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HIV care

‘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?

The PrEP ‘care continuum/cascade’: how would it look?

8 Mar, 17 | by Leslie Goode, Blogmaster

We take for granted the value of the care continuum (or ‘cascade’), now increasingly seen as the key measure of health system response to HIV (Cassell (STIs editorial)).   The application of this model to HIV has provided a benchmark for evaluation in contexts as diverse as Moscow (Wirtz & Beyrer (STIs)), South Africa (Schwartz & Baral (STIs)) or the Netherlands (van Veen & van der Sande (STIs)).   But could the same model also offer a means of evaluation in the case of other complex sexual health interventions such as PrEP (Pre-Exposure Prophylaxis)?

An on-line soon-to-be-published paper by Nunn & Chan (N&C), building on an earlier attempt by Kelley & Rosenberg (K&R), does precisely this.  An important difference from the earlier paper seems to be the more concrete definition of a larger number of steps (nine as against five) – especially in the central area of ‘uptake’ and engagement in care.  Here K&R define three stages: ‘need for awareness of PrEP and willingness to use it’, ‘need for good access to healthcare’, and ‘need for a prescription for PrEP.  N&C replace these with a more concrete conceptualization of the process in five stages involving: an occasion where PrEP access is facilitated (4); an appointment arising from that occasion where the assessment is performed (5); the prescription of PrEP, where indicated (6); the actual initiation of PrEP (i.e. when the client starts taking the pills) (7).  Also important is N&C’s substitution of two final steps – adherence (8)) then retention (9) for K&R’s single final step of ‘adherence’.  N&C point out that, whereas, with ART, ‘adherence’ is once-and-for-all and secures the ultimate goal of viral suppression, in the case of PrEP, we can envisage multiple trajectories depending on whether PrEP continues to be indicated (e.g. the client may no longer be exposed to risk).  Finally, K&R’s first step – ‘identifying at risk MSM’ – gives way to three: identifying at risk individuals (1), enhancing HIV awareness (2), enhancing PrEP awareness (3).

Is this nine-stage definition of a PrEP cascade overly “complex” (EECAAC2018)?

Answering such a question requires us to reflect on the function that the ‘cascade model’ is called upon to perform.  If the model divides up the total course of an intervention into a series of staged tasks, this is presumably because the health benefit depends on the completion of the whole intervention, yet the accomplishment of each step is necessary to the achievement of subsequent ones.  The idea of the cascade can provide a fair way of evaluating the progress of an intervention before its potential health benefits have been delivered – and can also identify the precise points at which the intervention is failing (i.e. where clients become ‘disengaged’).

It follows that each step should correspond to a potential outcome that is not inferable from previous or later outcomes but is worthy of independent evaluation.  If everyone who accesses PrEP (4) also attends an appointment at which suitability of PrEP is discussed (5), or everyone who adheres to PrEP (8) is also retained in PrEP (9), then steps (4) and (5), or steps (8) and (9), can be merged.  This is not stated in so many words by the authors of the model.  However, I would assume that it must lie at the basis of their thinking.

Changes in the WHO Guidelines for treatment of HIV

5 Nov, 15 | by Leslie Goode, Blogmaster

The WHO has released early its revised guidelines on the treatment of those infected with HIV (WHO early release guideline; WHO press release).  There are two important changes.  First, ART is recommended to all HIV infected individuals regardless of their CD4+ count.  Second, PrEP is recommended for people at ‘substantial’ risk of HIV infection as part of a comprehensive package of services.

The first of these revisions comes in the train of repeated rises over recent years in the recommended treatment threshold: first (2010), to350 CD4 per mm3; then (2013), from 350 to 500.  The latest revision is doubtless based on the results of randomized controlled trials (RCT) such as the START (Strategic Timing of Anti-Retroviral Therapy) trial (A Case for Immediate ART Initiation (STI/blog)).  The second builds on a WHO 2014 guideline which already recommended PrEP for MSM populations.  Here again recent RCTs demonstrating the effectiveness of PrEP, such as PROUD and IPERGAY (PrEP highly effective for HIV in MSM (STIs/blog)) will have played their part.

