence’ may depend on where you live.  Were the same kind of arguments to be applied in the case of the African countries discussed by S and K&M, they would need to take account of the very different health realities obtaining in those countries.

Partner-delivered HIV self-testing through antenatal clinics: the way ahead for partner notification in low-resource settings?

23 Nov, 16 | by Leslie Goode, Blogmaster

A recently published, Kenya-based, randomized controlled study (Masters & Thirumurthy/STIs) (M&T) evaluates a novel intervention that appears to combine in a fresh way elements of various innovative interventions for HIV prevention.  Recently published studies (e.g. Kissinger/STIs; Estcourt & Cassell/STIs) have explored the potential of ‘expedited’, or ‘accelerated’ partner therapy – where the partner of an index STI-infected individual is offered therapy through the infected individual directly, without a clinic attendance, or with only a telephone interview. They have also evaluated the benefits of ‘self-testing’ for HIV (e.g. Pai & Dheda/STIs).  The intervention trialled by M&T – partner delivered HIV self-testing – combines elements of these two types of interventions.  A third crucial element is that it takes advantage of the unique opportunity offered by antenatal and postpartum clinics in low resource settings (see Azeze & Haile/STIs; Sombie & Dabis/STIs; Ganiyu & Mason/STIs) to make contact with HIV-infected individuals who might otherwise have little access to health services.

In M&T’s study, participants attending antenatal and postpartum clinics (ANC) who were assigned to the intervention arm of the study (n=284/570) were offered two oral-fluid-based HIVselfing kits, one for themselves, one for their partner.  Discussion about HIV, self-testing, couple testing, and awareness of partner’s result were subsequently reported by index patients at monthly follow-up meetings over a three-month period.  This ANC-based, partner-delivered HIV self-testing intervention was evaluated against a control group (n=286/570) who were given an invitation card for conventional clinic-based HIV testing and encouraged to distribute the card to partners.

The primary outcome was reported partner HIV testing which was 91% for the intervention as against 52% for the control.  The intervention looked at couple testing (42% difference between intervention group and control), and awareness of partner’s HIV status (difference=39%).  0% participants in either group reported intimate partner violence (IPV) as a consequence of HIV testing.

Concerns around interventions of this kind tend to centre upon two things.  First, the absence of any direct contact between partner and health services, and consequent loss of an opportunity to test for the full range of STIs and help ensure integration into treatment (Estcourt & Cassell/STIs).  Second, worries as to the likelihood of IPV related to testing.  On the first, concern may be less where the self-test is for HIV, and the partner misses out on testing for the other STIs (Kissinger/STIs), than it would be where, as in many non-African settings, the self-test would generally be for Chlamydia or gonorrhoea and HIV could remain undiagnosed.  Regarding IPV, the authors note its lack of association with testing in the study (despite base-line reported rates of 27%).  They also point to the large proportion of eligible declining to participate (715/1,315).  This – taken together with zero cases of IPV – they interpret as a possible indication of the ‘agency’ of these women, and their capacity to make their own judgments regarding the possible impact of participation on their relationships.  The problem of ensuring engagement with care among those self-tested for HIV, however, is one that the authors acknowledge as still needing to be resolved.

As for the study itself, a primary limitation is self-reporting.  But here the authors note that misreporting is hardly likely to account for the differences between intervention and control arm – which is the evidence that the authors principally emphasize.

 

Where HPV vaccination loses the battle for public support: calculating the health implications for Japan

9 Nov, 16 | by Leslie Goode, Blogmaster

A recent brief contribution to The Lancet-Oncology (Tanaka & Ueda) uses predictions of the probable health outcomes of the suspension of the Japanese HPV vaccination programme to make the case for an urgent reassessment of the current policy.  This intervention is very timely.  The approved age for HPV vaccination for Japanese girls is a window of four years from 13-16 yrs, and the current year (2016-17) constitutes the fourth since the suspension of the programme (June 2013); so the current year is the last opportunity for a return to the initial HPV vaccination policy before the effects of the suspension (for the oldest in the cohort) become irrevocable.   From the following year on (2017-8), the authors argue, every additional year of suspension will exclude an additional age group from the protective effects of HPV vaccination – unless, that is, the eligibility period is extended to include older girls).  With a view to maximizing the impact of this message, they assess the impact of restarting vaccination in 2020 as against restarting in the current year.  They do this on two scenarios depending on whether or not vaccination, when resumed, is given to those who would have missed out in 2013-2017 as well as to those currently eligible.

