The Cost-Effectiveness of Directly Observed Highly-Active Antiretroviral Therapy in the Third Trimester in HIV-Infected Pregnant Women

Background: In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy. Methods and Findings: A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases. Conclusions: Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials

Ultrafast electron dynamics and cubic optical nonlinearity of free standing thin film of double walled carbon nanotubes

Ultrafast degenerate pump-probe experiments performed on a free standing film of double walled carbon nanotubes near the first metallic transition energy of outer tube show ultrafast ($97 fs$) photobleaching followed by a photo-induced absorption with a slow relaxation of $1.8 ps$. Femtosecond closed and open aperture z-scan experiments carried out at the same excitation energy show saturation absorption and negative cubic nonlinearity. From these measurements, real and imaginary part of the third order nonlinear susceptibility are estimated to be Re($\chi^{(3)}) \sim -2.2 \times 10 ^{-9} esu$ and Im($\chi^{(3)}) \sim 1.1 \times 10 ^{-11} esu$.Comment: 8 pages, 3 figure

Gas pressure sintering of silicon nitride

The Cooperative Research and Development Agreement (CRADA) with Materials and Electrochemical Research Corp. (MER) examined materials made with different starting {alpha}/{beta}Si{sub 3}N{sub 4} ratios and with the addition of sintering aids as coatings instead of powders. The samples were sintered by GPS using optimum densification parameters developed for high toughness materials in the ORNL program. High densities were achieved for all of the samples fabricated at ORNL and containing up to 50% {beta}-Si{sub 3}N{sub 4}. The effect of the type of {beta}-Si{sub 3}N{sub 4} seed on fluxural strength and fracture toughness indicated seeds fabricated by the reaction of either yttrium nitrate or Y{sub 2}O{sub 3} powder and Ube E-10 Si{sub 3}N{sub 4} developed materials with the highest flexural strength. However, the fracture toughness of these materials (at the 25% addition level) showed no improvement over the baseline composition having no {beta}-seed addition. The effects of the {beta}-seed content on flexural strength and fracture toughness were mixed. Higher toughnesses were observed with 50% {beta}-seed additions, while the other additive levels showed no consistent improvements

Learning from Interviews with HIV-Discordant Couples (Male Positive, Female Negative): The Challenges and Successes

This article examines the challenges and successes of recruiting participants and maintaining momentum in a small qualitative study on the experiences of HIV-discordant couples (where the male is HIV-positive and the female is HIV-negative) undergoing fertility assessment and/or treatment in Ontario, Canada, to reduce the risk of HIV transmission to the woman and fetus. The purpose of this article is to identify barriers and successes encountered in our study, consider how these are addressed in the literature, and highlight specific factors that need to be considered when studying a unique population similar to ours

Factors Associated With the Frequency of Monitoring of Liver Enzymes, Renal Function and Lipid Laboratory Markers Among Individuals Initiating Combination Antiretroviral Therapy: A Cohort Study

Background As the average age of the HIV-positive population increases, there is increasing need to monitor patients for the development of comorbidities as well as for drug toxicities. Methods We examined factors associated with the frequency of measurement of liver enzymes, renal function tests, and lipid levels among participants of the Canadian Observational Cohort (CANOC) collaboration which follows people who initiated HIV antiretroviral therapy in 2000 or later. We used zero-inflated negative binomial regression models to examine the associations of demographic and clinical characteristics with the rates of measurement during follow-up. Generalized estimating equations with a logit link were used to examine factors associated with gaps of 12 months or more between measurements. Results Electronic laboratory data were available for 3940 of 7718 CANOC participants. The median duration of electronic follow-up was 3.5 years. The median (interquartile) rates of tests per year were 2.76 (1.60, 3.73), 2.55 (1.44, 3.38) and 1.42 (0.50, 2.52) for liver, renal and lipid parameters, respectively. In multivariable zero-inflated negative binomial regression models, individuals infected through injection drug use (IDU) were significantly less likely to have any measurements. Among participants with at least one measurement, rates of measurement of liver, renal and lipid tests were significantly lower for younger individuals and Aboriginal Peoples. Hepatitis C co-infected individuals with a history of IDU had lower rates of measurement and were at greater risk of having 12 month gaps between measurements. Conclusions Hepatitis C co-infected participants infected through IDU were at increased risk of gaps in testing, despite publicly funded health care and increased risk of comorbid conditions. This should be taken into consideration in analyses examining factors associated with outcomes based on laboratory parameters

Case Series of Fertility Treatment in HIV-Discordant Couples (Male Positive, Female Negative): The Ontario Experience

