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HIV prevention

Boys’ BV?

4 Sep, 17 | by Leslie Goode, Blogmaster

Recent studies in STIs have drawn attention to the impact of the state of the microbiome of the female genital tract (FGT) and susceptibility to STIs – and, in particular, the protective effect of the hydrogen peroxide-releasing microbe Lactobacillus crispatus (L.c.) (Antonio & Hillier/STIs) (A&H). Such STIs include, not only BV (53% less likely with L.c., according to A&H), but apparently also HIV, gonorrhea and HSV-2, which show, according to a Uganda based study (Francis & Grosskurth/STIs) an association of BV estimated at RR 2.35, 1.3, 1.69, respectively. A recent study of 236 young women participating in the S. African FRESH cohort found that, of the 24 of these having a FGT microbiome dominated by L.c., none figured among the 31 HIV seroconversions (STI blogs: Susceptibility of sub-Saharan women to HIV). Haggerty & Ness/STIs (, in the PID Evaluation and Clinical Health Study, find a strong (RR 4.7) association of certain FGT microbiotic bacteria with PID. Finally, a mouse based study by Gilbert & Lewis (STI/blogs: Bacterial vaginosis associated bacterium) seems to confirm the hypothesis, proposed in 2001 by Shahmanesh/STIs (, that Gardnerella may indirectly cause NGU (non-gonococcal urethritis) by triggering the emergence of covert Escheridia coli.

But if the importance now seems established of the composition of the woman’s FGT microbiome for the susceptibility to a whole range of STI (BV, HIV, Ng, HSV-2, PID, NGU), what are we to think of the finding of a recent paper in mBio (the journal of the American Society for Microbiology) that bacteria in the penile microbiome play a comparable role in the case of men – at least, in respect to HIV?

Liu & Price;8/4/e00996-17) uses data from 182 uncircumcised men from Rakai, Uganda, 46 of whom go on, over a two-year period, to develop HIV. In the case of five genera of bacteria suspected of playing a role in the association between male circumcision and reduced HIV risk, a strong association was discovered between their baseline prevalence in the penile microbiome and the risk of infection with HIV. With each 10-fold increase in the abundance of Prevotella, and Diliaster, for example, an increased risk was noted (AOR: 1.63 and 1.57, respectively). Other genera associated with increased risk were Peptoniphilus, Finegoldia, Porphyromonas, Mobiluncus, Peptostreptococcus, and Murdochiella. HIV risk was also found to be associated with inflammatory markers – especially interleukin-8. Presence of the latter increased significantly with densities of anaerobic bacteria. The greatest risk was observed where three are more cytokines were detected. These findings lead the researchers to conclude that the response of the immune system to shifts in the penile microbiome facilitate infection by HIV.

Of course, this is precisely the mechanism that may account for the increased susceptibility to STI (including HIV) in women with FGT deficient in L.c.. However, the problem can be largely resolved in the case of men by means of circumcision.

The authors also make the interesting point that the bacterial dysbiosis that they observe in the male microbiome may be passed on to women through sexual activity – so that the genital microbiome is, to some extent, ‘shared’ between them. Presumably, this could also mean that voluntary male medical circumcision reduces this risk of HIV transmission for women as well as men to the extent that women are at less risk of infection with bacteria that render them susceptible to HIV.

‘Scoping’ location: the role of ‘place’/’space’ as an influence on HIV outcomes amongst young MSM

14 Mar, 17 | by Leslie Goode, Blogmaster

Bauermeister & Stephenson (B&S) is a scoping review addressing the impact of location – ‘space’ and ‘place’ – on HIV prevention and care outcomes for young MSM (YMSM).  It owes much to Diaz & Ayala and their concern to view human behaviour in terms of ‘social location’ ‘within a context of social oppressive factors’ rather than in terms of ‘individual identity’.  It focuses on 17 studies, selected for inclusion much as in a systematic review, but analyzed according to scoping methodology (i.e. with a view to mapping out the investigative territory rather than addressing a specific question).  Social location is translated by this study into concepts of ‘space’ and ‘place’.  Space here refers to the physical and geographical aspects of location such as proximity to services and transportation, and place to more socially constructed aspects – ‘the interpersonal exchanges and dynamics that result in physical and social resources in space’.