So how great are these effects?   On the first scenario (no catch-up for missed years), risk of HPV 16/18 infection at 20yrs is estimated for the 2013-6 year groups at around a steady 1.0%, given resumption of vaccination 2020, as against the 0.3-0.4% risk, with resumption in 2016; on the second, that steady 1% risk over the four missed years is replaced by an evenly paced decline from 1.0% to previous levels (0.3-0.4%) over the four-year period.

Of course, it is the long-term health impact of these HPV infections that constitutes the cost of the current Japanese policy, and, were it recognized, the strongest incentive for a resumption of vaccination.  Unfortunately, the full impact is very long term, and hard to quantify.  But some advanced indication of its potential scale is provided by the recent Finish ‘FUTURE’ trial that demonstrated an absence of CIN3 and ICC lesions in vaccinated participants (Paavonen/3/STIs), as well as, more indirectly, the enormous (c.90%) declines in genital wart presentations in Australia (Chow & Fairley/STIs; Ali & Donovan (STIs)) and New  Zealand (Wilson & Baker/STIs).  The benefits foregone by the unvaccinated will also include protection against head and neck – especially oropharyngeal – cancers (Field & Lechner/STIs; King & Sonnenberg/STIs), and against a small, but significant range of anogenital cancers in women (Prevention of anogenital cancers in women/STIs/blogs).  On a more positive note, however, there is some evidence for the benefit of ‘catch-up’ and incomplete vaccination (“Catch-up” and incomplete vaccination/STIs/blogs) as against those who have hitherto put this in doubt (STs/Chesson & Markowitz).

An important lesson of the Japanese experience for everyone concerned with HPV is the importance of public education.  The very poor levels of understanding revealed by a recent systematic review (Patel & Moss/STIs) amongst European adolescents is a timely warning that uninformed attitudes to HPV vaccination are not restricted to the Japanese.

Feasibility of infant circumcision as an HIV prevention tool

31 Oct, 16 | by Leslie Goode, Blogmaster

Recent trials have shown male circumcision (MC) to be associated with a reduced HIV incidence of up to 60%. For this reason UNAIDS has included ambitious goals for circumcision (20 millions MCs) as a major component of its HIV prevention strategies for 14 priority countries in sub-Saharan Africa (STI/blogs/Roll-out of UNAIDS voluntary male circumcision).  The achievement of this objective has met with considerable obstacles on the supply side – for instance, the lack of trained practitioners (STI/blogs/Roll-out of UNAIDS voluntary male circumcision; Kaufman & Ross/STIs); but constraints on the demand for MC have, if anything, proved still harder to surmount (STIs/blogs/cultural constraints on uptake of circumcision). The existence of circumcision as a traditional cultural practice amongst some populations can lead to its perception in other cultures as alien and externally imposed – even  hostile to one’s own tradition (David/STIs; Madhivanan & Klausner/STIs; STIs/blogs/cultural constraints on uptake of circumcision). Also, its traditional association with a certain phase in the life cycle can give rise to the feeling among older members of the community that it is inappropriate for people of their age (Mbabazi/STIs).

The cultural problems affecting demand have led some to reconsider the possible contribution of early infant circumcision (EIC) as a prevention tool – albeit on a longer view that the one envisaged by existing UNAIDS targets (Gray & Kigozi/STIs).  Kankaka & Gray (K&S), in a recent paper reporting a trial of such an intervention in Rakai Uganda, seem to corroborate (largely) positive findings of earlier investigations of EIC in other sub-Saharan countries (Young & Nordstrom (Y&N) (Kenya); Plank & Lockman (Botswana); Bowa & Stringer (Zambia)) that would indicate EIC could ultimately prove a highly effective form of prevention.  Of course, supply side problems with the recruitment and retention of adequately trained personnel remain.  For this reason, K&S – as indeed Y&N before them – investigated the impact of task-shifting from physicians to less highly trained practitioners; in the Uganda study, infants were randomly assigned to either ‘clinical officers’ (i.e. assistant physicians) or registered nurse midwives (RNMWs). Another feature of this study geared to testing the feasibility of the extension of EIS to remote areas was the decision to substitute topical analgesia for the dorsal penile nerve block used in earlier studies.  The trial assessed the safety of EIS (Mogen Clamp) as performed by more junior cadres of medical staff, and rated the degree of pain/discomfort experienced by the infants in terms of Neonatal Infant Pain scores (NIPS) – as well as testing out, in some rudimentary way, the acceptability of the intervention to mothers.