The removal of the threshold has resource implications that will pose a serious challenge in resource poor settings.  Writing in 2010 Hamilton and Crowley (STIs) estimated that setting the threshold for ART initiation at 250 CD4+ would by 2012 increase the need for treatment by a median of 15%, whereas setting at 350 CD4+ would increase it by 42% and 500 CD4+ by 84%. Contributors like Hallett & Garnett (STIs) (Zimbabwe) and Zwahlen (STIs) have sought to develop projections for individual countries.

Also, it has been argued that late diagnosis (even by current standards), and poor retention in care are significant factors in suboptimal health outcomes (Mubezi & Shuha (STIs)Hussey (STIs).  What the revised guidelines will deliver in real terms no doubt depends on the context of implementation.  Yet, even in the relatively more affluent settings (US), some recent research has argued for the reallocation of resources from linkage to retention in HIV care, in order to optimize utilization of scarce resources (Retention in Care (STI/blogs)Sherer (STIs). This could prove hard to square with the prioritization of ever lower thresholds for linkage to care – even if the recommended policy is in the interests of improving individual outcomes.

A case for immediate ART initiation in all HIV diagnosed, regardless of CD4+ count?

28 Aug, 15 | by Leslie Goode, Blogmaster

The year 2013 saw the WHO recommended threshold for treatment of HIV+ patients with ART rise from a count of 350 CD4+ per mm3 to one of 500 CD4+ per mm3.. The threshold had been fixed as early as three years before (2010) at 350 CD4+ per mm3 (WHO ART recommendations). These recommendations have doubtless been made with a view both to improving individual outcomes and preventing transmission. However, their implementation poses, and will continue to pose, a serious challenge, especially in resource-poor settings. Writing in 2010, Hamilton and Crowley (STIs) estimated that setting the threshold for ART initiation at 250 CD4+ would by 2012 increase the need for treatment by a median of 15%, whereas setting at 350 CD4+ would increase it by 42% and 500 CD4+ by 84%. Contributors like Hallett & Garnett (STIs) (Zimbabwe) and Zwahlen (STIs) have sought to develop projections for individual countries.

It may not be so long before the modellers have, once again, to revise their calculations. Results of the Strategic Timing of Antiretroviral Therapy (START) trial, a recent multi-continental RCT, make a case for not deferring ART initiation, regardless of the patient’s CD4+ count. A total of 4,865 patients in 35 countries were randomized to an immediate and a deferred initiation group, and followed over a three-year period. The trial compared primary end-points, including death and serious AIDS-related, and non-AIDS-related, health events, over a three-year period. Among the commonest AIDS-related events were tuberculosis, Kaposi’s sarcoma and malignant lymphoma. Non-AIDS related events included cardio-vascular disease and non-AIDS related cancers. Hazard ratios for serious AIDS-related and non-AIDS related, events were 0.28 and 0.61, respectively. There have been concerns about the negative health impact of ART especially on cardio-vascular disease. But no safety concerns in the immediate-initiation group were identified. However, as the authors recognize, the study was underpowered for investigating the potential negative effects of early ART initiation on individual non-AIDS related events, because of the relatively limited number of events and early termination of the deferred therapy strategy.

In principle, the benefits of raising the threshold for linkage to care are clear. In due course, we may expect to see yet another upward adjustment in the WHO threshold. However, recent studies point to inadequate availability of care, late diagnosis (even by current standards), and poor retention in care as significant factors in suboptimal health outcomes (Mubezi & Shuha (STIs); Hussey (STIs). So what such a change in guidelines would deliver in real terms is hard to evaluate, and no doubt depends on the context of implementation. Yet, even in the relatively more resource rich settings (US), some recent research has argued for the reallocation of resources from linkage to retention in HIV care, in order to optimize utilization of scarce resources (Retention in Care (STI/blogs); Sherer (STIs). This recommendation would seem hard to square with the prioritization of ever lower thresholds for linkage to care.

At all events, this study demonstrates the benefits to the individual of prompt linkage to care whatever the stage in the progression of his/her infection.