It is perhaps on account of the breadth of these goals and the methodology of scoping that no very conclusive findings emerge.  Where location assumes the more geographically defined characteristics of ‘space’, the findings underscore the importance of geographic information system (GIS) approaches (see also: Simms & Petersen (STIs editorial); Petersen & Simms (STIs)).  But elsewhere – especially where the concept of location shades into less physical definitions of context (i.e. ‘place’) – the evidence is more contradictory and sometimes appears counter-intuitive.   For example, there are studies that find a positive correlation between social disadvantage and higher levels of adherence to HIV prevention and care recommendations.  Apparently, however, income inequality (as measured by Gini ratio or male-to-female ratio of earnings) stands out across studies as an indicator of poorer YMSM outcomes.

In discussing the limitations of their study, the authors make the interesting point that in a field of investigation as hard to define and as open to fresh hypotheses as this, the tendency for studies reporting an insignificant or null finding not to make their way into the literature could contribute to a serious distortion of our understanding (i.e. ‘publication bias’).  As is evident from their discussion of the review findings, well-conducted studies reporting non-significant findings on the influence of location can make a valuable contribution to the debate (such as, for example,  Haley & Cooper (STIs), a paper published online on the related issue of influence of location on STIs).

A second intriguing question is raised by this review, even if it is perhaps not adequately discussed in it: whether social context is always translatable in terms of ‘geospatial’ location.  Does the concept of ‘place’, for example, really extend to the case of ‘virtual space’ – or does virtual space effectively break free of any geospatial definition?  The question is, of course, very pertinent, given the importance for this population in particular, of dating apps.  Interestingly, Yu & Shang (STIs), in a paper published online, make a case for characterizing an important category of YMSM (occupying a specific ‘place’ in contemporary China society) in terms of extreme geospatial mobility.  One would like to know how B&S would accommodate the paradoxical existence of social ‘places’ defined by the loss of geospatial definition.  Are we still really talking about place?

HIV prevention through HAART: a victim of its own success?

28 Feb, 17 | by Leslie Goode, Blogmaster

A recent study (Kalichman & Allen (K&A)) involving a series of four cross-sectional surveys (1996-2016) at a Gay Pride event in US Atlanta Georgia adds to the mounting body of evidence that substantial changes have occurred in community-held beliefs about the safety of certain sexual behaviours in the era of HIV treatment as prevention.

It might seem surprising, in view of the known effectiveness of ART as a preventative tool, that its deployment has generally failed to deliver the preventative benefits that might have been anticipated.  It is essential to achieve progress right along the ‘treatment cascade’, including, not only access to testing, but integration into treatment and viral suppression, for those benefits to be realized.  The fact remains that levels of infection amongst MSM, even in countries that have scaled up testing and treatment, have remained stable or are actually rising.

The obvious hypotheses, tested by K&A in this study, are that, 1., the perception of safety on the part of MSM has led to an increase in condomless anal sex, and that, 2., the growing incidence of STIs resulting from these sexual practices has itself had a direct impact in reducing the protective effects of ART.  (Of course, this is not to deny that sizeable proportion of the MSM community in the US – as in Australia (Mao & de Wit) – be successfully engaged in deliberate HIV risk-reduction strategies.)  The four surveys adopted identical measures and procedures, and involved ascertaining proportion of condom use during anal intercourse and number partners over the previous six months as well as assessment of beliefs regarding the preventive effectivess of ART (nine items of the questionnaire).

