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HIV infection

Susceptibility of heterosexual sub-Saharan women to HIV could be the result of cervicovaginal microbiome characteristics

30 Jan, 17 | by Leslie Goode, Blogmaster

Could part of the explanation for the apparent susceptibility of sub-Saharan African heterosexual women to HIV infection (eight-fold that of males) lie in the bacterial flora of their female genital tract (FGT)?

Studies published in STI journal have considered the relationship between a certain state of the FGT bacterial microbiome – especially the depletion of lactobacillus (Francis & Grosskurth/STIs) – and the susceptibility to BV (Antonio & Hillier/STIs; Hardy & Crucitti/STIs; Francis & Grosskurth/STIs; Haggerty & Ness/STIs), to pelvic inflammatory disease (Haggerty & Ness/STIs), and to other STIs (Francis & Grosskurth/STIs).  Others have observed the prevalence of Lactobacillus in the healthy FGT microbiome (Madhivanan & Krupp/STIs), and considered the impact on the FGT lining of practices of vaginal douching (Balkus & McClelland/STIs), hormonal contraception (Verwijs & Wijgert/STIs), and sexual debut (Jespers & Crucitti/STIs).

Highly relevant to all these discussions is a recently published study by Gosmann & Anahtar of a prospective cohort of 236 young HIV-negative women participating in the South African Ragon Institute’s FRESH study (Females Rising through Educations, Support and Health) in Kwa-Zulu Natal. The researchers were able to follow up their cohort for a total of 198.2 person-years, in the course of which 31 participants acquired HIV.  The researchers distinguish four ‘cervicotypes’ in respect to FGT bacterial flora; then determine their prevalence along with their association with ‘HIV target cells’ (i.e. activated CD4 T cells expressing the HIV co-receptor CCR5) and HIV acquisition.

The four cervicotypes correspond to the dominance of Lactobacillus crispatus and of Lactobacillus iners (CT1 and CT2, respectively), the preponderance of Gardnerella vaginalis (CT3), and a biome showing a far more diverse range of bacterial types (CT4).  Strikingly, the first two cervicotypes (CT1 and CT2) account for only 10% and 32% of women in the cohort; while, among white women in Western countries, the proportion showing Lactobacillus dominance would be c.90%.  The other 58% fall into the categories of high diversity communities with low Lactobacillus abundance (CT3 and CT4).  More interestingly still, none of the 31 HIV sero-conversions took place among the 10% of women with CT1-type bacterial flora.  Rather, sero-conversions were fairly evenly distributed among the other three cervicotypes, with some diminution of relative incidence in the CT2 category (i.e. nine sero-conversions, as opposed to 10 and 12 in CT3 and CT4 respectively).  Researchers observed a 17-fold increase in HIV target cells in women with a CT4-type cervico-vaginal microbiome as against those with CT1-type, and elevated levels of chemokines MIP-α and MIP-β which attract CCR5 expressing cells in women with diverse FGT bacterial communities.

Sadly, regimens aiming to restore Lactobacillus crispatus dominance (e.g. antibiotics or probiotic vaginal suppositories) show significant recurrence rates.  However, modifiable biological and behavioural factors may play a considerable role on Lactobacillus depletion in sub-Saharan African women (e.g. vaginal washing; antibiotic use; recent Trichomonas and HSV-2).  If so, then, as Baeten & McClelland/STIs point out, this would suggest the possibility of effective intervention strategies to reduce HIV transmission by improving vaginal health.

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.

 

PrEP highly effective against HIV in MSM and has limited impact on risk compensation

22 Oct, 15 | by Leslie Goode, Blogmaster

The year 2015 is likely to turn out a decisive one for the story of PrEP (pre-exposure prophylaxis for HIV).  After a slow and faltering beginning, with trials in sub-Saharan Africa dogged by problems of poor adherence (Haberer & Bangsburg/STI/blog; VOICE D/STI/blog; Hendrix & Bumpus/STI/blog), this intervention appears at last to have proved its worth – at least in high-risk populations such as MSM in Europe and America.  This is to be seen in a succession of results from recent or still ongoing trials.

