WHO/HIV/2013.15 GRADE table: When to start ART in pregnant women living with HIV? RANDOMIZED CONTROLLED TRIALS Author(s): Anglemyer A, Rutherford G Date: 2012-10-08 Question: Should asymptomatic pregnant women be started on ART with CD4 counts >350 cells/mm3 for their own health? Settings: Multiple countries throughout Europe, North, Central and South America, Africa and Asia and the Pacific Bibliography: Cohen 2011, SMART 2008, Grant 2011
© World Health Organization 2013
Quality assessment
No. of patients
Effect Quality Importance
No. of studies Death 1
Design
Risk of bias
Inconsistency
Indirectness Imprecision
Other ≥350 considerations cells/mm3
<350 cells/mm3
Relative (95% CI)
Absolute
randomized trials
no serious risk of bias
no serious inconsistency
serious1
very serious2 none
10/893 (1.1%)2
13/882 (1.5%)2
RR 0.77 (0.34 to 1.75)
3 fewer per 1000 CRITICAL ⊕OOO (from 10 fewer to VERY LOW 11 more)
Death or progression to AIDS 2 randomized trials no serious risk of bias no serious inconsistency serious1 serious3 none 44/1257 (3.5%)2 76/1196 (6.4%)2 RR 0.48 (0.26 to 0.91) 33 fewer per 1000 (from 6 fewer to 47 fewer) ⊕⊕OO LOW CRITICAL
Progression to AIDS 1 randomized trials no serious risk of bias no serious inconsistency serious1 very serious2 none 4/364 (1.1%)2 11/314 (3.5%)2 RR 0.31 (0.10 to 0.96) CRITICAL 24 fewer per 1000 ⊕OOO (from 1 fewer to 32 VERY LOW fewer)
Serious non-AIDS events and non-opportunistic diseases 1 randomized trials no serious risk of bias no serious inconsistency serious1 very serious2 none 2/249 (0.8%)2 12/228 (5.3%)2 RR 0.14 (0.03 to 0.64) 45 fewer per 1000 CRITICAL ⊕OOO (from 19 fewer to VERY LOW 51 fewer)
1 This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS
WHO/HIV/2013.15 Severe adverse events 1 randomized trials no serious risk of bias no serious inconsistency serious1 none none 127/886 (14.3%) 119/877 (13.6%) RR 1.06 (0.84 to 1.33)
© World Health Organization 2013
8 more per 1000 CRITICAL ⊕⊕⊕O (from 22 fewer to MODERATE 45 more)
1 2
Studies not conducted among pregnant women. Very few events. 3 Few events. 4 ART in the delayed group was actually initiated when the CD4 count fell below 250 cells/mm3, not 350. Author(s): Alexander W. Kay, Alicen B. Spaulding, Tara Horvath Date: 2012-11-27 Question: Should maternal triple antiretroviral (ARV) prophylaxis versus zidovudine (AZT) + single-dose nevirapine (SD-NVP) be used for preventing the mother-to-child transmission of HIV in pregnant women? Settings: Burkina Faso, Kenya, Malawi, South Africa Bibliography: Kesho Bora Study Group 2011, Kesho Bora Study Group 2012, Jamieson 2012
Quality assessment
No. of patients
Effect Quality Importance
No. of studies
Design
Risk of bias
Inconsistency
Indirectness Imprecision
Other considerations
Triple ARV
AZT + SDNVP
Relative (95% CI)
Absolute
Maternal mortality (48–52 weeks) 2 randomized trials no serious risk of bias no serious inconsistency serious1 very serious2 none 5/1261 (0.4%) 10/1080 (0.93%) RR 0.46 (0.16 5 fewer per 1000 (from 8 CRITICAL ⊕OOO to 1.29) fewer to 3 more) VERY LOW
Infant mortality (48–52 weeks) 2 randomized trials no serious risk of bias no serious inconsistency serious1 very serious2 none 47/1250 (3.8%) 66/1072 (6.2%) RR 0.64 (0.45 22 fewer per 1000 (from to 0.92) 5 fewer to 34 fewer) ⊕⊕OO LOW CRITICAL
Maternal morbidity (48–52 weeks) 3 23 randomized trials no serious risk of bias no serious inconsistency serious1 serious4 none 110/1261 (8.7%) 82/1080 (7.6%) RR 1.23 (0.94 17 more per 1000 (from 5 to 1.62) fewer to 47 more) ⊕⊕OO LOW CRITICAL
2 This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS
WHO/HIV/2013.15 Infant HIV infections (48–52 weeks) 2 randomized trials no serious risk of bias no serious inconsistency serious1 none none 97/1250 (7.8%) 111/1072 (10.4%)
© World Health Organization 2013
CRITICAL RR 0.74 (0.57 27 fewer per 1000 (from ⊕⊕⊕O to 0.95) 5 fewer to 45 fewer) MODERATE
Maternal TB (48 weeks) 1 randomized trials no serious risk of bias no serious inconsistency serious1 very serious2 none 4/849 (0.47%) 4/668 (0.6%) RR 0.79 (0.2 1 fewer per 1000 (from 5 to 3.13) fewer to 13 more) ⊕⊕OO LOW IMPORTANT
1 2
Neither included intervention directly replicated option “B” versus “A”, and both interventions included women with CD4 cell counts <350 cells/mm3. Very few events. 3 Combined count of all clinical severe adverse events. 4 Few events. 5 Defined in de Vincenzi (2011) as infant retention and Jamieson (2012) as retention of maternal-infant pairs. OBSERVATIONAL STUDIES Author(s): Alexander W. Kay, Alicen B. Spaulding Date: 2012-11-25 Question: Should antiretroviral (ARV) prophylaxis versus zidovudine (AZT) + single-dose nevirapine (SD-NVP) be used for pregnant women and their infants? Settings: Botswana Bibliography: Dryden-Peterson 2011
Quality assessment
No. of patients
Effect Quality Importance
No. of studies
Design
Risk of bias
Inconsistency
Indirectness Imprecision
Other considerations
Triple ART
AZT + SD-NVP
Relative (95% CI)
Absolute
Infant mortality (follow-up 6 months) 1 observational studies serious1 no serious inconsistency serious2 very serious3 none 10/258 (3.9%) 10/170 (5.9%) RR 0.66 (0.28 20 fewer per 1000 (from to 1.55) 42 fewer to 32 more) ⊕OOO VERY LOW CRITICAL
Infant HIV infections (follow-up 6 months)
3 This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS
WHO/HIV/2013.15 1 observational studies serious1 no serious inconsistency serious2 very serious3 none 1/258 (0.39%) 9/170 (5.3%)
© World Health Organization 2013 ⊕OOO VERY LOW CRITICAL
RR 0.07 (0.01 49 fewer per 1000 (from to 0.57) 23 fewer to 52 fewer)
1 2
Study did not randomize pregnant women with ≥350 CD4 cells/mm3 to early or late ART arms. Women were given triple ARV if they had CD4 cell counts less than or equal to 250 cells/mm3. 3 Very few events.
4 This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS