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HSV-2/HIV co-infection

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.

 

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).

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