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WHO May Recommend HAART for PMTCT: IAS
  WHO may change ARV guidelines for pregnant mothers: HAART reduces HIV transmission while breastfeeding
HIV Prevention at IAS 2009 - written by Jared Baeten, MD PhD Connie Celum, MD MPH University of Washington - (07/30/09)
This report reviews studies presented at IAS using HAART for PMTCT:
The Mma Bana Study from Botswana (Shapiro, abstract WELBB101) assessed virologic suppression in women with CD4 counts >200 who were started on HAART during late pregnancy. Among 560 women, plasma HIV RNA suppression (<400 copies/mL) was >90% at delivery and throughout 6 months of breastfeeding, using HAART regimens of abacavir/zidovudine/lamivudine or zidovudine/lamivudine/lopinavir/ritonavir. The overall HIV transmission rate was 1% and treatment-limiting adverse events were rare.
"The Kesho Bora study"
"the BAN study"
"Distressingly, in spite of tremendous progress in discovery of novel strategies to minimize HIV acquisition in infants, getting antiretrovirals to women at risk of transmitting HIV to their infants remains a tremendous operational challenge. The PEARL study collected ∼29,000 anonymous cord blood specimens from women delivering at centers in Cameroon, Cote d'Ivoire, South Africa, and Zambia between 2007 and 2008 (Coetzee, abstract WELBD101). Samples were tested for HIV and for antiretrovirals. Overall, 12% were HIV seropositive. Overall, only ∼50% of births received single-dose nevirapine prophylaxis, and drop off in successful delivery of PMTCT medications occurred at each step leading up to delivery (e.g., offering of HIV testing, acceptance of testing, receipt of results, receipt of nevirapine, injestion of nevirapine). System-wide interventions must continue to target better performance of this proven prevention service."
"The Kesho Bora study (de Vincenzi, abstract LBPEC01) randomized 824 pregnant women with CD4 counts between 200 and 500 to HAART versus standard short-course antiretroviral therapy near the time of delivery. Cumulative HIV infection rates were 5.6% in the HAART arm versus 9.3% in the short-course arm at 12 months, a 40% reduction (p=0.05). Subgroups analyses suggested the benefit was greatest among women with CD4 counts between 200 and 350."
"Finally, the BAN study (Chasela, abstract WELBC103) randomized 2637 pregnant women from Malawi with CD4 counts >250 to post-natal HAART or infant extended nevirapine prophylaxis. All received intrapartum short-course antiretrovirals, and a third control arm that included only the short-course regimen was stopped early. Infants were exclusively breastfed for 24 weeks then weaned over 4 weeks. At 28 weeks post-partum, HIV transmission rates were 6.4% for the control arm, 3.0% for the HAART arm (p=0.003 vs. control), and 1.8% for the infant prophylaxis arm (p<0.001 vs. control). The difference between the maternal HAART and infant prophylaxis arms did not reach statistical significance (p=0.1)"
5th IAS: Triple Antiretrovirals Cut Breastfeeding HIV Transmission Rate Below 1% - written by Mark Mascolini - (07/29/09)
The Mma Bana Study is the first randomized trial of triple antiretroviral regimens to control viral replication in mothers and to prevent mother-to-child transmission of HIV in utero, during delivery, and during breastfeeding. Five women taking coformulated abacavir/zidovudine/lamivudine transmitted HIV to their infants, 3 in utero and 2 while breastfeeding. One woman in each of the other two groups transmitted HIV, both in utero. Overall transmission rates were 1.8% with abacavir, 0.4% with lopinavir (P = 0.53 versus abacavir), and 0.6% with nevirapine. Overall transmission through 6 months was 1% (95% confidence interval 0.5% to 2.0%).
--Similar results in other studies reported at this meeting may impel the World Health Organization to recommend triple antiretroviral therapy for all HIV-infected women during pregnancy, delivery, and breastfeeding, according to Reuters [2].
TB Rate in South African Township Plummets After Antiretrovirals Arrive - written by Mark Mascolini - (07/29/09)
"Reduction in HIV infections by 12 months was 40% (p=0.052). There was no increase in adverse events with triple-ARV."

