Articles tagged as "Puerto Rico"

Minimal evidence for serious adverse events resulting from in utero ARV exposure

The PHACS SMARTT Study: assessment of the safety of in utero exposure to antiretroviral drugs.

Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR, 3rd. Front Immunol. 2016 May 23;7:199. doi: 10.3389/fimmu.2016.00199. eCollection 2016.

The Surveillance Monitoring for ART Toxicities (SMARTT) cohort of the Pediatric HIV/AIDS Cohort Study includes over 3500 HIV-exposed but uninfected infants and children at 22 sites in the US, including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARVs) and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental (ND), behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger) undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain) with exposure to combination ARVs (cARVs), any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a ND case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With ND testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir) were associated with lower performance, although all groups were within the normal range. No ARVs or classes were associated with lower performance between 5 and 13 years of age. Atazanavir and saquinavir exposure were associated with late language emergence at 1 year, but not at 2 years of age. The results of the SMARTT study are generally reassuring, with little evidence for serious adverse events resulting from in utero ARV exposure. However, several findings of concern warrant further evaluation, and new ARVs used in pregnancy need to be evaluated.

Abstract  Full-text [free] access 

Editor’s notes: The SMARTT study set out to determine the safety of in utero exposure to antiretroviral (ARV) therapy using a trigger-based surveillance design to identify adverse events in a cohort of HIV-positive mothers and their HIV-exposed but HIV-negative children in the United States of America and Puerto Rico. A ‘trigger’ was set off if participants met a predefined clinical or laboratory threshold, with additional specified evaluations to determine if they met a predefined adverse event “case” definition.  After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain, such as growth and development or language etc.) with exposure to combination ARVs or any ARV class. No single ARV prophylaxis was associated with an increased risk of overall case status on adjusted analysis. However, several ARVs had significant associations in unadjusted analysis, namely between (1) maternal PI-based ARV prophylaxis during pregnancy and premature delivery and low birth weight; and (2) exposure to atazanavir and a twofold-higher risk of congenital anomalies. Overall the results from this study are reassuring, but some of the findings warrant further evaluation.

Latin America, Northern America
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How gender norms and power may impact on the acceptability, access and adherence to microbicides

Optimizing HIV prevention for women: a review of evidence from microbicide studies and considerations for gender-sensitive microbicide introduction.

Doggett EG, Lanham M, Wilcher R, Gafos M, Karim QA, Heise L. J Int AIDS Soc. 2015 Dec 21;18(1):20536. doi: 10.7448/IAS.18.1.20536. eCollection 2015.

Introduction: Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women and girls at risk of acquiring HIV are also likely to affect their ability to use microbicides. Understanding how gendered norms and inequalities may pose obstacles to women's microbicide use is important to inform product design, microbicide trial implementation and eventually microbicide and other antiretroviral-based prevention programmes. We reviewed published vaginal microbicide studies to identify gender-related factors that are likely to affect microbicide acceptability, access and adherence. We make recommendations on product design, trial implementation, positioning, marketing and delivery of microbicides in a way that takes into account the gender-related norms and inequalities identified in the review.

Methods: We conducted PubMed searches for microbicide studies published in journals between 2000 and 2013. Search terms included trial names (e.g. "MDP301"), microbicide product names (e.g. "BufferGel"), researchers' names (e.g. "van der Straten") and other relevant terms (e.g. "microbicide"). We included microbicide clinical trials; surrogate studies in which a vaginal gel, ring or diaphragm was used without an active ingredient; and hypothetical studies in which no product was used. Social and behavioural studies implemented in conjunction with clinical trials and surrogate studies were also included. Although we recognize the importance of rectal microbicides to women, we did not include studies of rectal microbicides, as most of them focused on men who have sex with men. Using a standardized review template, three reviewers read the articles and looked for gender-related findings in key domains (e.g. product acceptability, sexual pleasure, partner communication, microbicide access and adherence).

Results and discussion: The gendered norms, roles and relations that will likely affect women's ability to access and use microbicides are related to two broad categories: norms regulating women's and men's sexuality and power dynamics within intimate relationships. Though norms about women's and men's sexuality vary among cultural contexts, women's sexual behaviour and pleasure are typically less socially acceptable and more restricted than men's. These norms drive the need for woman-initiated HIV prevention, but also have implications for microbicide acceptability and how they are likely to be used by women of different ages and relationship types. Women's limited power to negotiate the circumstances of their intimate relationships and sex lives will impact their ability to access and use microbicides. Men's role in women's effective microbicide use can range from opposition to non-interference to active support.

Conclusions: Identifying an effective microbicide that women can use consistently is vital to the future of HIV prevention for women. Once such a microbicide is identified and licensed, positioning, marketing and delivering microbicides in a way that takes into account the gendered norms and inequalities we have identified would help maximize access and adherence. It also has the potential to improve communication about sexuality, strengthen relationships between women and men and increase women's agency over their bodies and their health.

