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HIV/hepatitis C co-infection increases risk of hepatic decompensation

22 Apr, 14 | by Leslie Goode, Blogmaster

A recent study (Lo Re & Vincent (L&J)) presents disquieting findings regarding the relative risk of severe liver complications in HIV/Hepatitis C co-infected patients.

Hepatitis C (HCV) has received particular attention in STIs recently on account of its strong association with HIV sero-positivity in MSM (Yaphe & Klein (STIs)) and because of its growing incidence in some MSM populations (Giraudon & Barton (STIs)).  As for the outcomes of HCV in co-infected patients, there have been studies suggesting the benefit of ART in slowing progression of liver complications; but, L&J claim, theirs is the first to have established a significant difference in the outcomes of HIV co-infected patients.

L&J is a retrospective cohort study involving the records of 10,359 patients receiving care between 1997 and 2010 through the US Veterans Health Administration.  It establishes a relatively higher risk of hepatic decompensation for HCV co-infected, as opposed to HCV mono-infected patients:  HR 1.83 or HR 1.56 (depending on whether death is treated as a “competing risk”).  Cumulative incidence of decompensation at ten years for co-infected and mono-infected was, respectively, 7.4% and 4.8%.

The study also gives an indication of the impact of levels of ART success (in terms of maintenance of HIV RNA levels) on rates of hepatic decompensation in co-infected patients.  Co-infected patients who maintained HIV RNA levels at less than 1000 copies/mL had lower rates of hepatic decompensation than patients who did not, but these rates were still considerably higher than for mono-infected patients: HR 1.44.  Cumulative incidence of decompensation at ten years for co-infected with HIV RNA ≥ 1000 copies/mL was 7.6%.

In addition, the study examined various characteristics associated with higher levels of decompensation in co-infected patients – most interestingly, perhaps CD4 count at the study baseline.  Cumulative incidence of decompensation at ten years for co-infected patients with CD4 <200×106 was 8.1%, as against 6.9% for co-infected with CD4 ≥200×106.

The authors conclude that the considerably greater risk of decompensation in co-infected patients is only somewhat alleviated by effective ART.  They point out that their findings strongly support current guidelines for the earliest possible initiation of ART in co-infected patients, regardless of CD4 count, and may prompt earlier consideration of initiation of HCV to reduce the risk of liver complications

Could Chlamydia treatment failure be the result of genital contamination from persistent gut infection

6 Mar, 14 | by Leslie Goode, Blogmaster

The persistence of Chlamydia trachomatis  (Ct) infection in treated patients is generally attributed either to re-infection or poor treatment adherence.  To some, however, the evidence has suggested the operation of an additional factor – such as treatment failure (STIs/ Goetz & Bruisten; STIs/ Pitt & Ison; STIs/ Horner).

A recent study (Rank & Yeruva (R&Y)) develops an interesting hypothesis, based on evidence of Ct. infection in the gastro-intestinal (GI) tract of mice.  This supports the possibility that Ct. persistence in humans might be a result of ongoing Ct. infection of the gut, and re-infection of the genital via the lower GI tract (Yeruva & Rank).  According to R&Y’s research on animals, Ct. of the GI tract does not elicit an inflammatory response, and never resolves.  It provokes an immune response – but not at a level that would cure the GI infection.  The orthodoxy states that Ct. found in the human GI tract is “non-replicating”.  R&Y claim this not based on evidence.  So they see nothing to exclude the possibility that, in humans, as in mice, treatment failure may be due to auto-innoculation from the lower GI tract.

This hypothesis is highly relevant to discussion of Ct. persistence in this journal, which has arisen around such questions as: whether persistence is due to some factor other than re-infection or poor adherence, such as anti-microbial resistance (STIs/ Goetz & Bruisten; STIs/ Pitt & Ison); how important that factor is, and what it means for Chlamydia screening programs (STIs/ Regan & Hocking).  If R&Y’s hypothesis proves valid for humans as for mice, then that other factor – or, at least, some element of it – is explained, and would certainly need to be taken account of when modelling the effectiveness of screening programs.