Following the report of encouraging headline figures at last February’s Conference on Retroviruses and Opportunistic Infections (CROI), the UK PROUD study (Pre-exposure Option for reducing HIV in the UK immediate or Deferred) has published its results (McCormack & Gill; PROUD/STI/blog).  As stated in my earlier blog, this study, based in 13 UK clinics, aimed, in its design, to replicate real-life conditions in being an ‘open-label’, as opposed to a blind placebo controlled, randomized study.  September also saw the publication of a brief report of a San Francisco based study (Volk & Hare) investigating HIV and STI incidence amongst a comparable number of patients (650) referred for PrEP over 2 and a half year period in a clinical practice under the health insurance provider Kaiser Permanente.  Finally, the PROUD study refers to the still ongoing IPERGAY study run by French and Canadian researchers (IPERGAY; Molina & Delfraissy).  The latter differs from the PROUD study, first in respect to the PrEP regime followed, which is ‘on demand’ (i.e. before and after sex) rather than daily; second, in having a blind placebo controlled, rather than an ‘open-label’, design.

The three studies investigate relatively high-risk, largely MSM, populations – to judge by the high rates (c. 34%-50% within a year of follow-up) of STIs and especially (18%-32%) of rectal STIs.   Rates of HIV transmission, however, were, in all cases, similarly low.  As indicated in my blog (PROUD/STI/blog), the PROUD study headlined an HIV incidence of 1-2 per 100 person years (py) in the immediate initiation, as against 9 per 100 py in the ‘deferred initiation’ arm.  The IPERGAY study saw rates of 0.94 as against 6.75.  The San Francisco study was without a control arm, but saw zero cases of HIV among PrEP users over the two and a half year study period.  All this would suggest that amongst self-selecting high-risk MSM, PrEP interventions can be successful in preventing HIV transmission.  It would, however, be reassuring to know more about the impact of PrEP on risk compensation – always the supposed ‘Achilles heel’ of MSM PrEP (Cassell & Halperin) – especially as rates of STI incidence following PrEP initiation were very high in all studies.  Here the published version of the PROUD study has the advantage of being able to compare incidence of other STIs between the intervention and the control arm of the study.  No significant difference between the two arms was observed.  This was particularly encouraging as the PROUD study was designed to replicate the conditions of a real-life intervention in that those in the intervention arm knew they were taking PrEP, and could have adjusted their behaviour on the basis of this knowledge.

A final issue that PROUD and IPERGAY may begin to help health professionals to address is that of cost effectiveness.  The PROUD researchers calculate that ‘thirteen men in a similar population would need access to 1 year of PrEP to avert 1 HIV infection’.  This would make PrEP targeted at this group cost-effective at current prices if the cost of tenofovir and emtricitibine were halved.  It could also be achieved if the proposed intervention were to adopt the ‘on demand’ regimen trialled by IPERGAY:  namely, two tablets 2-24 hrs before sex, one taken 24hr, and a further tablet 48 hrs. after.  IPERGAY, it will be remembered, demonstrated the same 86% reduction in HIV incidence that was observed by PROUD.

Reported 86% effectiveness for MSM PrEP by PROUD study makes this intervention a viable option for UK health services

25 Mar, 15 | by Leslie Goode, Blogmaster

The Conference on Retroviruses and Opportunistic Infections has recently taken place.  At that event the UK PROUD (PRe-exposure Option for reducing HIV in the UK: immediate or Deferred) study of pre-exposure prophylaxis (PrEP) for MSM reported its results, prior to publication in the coming months.  The headline figure is an astonishing 86% for the reduction of risk of infection in the intervention group.  Hitherto, results of PrEP trials, largely conducted in Africa, have often been disappointing.  This is probably on account of poor adherence (VOICE D( STI/blog); Haberer & Bangsberg (STI/blog); Hendrix & Bumpus (STI/blog)).  The good result achieved here is no doubt attributable to good adherence.  It demonstrates, as these earlier trials have not, the true effectiveness of PrEP.