Triple-antiretroviral (ARV) prophylaxis during pregnancy and breastfeeding compared to short-ARV prophylaxis to prevent mother-to-child transmission of HIV-1 (MTCT): the Kesho Bora randomized controlled clinical trial in five sites in Burkina Faso, Kenya
Presented by Isabelle de Vincenzi (Switzerland).
I. de Vincenzi, Kesho Bora Study Group
World Health Organization, Department of Reproductive Health and Research, Geneva, Switzerland
Background: ARV interventions to reduce MTCT during late pregnancy and delivery are well established, but no randomized trial has assessed safety and efficacy of continued maternal ARVs during breastfeeding.
Methods: Between June 2005 and August 2008, HIV-infected pregnant women with CD4 200-500 cells/mL were randomized between 28 and 36 weeks of pregnancy to triple-ARV (ZDV+3TC+LPV/r to 6.5 months post-delivery or breastfeeding cessation if earlier) or short-ARV (ZDV through delivery plus single-dose NVP in labour). Infants received single-dose NVP. From September 2007, 1 week maternal ZDV+3TC was added to short-ARV regimen postpartum and 1 week ZDV for all infants. 12-month cumulative lifetable rates were compared using logrank tests.
Results: 824 women (413 triple-ARV, 411 short-ARV) delivered 805 live, singleton or first-born infants. Median enrolment CD4 was 335; 56% had CD4 200-350. By May 2009 all infants had been born ≥ 6 and 87% ≥ 12 months previously. 77% were breastfed median duration 21 weeks in both arms. 12-month cumulative incidence of HIV infection or death was 10.4% (95% CI 7.7-14.9%) [40 endpoints] with triple-ARV and 16.3% (13.0-20.5%) [62 endpoints] with short-ARV (36% risk reduction, p=0.023). 56 infants were infected by 12 months, 37 born to mothers with CD4 200-350; another 46 died. Cumulative HIV infection rates (95% CI) [infections] were:


Reduction in HIV infections by 12 months was 40% (p=0.052). There was no increase in adverse events with triple-ARV.
Conclusions: Twelve-month HIV-free survival was significantly better when mothers with CD4 200-500 received triple-ARV prophylaxis. Largest effect (HIV infections averted) was observed between 6 weeks and 6 months postpartum when ARV prophylaxis was received in triple-ARV but not short-ARV arm; and among women with CD4 200-350.

Both maternal HAART and daily infant nevirapine (NVP) are effective in reducing HIV-1 transmission during breastfeeding in a randomized trial in Malawi: 28 week results of the Breastfeeding, Antiretroviral and Nutrition (BAN) Study
Presented by Charles Chasela (Malawi), Charles Chasela (Malawi).
C. Chasela1, M. Hudgens2, D. Jamieson3, D. Kayira1, M. Hosseinipour1, Y. Ahmed3, G. Tegha1, R. Knight4, A.P. Kourtis3, D. Kamwendo1, I. Hoffman5, S. Ellington3, Z. Kacheche1, J. Wiener3, F. Martinson1, P. Kazembe6, I. Mofolo1, D. Long2, A. Soko1, S.B. Smith2, C. van der Horst7
1UNC Project, Lilongwe, Malawi, 2University of North Carolina, Department of Biostatistics, Chapel Hill, United States, 3U.S. Centers for Disease Control and Prevention, Division of Reproductive Health, Atlanta, United States, 4Principia International, Chapel Hill, United States, 5University of North Carolina, Chapel Hill, United States, 6Kamuzu Central Hospital, Lilongwe, Malawi, 7University of North Carolina, Division of Infectious Diseases, Chapel Hill, United States
Background: A randomized trial evaluated the safety and efficacy of maternal or infant antiretroviral (ARV) regimens, taken up to 28 weeks during breastfeeding in reducing rates of postnatal HIV-1 transmission among mother-infant pairs.
Methods: Entry criteria included HIV-1 infected mothers with CD4 > 250 cells/uL and infant birthweight ≥2000 grams. Intrapartum, mothers and infants received single dose nevirapine (NVP) and one week of twice-daily zidovudine/lamivudine (ZDV/3TC). In a 3x2 factorial design pairs were randomized within one week of birth to one of 3 ARV interventions: 1) maternal ZDV+3TC and lopinavir + ritonavir twice daily (MHAART), 2) infant NVP daily (INVP), or 3) no additional ARV (control), and 2 nutritional arms (with or without maternal nutritional supplement). Mothers breastfed exclusively for 24 weeks followed by rapid weaning. Kaplan-Meier method was used to estimate the cumulative risk of HIV infection or death at 28 weeks among infants who were HIV-1 free 1 week after birth. Rates were compared using the log-rank test, stratified by nutritional supplement.
Results: Among 2637 mother-infant pairs, in utero transmission as reflected by HIV-1 infection at 1 week was 4.9%. The estimated risk of HIV-1 transmission by 28 weeks in those uninfected at 1 week was higher in the control arm (6.4%) compared to either of the intervention arms (3.0% in MHAART (p=0.003) and 1.8% in INVP arm (p< 0.0001)). The estimated risk of HIV-1 transmission or death by 28 weeks was 7.6% in the control arm compared to 4.7% in the MHAART arm (p=0.03) and 2.9% in the INVP arm (p< 0.0001). Although this study was not powered to compare the two intervention arms, there was a trend favoring INVP prophylaxis in HIV free survival (p=0.07).
Conclusions: Either MHAART or INVP for 28 wks is effective in reducing HIV-1 transmission during breastfeeding.