The idea that persistence of Ct. in humans results from contamination from persistent GI tract infection seems to be a new one in the STI literature (though apparently cases have been documented by the veterinary literature in numerous animals as early as the 1950s).  It is certainly worthy of further investigation, given the implications that it would have, if proven, for diagnosis and management of human Ct. infection.  In that event, it would be necessary to consider, for example, what importance to attach to the clearing Ct. from the GI tract – and, supposing this to be necessary, how this would affect the nature and duration of treatment given for genital Ct..  In treating rectal Ct., for example, treatment with Azithromycin (≤13%) has been claimed to be inadequate (STIs/ Drummond & Donovan), while Hathorn & Goold find treatment with doxycycline to be a more effective alternative (STIs/ Hathorn & Goold).

HIV impact of ObamaCare reduced by US Supreme Court decision

5 Mar, 14 | by Leslie Goode, Blogmaster

What impact will the roll-out of the US Affordable Care Act (ACA) – ObamaCare – have on health insurance coverage of people with HIV?  A recently published “issue brief” on behalf of the US Centers for Disease Control and Prevention (CDC) offers a first estimate (Kates & Garfield (K&G)).

The ACA includes a provision to expand Medicaid 1. by extending it to non-disabled childless adults (a group at present excluded), and 2. by raising the threshold of eligibility from the present 100% of the Federal Poverty Level (FPL) to 138%.  This would have considerable impact on uninsured HIV infected-people, as a large proportion of them are non-disabled childless adults, and relatively poor.  Thanks to a recent Supreme Court decision, responsibility for the implementation of this ACA provision rests ultimately with state legislatures.  Thus far, only 26 of the 51 states have plans to go ahead with it.  The authors of the brief give estimates, firstly for the impact that the ACA would have had but for the Supreme Court ruling, and, secondly, for the impact it will have, assuming implementation by just the 26 states that of stated their intention to go ahead with it.

In the case of full implementation of Medicaid expansion, say K&G, c.47,000 of the c.70,000 uninsured adults retained in HIV care would immediately be brought under Medicaid, while a further c.20,000 could benefit from the second major ACA provision relevant to the HIV-infected – namely, the subsidized insurance coverage which will be supplied by Health Insurance Marketplaces (HIM).

But, with just 26 states planning to expand Medicaid provision, only c.26,500 additional people will be brought under Medicaid.  Of the c.20,000 who ought to have qualified, but will now fail to do so, some 5,000 may be able to gain subsidized cover with HIM (those at between 100% and 138% of FPL), while the remaining c.15,000 (those under the 100% bar for subsidized coverage by HIM) will remain entirely uninsured.  Many people in this situation will seek coverage under the Ryan White HIV/AIDS program, as they have done in the past.

So the beneficiaries of ACA among the HIV-infected will, according to this brief, be considerably reduced by the Supreme Court ruling.  But does it really matter whether the HIV-infected of the US are treated through an expansion of Medicaid, or through the Ryan White program?

The authors of the brief seem to be in no doubt that ACA would represent an improvement on the present arrangements – and principally for two reasons.  The first has to do the 700,000 HIV-infected (63%) who are undiagnosed, or not linked to – or else not retained in – HIV care.  A proportion of these (the authors reckon as many as 124,000), newly eligible for Medicaid under ACA, could have been brought into regular medical care through the program.  This is the first opportunity missed.  The second has to do with the possibility of addressing the unmet needs of a particularly needy population (i.e. the c.200,000 HIV-infected who are currently uninsured but eligible for cover under ACA) on a more general and ongoing basis than is possible through the Ryan White program.  These, according to K&G, are the benefits which will be largely foregone in states that do not to ratify the expansion of Medicaid.

Can mass isoniazid preventive therapy be used to control the TB-HIV epidemic in Africa?