Results were as follows.  For HIV negative men: condomless anal sex (CAS) increased from 43% (1997) to 61% (2015); reporting two or more condomless sex partners from 9% to 33%.  For HIV positive men:  CAS from 25% to 67%; reporting two or more condomless sex partners from 9% to 57%.  As regards beliefs that ART was protective, comparisons across survey times indicate a main effect for year of survey, F(3, 1829) = 6.3,p<0.01, with an effect across survey year for men who engaged in CAS, F(1,1829) = 9.3,p<0.01.  Most evident from figures is a precipitous drop in perception of risk amongst both groups between the third and fourth survey (2006 and 2016).

K&A’s hypotheses (one or both) would seem to be corroborated from another quarter by the observed association with the introduction of HAART of an increased infection rate of gonorrhoea and syphilis (Stolte & Coutinho (STIs)) and of viral STIs (de Laar & Richel (STIs)).  Indeed rates of MSM syphilis increase coinciding with HAART introduction have been so dramatic in some places (e.g. Buenos Aires (Bissio & Cassetti (STIs)) as to lead to a hypothesis that HAART agents may actually be impairing immunity to the virus (Rekart & Cameron (STIs); Tuddenham & Ghanem (STIs)).  Whatever the validity of the latter hypothesis, evidence of STI epidemics is consistent with evidence of attitudinal and behavioural changes, such as those proposed by K&A.

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.


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.


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.

Viral suppression through ART prevents HIV transmission between long-term sero-different MSM and heterosexual partners regardless of condom use

8 Sep, 16 | by Leslie Goode, Blogmaster

The HPTN 052 study demonstrated the preventative benefit of ART, showing a dramatic 96% reduction in HIV transmission in HIV+ participants randomized to early ART initiation compared with the group that deferred treatment.  This is very encouraging.  But from the perspective of a gay person considering the risk of engaging in condomless sex with a long-term HIV+ partner, these results do not provide an adequate basis on which to make a decision.  For a start, HPTN 052, like other such studies, focuses largely on heterosexual couples engaging in vaginal sex – which is recognized to carry only a fraction (c. 0.1) of the risk of HIV transmission of anal sex.  Besides, the study reports high levels (93%) of condom use.  Much remains obscure, therefore, as to the level of protection that a gay person could reasonably expect from ART against HIV transmission through condomless anal sex with a long-term partner.

This question is squarely addressed, however, in a recently reported prospective observational study – PARTNER (Partners of People on ART – A New Evaluation of the Risks) – involving 888 sero-different MSM (330) and heterosexual (548) couples reporting condomless sex who contributed a total of 1,238 eligible couple-years.  This study did not limit itself to establishing cases of transmission, but conducted phylogenetic analysis in those cases in order to determine whether or not the transmission had resulted from sex with the long-term partner.  Of the 11 transmissions that took place in the course of the 1,238 couple-years (10 amongst heterosexual, one amongst the MSM, couples), none were found to be phylogenetically linked.  The paper also examined the association between the HIV transmission which did take place (i.e. not from primary partner) and the sexual behaviours reported by HIV- partners.  Not surprisingly, this was found to be elevated in heterosexual couples where anal sex was reported, and in MSM where anal sex was receptive and receptive with ejaculation (1.68 and 2.70 per 100 couple-years, respectively).

With the couple-years accrued hitherto, appreciable levels of risk over the long-term, especially with anal sex, cannot yet be excluded: a rate of 2.2 per 100 couple-years remains the upper limit (20% over ten years) – though, of course, the risks could prove to be considerably lower than this.   With a view to arriving at a more precise estimation, the MSM side of the PARTNERS study remains ongoing.  So far, however, the news seems to be good.

Aside from its implications for personal decision-making about condom use, the question of the preventative effectiveness of ART could presumably also have relevance for health policy decisions affecting resource allocation that involve determining the relative priority to be accorded to interventions promoting engagement and retention in treatment as against other interventions (e.g. PrEP) (Punyacharoensin & White/STIs/blogNHS kicks PrEP into the long grass/STIs/blogs). The greater the effectiveness of viral suppression through ART as an HIV prevention tool, the better the case for prioritizing interventions to achieve higher targets for engagement and retention in treatment.

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