Kevin Gough

Fertility desires and intentions of HIV-positive women of reproductive age in Ontario, Canada: a cross-sectional study.

Background Improvements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada. Methodology/Principal Findings A cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18–52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled “The HIV Pregnancy Planning Questionnaire” designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32–43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%–73%) desired to give birth and 57% (95% CI, 53%–62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age<40) (p<0.0001), African ethnicity (p<0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02). Conclusions/Significance The proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration.

Incidence of and risk factors for tenofovir‐induced nephrotoxicity: a retrospective cohort study

Despite the recent publication of case reports describing various manifestations of tenofovir‐related nephrotoxicity, data regarding the incidence of and risk factors for this adverse effect are currently lacking.

Severe Anemia Secondary to a Probable Drug Interaction between Zidovudine and Valproic Acid

A 42-year-old man with human immunodeficiency virus (HIV) infection and a history of complex partial seizures developed severe anemia after the addition of valproic acid to his stable antiretroviral regimen of zidovudine, lamivudine, and abacavir. The inhibition of zidovudine glucuronidation by valproic acid and the resultant zidovudine hematologic toxicity is the proposed mechanism of the interaction.

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.

Long-Term Follow-up of a Cohort of HIV-Infected Patients Who Discontinued Maintenance Therapy for Cytomegalovirus Retinitis

Abstract Purpose: To determine the long-term safety of discontinuation of maintenance therapy for cytomegalovirus retinitis (CMVR) and to identify predictors for relapse. Method: This was a prospective cohort study. Patients with treated CMVR who responded to HAART were followed by ophthalmologic assessment, markers for CMV replication (blood and urine cultures, CMV antigenemia, CMV DNA by PCR), and in vitro lymphoproliferative responses to CMV and other antigens after discontinuation of CMVR maintenance therapy. Results: 23 patients were followed a median of 34 (range, 5-61) months. Median CD4 count was 321/mm3 at enrollment and 395/mm3 at last follow-up. HIV RNA was <50 copies/mL in 78% of patients at enrollment and 65% at last follow-up. One CMVR reactivation occurred at 12 months at a CD4 count of 395/mm3 (21%) and HIV RNA <50 copies/mL. Urine cultures were a poor predictive marker for reactivation. Other CMV replication markers had good negative predictive value. 96% of patients had a good lymphoproliferative response to CMV antigen in vitro. Conclusion: Maintenance therapy for CMVR can safely be discontinued in patients who have responded to HAART. Combining our results with the published literature, the risk of reactivation is estimated at 0.016 per person year of follow-up. Markers to predict relapse and the need for re-initiation of maintenance therapy are not yet identified.

Non-occupational post-exposure prophylaxis for HIV at St Michael's Hospital, Toronto: a retrospective review of patient eligibility and clinical outcomes:

Stringent eligibility criteria, drug costs and antiretroviral toxicities are challenges in delivering HIV non-occupational post-exposure prophylaxis (nPEP). We reviewed patients’ nPEP eligibility and clinical outcomes at St Michaels Hospital, Toronto, Canada to identify opportunities for improvement. Of 241 patients, 59%, 36% and 6% presented for high- (receptive anal/vaginal, blood), medium- (insertive anal/vaginal) and low-risk (oral) sexual exposures, respectively, and nearly all (93%) presented within 72 hours. Of 205 patients given nPEP, 20 were known to have discontinued nPEP prematurely: three due to costs but none due to toxicities. Two HIV seroconversions occurred in patients with suspected ongoing potential exposures. Five asymptomatic syphilis diagnoses were made among 71 tested. Only 39% and 19% of nPEP patients returned to our institution for follow-up at 3–4 and six months, respectively. Our findings underscore the feasibility and importance of nPEP programmes to HIV and sexually transmitted infection control, while identifying opportunities for improvement.