24 Feb, 14 | by Leslie Goode, Blogmaster

“We cannot win the battle against AIDS if we do not also fight TB”, Nelson Mandela has famously said.  His insistence on the importance of TB is understandable, when it is remembered that 82% of all cases of TB-HIV co-infection are concentrated in sub-Saharan Africa, and many Africans infected with HIV die from TB (STI/ Kaireh & Dao; STI/ Ogbuagu).  On an individual level, the treatment of co-infection has seen impressive results (STI/ Ogbuagu).   Against the contemporary background of recent demonstrations that ART can also have a preventative effect at population level, Mandela’s remarks raise the question – given the independent but interlinked nature of the two epidemics – whether the timely treatment of TB could not also have a population-level effect, thus allowing us to tackle the co-infection epidemic from the TB as well as the HIV end.

The recently reported Thibela randomized control study of isoniazid therapy among South African gold miners (Churchyard & Grant) has investigated whether comprehensive screening, followed by treatment of either active or latent TB within a community could serve, by itself, to disrupt TB transmission, given the high level in HIV in this population.  There has been evidence of the limited durability of the efficacy of isoniazid preventative therapy, which is not encouraging (Johnson & Whalen).  However, a 1960s trial in Alaska appeared to demonstrate a 55% decline in infection over five years (Comstock & Snider).  Besides, Churchyard & Grant’s population of 78,744 South African gold miners in 15 settlements  seem ideally suited for the intervention, given they live in hostels and mix predominantly with those from the same mine.

The study implemented screening and therapy over nine months in the intervention clusters, then measured relative TB incidence as compared with the control clusters over the 12 months after the intervention; it also measured TB prevalence at study completion.  In addition to the effectiveness of the intervention in disrupting TB transmission over the entire communities, the researchers analysed the efficacy of the isoniazid therapy in relation to a group of 10,909 miners surveyed at baseline.

It was found that the intervention had no significant population-level effect on incidence (3.02 cases per 1000 person years in the intervention, as against 2.95 in the control), or prevalence (2.35% vv. 2.14%).  This was despite the isoniazid therapy being demonstrated to have a substantial direct impact on TB incidence in the course of the intervention (1.10 cases per 100 person years in the intervention clusters, as against 2.91 cases in the control).  Though participation and retention was variable across the clusters, even where they were excellent, there was no significant improvement in these results.

The lack of epidemiological effectiveness could have been the result of post-treatment re-infection, but also of the very high prevalence of HIV (as well, perhaps, of silicosis) among the miners.  The latter factor represents the most obvious difference between this study population and that of 1960s Alaska.  As regards the potential effectiveness of community-wide isoniazid interventions to interrupt TB epidemics in sub-Saharan Africa, the study offers little grounds for optimism.  It recommends expanding strategies for controlling HIV and developing systems that minimize the time from receiving a positive TB result until treatment.  But also points to an interesting potential role for mathematical modelling to identify strategies for dealing with the TB-HIV co-epidemic.

iPrEx finds no evidence that PrEP use is associated with risk compensation

14 Feb, 14 | by Leslie Goode, Blogmaster

A great concern in respect to the deployment of Pre-Exposure Prophylaxis (PrEP) as an HIV prevention tool is risk compensation - i.e. the possibility that the protection afforded by PrEP would itself encourage sexual risk-taking (STI blogs/Sugarman & Mayer).  Recent studies of PrEP efficacy would seem an unpromising context in which to assess the likely impact of such a factor, given that a dependable level of HIV protection – such as might encourage risk-taking behaviour – is precisely what these studies are seeking to demonstrate.  This difficulty has not deterred the researchers, however.  The most recent attempt to evaluate risk compensation in such a context (Marcus & Grant) (M&G) is a spin-off from the recent iPrEx study of the efficacy of PrEP using metricitabine/tenofovir disoproxil fumarate (FTC/TDF) in 2,500 MSM and transgender women (recruited at 11 sites in Peru, Ecuador, South Africa, Brazil, Thailand and the US) (Grant and Glidden (2010)).  Marcus and Grant’s study follows closely on another spin-off risk-compensation study arising from the Partners PrEP study covered in an earlier STI blog (STI blog/Mugwanya & Baeten).