The success of combination antiretroviral therapies for the treatment of human immunodeficiency virus (HIV) has resulted in prolonged life expectancy (over 40 years from diagnosis) and an improved quality of life for people living with HIV. The risk of vertical HIV transmission during pregnancy has been reduced to less than 1%. As a result of these breakthroughs and as many of these individuals are of reproductive age, fertility issues are becoming increasingly important for this population. One population in which conception planning and reduction of horizontal HIV transmission warrants further research is HIV-discordant couples where the male partner is HIV-positive and the female partner is HIV-negative. Sperm washing is a technique carried out in a fertility clinic that separates HIV from the seminal fluid. Although sperm washing followed by intrauterine insemination significantly reduces the risk of horizontal HIV transmission, there has been limited access to the procedure in North America. Furthermore, little is known about the conception decision-making experiences of HIV-discordant couples who might benefit from sperm washing. Chart reviews and semi-structured interviews were completed with 12 HIV-discordant couples in Ontario, Canada. Couples were recruited through HIV clinics and one fertility clinic that offered sperm washing. Participants identified a number of factors that affected their decision-making around pregnancy planning. Access to sperm washing and other fertility services was an issue (cost, travel and few clinics). Participants identified a lack of information on the procedure (availability, safety). Sources of support (social networks, healthcare providers) were unevenly distributed, especially among those who did not disclose their HIV status to friends and family. Finally, the stigmatisation of HIV continues to have a negative affect on HIV-discordant couples and their intentions to conceive. Access to sperm washing and fertility service is significantly limited for this population and is accompanied with a number of challenges

Open-Circuit Photovoltage and Charge Recombination at Semiconductor/Liquid Interfaces

The open-circuit photovoltage (Voc) of semiconductor/ liquid junction solar cells is a critical parameter in determining the energy conversion efficiency. The fundamental process controlling Voc is the recombination of photoexcited electrons and holes. 1' 2 The lower the recombination rate, the larger the Voc. The predominant energy-loss mechanism is determined by competition among the following processes: majority-carrier thermionic emission over the surface barrier, ~ majority-carrier charge transfer across the semiconductor/liquid interface, ~' 4 minority-carrier diffusion/recombination in the bulk of the semiconductor, ~' 8 space-charge recombination, 7 and surface recombination mediated by recombination centers. 8-13 The extent to which each of these processes is understood differs considerably. For example, expressions describing the minority-carrier diffusion/recombination in the bulk semiconductor contacting a redox electrolyte is obtained by direct analogy to formulas developed for solid-state p-n junction devices. ~ When bulk diffusion/recombination is the dominant recombination process, the dependence of Vo~ on the semiconductor bandgap, doping level, and minority-carrier diffusion length can be expressed in simple analytic forms? In contrast, surface recombination has generally been treated in a more complex fashion by numerical simulation. TM In cases in which Voe is limited by surface recombination, no simple analytic expression exists for relating Vo~ and the surface recombination velocity (Sr)-Several groups TM have considered theoretically the effect of surface recombination on the performance of photoelectrochemical (PEC) cells. Although each treatment has achieved some success in describing a certain aspect of the effect of surface recombination, these treatments are generally considered qualitative3 ~ For the most part, it has been difficult to extract quantitative information on surface recombination from * Electrochemical Society Active Member. Visiting professor, on leave of absence from Korea University, Seoul, Korea. experimental results because of the number of adjustable (and often arbitrary) parameters involved in numerical analyses. Up to now, only one study 11 has dealt directly with the dependence of Voc on the surface recombination current; however, because bias-independent surface recombination currents in arbitrary units were used in the numerical calculation, it is difficult to apply the model of this study for interpreting quantitatively experimental measurements. Other studies 8-I~ have focused mainly on the general shape of the photocurrent-voltage (J-V) curves, without addressing the dependence of Voo on Sr. b The absence of a theoretical framework relating Sr to Vo~ impedes the understanding of such processes at the solid/liquid interface. In this article, we derive a simple quantitative expression, based on semiconductor solid-state theory, that directly relates Sr to Voc. The applicability of the expression to account for the PEC behavior of n-St/acetone with FeCp~ j~ (ferrocenium ion/ferrocene) is then investigated. Based on J-Vdata and the dependence of Voe on both the temperature and the concentration of FeCp~, we are able to exclude other possible recombination channels and identify surface recombination as the dominant recombination process in determining Voc. The surface recombination velocity deduced from experimental results compares favorably with reported values. The application of the analytic expression to other PEC systems reported in the literature is also discussed. b The effect of surface recombination is generally discussed in terms of the photoeurrent onset potential. However, unlike the concept of the "open-circuit photovoltage," the "photoeurrent onset potential" is an empirical quantity that cannot be precisely defined. The photocurrent onset potential depends on both Voc and the fill factor. The latter two parameters are more definable quantities and are more relevant in calculating the PEC conversion efficiency

