An Economic Evaluation of Conception Strategies for Heterosexual Serodiscordant Couples with HIV-positive Male Partners

An economic evaluation of the three interventions to conceive without the sexual transmission of HIV between heterosexual, HIV-discordant couples with positive male partners can inform policy decisions to subsidize pregnancy planning in this setting, as there is currently no coverage as such in Ontario. A decision tree and Markov model were designed to determine the short and long-term outcomes of unprotected intercourse restricted to timed ovulation (UIRTO), sperm washing with intrauterine insemination (SWIUI), and unprotected intercourse restricted to timed ovulation with pre-exposure prophylaxis (UIRTO-PrEP). In the short-term, UIRTO was the most cost-effective strategy. In the long-term, cases of negligible HIV transmission risk determined UIRTO-PrEP as the preferred option, while SWIUI was the choice method when this risk was high. There remains a viable risk of HIV transmission between discordant couples during attempts to conceive that require the concurrent and subsidized use of UIRTO-PrEP or SWIUI to protect against HIV infection.MAS

Preventing Osteoporotic Fractures in Men Living with HIV: Model Calibration and Economic Evaluation Studies

I aimed to provide Ontario’s public healthcare payers with an economic evaluation of fracture prevention strategies for HIV-positive men who take antiretroviral therapy (ART). When developing microsimulations models for this purpose, calibration is critical and computationally expensive. Studies that explore efficient calibration methods for microsimulation models are limited. As such, I sought to determine whether simulated annealing or Nelder-Mead is the best-performing parameter search algorithm to calibrate a microsimulation model in project one; determine whether a discrete-event simulation model of fractures leads to more efficient calibrations than a patient-level, discrete-time simulation model in project two; and, estimate the cost-effectiveness of osteoporosis screening and treatment strategies in ART-treated men over a lifetime horizon in project three. For projects one and two, I constructed a Markov microsimulation model that tracked bone loss and incident fractures. All calibrations were based on 4 calibration targets, 12 calibration inputs, a binomial log-likelihood goodness-of fit measure, and first-order searches in a simulated sample of 1000. I assessed calibration performance according to differences in the goodness-of-fit and the time to identifying a good parameter set. In project one, both algorithms produced good sets that had similar fit, but simulated annealing identified the sets two times faster than Nelder-Mead. In project two, both model structures generated similarly accurate good sets, while the discrete-event simulation generated these three times as quickly as the discrete-time simulation. In project three, I evaluated 13 strategies for initiating osteoporosis treatment based on Fracture Risk Assessment Tool (FRAX) scores, with and without bone mineral density (BMD). The base-case included 50-year-old, HIV-positive men who took ART for ≥3 years and did not have a history of fractures or osteoporosis treatment. I incorporated the calibrated results from projects 1 and 2 in project 3’s probabilistic analysis. I discounted outcomes annually by 1.5%. At a willingness-to-pay threshold of $50,000/QALY, it is most cost-effective to assess FRAX without BMD, offer treatment if FRAX is ≥10%, and re-screen annually. Collectively, these studies suggest using simulated annealing and discrete-event simulation as efficient calibration methods; as well as that the payer should not pay for BMD screening in older HIV-positive men.Ph.D

Amniocentesis in the HIV-Infected Pregnant Woman: Is There Still Cause for Concern in the Era of Combination Antiretroviral Therapy?

The current standard of care in Canadian obstetrical practice is to offer pregnant women the opportunity for prenatal investigation to diagnose congenital abnormalities. Prenatal amniocentesis is Canada’s most commonly practiced invasive procedure for the diagnosis of chromosomal and single gene disorders. The potential risk of intrapartum HIV transmission during amniocentesis raises several ethical concerns and limits the availability of prenatal genetic testing for HIV-positive pregnant women. Complete virological suppression with antiretroviral therapy may alleviate the risk of mother-to-child transmission during amniocentesis and increase accessibility of this important diagnostic tool in the HIV-positive population. The present report describes a case involving a 32-year-old HIV-positive pregnant woman whose plasma viral load was undetectable on antiretroviral therapy; she underwent successful prenatal amniocentesis without transmission of HIV to her infant.Peer Reviewe

Systematic review of HIV transmission between heterosexual serodiscordant couples where the HIV-positive partner is fully suppressed on antiretroviral therapy.