Not only were participants in the Marcus & Grant study uncertain of the degree of protection that PrEP would afford (the eventual outcome was a 44% reduced risk of HIV acquisition, and 92% reduction for participants with detectable drug levels); they were also, of course, unaware of whether they had been assigned to the intervention or placebo arm of the study.  Marcus & Grant therefore use perceived treatment assignment and belief in PrEP efficacy as surrogates for the assurance of HIV protection which future PrEP users might be tempted to see as offsetting any increase in their risk-taking behaviour.  Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and belief in PrEP efficacy were assessed at 12 weeks.  Practice of receptive anal intercourse without condom (ncRAI) was taken as the indicator of sexual risk-taking behaviour.

Findings of the study were as follows.  Mean number of RAI partners decreased (10-6) in the first twelve weeks from baseline, then remained more or less constant, while condom use with RAI partners rose in the same period (c.50-c.75%), and then plateau-ed.   The researchers found no indication of any association between risk-taking and participation in the trial – we may wonder though whether anyone would have expected there to be one.    However, a clear association emerged between ncRAI/no ncRAI at base line and perceived assignment to PrEP/placebo (53%/47% for PrEP, and 61%/39% for placebo).  Marcus and Grant are inclined to interpret this association as a reflection of the impact of risky behaviour on attitudes to treatment (“the belief could have served as a psychological mechanism to reduce concerns about sexual behaviour”), rather than that of treatment optimism on sexual behaviour.  However, the key finding for our authors was the absence of any difference in risk behaviour (ncRAI) between the treatment optimists and the treatment pessimists – and between those who claimed to have greater confidence in PrEP efficacy and those who claimed to have less.  This suggests the absence of a risk compensation effect.

A number of study limitations are discussed in the paper (not least of which that of reporting bias), but not the limitation that is patently the most serious: namely the questionable adequacy of perceived treatment assignment as a surrogate for the assurance of a certain level of PrEP efficacy.

On this point Mugwanya and Baeten (W&B) offer an interesting comparison (STI blog/Mugwanya & Baeten).  Participants in the intervention arm of the Partners PrEP study were informed of the study outcome (indicating a 96% reduction in HIV transmission between infected and uninfected partners), and follow-up, including monitoring of STI incidence, was continued for a further year, allowing comparison between sexual behaviour of participants before and after knowledge of PrEP efficacy.  M&B seem to corroborate the Markus & Grant’s finding of no risk compensation – and on the basis of far more solid evidence.  However, M&B’s finding relates to the behaviour of heterosexual couples, and is prima facie unlikely to be generalizable to the behaviour of MSM and transgender women.

Prospects for a high sensitivity point-of-care test for Chlamydia

14 Feb, 14 | by Leslie Goode, Blogmaster

A recent paper (Krölov&Langel) describes a technique for the diagnosis of Chlamydia trachomatis which, if developed into a point-of-care test (POCT), could be performed in just twenty minutes and would achieve a considerably greater sensitivity (83%) than any of the POCT alternatives to the current laboratory testing process using Polymerase Chain Reaction (PCR).  The technique – Recombinase Polymerase Amplification – is a Nuclear Acid Amplification (NAAT) test (like PCR), but one that allows a simplification of the complex stage of sample preparation such that it can be accomplished swiftly outside a laboratory setting.

The problem with PCR is that because it depends on a laboratory process, patients have to make a second visit to their health care provider in order to receive their diagnosis and treatment – and, some may fail to make that visit.  Existing POCT alternatives, however, seriously under-perform on the score of sensitivity (generally under 60% – and in many cases much worse).