Retention in care rather than diagnosis may prove the ultimate challenge for US HIV response

25 Mar, 15 | by Leslie Goode, Blogmaster

The real challenge which the US HIV/AIDS epidemic poses for the US public health services is not simply to achieve higher levels of diagnosis – but, far more than that, to improve linkage to, and retention in, care.  This claim is hardly controversial. But it is thrown into stark relief in a recent study by Skarbinski & Mermin, which estimates the number of HIV transmissions attributable to non-retention in care for 2009.

The authors employ the notion of a five-phase “care continuum”.  Using population data from the National HIV Surveillance System and medical data from the National HIV Behavioral Surveillance System and the Medical Monitoring Project, they estimate the number of HIV transmissions occurring at each phase.  The phases in the continuum are: (1) infected, but undiagnosed; (2) diagnosed, but not retained in care (attending at least one visit to a medical care provider Jan. – April 2009); (3) diagnosed, retained in care, but not given ART; (4) diagnosed, retained in care, prescribed ART, but not virally suppressed; (5) virally suppressed.

The reduction in attributable transmissions achieved for those diagnosed but not retained in care (phase 2), as compared with those who remain undiagnosed (phase 1), is 19%.  (It is probably due to a decrease in HIV-discordant unprotected sex).  But the reduction achieved for those who achieve viral suppression (phase 5), as compared with those who remain undiagnosed, is 94%.  In estimating the epidemiological impact of these reductions, we need to factor in the percentage of the infected population at each phase.  The large proportion (45.2%) of the HIV infected who are diagnosed but not retained (phase 2) explains the very high proportion of total transmissions (61.3%) attributable to this phase.  By comparison, only 30.2% are attributable to the undiagnosed (phase 1), and 2.5% to the virally suppressed (phase 5).  The low epidemiological impact of those at phases 3 and 4 is due to the relatively low proportion of those infected who remain in these phases.

The message, then, is that achieving greater success in retaining the HIV diagnosed in care may prove the key to combating the epidemic at population level.  Of course, diagnosis remains the indispensable first step.  But the potential gains of diagnosis will be only very partially experienced, so long as such a large proportion of those diagnosed are not retained in care.  Of course, improving retention in care may constitute a somewhat different – and perhaps more difficult – challenge for the US health services from diagnosis.  The specific problems of the US health system in this regard are discussed by Sherer (STI), and the characteristics of individuals “lost to follow up” by Haddow & Mercey (STI) and Lee & Gazzard (STI).  Local attempts to address these problems through a more “wrap-around” approach to health care in the US are described in my blog Bocour & Less (STI/blog) (see Bocour &  Less).  There has also been interest in the computer assisted self-interviewing in order to engage those lost to care (Dombrowski & Golden (STI)).

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.

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.

UNAIDS assesses progress towards #HIV Millennium Development Goal

28 Oct, 13 | by Leslie Goode, Blogmaster

In the run-up to the 2013 General Assembly of the UN in New York, a new report from the Joint United National Program on HIV/AIDS seeks to give an overview of progress to date towards Millenium Goal 6 – the goal of halting and beginning to reverse the HIV/AIDS epidemic by 2015 (UNAIDS Report 2013).  Progress is evaluated in terms of the ten targets and elimination commitments established by the 2011 UN Political Declaration.

The headline figures relate largely to the targets involving specific health outcomes (5 targets out of 10l).  At 33%, the decline between 2001 and 2013 from 3.4 to 2.3 million in annual new HIV infections is perhaps within striking distance of the 50 % target (no.1) set by the Declaration, and at 36%, the reduction in HIV-related TB deaths is similarly within reach of an identical 50% target (no.5).  A sharp reduction – of 35% between 2009 and 2012 – in mother-to-child transmission is also encouraging, though, say the authors, the target (no. 3) of “elimination” will require greater integration of HIV and antenatal care than has so far been achieved.  As regards ART, the world looks set to achieve the regard of 15 million in treatment by 2015 (no.4), with 61% of those eligible under WHO guidelines already receiving treatment.  Efforts fall woefully short, however, in respect to the target (no.2) of halving HIV transmission in injecting drug users.