A Prospective Study of Body Fat Redistribution, Lipid, and Glucose Parameters in HIV-Infected Patients Initiating Combination Antiretroviral Therapy

Abstract Purpose: To prospectively determine incidence, prevalence, and extent of lipodystrophy (LD) and associated metabolic changes. Method: This was a prospective cohort study. Body habitus changes were determined by anthropometrics, photography, and regional dual-energy X-ray absorptiometry (DXA) scan. Metabolic parameters included triglyceride (TG), total (TC), LDL and HDL cholesterol, glucose, and insulin. Results: 68 patients were included. 51 (75%) received protease inhibitor (PI)-based and 17 (25%) non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ARV) and 90% a thymidine analogue. Statistically significant increases in TC, TG, LDL, and HDL by 12 months developed on PI but only in TC for NNRTI. At 24 months, on DXA scanning, there were no statistically significant changes in median limb or total body fat on NNRTI but a statistically significant decrease in limb fat on PI (p = .01). There was considerable individual variation with overall 3 (7%) patients having >20% increases and 16 (36%) with >20% decreases in limb fat and 6 (14%) having >20% increases and 7 (16%) with >20% decreases in total body fat. Conclusions: Lipid changes occurred early and progressed. Median changes in body fat were minor and more common on PI, but individual variation in change was large, challenging the use of medians or threshold changes to predict impact of different ARV agents.

Severe acute respiratory syndrome in pregnancy.

BACKGROUND: There is limited worldwide experience with severe acute respiratory syndrome (SARS) in pregnancy. We present a case of SARS complicating pregnancy in the third trimester, with outcome data on both the mother and baby. CASE: A 33-year-old gravida 2 para 1 fulfilling the World Health Organization case definition for probable SARS was admitted to our institution at 31 weeks of gestation with fever, a dry cough, and patchy infiltrates on chest X-ray. The patient was previously healthy and acquired SARS from close contact with an infected family member. Convalescent serology results were positive for antibodies to coronavirus. She stayed in hospital for 21 days and did not require intensive care admission or ventilatory support. Labor occurred spontaneously at term, and a healthy female baby was delivered with no evidence of infection. CONCLUSION: Severe acute respiratory syndrome in pregnancy is a potentially life-threatening illness with complicated management issues. Hospitalization and care by a multidisciplinary team may optimize chances for a good outcome.

Early-onset pentamidine-associated second-degree heart block and sinus bradycardia: case report and review of the literature.

Although various manifestations of pentamidine‐induced cardiotoxicity have been reported, to our knowledge, second‐degree heart block associated with this agent has not been described. In addition, cardiac adverse effects usually develop after at least 6 days of therapy. We describe a 54‐year‐old, human immunodeficiency virus–positive man with a history of sulfonamide allergy who received treatment with pentamidine for Pneumocystis jiroveci pneumonia. After only the third dose of pentamidine, it was noted that the patients heart rate had decreased to 48 beats/minute. Subsequently, five episodes of Wenckebach (Mobitz type 1) heart block with a ventricular rate of 28 beats/minute were observed on continuous cardiac telemetry. Serum electrolyte and creatinine levels remained within normal limits. Within 4 days of discontinuing the pentamidine, the patients heart rate stabilized at 80 beats/minute without further intervention. Clinicians should be vigilant when monitoring for cardiotoxicity in patients receiving pentamidine throughout the duration of therapy. In addition, they should continue to reserve its use for moderate‐to‐severe Pneumocystis jiroveci pneumonia for which trimethoprim‐sulfamethoxazole is ineffective or contraindicated.

Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study

BackgroundAlthough some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations.MethodsHIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for Cmin and Cmax were drawn weekly for 3 weeks. The ratio of each individual’s median Cmin and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed Cmin and Cmax ratios.ResultsData from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral Cmin and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher Cmin. No significant correlates for Cmax were found.ConclusionsCompared to historical control data, Cmin in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral Cmin ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations.Trial registrationNCT00433979