Abstract  Full-text [free] access

Editor’s notes: This paper presents a review of the evidence of microbicides research to understand gender-associated factors that could impact on acceptability, access and adherence. These gender norms include women and men’s sexual norms and power differentials in intimate partner relationships. This review included studies conducted between 2000 and 2013 and thus only includes papers on hypothetical research and clinical trials. While the studies were conducted in a variety of contexts the authors found a number of similar norms and power differentials.

In relation to sexual norms, the review revealed findings on sexual risk, sexual pleasure, and sexual preferences. In terms of sexual risk there were differing opinions across the studies of which women were most likely to need microbicides. Some studies suggested that microbicides should be focused on women in steady partnerships where condom negotiation is difficult, while others suggested focusing on key populations such as sex workers. Across many studies the potential for promoting sexual pleasure for both women and men emerged as an advantage of microbicides, and had an impact on acceptability. However, many of the studies highlighted how men’s sexual pleasure takes precedence. In relation to sexual preferences, the much touted idea that men prefer ‘dry’ or ‘tight’ sex was challenged by some of the studies, which found that the lubricating effect of the gel was acceptable.

The review also uncovered issues associated to power inequalities in intimate partner relationships, including power to control time of sex, male partner engagement and communication, and intimate-partner violence. Women reported in many studies their lack of power to control the timing of sex and this is seen as likely to impact on their ability to use coitally-dependant microbicides. However, there is some evidence that men supported women’s use of the gel, although this depended on the type of relationship. While microbicides have been promoted as products that women can use without a partner’s knowledge the review illustrated that women do prefer to communicate with their partners about their use and there is evidence of joint-decision making. Further, there was evidence of women experiencing intimate partner violence in relation to trial participation. There is also some evidence that women were less likely to discuss or use microbicides in violent relationships.

This highly comprehensive review concludes that while microbicides will not empower women they do have the potential to enhance women’s agency in relation to their health and sexuality and may improve communication in their relationships. However, the authors conclude that gender norms and power differentials may impact on acceptability, access and adherence.

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Safety of tenofovir during pregnancy

Safety of tenofovir during pregnancy for the mother and fetus: a systematic review.

Wang L, Kourtis AP, Ellington S, Legardy-Williams J, Bulterys M. Clin Infect Dis. 2013 Dec;57(12):1773-81. doi: 10.1093/cid/cit601. Epub 2013 Sep 17.

Tenofovir disoproxil fumarate (TDF) safety during pregnancy has important public health implications. This review summarizes TDF safety during pregnancy, focusing on pregnancy outcomes, congenital anomaly risk, and other potential toxicities on neonates. Although information is limited, TDF appears to be safe during pregnancy. In 6 studies of human immunodeficiency virus type 1 (and/or hepatitis B virus)-infected women receiving TDF during pregnancy, adverse events were mild to moderate; none were considered to be TDF-related. Five studies that followed in utero TDF-exposed infants showed no increased risk of growth or bone abnormalities. One study showed slightly lower infant height at age 1 year, but the significance is unclear. The Antiretroviral Pregnancy Registry database, with 1 800 pregnancies exposed to TDF in the first trimester, does not indicate increased congenital anomaly risk with TDF exposure. More evidence collected prospectively, ideally with bone density measurements and randomized trial design, will be optimal to determine the effects of antenatal TDF exposure on children's health.

Abstract  Full-text [free] access

Editor’s notes: Tenofovir is a well-tolerated antiretroviral drug which is effective against HIV and hepatitis B. Due to these favourable characteristics and its once-daily dosing, tenofovir is increasingly used in clinical practice. As a result, more women are exposed to this drug at conception and during pregnancy. Tenofovir is classified by the US Food and Drug Administration as a pregnancy category B drug. This means that there is insufficient evidence to determine risk in humans. The authors of this paper provide the reader with an updated systematic review of the safety of tenofovir in pregnancy. Amongst the studies looking at adverse events in infants and mothers, no serious adverse events occurred which were attributed to tenofovir. Likewise, no study identified an increased risk of growth or bone abnormalities in infants up to two years of age. These studies need to be interpreted with caution as many studies had small sample sizes and in some studies the duration of exposure to tenofovir was short (single dose-seven days). Arguably, the most reassuring evidence comes from the antiretroviral pregnancy registry database report, which showed no increased risk of congenital anomalies amongst 1 800 infants exposed to tenofovir in utero. This systematic literature review notes the paucity of available evidence to guide decision-making and highlights the need for further studies to determine the risk to humans of tenofovir exposure during pregnancy.

HIV Treatment
Africa, Asia, Europe, Northern America
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