The UK trial included 545 participants at 13 practices. 276 were randomized to receive PrEP immediately, while the remaining 269 received it after a year.  Earlier PrEP trials have been blind and placebo-controlled.  But this design had the advantage of demonstrating the effectiveness of PrEP in real life. The participants were aware if they were taking the active drug and could have changed their sexual behaviour accordingly.  Given one of the major concerns around PrEP is that of risk compensation – i.e. taking advantage of the protection of PrEP to engage in more risky behaviour than they would otherwise (Marcus & Grant (STI/blog); Baeten & Celum (STI/blog)) – this was a valuable aspect of the trial.

In the period to October 2014, there were 22 HIV infections – 3 in the immediate, and 19 in the deferred group.  This gives us the headline figure of 86%.  At this point, ethical considerations dictated that the study design be changed so all participants received PrEP from then on.  Initially, this study was intended to be a pilot, and to be followed by a larger scale trial.  The decisiveness of the interim findings, however, led to cancellation of that further study.  (For an interesting commentary on the need for researchers to keep pace with changing ethical parameters, see Cohen & Sugarman (STI/blog)).  Cost-effectiveness analyses are apparently underway.  No details are given in the report.  But evidently the high effectiveness observed in the study will allow investigators to present a far more positive case for PrEP than has been warranted by earlier trials (see Borquez & Hallett (STI); Gomez & Hallett (STI/blog); Cremin & Garnett (STI)).  They are also working with stakeholders on how PrEP services could be commissioned across NHS and local authorities.

Does risk compensation behaviour neutralize the benefits of voluntary medical male circumcision?

18 Aug, 14 | by Leslie Goode, Blogmaster

The effectiveness and feasibility of voluntary medical male circumcision (VMMC) as a preventative intervention against HIV has been demonstrated in a variety of non-circumcising African communities.  The WHO has designated 14 countries in southern and eastern Africa as priority areas for VMMC scale-up.  Attempts to model the progress of the epidemic have long sought to factor in the potential contribution of VMMC (STIs/Hallett & Abu-Raddad).  However, the possibility of risk-compensation remains an ongoing concern (i.e. that the known preventative effects of VMMC will lead to increased sexual risk-taking).  Current evidence has been largely limited to behavioural evaluations and extended follow-up in populations where RCTs of VMMC were being conducted (e.g. Rakai, Uganda; Orange Farm, South Africa; Kisumu, Kenya).  The evidence has been reassuring, by and large.  Yet it is also inconclusive – for two reasons: first, on account of the rigorous risk reduction counselling invariably provided by these trials, which is far in excess of what would be offered in operational settings; second, due to the lack of certainty as to the preventative effectiveness of VMMC that prevailed at the time when these RCTs were being conducted.  These are precisely the issues that bedevil studies seeking to evaluate risk compensation in the context of pre-exposure prophylaxis (PrEP): see STIs/blog/Marcus & Grant; STIs/blogs/Mugwanya & Baeten.

A recent prospective, longitudinal study conducted in Nyanza Province, Kenya (Westercamp & Bailey) claims to mark an important step forward towards understanding the relation between VMMC and sexual risk-taking in everyday operational settings.  Participants in the study were not exposed to unrealistic levels of risk reduction counselling, and the preventative efficacy of VMMC had already been well established prior to commencement of the study.  Participants were followed up, at six monthly intervals over a two year period, having assigned themselves either to a circumcision (1,5888) or a control (1,599) group, using (as far as possible) audio computer-assisted self-interview questionnaires to investigate sexual behaviour.