Some researchers – including contributors to STIs (STIs/Skidmore; STIs/Gaydos; STIs/Dommelen&Hoebe) – have viewed the availability of such poorly performing tests as entirely detrimental.  On the other hand, the scale of the problem of patients lost to follow-up no doubt varies with place and time – and what is required of POCT may not be the same in all contexts (STIs/Rompalo&Gaydos).  Others, therefore, have taken a more positive view of the impact of less than perfect POCTs – to extent of acknowledging their potential role in certain contexts, or in combination with other interventions (Swain&Singh).  A recent modelling study (STIs/Huang&Barnes) has sought to set the conditions of cost-effectiveness for such a POCT in terms of thresholds for sensitivity, cost of POCT, and “willingness to wait” for the result.

Above all, however, the potential of the less than perfect POCT depends on the size of the “lost to follow up” problem.  The Swain and Singh (S&S) model assumes a 93.5% rate of return for treatment achieved for their sample by the Baltimore STD clinics engaged in their study in 2010.  This rate does not seem higher that than would be expected in STD clinics in developed countries nowadays (e.g. the UK).  It is certainly a good deal better than the 80% given by Schwebke & Hook for Alabama in 1994 – which has since been cited by Swain & Singh (2004) and Krölov & Langel (2014).  Assuming the rate of 93.5% lost to follow-up, Swain and Singh estimate degrees of sensitivity that would be needed at a given cost per test for the POCT to achieve a cost-effectiveness that would equal that of the current PCR tests.  Thus for a cost per test of $30 a POCT with approx. 85% sensitivity would be required; for a cost per test of $35, a sensitivity of 90%.  All of these predictions assume a POCT that would require the patient to wait 40’, and fairly low stated levels of “readiness to wait” (e.g. only 48% on the basis of a patient questionnaire).  On the basis of such admittedly rather rough and ready assumptions, the sensitivity of the proposed POCT seems to come at least range of parity with PCR as regards cost-effectiveness.

But these estimates all assume levels of “lost to follow up” such as we find in an STD clinic in developed countries.  This situation could, of course, be very different – and more favourable to POCTs – amongst specific populations and less developed countries where rates of return for follow-up could be much lower.  A more interesting and relevant modelling study than that of Swain and Singh would have shown the relation between proportion of “lost to follow up” and sensitivity for a given cost per test, rather than treating proportion of “lost to follow up” as the fixed parameter.

Pre-test HIV risk reduction counselling is not worth the money

2 Jan, 14 | by Leslie Goode, Blogmaster

A large US randomized control trial of the impact on STI risk of HIV risk reduction counselling in conjunction with the HIV test (Metsch & Colfax) challenges the view that pre-test counselling constitutes an efficient use of limited resources – at least in the US setting.

Counselling has long had an important place in the struggle against HIV/AIDS.  The established form of individual patient-centred counselling focussing on the discussion of the patient’s specific behaviours and the negotiation of achievable risk-reduction steps goes back to 1993.  Its effectiveness was apparently confirmed by the 1998 Project RESPECT study (STIs/Rietmeijer).  More recently (2008), however, a systematic review by the US Preventive Services Task Force (Lin & Bauer) could cite only one study – namely,  RESPECT – as showing an effect on subsequent STI acquisition.  A systematic review of 14 studies (of which 12 in the US), published 2007 in STIs, reached no very definitive conclusions (STIs/Ward & Radcliffe), though at about that time (2007) counselling was included in the UK National Institute of Clinical Excellence (NICE) guidelines (STIs/Ward).  Now, in the US, the resource implications of the National Strategy goal of increasing the percentage of HIV infected who know their status from 79% to 90% by 2015 has raised the question whether the resources expended on pre-test counselling could not be better spent.