Favorable pregnancy outcomes with reduction of abortion, stillbirth, and prematurity rates in a large cohort of HIV+ women in Southern Africa receiving highly active antiretroviral therapy (HAART) for prevention of mother-child-transmission (PMTCT) - DREAM Study
Presented by Leonardo Palombi (Italy).
M.C. Marazzi1,2, L. Palombi1,3, K. Nielsen-Saines4, J. Haswell5, I. Zimba6, M. Maulidi7, N. Abdul Magid6, L. Richard5, E. Buonomo3, P. Scarcella3, S. Ceffa1, G. Paturzo1, P. Narciso8, G. Liotta3
1DREAM Program, Community of S. Egidio, Rome, Italy, 2LUMSA University, Rome, Italy, 3University of Tor Vergata, Public Health, Rome, Italy, 4UCLA, Pediatrics, Los Angeles, United States, 5DREAM Program, Community of S. Egidio, Blantyre, Malawi, 6DREAM Program, Community of S. Egidio, Maputo, Mozambique,7DREAM Program, Community of S. Egidio, Lilongwe, Malawi, 8INMI 'L.Spallanzani', Rome, Italy
Background: Pregnancy outcomes in HIV+ women are rarely assessed in resource-limited settings. We evaluated outcomes in a large cohort receiving HAART for PMTCT purposes in Sub-Saharan Africa.
Methods: Files of 3,273 HIV+ pregnant women receiving care in Malawi and Mozambique from 7/2005 to 12/2008 at our centers were reviewed. Women were offered nevirapine-based HAART at 14 wks (if elegible for own health) or 25 wks gestation until 6 months postpartum. Abortion and stillbirths were defined as fetal death at < or ≥ 32 wks gestation.
Results: Median baseline CD4 count and viral load (VL) were 357/mm3 and 4Log c/ml. Median pregnancy duration was 39.1 wks. Median time of pre-delivery HAART was 83 days (CL95%53-108). Maternal mortality was 1.2% and significantly associated with HAART (7.4% if no HAART vs. 0.7 HAART ≥ 90 days before delivery) and CD4 threshold (3.2% vs. 0.7% if ≥ 200; p< 0.001). Abortion and stillbirth were 25.7% (18/70) in women with no HAART and 4.3% (125/2,909) in women receiving HAART for >30 days (p< 0.001). Prematurity was strongly associated with short/absent HAART: 70.8% reduction overall (Mantel-Heanszel OR=0.16; CL95%:0.12-0.21) and within each CD4 strata. Body Mass Index (OR 0.27; CL95% 0.15-0.50) and VL at delivery (OR 1.44; CL95% 1.22-1.70) were strongly associated with prematurity by multivariate analysis. Low birth weight was 11.5% and not associated with HAART duration or CD4 count.


Conclusion: HAART was strongly associated with improved pregnancy outcomes including reduction in prematurity, regardless of CD4 strata. HAART is beneficial for PMTCT AND protects against unfavorable pregnancy outcomes.
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