Table 4.

GRADE evidence profile: tenofovir and emtricitabine versus alternative NRTI regimens in pregnant women living with HIV for outcomes that are different in different settings*

Outcome Time frame	Study results and measurements	Absolute effect estimates		Certainty in effect estimates (quality of evidence)	Summary
		Alternative-NRTI ART	Tenofovir/FTC ART
Low and medium resourced settings (high baseline risk of stillbirth and early neonatal mortality, no access to early hepatitis B vaccination series):
Stillbirth and early neonatal mortality 20 weeks’ gestational age to 1 week postpartum	Relative risk: 4.40 (95% CI 1.75 to 11.01) Based on data from 897 patients in three studies Follow-up 1 week postpartum	69† per 1000	304 per 1000	Moderate/low‡ Due to serious imprecision	Tenofovir/FTC probably increases the risk of stillbirth and early neonatal mortality.
		Difference: 235 more per 1000 (95% CI 52 more to 691 more)
Vertical hepatitis B transmission 6–12 months	Relative risk: 0.26 (95% CI 0.01 to 4.77) Based on data from 1037 patients in nine studies Follow-up neonate to 12 months	111§ per 1000	29 per 1000	Low¶ Due to very serious imprecision	There may not be no important difference in vertical hepatitis B transmission.
		Difference: 82 fewer per 1000 (95% CI 110 fewer to 418 more)
High-resourced settings (lower baseline risk of stillbirth and early neonatal mortality, access to early hepatitis B vaccination series):
Stillbirth and early neonatal mortality 20 weeks’ gestational age to 1 week postpartum	Relative risk: 4.40 (95% CI 1.75 to 11.01) Based on data from 897 patients in three studies Follow-up 1 week postpartum	15** per 1000	66 per 1000	Moderate/low‡ Due to serious imprecision	Tenofovir/FTC probably increases the risk of stillbirth and early neonatal mortality.
		Difference: 51 more per 1000 (95% CI 11 more to 150 more)
Vertical hepatitis B transmission 6–12 months	Relative risk: 0.26 (95% CI 0.01 to 4.77) Based on data from 1037 patients in nine studies Follow-up neonate months to 12 months	10†† per 1000	3 per 1000	Moderate¶ Due to serious imprecision	There is probably no important difference in vertical hepatitis B transmission.
		Difference: 7 fewer per 1000 (95% CI 10 fewer to 38 more)

Full interactive evidence profile available at https://www.magicapp.org/goto/guideline/VLpr5E.

*See table 3 for outcomes consistent across populations.

†Baseline risk is inferred from an observational study in Botswana.⁵¹

‡Moderate certainty when combined with lopinavir/ritonavir, low certainty when combined with a different third antiretroviral.

§Baseline risk is inferred from an observational study in the USA.⁵⁰

¶We considered rating down for risk of bias because the indirect comparison relies on one study of tenofovir versus placebo that was not adequately blinded.³⁸ However, we decided not to rate down because any plausible confounding would have favoured the control group (eg, about 8% more infants were delivered by caesarean section in the control group) and all infants received the full early hepatitis B vaccination series and hepatitis B immunoglobulin.

**Estimate of baseline risk comes from an observational study in the USA.⁹²

††Estimate of baseline risk is based on the risk ratio of lamivudine versus placebo from our network meta-analysis (0.28) and the baseline risk of hepatitis B transmission without any intervention (38.3%).⁸³

ART, antiretroviral therapy; FTC, emtricitabine; GRADE, Grading of Recommendations Assessment, Development and Evaluation; NRTIs, nucleoside/nucleotide reverse transcriptase inhibitors.