The recently reported Project AWARE study (Metsch & Colfax) is comparable in scale to Project RESPECT (5,012 participants over nine clinics).  It revisits the same question of the effectiveness of pre-test counselling, though in the contemporary context of the existence of effective therapies.   It also includes among its participants, men who have sex with men, an important group who were not included in Project RESPECT.  Project AWARE divided participants between a “counselling” arm, who received c. 20’ of individual patient-centred counselling (as described above) along with their point-of-care HIV test, and a control arm, who were given information only.  Tests for STIs, plus a computer interview, were administered at base-line, and at six months follow-up.

The results showed no significant difference in six months STI incidence between the intervention and the control arm: for the 2,039 participants in the counselling arm, there were 250 (12.3%) incident cases; for the 2,032 in the information only arm there were 226 (11.1% incident) cases.  Furthermore, there was no significant difference in sexual behaviour at six months between the two groups in respect to number of sex acts, number of unprotected sex acts, and number of unprotected partners: though there was a small difference in the reported number of partners (2.7 in “counselling” as against 3 in “information only”).  The authors conclude that if pre-test counselling resulted in changes in sexual behaviour, such changes were not sufficient to affect cumulative STI incidence.

An important limitation, as stated by the authors, is that the results are not “generalizable to international settings”.  STI journal has featured a number of studies indicating the effectiveness of voluntary testing and counselling (VCT) in limited resource settings, whether changes of behaviour are the result of the counselling itself, or a change of attitude prior to the decision to attend VCT: see (Kenya) STIs/Arthur & Gilks; (South Africa) STIs/Nshiniyimana & Bruyn; (Zambia) STIs/Sikasote & Murray.  Another clearly stated limitation is that the study applies only to the established type of 20’ individual patient-centred intervention they describe – not to other types, such as, for example, the couple-based intervention very positively evaluated by LaCroix & Johnson (STIs/LaCroix & Johnson).

Emergence in Guinea-Bissau of an HIV-1 recombinant variant associated with three-fold increase in disease progression

30 Dec, 13 | by Leslie Goode, Blogmaster

Studies, including some in STIs journal, have mapped the geographical distribution of HIV types, subtypes, recombinant variants (CRF): see: (Middle East) STIs/Mumtaz&Abu Raddad; (Sub-saharan Africa) STI blogs/Tatem&Salemi.  Such work has potential importance for our understanding of the evolution of HIV resistance, and also for the identification and targeting of established and nascent epidemics among core risk groups in a population.

A recent paper (Palm&Medstrand) takes this kind of research in a less familiar direction, by examining the association between subgroup and rate of disease progression in Guinea-Bissau.  Should certain subgroups or recombinant variants prove to be associated with much swifter disease progression, this knowledge would be relevant to the management of patients (monitoring and testing intervals), as well as being essential to our understanding of the scale of the HIV problem in the area concerned and its implications for planning a response.

Problems for earlier research, according to these authors, include obtaining estimated dates of sero-conversion, and a tendency towards “broad brush” comparisons between groups combining a diversity of subgroups and recombinant variants.  Palm & Medstrand had data for seroconversion as well as disease progression from a longitudinal cohort of police officers in Guinea-Bissau, including 225 treatment-naive HIV-1 seroincident individuals, going back to 1990 and continuing, with the exception of the two-year interval (1998-9) of the civil war, to the introduction of the national treatment program in 2005. They analyse disease progression (time from sero-conversion to AIDS and AIDS-related death) for each subtype/CRF independently.

The overall epidemiological picture for Guinea-Bissau has undergone a transformation since the nineties of the last century (STIs/Mansson&Norrgren).  The 147 individual samples, for which sequencing and assignment of subgroup was possible, demonstrated a distribution of HIV-1 subtype/CRF that resembled previous recent estimates for Guinea-Bissau, including, almost exclusively: subtype A3 (29%), CRF 02_AG (53%), plus a recombinant of these two, A3/02 (13%).  Compared with A3 (which showed the slowest disease progression), CRF02_AG was associated with a risk ratio for progression to AIDS and AIDS-related death of 1.4 and 2.2, respectively; A3/02 with a risk ratio of 2.6 and 2.9, respectively.