On all accounts, the trial produced very satisfactory results.  The rate of adverse events with RNMWs was low, and indeed comparable to rates that might be expected with physicians (1.6%), and the NIPS scores suggested that 76% of infants experienced mild pain or less, and only 1.6% experienced severe pain.  So far as the supply-side difficulties are concerned, these results are encouraging.  There could, of course, also be demand-side constraints with EIS, equivalent to those observed with adult circumcision.  Yet, of the 701 infant-mother pairs registered as potential participants, 74% (no.= 525) consented (as compared to 60% in the Botswana study (Plank & Lockman), but only 11% in the Zambia study (Bowa & Stringer)).  Maternal satisfaction rates were 99.6% for clinical officers, and 100% for RNMWs.  The cultural acceptability may vary somewhat between populations – yet, to the extent that EIS remains distinct from cultural practices, its dissemination may be less at risk of being perceived in non-medical terms as an alien or hostile cultural imposition.  Moreover the evidence suggests that experience of pain increases with age.

 

Prevention of anogenital cancers in women may be an additional benefit of HPV vaccination

14 Oct, 16 | by Leslie Goode, Blogmaster

Cervical cancer is evidently the most important, but by no means the only, health risk that vaccination against HPV aims to avert. The potential impact of vaccination on other cancers (not to mention genital warts) may also be a factor in estimating the cost benefit of achieving higher vaccination coverage, as well as determining priorities for vaccination programmes (e.g. the relative importance of achieving high coverage for males).  Recent studies have investigated the role of HPV in the rising incidence of head and neck – especially oropharyngeal – cancers (Field & Lechner/STIs; King & Sonnenberg/STIs), and in the development of anal cancers amongst MSM (Poynten & Garland/STIs).  The dramatic impact of vaccination programmes on the prevalence of genital warts has already been attested both in Australia, where vaccination was introduced in 2007 (Chow & Fairley/STIs ), and, more recently in the UK (Canvin & Mesher/STIs ).

In addition to these benefits of HPV vaccination, a recent Danish nationwide cohort study (Sand & Kjaer (S&K)) draws attention to another relatively limited, but nevertheless significant, benefit in the shape of a range of anogenital cancers in women – i.e. anal, vaginal and vulvar cancers.  These seem to be strongly associated with the occurrence of high grade cervical intraepithelial neoplasia (CIN2 & 3), and should therefore be numbered amongst the adverse effects of HPV that vaccination may help to prevent.  Given the relative rarity of these cancers (total yearly incidence in UK, both male and female, is currently about a quarter of that of oropharyngeal cancers), an important advantage of S&K’s study is its impressive scale.  It investigates no less than 2.8 million women born 1918-1990 over the period from 1978 to 2012. Also, unlike similar studies, it is able to control not only for age, but for a range of potential confounders such as socio-economic status and smoking.  The use of CIN2/CIN3 as a proxy for HPV infection seems well supported by the evidence (Tachezy & Vonka/STIs; Azwa & Harun (STIs)).

The key findings of the study were as follows.  Relative risk of anal, vulvar and vaginal cancers following CIN2/3 as against no such history was found to be greatly increased: RR 2.8, 2.5, 8.3 after CIN2; 4.1, 3.9, 17.4 after CIN3.  Risk was particularly high in the first year after CIN; but the increased risk persisted, suggesting the effect could not be attributed to surveillance bias.  So, for example, analysis showed increased risks of anal, vulvar and vaginal cancers at ≥25 years after CIN3 diagnosis of RR 4.8, 3.2, and 5.5, respectively.  In non-cervical anogenital cancer, HPV16 was the most frequently detected HPV type.  The fact that cancer risk following CIN3 is substantially greater than it was following CIN2 suggests to the authors that the cause of both may be attributable to an inadequate immune response to HPV in certain women, leading to a failure to clear the infection.  The propensity of persistent HPV to spread to the entire anogenital region explains the range of cancers (anal, vaginal, vulvar) in respect to which these women seem to be at heightened risk (see Simpson & Turner/STIs ).

