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Practice Rapid Recommendations

Antiretroviral therapy in pregnant women living with HIV: a clinical practice guideline

BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3961 (Published 11 September 2017) Cite this as: BMJ 2017;358:j3961

Drug names

There are a large number of different antiretroviral drugs used by people with HIV. These drug names and abbreviations will be used throughout this article. Protease inhibitors(PIs) Nucleoside reverse transcriptase inhibitors(NRTIs) TDF FTC AZT 3TC TenofovirEmtricitabine Zidovudine LamivudineAbacavir Non-nucleoside reverse transcriptase inhibitors (NNRTIs) LPV/r Lopinavir (boosted with ritonavir) ATZ/r EFV DRV/r RAL RPV ABC Atazanavir (boosted with ritonavir) Darunavir (boosted with ritonavir) Efavirenz Rilpivirine Integrase inhibitors Raltegravir

Population

Pregnant womenliving with HIV Already recieving combination antiretroviral therapy (cART) New diagnosis / not recieving cART at least one additional antiretroviral CD4≥ 350 This recommendation compares different combined antiretroviral medications that may be given to women during pregnancy, to reduce the risk of vertical transmission to the child. Intrapartum antiretroviral therapy only Generally not recommended.Vertical transmission ≈ 50–300 babies in 1000 or Combination antiretroviral therapy (cART) at least one additional antiretroviral at least one additional antiretroviral + + + + Vertical transmission ≈ 5 babies in 1000.No increased vertical transmission with vaginal delivery or breastfeeding.Possible increase in premature birth compared to AZT monotherapy or no maternal ART (particularly with protease inhibitors) CD4< 350 For women with low CD4 levels, cART may reduce AIDS-defining illness.cART may also reduce maternal mortality, especially if CD4 level is below 200 mono-therapy Vertical transmission ≈ 10–15 babies in 1000 AZT Nucleoside reverse transcriptase inhibitor Zidovudine AZT TDF Nucleoside reverse transcriptase inhibitor Tenofovir TDF FTC Nucleoside reverse transcriptase inhibitor Lamivudine FTC AZT Nucleoside reverse transcriptase inhibitor Zidovudine AZT 3TC Nucleoside reverse transcriptase inhibitor Lamivudine 3TC

Recommendation 1

or TDF + FTC- based therapy AZT + 3TC- based therapy Zidovudine + lamivudine-based antiretroviral therapy. Tenofovir + emtricitabine-based antiretroviral therapy. TDF FTC + Treatment backbone: Combined with one of: ATZ/r EFV DRV/r RAL RPV AZT 3TC + Treatment backbone: Combined with one of: LPV/r ATZ/r EFV DRV/r RAL RPV ABC or TDF + FTC- based therapy AZT + 3TC- based therapy Zidovudine + lamivudine-based antiretroviral therapy. Tenofovir + emtricitabine-based antiretroviral therapy. Favours TDF + FTC cART Favours AZT + 3TC cART + Treatment backbone: Combined with one of: + Treatment backbone: Combined with one of: ABC Nucleoside reverse transcriptase inhibitor Abacavir ABC RPV Non-nucleoside reverse transcriptase inhibitor Rilpivirine RPV EFV Non-nucleoside reverse transcriptase inhibitor Efavirenz EFV RAL Integrase inhibitor Raltegravir RAL ATZ/r Protease inhibitor Atazanavir (boosted with ritonavir) ATZ/r DRV/r Protease inhibitor Darunavir (boosted with ritonavir) DRV/r LPV/r Protease inhibitor Lopinavir (boosted with ritonavir) LPV/r 3TC Nucleoside reverse transcriptase inhibitor Lamivudine 3TC AZT Nucleoside reverse transcriptase inhibitor Zidovudine AZT RPV Non-nucleoside reverse transcriptase inhibitor Rilpivirine RPV EFV Non-nucleoside reverse transcriptase inhibitor Efavirenz EFV RAL Integrase inhibitor Raltegravir RAL ATZ/r Protease inhibitor Atazanavir (boosted with ritonavir) ATZ/r DRV/r Protease inhibitor Darunavir (boosted with ritonavir) DRV/r TDF Nucleoside reverse transcriptase inhibitor Tenofovir TDF FTC Nucleoside reverse transcriptase inhibitor Emtricitabine FTC

Strong Weak We suggest a zidovudine and lamivudine-based antiretroviral regimen over one that includes tenofovir and emtricitabine All Applies to Click fordetails Weak Benefits outweigh harms for the majority, but not for everyone. The majority of patients would likely want this option. Strong Benefits outweigh harms for almost everyone. All or nearly all informed patients would likely want this option.

Comparison of benefits and harms

Favours TDF + FTC cART Favours AZT + 3TC cART Events per 1000 people All settings Evidence quality No important difference The panel found that these differences were not important for most patients, because the intervention effects were negligible and/or very imprecise (such as statistically not significant)

HIV vertical transmission 5 4 No important difference Low More

Risk of Bias No serious concerns Imprecision No serious concerns Indirectness Possible Inconsistency No serious concerns Publication bias No serious concerns There may not be an important difference in vertical HIV transmission based mainly onobservational data Additionalconcerns +

Maternal laboratory AEs Moderate 117 138 No important difference More

Risk of Bias No serious concerns Imprecision Serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns There may not be an important difference in maternal serious laboratory adverse events

Maternal clinical AEs Moderate 20 20 No important difference More

Risk of Bias No serious concerns Imprecision No serious concerns Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns There is probably no important difference in maternal serious clinical adverse events

Premature births (<34 weeks) Low 74 42 fewer 32 More

Risk of Bias No serious concerns Imprecision Serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns There may not be an important increase in early prematurity with TDF/FTC
Low/medium resourced settings Events per 1000 people Evidence quality