Recombinant variant A3/02 shows the fastest progression rate reported to date.  Given the three-fold difference in progression rate between HIV-1 A-like subtypes/CRFs, the authors stress the importance of determining the HIV-1 subtype of infected individuals.

Partners PrEP sub-study finds no evidence that PrEP use is associated with risk compensation behaviour

21 Nov, 13 | by Leslie Goode, Blogmaster

How useful is pre-exposure prophylaxis (PrEP)?  The Partners PrEP randomized control study of daily pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-discordant couples in Uganda and Kenya has indicated that, given adequate adherence, PrEP has high biologic efficacy.  The study itself (Baeten & Celum) demonstrates levels of risk reduction of 75%; while a spin-off sub-study from the original trial, monitoring adherence (STI blog/Haberer & Bangsberg ), has established that, with high adherence (c. 97%), levels of protection are even higher than the study might suggest (none of the 14/1,147 sub-study participants who sero-converted were from the intervention arm of the study).

These results have fed into recent attempts to model the likely effectiveness of PrEP.  The consensus hitherto seems to be that PrEP is a relatively high-cost intervention most likely to be cost-effective as an addition to ART in countries where the burden of HIV is high, and rates of male circumcision low – such as southern Africa (Verguet & WalshYing and Barnabas).

Last month saw the online publication of a second interesting spin-off sub-study of Partners PrEP (Mugwanya & Baeten).  It undertakes a longitudinal analysis of data from the original trial to address what is perhaps the greatest concern affecting the implementation of PrEP as a public health intervention (STI blog/Sugarman & Mayer), that of risk compensation – i.e. the possibility that the security promised by PrEP will itself encourage sexual risk-taking behaviour.  M&B’s results, along with those of any future studies of this issue, will no doubt serve to inform the assumptions of future models.

In July 2011 the Partners PrEP study reported its findings, and the placebo arm of the trial was closed.  However, follow-up of 3,024 participants continued.  This allowed data on their sexual activity to be collected over a period which spanned the 12 months preceding – and the 12 months following – the disclosure to participants of the results of the study.  These data included unprotected sex acts and total sex acts over this period, both within the primary relationship as registered by the study and outside that relationship.

Within the primary relationship (i.e. with the registered HIV-infected partner), the crude average frequency of unprotected/total sex acts within the primary relationship was 59/414 per 100 person- months prior to, and 53/361 following, unmasking.  Outside that primary relationship the frequency of unprotected total sex acts was 49/62 as opposed to 67/84. So there appears to be a fall in unprotected/total sex acts with the primary sex partner as between the two halves of the period, and a small, but significant, rise in unprotected/total sex acts outside this relationship.  The latter rise (unprotected sex acts outside the primary relationship) is helpfully quantified at an average of 6.8 sex acts per year following unmasking as against an average of 6.2 acts in a predicted counterfactual scenario had patients remained unmasked.  M&B place this figure in the context of the estimated doubling of risk-behaviour, which modellers suggest would be required in order to see any attenuation in the effectiveness of PrEP.

The authors suggest – optimistically perhaps – that the small decrease in unprotected sex following enrolment indicates that PrEP delivered in the context of an HIV prevention package may be synergistic for risk reduction.  However, they also point to an earlier study (Ndase & Thomas) that finds this overall pattern of decline in sex acts with primary partner and rise in sex acts outside the primary relationship to be indicative of dissolution of the primary relationship and formation of new relationships.  They also observe that unprotected sex without outside partners was “high among the few participants who reported sex outside the primary partnership” – an observation that accords with recent study findings that a quarter of HIV infections in sero-discordant partnerships arise from non-primary partners.

