Antiretroviral therapy (ART) for treating HIV infection in ...Presentation Transcript
Antiretroviral therapy (ART) for treating HIV infection in ART-eligible pregnant women: a Cochrane review Clinical www.cochranejournalclub.com
What are the effects of antiretroviral therapy (ART) for the treatment of HIV infection in clinically or immunologically eligible pregnant women?
What ART regimen should be started for these women?
What is the optimal time to start therapy in relation to the woman’s laboratory parameters and gestational age?
Source: Sturt AS, Dokubo EK, Sint TT. Antiretroviral therapy (ART) for treating HIV infection in ART-eligible pregnant women. Cochrane Database of Systematic Reviews 2010, Issue 3. Art.No.: CD008440. DOI: 10.1002/14651858.CD008440 www.cochranejournalclub.com
This Cochrane review focuses on the use of antiretroviral therapy (ART) for treating HIV infection in ART-eligible pregnant women. ART for mothers who require treatment of HIV for their own health plays a significant role in decreasing mother-to-child transmission (MTCT).
MTCT is the main way in which children acquire HIV infection. Strategies to reduce MTCT include maternal and infant use of ART, caesarean section before onset of labour or rupture of membranes, and complete avoidance of breastfeeding.
This review is one in a series performed for the revision of the WHO Guidelines on ART during pregnancy and ART for HIV infections in adults and adolescents.
A Cochrane intervention review, including both randomised trials and observational studies.
Relevant trials were identified from the Cochrane Central Register of Controlled Trials, PubMed, LILACS and Web of Science/Web of Social Science.
Searches were also done of the proceedings of several conferences, and experts were contacted for additional information.
Meta-analyses were not possible because of the differences across the eligible studies. The findings of each study are summarised and conclusions are drawn based on the overall consistency of the evidence.
PICO(S) to assess eligible studies
Participants: pregnant women who require ART for their own health, in accordance with the 2006 WHO guidance.
Intervention and Comparison: a clearly defined ART regimen and the use of a comparison group.
Maternal outcomes: mortality; severe adverse events; clinical, immunological, and virological response to ART; resistance resulting in ART discontinuation or virological failure; and adherence and tolerability to treatment, and retention in care.
Infant outcomes: severe adverse events, including stillbirth, prematurity, low birth weight and teratogenicity; HIV-free survival; MTCT of HIV; and resistance to subsequent ART.
Studies: randomised trials and observational studies when randomized evidence was limited, incomplete, or unavailable.
Description of eligible studies
Three randomised trials and six observational studies.
Mma Bana study: 560 HIV-infected pregnant women randomised at four sites in Botswana, comparing two different ART regimens from 26-34 weeks gestation until up to six months after birth.
Kesho Bora study: 824 HIV-infected pregnant women randomised at five sites in Burkina Faso, Kenya and South Africa, comparing triple ART from 28-36 weeks gestation until six months after birth versus short-course prophylaxis (therapy from 28-36 weeks gestation to one week after delivery).
Nairobi study: 58 HIV-1-infected pregnant women randomised at an antenatal clinic in Kenya, with the primary outcome of the effects of two ART regimens on HIV-1 viral load in breast milk.
Treatments used in randomised trials www.cochranejournalclub.com Study Treatment 1 Treatment 2 Mma Bana zidovudine (AZT) + lamivudine (3TC) + abacavir (ABC) (from 26-34 weeks gestation until up to 6 months post partum) AZT + 3TC + lopinavir/ritonavir (LPV-r) (from 26-34 weeks gestation until up to 6 months post partum) Kesho Bora AZT + 3TC + LPV-r (from 28-36 weeks gestation until 6 months post partum) AZT (from 28-36 weeks gestation until labour) then AZT + 3TC + single-dose nevirapine (sdNVP) (at onset of labour) then AZT+ 3TC (for one week after delivery) Nairobi AZT + 3TC + NVP (from 34 weeks gestation until 6 months after delivery) AZT (from 34 weeks gestation and intrapartum) then NVP (at the onset of labour) with a single dose of NVP to the baby within 72 hours of delivery
Results Maternal outcomes (randomised trials)
Mma Bana: no significant difference in grade 3 or 4 severe adverse laboratory events (11.6% vs 14.7%, RR 0.79, 95% CI 0.51-1.21) or in severe adverse events requiring treatment modification (2.2% vs 2.5%, RR 0.89, CI 0.30-2.61). One of the 560 randomised women died (RR 0.35, 95% CI 0.01-8.44). No significant difference in virologic suppression at delivery (96% vs 93%) and during breastfeeding (92% vs 93%).
Kesho Bora: no significant difference in severe adverse events (RR 1.09, CI 0.77-1.53) between women in the triple ART group (14.3%) and those allocated short course therapy (13.1%).
Results Infant outcomes  (randomised trials)
Mma Bana: no significant difference in MTCT in utero (0.4% vs 1.1%, RR 0.35, CI 0.04-3.34) or at 6 months (0.4% vs 2.1%, RR 0.17, CI 0.02-1.44) between the two ART regimens.
Kesho Bora: no significant difference in MTCT at birth (1.7% vs 2.2%, RR 0.78, CI 0.29-2.07) or at 6 weeks (3.3% vs 4.8%, RR 0.69, CI 0.34-1.37), but significant reductions for triple ART at 6 month (4.9% vs 8.5%, RR 0.58, CI 0.33-0.99) and 12 months (5.5% vs 9.5%, RR 0.58, CI 0.34-0.97). There was a significant reduction in infant HIV transmission or death at 12 months (10.4% vs 16.3%, RR 0.64, CI 0.44-0.92) for the ART group.
Results Infant outcomes  (randomised trials)
Mma Bana: significant difference in premature births in the AZT/3TC/LPV-r group compared with the AZT/3TC/ABC group (22.6% vs 14.8%, RR 1.52, CI 1.07-2.17); but no significant differences in stillbirths (1.8% vs 2.8%, RR 0.65, CI 0.21-1.96), low birth weight (16.7% vs 13.1%, RR 1.27, CI 0.85-1.91), or grade 3 or 4 severe adverse events (46.3% vs 41.0%, RR 1.13, CI 0.93-1.37).
Kesho Bora: no significant differences in stillbirths (1.0% vs 1.0%, RR 1.00, CI 0.25-3.95) premature births (13.4% vs 10.9%, RR 1.23, CI 0.85-1.79), low birth weight (11.2% vs 7.7%, RR 1.46, CI 0.94-2.25), or grade 3 or 4 severe adverse events (30.8% vs 32.5%, RR 0.95, CI 0.77-1.16).
In ART-eligible pregnant women with HIV infection, ART is a safe and effective means of providing maternal virologic suppression, decreasing infant mortality and reducing MTCT.
Three regimens have been shown to decrease MTCT (AZT/3TC/NVP, AZT/3TC/LPV-r and AZT/3TC/ABC).
More research is needed regarding the optimum time to start therapy, the use of specific regimens and their maternal and infant side-effect profiles.
Cochrane Journal Club discussion points
Antiretroviral therapy (ART) for treating HIV infection in ART-eligible pregnant women