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Mother to child HIV transmission

Vertical HIV transmission may be influenced by complex synergies with other STI – such as Cytomegalovirus

26 Jul, 17 | by Leslie Goode, Blogmaster

The apparently greater susceptibility of sub-Saharan African women to HIV infection has led researchers to consider the various potential synergies between HIV and other genital infections (White & Glynn (STIs); Lurie & Matthews (STIs)) or conditions of the vaginal microbiome (The susceptibility of heterosexual sub-Saharan women (STI/blog)).  A recent study, Adachi & Nielson-Saines, brings this wider perspective to bear on mother-to-child transmission, casting some fresh light on the complex interrelation between the ‘vertical’ transmission of HIV and active and Cytomegalovirus (CMV) viruria.

The study is a late spin-off from HPTN-040 (reported in a 2012 paper by Nielson-Saines & Mofenson IN&M).  This compared the efficacy of different post-partum ART regimes for HIV infected children.  The original participants were c. 1,700, largely S. American women who presented in late pregnancy with HIV.  Matched urine specimens were available for 264 mother-child pairs.  Researchers returned to these specimens after the closure of the main trial in order to investigate through PCR testing the impact of CMV viral shedding on vertical transmission of Cytomegalovirus (CMV) and its concomitants.

The results were as follows.  Out of the 264 maternal urine samples 24 (9.2%) showed evidence of CMV shedding. Matching these maternal samples with infant samples revealed vertical CMV transmission in 10/264 cases.  Five of these were from among the 24 with maternal shedding (20.8%); five were from among the 240 without shedding (2.1%).  When the ratio of transmissions with shedding to transmissions without shedding was adjusted for mode of delivery, maternal gonorrhoea and maternal HIV viral load, it came out at 29.7%.   Women with CMV viral shedding also showed significantly higher odds of HIV transmission to their infants (aOR = 5.6%).

These findings are striking; but what is their relevance?  Maternal CMV shedding may indeed be a very good marker of vertical CMV and HIV transmission.  Presumably, however, health workers would give appropriate anti-retroviral therapy to 100% of infants at risk of HIV infection in any case – and anti-retroviral therapy has been shown to deal successfully with the CMV, without the need to give additional, and potentially toxic, drugs specifically for the CMV (Anfumborn & Tejiokern). So N&M’s research have little implications for management of these infections.

However, their importance may lie in showing how the problem of HIV – including vertically transmitted HIV – cannot be isolated from the wider problem of STI and sexual health in general. Maternal HIV may, for example, increase the likelihood of CMV transmission, and CMV infection of the infant may, in turn, lead to a more rapid progression of HIV.  Complex synergies with vertical HIV transmission may operate in the case of other STI as well – such as HSV-2 (Sivarajah & Tan (STIs)).  So the messages to take away may include not just ‘the necessity of controlling maternal HIV infection during pregnancy through cART’, but also the importance of STI control – above all through the promotion of practices of safe sex.

 

Health vulnerability of peri-natally HIV-infected youth: a growing problem throughout the world

3 May, 17 | by Leslie Goode, Blogmaster

Mother-to-child, or ‘vertical’, transmission of HIV is not just a problem for developing countries; even in countries like the US and the UK, peri-natal transmission has probably not been eliminated.  But, with routine ‘opt-out’ ante-natal testing (BHIVA guidelines on HIV testing), cases are increasingly likely to involve births that have taken place overseas or before parental diagnosis (CHIVA guidelines on child testing) – cases that, for various reasons, may be difficult for health services to access (Editorial: ‘Don’t Forget the Children’ (STI)). Yet, even with such events becoming less frequent, and the increasing survival of peri-natally HIV-infected youth (PHIVY) beyond infancy, there remains the problem of managing those already infected, as they transition, in growing numbers, from childhood into adolescence and young adulthood. 

               Such problems are very considerable, according to Nailan & Ciaranello (N&C) – especially for adolescents (13-17yrs) and young adults (18-30yrs).  This recent study offers an analysis of data of PHIVY aged 7-30 years from two cohort studies in the US, the Pediatric HIV/AIDS Cohort Study (PHACS) and the International Maternal Pediatric Adolescent AIDS Clinical Trials study (IMPAACT).  As compared with the younger group (7-13 yrs), adolescents (13-18yrs) and young adults (18-30yrs) are likely to spend considerably more time with inadequate viral suppression (5% and 18% vs 2% with CD4 count <200/µL; 30% and 44% vs 22% with a viral load of 400 copies/mL), and to suffer correspondingly greater mortality (c.1 per 100 person-years amongst young adults) as well as HIV related events (c. 2 and 4 per 100 py. for CDC C and B category events amongst 18-30 yrs; c. 1 and 3 per 100 py. for CDC C and B category events amongst 13-18yrs).  The authors attribute inadequate viral suppression, and high mortality/morbidity, to poor adherence and retention in care. 

               The vulnerability of PHIVY as a group to poor health outcomes is not a problem unique to the US.  In the UK c.1,950 PHIVY are monitored through the Collaborative HIV Pediatric Study (CHIPS) cohort, and the data indicate comparable problems of inadequate viral suppression (around one in ten (CHIVA guidelines on transition)).  In some developing countries the health problems of this group are still more evident.  De Matos & dal Fabbro (STI), analysing the data for a cohort of 78 patients, aged 11-15 in 2009, from a municipality in Brazil, report five deaths, amongst other serious health events.  More generally, the UNAIDS 2016 Report (The ‘life-cycle’ approach (STI/blogs) points, in the case of sub-Saharan Africa, to the recent tripling in peri-natally infected 15-19 yr olds who now account for 40% of all HIV-infected 15-19 yr olds in the region.  Not only does poor adherence pose problems for PHIVY themselves; Nailan & Ciaranello also draw attention to the danger they represent for society at large, given rates of pregnancy and risky sex that appear no lower than in the general population, along with heightened transmission risk resulting from poor viral suppression, and, in some cases, emerging drug resistance.

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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