Hepatitis B vertical transmission Low 111 No important difference 29 More

Risk of Bias No serious concerns Imprecision Very serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns There may not be an important difference in vertical hepatitis B transmission

Stillbirth/neonatal mortality Low 304 235 fewer 69 More

Risk of Bias No serious concerns Imprecision Serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns TDF/FTC may increase the risk of stillbirth and early neonatal mortality
High resourced settings Events per 1000 people Evidence quality

Hepatitis B vertical transmission Moderate 3 10 No important difference More

Risk of Bias No serious concerns Imprecision Serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns There is probably no important difference in vertical hepatitis B transmission

Stillbirth/neonatal mortality Low 66 51 fewer 15 More

Risk of Bias No serious concerns Imprecision Serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns TDF/FTC may increase the risk of stillbirth and early neonatal mortality
See all outcomes
Women in these situations might be more likely to choose regimens with a tenofovir/emtricitabine backbone: Preferences and values Resourcing Other considerations Zidovudine/lamivudine is available as a low-cost generic around the world, while tenofovir/emtricitabine remains on patent in several countries. The evidence applies less in areas with high hepatitis B disease activity, high resource settings, or where access to one of the options is limited. Lamivudine-resistant hepatitis B Severe anemia Lamivudine-resistant HIV Drug allergy Women taking other medications with serious interactions Women who place a high value on a once-daily regimen Zidovudine-resistant HIV Alternatives are not available

Recommendation 2

or TDF + FTC + LPV/r The specific combination of drugs tested in the PROMISE trial TDF FTC + Treatment backbone: Combined with: AZT + 3TC- based therapy Zidovudine + lamivudine-based antiretroviral therapy. AZT 3TC + Treatment backbone: Combined with one of: LPV/r ATZ/r EFV DRV/r RAL RPV ABC Favours TDF + FTC + LPV/r Favours AZT + 3TC cART LPV/r Protease inhibitor Lopinavir (boosted with ritonavir) LPV/r ABC Nucleoside reverse transcriptase inhibitor Abacavir ABC RPV Non-nucleoside reverse transcriptase inhibitor Rilpivirine RPV EFV Non-nucleoside reverse transcriptase inhibitor Efavirenz EFV RAL Integrase inhibitor Raltegravir RAL ATZ/r Protease inhibitor Atazanavir (boosted with ritonavir) ATZ/r DRV/r Protease inhibitor Darunavir (boosted with ritonavir) DRV/r LPV/r Protease inhibitor Lopinavir (boosted with ritonavir) LPV/r 3TC Nucleoside reverse transcriptase inhibitor Lamivudine 3TC AZT Nucleoside reverse transcriptase inhibitor Zidovudine AZT TDF Nucleoside reverse transcriptase inhibitor Tenofovir TDF FTC Nucleoside reverse transcriptase inhibitor Emtricitabine FTC

Strong Weak We recommend a zidovudine and lamivudine-based antiretroviral regimen over tenofovir and emtricitabine with ritonavir-boosted lopinavir All Applies to Click fordetails Weak Benefits outweigh harms for the majority, but not for everyone. The majority of patients would likely want this option. Strong Benefits outweigh harms for almost everyone. All or nearly all informed patients would likely want this option.

Comparison of benefits and harms

Favours TDF + FTC + LPV/r Favours AZT + 3TC cART Events per 1000 people All settings Evidence quality No important difference The panel found that these differences were not important for most patients, because the intervention effects were negligible and/or very imprecise (such as statistically not significant)

HIV vertical transmission 5 4 No important difference Low More

Risk of Bias Possible Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns There may not be an important difference in vertical HIV transmission based mainly onobservational data Additionalconcerns +

Maternal laboratory AEs Moderate 117 138 No important difference More

Risk of Bias No serious concerns Imprecision Serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns There is probably no important difference in maternal serious laboratory adverse events

Maternal clinical AEs Moderate 20 20 No important difference More

Risk of Bias No serious concerns Imprecision No serious concerns Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns There is probably no important difference in maternal clinical adverse events

Premature births (<34 weeks) Moderate 74 42 fewer 32 More

Risk of Bias No serious concerns Imprecision Serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns There is probably an important increase in early prematurity with TDF/FTC
Low/medium resourced settings Events per 1000 people Evidence quality

Hepatitis B vertical transmission Low 29 111 No important difference

Risk of Bias No serious concerns Imprecision Very serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns There may not be an important difference in vertical hepatitis B transmission

Stillbirth/neonatal mortality Moderate 304 235 fewer 69 More

Risk of Bias No serious concerns Imprecision Serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns TDF/FTC probably increases the risk of stillbirth and early neonatal mortality
High resourced settings Events per 1000 people Evidence quality

Hepatitis B vertical transmission Moderate 3 10 No important difference More

Risk of Bias No serious concerns Imprecision Serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns There is probably no important difference in vertical hepatitis B transmission

Stillbirth/neonatal mortality Moderate 66 51 fewer 15

Risk of Bias No serious concerns Imprecision Serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns TDF/FTC probably increases the risk of stillbirth and early neonatal mortality
See all outcomes
Women in these situations might be more likely to choose regimens with a tenofovir/emtricitabine backbone: Preferences and values Resourcing Other considerations Zidovudine/lamivudine is available as a low-cost generic around the world, while tenofovir/emtricitabine remains on patent in several countries. The evidence applies less in areas with high hepatitis B disease activity, high resource settings, or where access to one of the options is limited. Lamivudine-resistant hepatitis B Severe anemia Lamivudine-resistant HIV Drug allergy Women taking other medications with serious interactions Women who place a high value on a once-daily regimen Zidovudine-resistant HIV Alternatives are not available

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