Tenofovir (all routes except local)

Very preterm (28 to 32 weeks)

R analysis
id Study   Lib. in paper Exposition period    Study type  Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S5189
R13505
The EPPICC study group, 2019 Very preterm delivery (< 34 weeks of gestation) 2nd and/or 3rd trimester cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine-based Exposed group: TDF (mix or unspecified regimens) Indication: HIV 1.27 [0.84;1.91] 42/1,122   173/5,122 215 1,122
ref
S5145
R13413
Caniglia, 2018 Very preterm (<32 weeks) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine/nevirapine Exposed group: TDF/emtracitabine/efavirenz Indication: HIV 0.39 [0.26;0.59] 37/1,108   53/637 90 1,108
ref
S5144
R14052
Chetty, 2018 Preterm (< 32 weeks of gestation) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Control group: zidovudine Exposed group: TDF/(emtracitabine or lamivudine)/efavirenz Indication: HIV 1.84 [0.51;6.73] C 10/959   3/528 13 959
ref
S5134
R13383
Floridia, 2018 Very preterm delivery (< 32 weeks) during pregnancy (anytime or not specified) cohort exposed to other treatment, sick Adjustment: No Control group: Abacavir/Lamivudine-based Exposed group: TDF/emtricitabine-based Indication: HIV 0.40 [0.17;0.96] 11/573   10/216 21 573
ref
S5155
R13462
Rough, 2018 Very preterm (delivery before 34 weeks of completed gestation) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine-based Exposed group: TDF/emtricitabine-based Indication: HIV 0.99 [0.66;1.48] 47/960   67/1,593 114 960
ref
S5211
R13514
Malaba, 2017 Very preterm (28–32 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Control group: Unexposed, disease free Exposed group: TDF/emtricitabine-based Indication: HIV 3.00 [0.71;12.67] C 27/1,271   2/278 29 1,271
ref
S5258
R13591
Zash (Controls exposed to other treatments), 2017 Very preterm birth (< 32 weeks) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Control group: zidovudine/lamivudine-based Exposed group: TDF (mix or unspecified regimens) Indication: HIV 0.69 [0.53;0.90] C 152/3,463   95/1,532 247 3,463
ref
S5131
R13342
Fowler, 2016 Very preterm delivery (<34 weeks) 2nd and/or 3rd trimester randomized controlled trial exposed to other treatment, sick Adjustment: Randomisation Control group: zidovudine/lamivudine/lopinavir–ritonavir Exposed group: TDF/emtricitabine/lopinavir–ritonavir Indication: HIV 2.38 [1.07;5.30] C 20/335   9/346 29 335
ref
Total 8 studies 0.93 [0.61;1.42] 758 9,791
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF The EPPICC study group, 2019The EPPICC study group, 2019 1.27[0.84; 1.91]2151,12216%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Caniglia, 2018Caniglia, 2018 0.39[0.26; 0.59]901,10816%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Chetty, 2018Chetty, 2018 1.84[0.51; 6.73]139597%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Floridia, 2018Floridia, 2018 0.40[0.17; 0.96]2157311%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Rough, 2018Rough, 2018 0.99[0.66; 1.48]11496016%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Malaba, 2017Malaba, 2017 3.00[0.71; 12.67]291,2716%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Zash (Controls exposed to other treatments), 2017Zash, 2017 1 0.69[0.53; 0.90]2473,46318%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Fowler, 2016Fowler, 2016 2.38[1.07; 5.30]2933511%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (8 studies) I2 = 79% 0.93[0.61; 1.42]7589,7910.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls exposed to other treatments;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.93[0.61; 1.42]7589,79179%NAThe EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Rough, 2018 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 Fowler, 2016 8 case control studiescase control studies 0 RCTRCT 2.38[1.07; 5.30]29335 -NAFowler, 2016 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.00[0.71; 12.67]291,271 -NAMalaba, 2017 1 exposed to other treatment, sickexposed to other treatment, sick 0.86[0.57; 1.32]7298,52080%NAThe EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Rough, 2018 Zash (Controls exposed to other treatments), 2017 Fowler, 2016 7 Tags Adjustment   - No  - No 0.89[0.45; 1.76]3106,26661%NAChetty, 2018 Floridia, 2018 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 4   - Randomisation  - Randomisation 2.38[1.07; 5.30]29335 -NAFowler, 2016 1   - Yes  - Yes 0.79[0.39; 1.59]4193,19089%NAThe EPPICC study group, 2019 Caniglia, 2018 Rough, 2018 3 Control group   - Abacavir/Lamivudine-based  - Abacavir/Lamivudine-based 0.40[0.17; 0.95]21573 -NAFloridia, 2018 1   - Unexposed, disease free  - Unexposed, disease free 3.00[0.71; 12.67]291,271 -NAMalaba, 2017 1   - zidovudine  - zidovudine 1.84[0.51; 6.73]13959 -NAChetty, 2018 1   - zidovudine/lamivudine/lopinavir–rit ...  - zidovudine/lamivudine/lopinavir–ritonavir 2.38[1.07; 5.30]29335 -NAFowler, 2016 1   - zidovudine/lamivudine/nevirapine  - zidovudine/lamivudine/nevirapine 0.39[0.26; 0.59]901,108 -NACaniglia, 2018 1   - zidovudine/lamivudine-based  - zidovudine/lamivudine-based 0.93[0.64; 1.35]5765,54569%NAThe EPPICC study group, 2019 Rough, 2018 Zash (Controls exposed to other treatments), 2017 3 Exposed group   - TDF (mix or unspecified regimens)  - TDF (mix or unspecified regimens) 0.92[0.51; 1.66]4624,58583%NAThe EPPICC study group, 2019 Zash (Controls exposed to other treatments), 2017 2   - TDF/(emtracitabine or lamivudine)/e ...  - TDF/(emtracitabine or lamivudine)/efavirenz 1.84[0.51; 6.73]13959 -NAChetty, 2018 1   - TDF/emtracitabine/efavirenz  - TDF/emtracitabine/efavirenz 0.39[0.26; 0.59]901,108 -NACaniglia, 2018 1   - TDF/emtricitabine/lopinavir–ritonavir  - TDF/emtricitabine/lopinavir–ritonavir 2.38[1.07; 5.30]29335 -NAFowler, 2016 1   - TDF/emtricitabine-based  - TDF/emtricitabine-based 0.92[0.39; 2.16]1642,80468%NAFloridia, 2018 Rough, 2018 Malaba, 2017 3 Indication   - HIV  - HIV 0.93[0.61; 1.42]7589,79179%NAThe EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Rough, 2018 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 Fowler, 2016 8 All studiesAll studies 0.93[0.61; 1.42]7589,79179%NAThe EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Rough, 2018 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 Fowler, 2016 80.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.70.8830.000The EPPICC study group, 2019Caniglia, 2018Chetty, 2018Floridia, 2018Rough, 2018Malaba, 2017Zash (Controls exposed to other treatments), 2017Fowler, 2016

Asymetry test p-value = 0.3086 (by Egger's regression)

slope=-0.6070 (0.3818); intercept=1.7746 (1.5957); t=1.1122; p=0.3086

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.00[0.71; 12.67]291,271 -NAMalaba, 2017 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.86[0.57; 1.32]7298,52080%NAThe EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Rough, 2018 Zash (Controls exposed to other treatments), 2017 Fowler, 2016 70.510.01.0