The result?  No risk-compensation, apparently.  In fact, the findings show an increase of 30%/6% in condom use at last sex (for the circumcised/control group), and a broadly comparable decline for both groups across a range of indicators, including transactional sex in the last six months (26-12%), most recent sex with a casual partner (20-12%), and having multiple partners in the last six months (26-16%).  The only adverse finding was an increase in sexual activity for both groups among the younger participants – but this seems to be largely explained by transition to married status.

The decline might be due to some limited exposure to HIV education through participation, or reflect “cognitive dissonance” – i.e. the re-evaluation of behaviours in the light of the personal investment involved in getting circumcised.  But there is evidence it might be part and parcel of a decrease in sexual risk-taking in the community at large due to the implementation of the VMMC programme over the period of the study 2008-2011.  A curious finding was the greatly reduced perception of high HIV risk among the “cross-over group” of those 20% of the control group who subsequently chose to be circumcised, as against the perceptions of those who initially assigned themselves to the circumcision group.  This, according to the authors, suggests that men motivated to early adoption of VMMC may represent a higher risk group.  When this finding is taken together with recent evidence of high (90%) acceptance of VTC services among men undergoing circumcision, the case stacks up for ensuring the provision of high-quality counselling as a priority throughout the commencement and rapid initial sale up of VMMC services.

HIV epidemic among heterosexual non-intravenous drug-users: could HSV-2 co-infection be the driver?

24 Jul, 14 | by Leslie Goode, Blogmaster

Why such high HIV prevalence reported for non-injecting drug users who are predominantly heterosexual?  This reaches 37% in Porto Alegre, Brazil; 43% in China; 13% in Canada; 20% in Florida; 19% in New York City; 24% in Portugal; 29% in Russia?  Possible factors include impaired decision making under the influence of drugs or the exchange of sex for drugs.  Studies published in STI Journal also propose high prevalence of, amonst other STI infections,  HSV-2 as a particular risk for HIV amongst non-injecting drug users (STIs/Plitt & Taha), and comparable groups, e.g. Tanzanian female bar-workers (STIs/Riedner & Hayes).  HSV increases susceptibility to HIV through disruption of the epithelial surface, as well as increasing transmissibility from persons co-infected with HSV and HIV through raising levels of plasma HIV-1 RNA.

A recent study of non-injecting drug users (NIDU)  (Jarlais & Cooper) attending a New York drug detoxification centre and a methadone maintenance programme – 785 over the period 1995-1999 and 1,764 over the period 2005-2011 – claims that HSV-2 co-infection is the principal driver of HIV transmission, especially amongst female NIDUs.  Over both periods that latter group shows: very high levels of HSV-2 mono-infection (78% and 86% respectively), high levels of HIV/HSV-2 co-infection (10% and 21%, and negligible HIV mono-infection.  The pattern is similar though less pronounced in the case of males.  As between the two periods (1995-1999 & 2005-2011) there is a doubling in the prevalence of HIV (from 7% to 13% overall) which is represented more or less uniformly across all ethic and behavioural groups.  Though the specific quantitative contribution of HSV-2 to the HIV infection cannot be determined by this type of study, these results suggest that the rise in HIV among NIDUs should be considered an epidemic of HSV-2/HIV co-infection, and that HSV-2 is likely to be the driver of the increased HIV incidence.

So what should be done to minimize HIV transmission among non-injecting drug users?  The obvious response would be suppressive HSV-2 therapy.  Unfortunately, however, trials have not as yet shown this to be effective in reducing HIV transmission (STIs/Mujugira & Wald; Barnabas & Celum).  The authors recommend further research into the effectiveness of higher dosages of HSV-2 suppressive therapy: also of HSV-2 suppressive therapy prior to ART or in combination with ART – since a recent study found evidence of HIV in the semen of men who had reached viral suppression on ART (Politch & Anderson).  At all events, HIV/HSV-2 co-infected NIDUs would appear to be a priority for ART as prevention, and the authors recommend providing ART to this group at all CD4 cell counts.  (New York introduced in 2011 a new policy of offering ART to all HIV sero-positive persons in the city regardless of CD4 count).

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.

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”.

 

 

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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