The risk of sexual HIV transmission in serodiscordant couples when the HIV-positive partner has full virologic suppression on combination antiretroviral therapy (cART) is debated. This study aims to systematically review observational studies and randomized controlled trials (RCTs), evaluating rates of sexual HIV transmission between heterosexual serodiscordant couples when the HIV-positive partner has full suppression on cART.We searched major bibliographic databases to November 2012 for relevant observational studies and RCTs without language restrictions. Conference proceedings, key journals and bibliographies were also searched. Studies reporting HIV transmission rates, cART histories and viral loads of the HIV-positive partners were included. Two reviewers extracted methodologic characteristics and outcomes. Of 20,252 citations, 3 studies met all eligibility criteria with confirmed full virologic suppression in the HIV-positive partner. We included 3 additional studies (2 cohort studies, 1 RCT) that did not confirm viral suppression in the HIV-positive partner at transmission in a secondary meta-analysis. Methodologic quality was reasonable. The rate of transmission in the 3 studies confirming virologic suppression was 0 per 100 person-years (95% CI = 0-0.05), with low heterogeneity (I(2) = 0%). When we included the 3 studies that did not confirm virologic suppression, the rate of transmission was 0.14 per 100 person-years (95%CI = 0.04-0.31) (I(2) = 0%). In a sensitivity analysis including all 6 studies, the rate of transmission was 0 per 100 person-years (95%CI = 0-0.01) after omitting all transmissions with known detectable or unconfirmed viral loads, as full suppression in these cases was unlikely. Limitations included lack of data on same-sex couples, type of sexual intercourse (vaginal vs. anal), direction of HIV transmission, exact viral load at the time of transmission, sexually transmitted infections (STI) rates, and extent of condom use.Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health. More research is needed to explore HIV transmission risk between same-sex couples

Flow diagram (selection strategy) of included studies.

<p>Flow diagram (selection strategy) of included studies.</p

Data reported in included studies.

<p>ART, antiretroviral therapy.</p>*<p>The follow up duration for those in the early therapy group was 1585.3 person-years as per the Cohen et al publication <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055747#pone.0055747-Cohen2" target="_blank">[15]</a>. Through personal communication <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055747#pone.0055747-Mastro1" target="_blank">[36]</a>, we identified that the follow up for the 693 couples in the delayed treatment arm who did not start ART was 1121.2 person-years. There were 184 couples where the HIV-positive started ART, with 276.5 person-years of follow up before the start of ART and 169.5 person-years of follow up after the start of ART.</p

Forest plots of HIV transmission rates per 100 person-years with and without transmissions with unconfirmed viral suppression at the time of suppression.

<p><i>Footnote:</i>The first forest plot is the summary of HIV transmission rates per 100 person-years with 95% confidence interval for 6 studies with confirmed and unconfirmed viral suppression at time of transmission. The second forest plot is the sensitivity analysis of the 6 studies with confirmed and unconfirmed viral suppression at the time of transmission with forest plot of the summary of HIV transmission rates per 100 person-years with 95% confidence interval reporting on HIV transmission when HIV-positive partner on combination antiretroviral therapy had confirmed viral suppression, omitting transmissions occurring with known or unconfirmed detectable viral loads at the time of transmission (i.e. 3 studies had 4 transmissions with known or unconfirmed detectable viral loads and these transmissions were excluded, while leaving the rest of data in the analysis).</p

Characteristics of included studies.

<p>cART, combination antiretroviral therapy; IQR, interquartile range.</p