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.