The findings of the study seem reassuring.  They raise two questions, however.  The first concerns the impact of the probable gap between the HIV prevention package accompanying any real-life PrEP implementation and the package made available to the participants in Partners-PrEP.  The second concerns the impact of new partnership formation on unprotected sex over the longer term.  It is here that the findings of M&B would lead us to expect the greatest challenge to PrEP; yet the true extent of such a challenge is something of which their study can offer us only the most preliminary impression.

What can cost-effectiveness modelling tell us about the feasibility of eliminating congenital syphilis in sub-Saharan Africa?

20 Nov, 13 | by Leslie Goode, Blogmaster

The WHO global initiative for the elimination of congenital syphilis (2007) set the goal of expanding antenatal testing to >90% by 2015.  In sub-Saharan Africa (SSA) recent estimates place the number of mothers infected with active syphilis at 535,000 p.a..  Adverse outcomes – stillbirths, neo-natal morbidity and congenital disease – affect 53%-82% of these pregnancies, as compared with 10%-21% of women without syphilis.  Yet, perhaps surprisingly,  74% of pregnant women in SSA are reported to attend an antenatal clinic at least once.  Administration at the routine visit of a simple point-of-care test (POCT), plus, in the case of detection, an intra-muscular injection of benthazine penicillin, is all that, in most cases, would be required to deal with the problem.

A recent modelling study (Kuznik & Manabe ) seeks to make the economic case for universal POCT syphilis screening in 43 countries in SSA.  It estimates the cost of increasing syphilis testing at antenatal clinics from whatever it is at present to 100% through universal adoption of the immunochromatographic strip test (ICT), and the benefits that would result in terms of saved lives and reduced morbidity.  It then calculates the cost-benefit in US dollars per Disability Adjusted Life Year (DALY).

The findings are given for each of the 43 countries considered. Here are the aggregate findings for SSA as a whole.  In order to ensure screening coverage for the 23.5 million (74%) pregnant mothers attending ante-natal clinics, the cost is estimated at a comparatively modest US$20.8 million per year, and would, it is claimed, reduce incidence of still-birth, neo-natal death and congenital syphilis by 64,000, 25,000 and 32,000, respectively.  Of the 43 countries in the model the cost of such an intervention per DALY averted would be less than US$20 in 37 cases, and less than US$10 in 23 cases.

The study claims to be the first to have evaluated the cost-effectiveness of ICT across SSA.  What is the value of this exercise?  It seems to consist primarily in the extra rhetorical “punch” it can lend to the argument in favour of doing something – and something very cheap - in order to alleviate the deplorable ravages of perinatal mortality and morbidity due to syphilis.  One can only applaud the intentions of its authors.  At the same time, one is struck by the inadequacy of the measure employed (cost per DALY ) to capture any real sense of the economic (let alone human) cost of MCST.  The impressive figures they arrive at for cost-effectiveness of the proposed interventions owes not a little to the fact that the lost life-years averted happen to be those of the stillborn or neonatal deceased.  This does not belittle the cost, but feels a rather odd way of looking at perinatal outcomes.  Consequently the whole exercise, while it may be well-intentioned and ticks all the official boxes, strikes this reader at least as rather specious.  One wonders if it can offer any real ground for the prioritization of MCST as against other equally laudable interventions: if it does, one feels somehow that it ought not to!

Relevant to the real economic cost confronting any country deciding to switch to the ICT would presumably be the relative cost of the ICT compared to an established alternative (e.g. Rapid Plasma Reagin (RPR)).  After all, using ICT to make up the shortfall in current testing levels presupposes the country has made the switch from RPR to ICT – which may already have cost implications (Vickerman and Watts).  Ultimately, however, the main the challenge of making this switch, may not be economic cost at all, but a problem of institutional organization and training (STI blog/Peeling & Mabey).   Peeling & Mabey observe in relation to one area in which POCT for syphilis was being introduced as part of a trial “a 65% drop over the first six months in the percentage of antenatal clinics 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”.  Here and elsewhere (Peeling & Mabey) make the case for the importance of “programme science” to “address the gap” between test performance and successful deployment.

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