Expert consensus statement on the science of HIV in the context of criminal law

INTRODUCTION: Globally, prosecutions for non-disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence. DISCUSSION: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant. CONCLUSIONS: The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.publishersversionpublishe

Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: Final results of two randomised, placebo-controlled trials

BACKGROUND: Two randomised, placebo-controlled trials-BENCHMRK-1 and BENCHMRK-2-investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end of the study). METHODS: Integrase-inhibitor-naive patients with HIV resistant to three classes of drug and who were failing antiretroviral therapy were enrolled. Patients were randomly assigned (2:1) to raltegravir 400 mg twice daily or placebo, both with optimised background treatment. Patients and investigators were masked to treatment allocation until week 156, after which all patients were offered open-label raltegravir until week 240. The primary endpoint was previously assessed at 16 weeks. We assessed long-term efficacy with endpoints of the proportion of patients with an HIV viral load of less than 50 copies per mL and less than 400 copies per mL, and mean change in CD4 cell count, at weeks 156 and 240. FINDINGS: 1012 patients were screened for inclusion. 462 were treated with raltegravir and 237 with placebo. At week 156, 51% in the raltegravir group versus 22% in the placebo group (non-completer classed as failure) had viral loads of less than 50 copies per mL, and 54% versus 23% had viral loads of less than 400 copies per mL. Mean CD4 cell count increase (analysed by an observed failure approach) was 164 cells per μL versus 63 cells per μL. After week 156, 251 patients (54%) from the raltegravir group and 47 (20%) from the placebo group entered the open-label raltergravir phase; 221 (47%) versus 44 (19%) completed the entire study. At week 240, viral load was less than 50 copies per mL in 193 (42%) of all patients initially assigned to raltegravir and less than 400 copies per mL in 210 (45%); mean CD4 cell count increased by 183 cells per μL. Virological failure occurred in 166 raltegravir recipients (36%) during the double-blind phase and in 17 of all patients (6%) during the open-label phase. The most common drug-related adverse events at 5 years in both groups were nausea, headache, and diarrhoea, and occurred in similar proportions in each group. Laboratory test results were similar in both treatment groups and showed little change after year 2. INTERPRETATION: Raltegravir has a favourable long-term efficacy and safety profile in integrase-inhibitor-naive patients with triple-class resistant HIV in whom antiretroviral therapy is failing. Raltegravir is an alternative for treatment-experienced patients, particularly those with few treatment options

Factors influencing the experience of sexual and reproductive healthcare for female adolescents with perinatally-acquired HIV: a qualitative case study

Background: Young people living with perinatally-acquired HIV require age-appropriate support regarding sex and relationships as they progress towards adulthood. HIV affects both genders but evidence suggests that young women are particularly vulnerable to sexual abuse and more prone to engaging in sexual behaviours to meet their daily survival needs. This can result in poor sexual and reproductive health (SRH) outcomes. HIV services in Malawi provide support for young women’s HIV-related clinical needs, but it is unclear whether there is sufficient provision for their SRH needs as they become adults. This paper explores the sex and relationship experiences of young women growing up with perinatally-acquired HIV in order to understand how to improve SRH care and associated outcomes. Methods: A qualitative case study approach was adopted in which each ‘case’ comprised a young woman (15–19 years) with perinatally acquired HIV, a nominated caregiver and service provider. Participants were purposively selected from three multidisciplinary centres providing specialised paediatric/adolescent HIV care in Malawi. Data was collected for 14 cases through in-depth interviews (i.e. a total of 42 participants) and analysed using within-case and cross-case approaches. The interviews with adolescents were based on an innovative visual method known as ‘my story book’ which encouraged open discussion on sensitive topics. Results: Young women reported becoming sexually active at an early age for different reasons. Some sought a sense of intimacy, love, acceptance and belonging in these relationships, noting that they lacked this at home and/or within their peer groups. For others, their sexual activity was more functional – related to meeting survival needs. Young women reported having little control over negotiating safer sex or contraception. Their priority was preventing unwanted pregnancies yet several of the sample already had babies, and transfer to antenatal services created major disruptions in their HIV care. In contrast, caregivers and nurses regarded sexual activity from a clinical perspective, fearing onward transmission of HIV and advocating abstinence or condoms where possible. In addition, a cultural silence rooted in dominant religious and traditional norms closed down possibilities for discussion about sexual matters and prevented young women from accessing contraception. Conclusion: The study has shown how young women, caregivers and service providers have contrasting perspectives and priorities around SRH care. Illumination of these differences highlights a need for service improvement. It is suggested that young women themselves are involved in future service improvement initiatives to encourage the development of culturally and socially acceptable pathways of care