The remaining five targets include: closing the “resources gap” (no.6); service integration (no.10); various “elimination” targets involving structural change – i.e. gender inequality (no.7); stigma (no.8); entry and residence restrictions (no. 9).  So far as resources are concerned (no.6), the available US$18.9 billion for 2012 is up by an encouraging 10% on 2009, though still short of the target of US$22-24 for 2015.  On integration (no.10), things are also moving in the right direction, with 53% reporting integration of HIV and TB services, and an encouraging two thirds already integrating HIV and sexual and reproductive services. However, on all the elimination targets (no.7-9), progress seems very slow: <50%  of countries allocate funds for women’s organizations, integrate HIV and antenatal services, or engage men in national responses (no.7); 60% of countries report laws which present obstacles to effective HIV prevention (no.8); only eight countries have eliminated restrictions on freedom of movement (no.9).

It is interesting to read this report in the light of the concerns widely voiced prior to, and contemporaneously with, the 2011 UN Political Declaration, that the Millennium Goals risked favouring an “outcomes-based” emphasis on “quick-fix” interventions – and that a more “holistic” approach was needed, along with “smarter metrics”( STI blog: Right Way Forward?; STI blog: MDGs Bad for your Health?) .  These concerns seem to be reflected in the formulation of the 2011 targets, with their emphasis on holistic factors (no.s 7-9), and on service integration (UNAIDS Report 2011).  It is precisely in these latter areas that the progress noted by the recent UNAIDS report seems slowest, and is hardest to evaluate.  Regarding HIV integration (no. 10), however, the authors note that “a clear trend towards integration of HIV with diverse systems and sectors apparent”, though they also call for “greater efforts”.

 

 

Should ART provision be decentralized to health centres in low and middle income countries?

12 Aug, 13 | by Leslie Goode, Blogmaster

With the realization of the value of ART as a means of preventing HIV transmission, the question of how best to retain HIV-diagnosed in care becomes all the more pressing.  Recent STI blogs have covered such topics as the potential role of computer-generated reminders in retaining patients (sti blogs03/05/13), as well as the re-engagement of patients lost to care in a developed world context (sti blogs17/06/13).  But what about the retention of the HIV diagnosed in limited-resource settings such as sub-Saharan Africa?  Here, the stakes seem even higher – given the severity of the epidemic, and likely obstacles to full engagement such the relative inaccessibility of medical facilities to poor people living in rural settings (sti-Fried & Eyles).  What is the evidence that decentralizing HIV care from hospitals to local health care centres or the community could help to improve retention in care, and thereby contribute to controlling the epidemic?

A recent systematic review (Kredo & Gardner) produced by the Cochrane Collaboration surveys the few studies that address this question, and its results have fed into the recent WHO guidelines (WHO 2013 ART guidelines).

The paper itself considers care options within the three general categories of “partial decentralization” (ART initiated by hospital, maintained by local health centre), “full decentralization” (ART both initiated and maintained by health centre), and “decentralization to the community” (ART initiated by hospital or health centre and maintained by the community).  The options are examined in regard to their impact on loss to care, mortality, and attrition (a combination of loss to care + mortality).

Most of the evidence surveyed (i.e. 12/16 studies) consists in retrospective cohort studies susceptible to various kinds of bias.  Consequently the evidence is largely graded low or very low quality.  However, the review flags up some moderate quality evidence that:

–           partial decentralization is associated with reduced attrition at 12mnths. (RR=0.46)

–          full decentralization is associated with reduced loss to care at 12 mnths. (RR=0.3)

–          decentralization to health centres and decentralization to the community have a similar impact on loss to care, mortality and attrition.

The low and very low quality evidence regarding other associations points almost entirely in the direction of decentralization having a positive impact on retention in care.

On this basis the WHO guidance on the operational aspects of HIV management proposes the de-centralization of ART delivery and its integration with maternal and child health clinics, along with other strategies to improve retention in HIV care and task-shifting to close human resource gaps.

The studies reviewed demonstrate that that decentralization is at least feasible.  However, the authors also remind us in their conclusion that the decentralizing measures, to which they refer, “were in the context of a range of support structures and investments to ensuring delivery, including training, supervision and additional devices such as computer-aided or checklist-based decision aids”.  The implication seems to be that, without such support structures and investments – which may be difficult to achieve in certain contexts (for an interesting parallel see: sti blog25/6/12) the benefits of decentralization cannot be counted on.

