Fiona Smaill

Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy

Symptomatic and asymptomatic bacteriuria is common in pregnant women. A history of previous urinary tract infections and low socioeconomic status are risk factors for bacteriuria in pregnancy. Escherichia coli is the most common aetiologic agent in both symptomatic and asymptomatic infection and quantitative culture is the gold standard for diagnosis. Treatment of asymptomatic bacteriuria has been shown to reduce the rate of pyelonephritis in pregnancy and therefore screening for and treatment of asymptomatic bacteriuria has become a standard of obstetrical care. Antibiotic treatment of asymptomatic bacteriuria is associated with a decrease in the incidence of low birth weight, but the methodological quality of the studies limits the strength of the conclusions that can be drawn. Debate exists in the literature as to whether treated pyelonephritis is associated with adverse fetal outcomes. There is no clear consensus in the literature on antibiotic choice or duration of therapy for infection. With increasing antibiotic resistance, consideration of local resistance rates is necessary when choosing therapy.

Pathogen inactivation: making decisions about new technologies Report of a consensus conference

Methods to remove and inactivate pathogens, used extensively in the manufacture of plasma protein fractions, have all but eliminated transmission of infectious agents by these products. 1 Technologies for reducing the risk of infection from single donor blood components have not been embraced as enthusiastically. Several methods have been introduced in Europe. Treatment with solvent/detergent (S/D) or methylene blue have both been applied to plasma components, and psoralen treatment of platelets (PLTs) has begun in several countries. 2-4 Although S/D-treated pooled plasma has been approved for use in the United States and Canada, none of these methods has been adopted for single-donor products in North America. Reasons for slow acceptance include 1) the current safety of the volunteer blood supply; 2) the success of surveillance and development of screening tests to deal with emerging pathogens; 3) the inability of current technologies to inactivate some agents such as spores, prions, and certain small nonencapsulated viruses; 4) concerns regarding remote risks from the residual chemical agents used during the pathogen inactivation (PI) process; 5) absence of any single method to treat whole blood or all components; and 6) the costeffectiveness of these technologies especially compared to strategies to reduce noninfectious risks of transfusion. 5

Self-Reported Preconception Care of HIV-Positive Women of Reproductive Potential: A Retrospective Study

Objectives: We determined the proportion and correlates of self-reported pregnancy planning discussions (that is preconception counseling) that HIV-positive women reported to their family physicians (FPs), HIV specialists, and obstetrician/gynecologists (OB/Gyns). Methods: In a cross-sectional substudy, HIV-positive women of reproductive potential were asked whether their care providers discussed pregnancy planning. Logistic regression was used to calculate odds ratios for the correlates of preconception counseling. Results: A total of 431 eligible participants (median age 38, interquartile range = 32-43) reported having discussion with a physician (92% FP, 96% HIV specialists, and 45% OB/Gyns). In all, 34%, 41%, and 38% had their pregnancy planning discussion with FP, HIV specialist, and Ob/Gyns, respectively; 51% overall. In the multivariable model, significant correlates of preconception counseling were age (P = .02), marital status (P < .01), number of years living in Canada (P < .001), and age of youngest child (P < .01). Conclusions: Preconception care in our cohort was suboptimal. We recommend that counseling on healthy preconception should be part of routine HIV care.

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.

A large prospective study assessing injection site reactions, quality of life and preference in patients using the Biojector® vs standard needles for enfuvirtide administration*

To determine the severity of injection site reactions (ISRs), patient quality of life (QoL) and preference when enfuvirtide is administered by the Biojector® (Bioject, Medical Technologies, Inc., Tualatin, OR, USA) relative to standard needles.

Randomized Controlled Trial of Once-Daily Tenofovir, Lamivudine, and Lopinavir/Ritonavir Versus Remaining on the Same Regimen in Virologically Suppressed HIV-Infected Patients on Their First PI-Containing HAART Regimen

Abstract Purpose: To assess the effects of switching to once-daily (QD) lopinavir/ritonavir (LPV/r)-based combination therapy in HIV-infected patients who are virologically suppressed (HIV viral load <50 copies/mL) on their first protease inhibitor (PI)-containing regimen. Method: In this 48-week, prospective, open-label, randomized study, patients were either switched to once-daily LPV/r, tenofovir (TDF), and lamivudine (3TC) (QD arm) or remained on their existing regimen (control arm). The primary endpoint of the study was the proportion of patients maintaining virologic suppression following 48 weeks of treatment. Results: Fifty and 22 patients were randomized to the QD and control arms, respectively. At week 48, there was no significant difference in virological suppression between the QD and control arms using intent-to-treat (missing = failure) analysis (p = .44). There was no significant difference in discontinuation rates between the two arms (p = .66). Significantly more patients randomized to the QD arm reported gastrointestinal adverse events compared with the control arm (p = .009). There were no study drug-related serious adverse events. Conclusion: For patients who are already virologically suppressed on their first PI-containing regimen, switching to a QD regimen of TDF+3TC+LPV/r resulted in similar rates of virologic suppression when compared with staying on existing therapy.

