Additional file 1: of A scoping review of rapid review methods

Includes five appendices with supplementary data. (PDF 603 kb

Study Flow Diagram.

<p>Breakdown of the number of studies identified in the literature, assessed for eligibility, and finally included in the rapid scoping review.</p

Aggregate Newcastle-Ottawa Scale results.

<p>Items: 1. Representativeness of the exposed cohort: A, Truly representative of the average HIV-infected pregnant woman taking ART in the community; B, somewhat representative of the average HIV-infected pregnant woman taking ART in the community; D, no description of the derivation of the cohort. 2. Selection of the non-exposed cohort: A, drawn from the same community as the exposed cohort; B, drawn from a different source; C, no description of the derivation of the non-exposed cohort. 3. Ascertainment of exposure: A, Secure record (e.g., medical records, surgical records); B, Structured interview; D, No description. 4. Demonstration that outcome of interest was not present at start of study: A, Yes; D, No description. 5. Comparability of cohorts on the basis of the design or analysis: A, study controls for age and one other important factor; C, study controls for any other important factor; D, study does not control for any important factor or it is not described. 6. Assessment of outcome: A, Independent OR blind assessment; D, No description. 7. Was follow-up period long enough for outcomes to occur: A, yes; D, No description. 8. Adequacy of follow-up of cohorts: A, complete follow-up—all subjects accounted for; B, subjects lost to follow-up unlikely to introduce bias—small number lost, or description provided of those lost; C, follow-up rate is inadequate and no description of those lost; D, no statement.</p

Funnel plots including specific antiretroviral drugs by outcomes reported.

<p>Funnel Plots including Antiretroviral Specific Drugs by Outcomes reported. Legend: A) Total Congenital Malformations—20 studies (9 RCTs, 11 Cohorts), # 7503 patients, # 16 treatments B) Mother-to-Child Transmission of HIV–# 11 studies (3 RCTs, 8 Cohorts), # 10786 patients, # 6 treatments C) Infant and child deaths–#13 studies (8 RCTs, 5 Cohorts), # 11385 patients, # 8 treatments D) Preterm births– 35 studies (8 RCTs, 1 Case-control, 26 Cohorts), # 20576 patients, # 17 treatments E) Stillbirths –26 studies (13 RCTs, 13 Cohorts), # 17507 patients, # 20 treatments, F) Low birth weight– 30 studies (10 RCTs, 19 Cohorts, 1 Case-control), # 21848 patients, # 16 treatments.</p

Study, patient, and interventions characteristics.

<p>Study, patient, and interventions characteristics.</p

Network diagrams of antiretroviral medications for each outcome.

<p>Legend: A) Total Congenital Malformation B) Major Congenital Malformation C) Minor Congenital Malformation D) Mother to Child Transmission E) Infant and child deaths F) Preterm births G) Stillbirths H) Low birth weight. Each node represents an antiretroviral medication and each line represents a direct comparison between medications. The nodes are weighted according to the number of patients in each medication, and the lines are weighted according to the number of studies included in the direct comparison. Abbreviations: ABC, Abacavir; ddI, Didanosine; CM, Congenital Malformations; IND, Indinavir; 3TC, Lamivudine; LOP, Lopinavir; MTCT, Mother to Child Transmission; NVP, Nevirapine; NLF, Nelfinavir; NoT, No Treatment; PLC, Placebo; SAQ, Saquinavir; d4T, Stavudine; EFV, Sustiva; RIT, Ritonavir; ZDV, Zidovudine.</p

Rank-heat plot of 28 antiretroviral treatments (28 radii) and seven safety outcomes (seven concentric circles).

<p>Each sector is colored according to the SUCRA value of the corresponding treatment and outcome using the transformation of three colors red (0%), yellow (50%), and green (100%). Abbreviations: ABC, Abacavir; CM, Congenital Malformations; ddI, Didanosine; IND, Indinavir; 3TC, Lamivudine; LOP, Lopinavir; LBW, Low Birth Weight; NVP, Nevirapine; NLF, Nelfinavir; SAQ, Saquinavir; d4T, Stavudine; SUCRA, surface under the cumulative ranking curve; EFV, Sustiva; RIT, Ritonavir; ZDV, Zidovudine.</p

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs

<div><p>Background</p><p>Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analysis (NMA) was to evaluate the comparative safety and effectiveness of ART drugs in children exposed to maternal HIV and ART (or no ART/placebo) across different study designs.</p><p>Methods</p><p>We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception until December 7, 2015). Primary outcomes were any congenital malformations (CMs; safety), including overall major and minor CMs, and mother-to-child transmission (MTCT; effectiveness). Random-effects Bayesian pairwise meta-analyses and NMAs were conducted. After screening 6,468 citations and 1,373 full-text articles, 90 studies of various study designs and 90,563 patients were included.</p><p>Results</p><p>The NMA on CMs (20 studies, 7,503 children, 16 drugs) found that none of the ART drugs examined here were associated with a significant increase in CMs. However, zidovudine administered with lamivudine and indinavir was associated with increased risk of preterm births, zidovudine administered with nevirapine was associated with increased risk of stillbirths, and lamivudine administered with stavudine and efavirenz was associated with increased risk of low birth weight. A NMA on MTCT (11 studies, 10,786 patients, 6 drugs) found that zidovudine administered once (odds ratio [OR] = 0.39, 95% credible interval [CrI]: 0.19–0.83) or twice (OR = 0.43, 95% CrI: 0.21–0.68) was associated with significantly reduced risk of MTCT.</p><p>Conclusions</p><p>Our findings suggest that ART drugs are not associated with an increased risk of CMs, yet some may increase adverse birth events. Some ART drugs (e.g., zidovudine) effectively reduce MTCT.</p></div

Aggregate EPOC risk-of-bias appraisal results.

<p>Abbreviations: EPOC, Effective Practice and Organization of Care; High, High risk of bias; Low, Low risk of bias; Unclear, Unclear risk of bias; NA, Not Applicable. Items: 1. Random sequence generation. 2. Allocation concealment. 3. Similar baseline outcome measures. 4. Similar baseline characteristics. 5. Incomplete outcome data. 6. Blinding. 7. Contamination. 8. Selective outcome reporting. 9. Other bias.</p

Additional file 1: of Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis

Protocol (PDF 121 kb