HIV+ mothers without ART: when and how should they wean?

18 Jun, 13 | by Leslie Goode, Blogmaster

Without antiretrovirals, breastfeeding contributes 28% to the risk of mother-to-child HIV transmission (MTCT) (http://sti.bmj.com/content/88/Suppl_2/i44.abstract?sid=fcfaeecc-767f-4db8-b644-77db5aa8db63).  Antiretroviral drugs make achieving he WHO goal of near elimination of MTCT imaginable (http://sti.bmj.com/content/87/3/261.full; http://sti.bmj.com/content/86/Suppl_2/ii48.abstract?sid=fcfaeecc-767f-4db8-b644-77db5aa8db63).  But, in the meantime, what advice should be given to HIV+ mothers in those low-resource settings where antiretrovirals are still not available?

In this context, the health benefits of breastfeeding may yet override the risks of MTCT, as indicated by recent WHO guidance (http://depts.washington.edu/ghivaids/reslimited/case5/discussion.html#ref).  But when and how should infants be weaned in order to minimize the inevitable risk?  To give the best advice, we need to know more about how MTCT takes place.  A recent study (Louise Kuhn et al.) seeks to fill gaps in our knowledge by examining the relation between weaning and HIV concentration in breast milk (http://stm.sciencemag.org/content/5/181/181ra51.abstract?sid=c20e20f7-1f36-474d-99dc-ac2c265d505f).

958 Zambian mothers and their infants were randomized to wean abruptly (4 months) or continue breastfeeding, and HIV concentrations were measured at 4 and 4.5 months.  Two weeks after weaning HIV-1 concentrations in the milk of the abrupt weaners – median RNA, 2780 copies/ml. ; DNA, 14 copies/ml. – were observed to be dramatically higher than for non-abrupt weaners – median RNA, <50 copies/ml.;  DNA, <1 copy/ml..  Furthermore, HIV concentrations were higher even where breast-feeding was non-exclusive (median RNA 293 copies/ml.; DNA, 2 copies/ml.).

It would appear from this that the risks of MTCT are not evenly distributed over the period during which the child is breastfed, but spike quite abruptly at the time when weaning takes place.  The physiological explanation of this phenomenon remains unclear; the authors propose as most likely the opening of the paracellular tight junctions of the mammary gland, which is known to occur during weaning.  The fact that other studies have reported no association between non-exclusive breast-feeding and HIV-1 concentrations may, in the authors’ view, be attributable to their failure to focus on the short interval of time following disruption of full breast-feeding.

The validity of these findings, if confirmed by further studies, lends weight to the existing WHO recommendation for mothers to reduce breast-feeding frequency gradually over the weeks leading up to the last planned breast milk feed (http://www.avert.org/pmtct-guidelines.htm).  Evidently, abrupt weaning following exclusive breast-feeding, if genuinely achieved, would eliminate the PMCT risk through breast milk (though weaning abruptly is associated with maternal morbidity).  The problem, however, is that even minimal deviation from abrupt weaning presents the most acute risk of PMTC.

So, gradual weaning seems advisable, accompanied, as the authors suggest, by the expression and discarding of breast milk to relieve engorgement.  Where antiretrovirals are being offered for the child’s health, HIV-1 infected women should continue the antiretrovirals they used through lactation over the full duration of time when any breast milk exposures occur.  Existing WHO guidelines regarding ART regimes for these mothers stipulate that drugs should be continued until one week after breastfeeding is finished (http://www.avert.org/pmtct-guidelines.htm).  The authors point out that in the light of their findings, the “one or two-week period” that “has been considered adequate” may be too short.  At all events the existing WHO guidelines seem inadequate, given the complexity of the practical issues surrounding weaning, and the acuteness of PMTC risk concentrated at this stage.

This study focuses on the issue of weaning as it presents itself for breast-feeding mothers without ART.  The authors point to the urgent need for further research of the dynamics of PMCT through breast-milk when ART is being given.  They also urge the importance of pursuing the same investigation in relation to the weaning of the older infant – given the WHO guidelines have now shifted to encourage weaning at a later stage (post 12 months).  Further clarification through research in this area seems urgently needed.

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