Fresh WHO guidelines on gonorrhoea management + latest US surveillance data on gonorrhoea resistance

13 Oct, 16 | by Leslie Goode, Blogmaster

The emergence in various locations of resistant strains of Neisseria gonorrhoeae (Ng) is narrowing the therapeutic options. The recent (July 2016) WHO Guidelines, revised from 2003, reflect the concern both to treat effectively and steward our remaining defences against the infection in a globally coordinated manner.  They recommend either dual therapy with either single dose 250g intra-muscular ceftriaxone or 400g oral cefixime combined with 1g oral azithromycin (preferred options), or else single therapy with either ceftriaxone, cefixime or 2g spectinomycin).  The choice between these options will depend on local considerations, including Ng susceptibility data.   In the event of treatment failure following WHO-recommended dual therapy, they recommend any of: 500mg ceftraxone, 800mg cefixime, 240mg gentamicin, or 2g spectinomycin, each of them in combination with 2g azithromycin.

Reported surveillance data for a given location will be crucially important, then, for determining at local level the best options for treatment.  Given the global dimension of the threat, however, this data may also be potential evidence for global trends.  Hence the wider interest of the latest (2014) US surveillance data from the Gonococcal Isolate Surveillance Project (GISP)).  Hitherto, the US picture (as in the UK) has been one of steady progression (2006-2011) in prevalence of Ng isolates exhibiting reduced susceptibility (cefixime: MIC ≥0.25 μg/mL; ceftriaxone: MIC ≥0.125 μg/mL), interrupted by a decline in 2013; this is the pattern both for cefixime (0.1%-1.4%-0.4%) and ceftriaxone (0.1%-0.4%-0.1%) (see also Kirkcaldy & Bolan (STIs)).

So where do the latest (2014) data point? As regards cefixime, to a return to the pre-2013 upward trend, it seems, with prevalence rising once again from 0.4% to 0.8%; with ceftriaxone, to the maintenance of the 2013 prevalence level (0.1%).  Presumably, it is the prevalence levels of ceftriaxone that, in the US, constitute the primary focus of concern – since, as in the UK, that is the drug currently recommended, along with azithromycin, for dual therapy.  (See  Town & Hughes (STI) for  an equivalent report of ceftriaxone resistance in the UK).  But the greatest surprise of the 2016 GISP report is the sudden rise of decreased susceptibility to azithromycin: from 0.6% prevalence of reduced resistance strains (MIC ≥2.0 μg/mL) in 2013 to 2.5% in 2014.  The report comments that the recommended dual therapy with azithromycin is unlikely to be a contributor to this trend – though it is possible, they argue, that the small increase in the azithromycin monotherapy by US STD clinics over the last decade could have had some influence on the prevalence of azithromycin resistant strains.  There is evidence of high or rising levels of azithromycin resistance in other locations (Dillon & Thakur (STIs); Bala & Ramesh (STIs)), including, recently, the UK (Chisholm & Fifer/STIs).

Cochrane says: Chlamydia screening may have very limited impact, but more research is needed

3 Oct, 16 | by Leslie Goode, Blogmaster

There is a strong rationale for systematic Chlamydia screening, and it is widely recommended and practised. Yet there are harms associated with the screening process (Low(STIs)), and, of course, serious concerns about its cost-effectiveness (De Wit & Kretzschmar (STIs)).  This lends urgency to the question of whether Chlamydia screening works – addressed in a recently published systematic review for the Cochrane Database:  ‘Screening for genital chlamydia infection’.

It all depends, the authors claim, on what we want screening to do: whether it’s a general reduction of prevalence in the population that we’re aiming at, or the prevention of serious sequelae such as PID (Pelvic Inflammatory Disease) in individuals.  The strict Cochrane exclusion criteria (especially that of ‘reporting a pre-specified primary outcome’) reduce the pool of evaluated studies to just two addressing the impact of screening on Chlamydia prevalence – only one of which (not, as it happens, an RCT) addresses impact on prevalence in the general population (Schmid & Kretzschmar (STIs)).  Regarding the impact of screening on reduction of PID incidence, the field narrows to just four RCTs (Andersen & Olesen (STIs);  Ostergaard & Olesen; Oakeshott & Hay; Scholes & Stamm).