In early HIV infection, immediate vs deferred antiretroviral therapy reduced serious illnesses at 3 years

Question In adults with HIV infection and CD4+ count >500 cells/mm3, does immediate antiretroviral therapy (ART) reduce serious AIDS-related or nonAIDS-related illnesses compared with deferred ART? Methods Design Randomized controlled trial (Strategic Timing of Antiretroviral Therapy [START] study). ClinicalTrials.gov NCT00867048. Allocation Concealed.* Blinding Blinded* (outcome adjudicators). Follow-up period Mean 3 years. Setting 215 centers in 35 countries. Patients 4685 generally healthy patients 18 years of age (median age 36 y, 73% men, median CD4+ count 651 cells/mm3) who were HIV positive, had 2 CD4+ counts >500 cells/mm32 weeks apart 60 days before enrollment, and had not started ART. Exclusion criteria included pregnancy, breastfeeding, or history of AIDS. Intervention ART started immediately (n =2326) or deferred until CD4+ count reached 350 cells/mm3 or an AIDS-related event or other condition requiring ART occurred (n =2359). Outcomes Primary outcome was a composite of serious AIDS-related events (death due to AIDS or any AIDS-defining event other than nonfatal herpes simples virus infection or esophageal candidiasis) or serious nonAIDS-related events (death not related to AIDS, cardiovascular disease, end-stage renal disease, decompensated liver disease, or nonAIDS-defining cancer other than basal cell or squamous cell skin cancer). Other outcomes included components of the composite outcome, all-cause mortality, grade 4 events (symptomatic, nonAIDS-related, potentially life-threatening events requiring medical intervention), and unscheduled nonAIDS-related hospitalization. Patient follow-up 95% (intention-to-treat analysis). Main results Immediate ART reduced serious AIDS-related and nonAIDS-related events compared with deferred ART; groups did not differ for all-cause mortality, grade 4 events, or unscheduled nonAIDS-related hospitalizations (Table). Conclusion In adults with HIV infection and CD4+ count >500 cells/mm3, immediate antiretroviral therapy reduced serious illnesses compared with deferred therapy. Immediate vs deferred antiretroviral therapy (ART) in adults with HIV infection and CD4+ count >500 cells/mm3 Outcomes Event rates At a mean 3 y of follow-up Immediate ART Deferred ART RRR (95% CI) NNT (CI) Composite primary outcome 1.8% 4.1% 56% (38 to 70) 44 (36 to 66) Serious AIDS-related event 0.60% 2.12% 72% (50 to 85) 66 (56 to 95) Serious nonAIDS-related event 1.2% 2.0% 39% (3 to 62) 130 (82 to 1692) All-cause mortality 0.52% 0.89% 42% (17 to 72) NS Unscheduled nonAIDS-related hospitalization 11% 12% 8.5% (7 to 22) NS RRI (CI) NNH Grade 4 event 3.14% 3.09% 1% (27 to 38) NS NS = not significant; other abbreviations defined in Glossary. RRR, RRI, NNT, and CI calculated from hazard ratios and deferred ART event rates in article. Serious AIDS-related event or serious nonAIDS-related event. Commentary The START and TEMPRANO trials provide long-awaited definitive evidence for universal HIV treatment. No further studies of delayed treatment can be justified unless they evaluate implementation strategies. Although the WHO guidelines for starting ART have been evolving and CD4+ count cutpoints increasing, a pragmatic approach had been taken to establish criteria for treatment based as much on the realities of delivering HIV care as on evidence of treatment effectiveness. Although some HIV guidelines were already endorsing treatment regardless of CD4+ count (1), the results of these 2 RCTs provide strong evidence in support of this recommendation, and the recently updated WHO guidelines now recommend universal HIV treatment (2). A treat-all policy across diverse populations has been shown to be feasible and acceptable, with evidence of early benefits and no obvious disadvantages (3). Some clinicians have been hesitant to advocate strongly for a universal approach to treat early because of questions about toxicity, cost, viral resistance, and patient adherence and the lack of robust data from randomized trials. It is reassuring that START and TEMPRANO confirm that early treatment did not increase adverse events overall; however, issues of long-term adherence were not addressed given the relatively short duration of the trials. In the START trial, which enrolled patients from 35 countries that had various models of care, incomes, and geographies, all reported subgroups benefitted from early treatment. In both START and TEMPRANO trials, early treatment prevented tuberculosis (TB) and bacterial infections, which are often overlooked as complications of HIV infection. Given the coepidemics of TB and HIV, implementation of early HIV treatment could substantially affect TB rates. TEMPRANO also reinforced what we already know: IPT works in populations with HIV and a high rate of TB. There is an imperative to scale up IPT without delay as part of joint TB and HIV programming. ART reduces the risk for sexual transmission of HIV (4), and universal treatment for all, together with preexposure prophylaxis (2), has the potential to affect millions of lives and prevent countless deaths. The public health implications are enormous. However, although we often talk about the challenges of scale-up in the poorest countries, we must also address the large gaps in the HIV care continuum (5): Patients who are marginalized, are poor, or have mental health issues or addictions are often not engaged in care. It is easy to incorporate the results of these trials into strong evidence-based guidelines, although their implementation will need an increased global commitment to care for everyone living with HIV.