Respecting the impact on prevalence, Schmid & Kretzschmar (STIs) observe very little effect (RR 0.96), but the quality of evidence is rated, on Cochrane criteria, as ‘low’.  As for PID prevention, an effect was observed (overall RR 0.68), but unfortunately was considerably less pronounced in the two studies with low risk of selection bias (Andersen & Olesen (STIs) and Oakeshott & Hay) (RR 0.80) than with the other two studies ((RR 0.42).  This evidence was consequently downgraded from ‘high’ to ‘moderate’.

So there continues to be no evidence at present for a positive impact of screening on general prevalence, though further research could possibly modify this assessment.  As regards the incidence of PID, some limited degree of positive impact may have been demonstrated – though whether systematic screening interventions will turn out to be cost-effective is another question (De Wit & Kretzschmar (STIs)).  The reviewers point out there is another important trial that is still on-going (hence not eligible for inclusion): Hocking (STIs).  The latter – a study being undertaken in Australian GP practices – involves ‘opportunistic’ testing (as defined by Low (Low(STIs)) rather than screening proper (i.e. ‘systematic’ screening).  However, given that this is the form of intervention being undertaken in many places including the UK, its final results will no doubt be of great interest.  On the basis of the study’s findings to date, the verdict seems unlikely to be favourable (Yeung & Temple-Smith (STIs)).

First study of population-level preventative impact of Medical Male Circumcision and ART on HIV incidence in a country of sub-Saharan Africa

14 Sep, 16 | by Leslie Goode, Blogmaster

Clinical studies have demonstrated the potential effectiveness of ART (HPTN 052) and Voluntary Medical Male Circumcision (VMMC) (Gray & Kigozi/STIs) as preventative measures against HIV.  This led WHO/UNAIDS to launch a Joint Strategic Action Framework (JSAF) setting a target in 14 priority sub-Saharan countries of 80% VMMC by 2016.

What, then, are the potential gains of ART and VMMC interventions in these countries?  Comparative ecological studies have shown the population-level impact of male circumcision as a cultural practice (MacLaren & Vallely/STIs). Various mathematical modelling studies have sought to quantify that potential effect of interventions both in the realm of VMMC (Jenness & Cassels/STIs) and ART (Shafer & White/STIs)  (though other studies have highlighted the challenges that scale-up of these interventions is likely to present (Kaufman & Ross/STIs)).

Now, for the first time, a study has sought to quantify the real-life population-level impact of these interventions.  Kong & Gray (K&G) base their study on data from the 1999-2013 Rakai Community Cohort Study (Uganda)).  Among the 45 Rakai communities (44,688 participants surveyed over 24.6 years), VMMC coverage had, by 2013, increased from 19% to 39%, and ART had risen, in males, from 0% to 21%, and, in females, from 0% to 26% – and HIV incidence had fallen, concurrently, from 1.25 per 100 person-years to 0.84 per 100 person-years in males, and from 1.25 to 0.99 in females.  As regards VMMR, each 10% increase in the rate was associated amongst males with a decline in incidence that could be quantified, on multivariate analysis, at 0.87 – though, in females, the reduction was statistically insignificant.  As for ART, the decline attributable was not statistically significant in either case, but, when ART coverage was modelled as a categorical variable, and coverage of over 20% was compared with coverage of under 20%, a decline in HIV incidence was observed in the former group of the order of 0.86 among males, and 0.77 among females.

These results are not surprising.  VMMC is, in the first instance, protective of men – though, of course, in the longer term women too will benefit from any population-level effect. (There is, in fact, a worrying possibility, investigated by Maughan-Brown & Thornton/STIs, that men could incorrectly assume that their VMMC will be directly protective of their partners, and modify their behaviour accordingly.)  As for ART, here too the (as yet) limited impact in Rakai is what we might have expected.  Tanser & Newell, in a South Africa-based study only observed significant association when ART coverage was over 30%.  However, population level decline in incidence – especially that associated with VMMC – is encouraging.  The results of this study allow us to predict that increasing VMMC coverage more than 40% could reduce male incidence by approximately 39% at population level.   A major limitation of the study, of course, is its assumption that sexual networks, and hence HIV transmissions, are internal to the community. However, a recent study by Chemaitelly & Abu-Raddad/STIs would seem to indicate that, in a context like sub-Saharan Africa the contribution of networks going beyond the wider community is likely to be limited.

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