Blazquez, MCV

Doro Altan, AM

Germano, P

Gomes, AdC

Guidotti, G

Liotta, G

Loureiro, S

Mancinelli, S

Marazzi, MC

Narciso, P

Nielsen-Saines, K

Palombi, L

Perno, CF

LIOTTA, GIUSEPPE

PERNO, CARLO FEDERICO

MANCINELLI, SANDRO

DORO ALTAN, ANNA MARIA

Nielsen Saines, K

PALOMBI, LEONARDO

SHORT REPORTImplementing anti-retroviral triple therapy to prevent HIVmother-to-child transmission: a public health approachin resource-limited settingsCristina M. Marazzi & Paola Germano &Giuseppe Liotta & Giovanni Guidotti &Sandra Loureiro & Aurelio da Cruz Gomes &Maria C. Valls Blazquez & Pasquale Narciso &Carlo F. Perno & Sandro Mancinelli &Annamaria Doro Altan & Karin Nielsen-Saines &Leonardo PalombiReceived: 13 October 2006 /Accepted: 18 December 2006 / Published online: 18 January 2007# Springer-Verlag 2007Keywords HIVMTCT. Anti-retroviral therapy . Publichealth . Resource-limited settingsWe conducted a retrospective cohort study of HIV-infectedpregnant women and their infants enrolled in the DREAMprogramme for prevention of HIV mother-to-child trans-mission (MTCT) in Mozambique. All women deliveringbetween May 2002 and December 2005 were offeredparticipation. The programme consisted of the provisionof highly active anti-retroviral therapy (HAART) topregnant women until 6 months postpartum, and formula,clean water, nutritional supplementation, and continuingHAART to mothers if necessary.In Mozambique 1,259 HIV-positive pregnant womenwere offered participation: 212 (14.4%; CL95% 12.6–16.2)refused, 54 (3.7%; CL95% 2.5–4.9) dropped out duringpregnancy, and eight women died. The remaining 985women participated, giving birth to 958 infants, including21 sets of twins. An additional 28 babies were stillborn.Spontaneous abortions occurred in 20 cases. Discontinua-tion of anti-retroviral (ARV) therapy by mothers was 3.7%(54/1,464) before delivery, 1.5% in the first month (23/1,464), and 1.5% (22/1,464) between the first and sixthmonths after delivery. Overall drop-out rates were 5.2%(CL95% 4.6–5.8). Approximately 80% of pregnant womencompleted the treatment protocol.Eur J Pediatr (2007) 166:1305–1307DOI 10.1007/s00431-006-0405-8All authors are also affiliated with the DREAM Programme (DrugResources Enhancement against AIDS and Malnutrition).C. M. MarazziLUMSA University,Rome, ItalyP. GermanoCommunity of Sant’Egidio—DREAM programme,Rome, ItalyG. Liotta :C. F. Perno : S. Mancinelli :A. D. Altan : L. PalombiUniversity of Tor Vergata,Rome, ItalyG. GuidottiNational Institute of Health,Rome, ItalyS. Loureiro :M. C. V. BlazquezDREAM Programme,Maputo, MozambiqueA. d. GomesCatholic University of Beira,Beira, MozambiqueP. NarcisoNational Institute of Infectious Disease “L. Spallanzani”,Rome, ItalyK. Nielsen-Saines (*)Department of Pediatrics,David Geffen UCLA School of Medicine,MDCC 22-442 10833 LeConte,Los Angeles, CA, USAe-mail: knielsen@mednet.ucla.eduAnti-retroviral treatment induced a significant reductionin virus load, with the percentage of women with fewerthan 1,000 viral copies per millilitre (c/ml) rising from 17%at baseline to 90% by the time of delivery. A total of 707children were tested at 1 month of age, and 467 were re-tested at 6 months. The HIV incidence rate was 3.8%(CL95% 3.1–4.5) at 1 month, with an additional 1.5%(CL95%: 0.9–2.1) of babies testing positive at 6 months.The cumulative intention-to-treat incidence rate was 5.3%at 6 months. When data for women who stayed ontreatment for the full duration of the protocol were analysedseparately, vertical transmission rates dropped to 1.4% at6 months. Maternal mortality was 0.8% (eight deaths in 993pregnancies). The incidence rate of significant hepatic,dermatological and haematological adverse reactions toanti-retroviral agents on a sub-sample of 778 pregnantwomen was 6.1% (CL95% 4.2–8.0), 3.2% (CL95% 2.0–3.4) and 14.1% (CL95% 11.6–16.6), respectively.Base-line parameters, risk factors for vertical transmis-sion, and multivariate analysis of the determinants of HIVpositive status are shown in Tables 1, 2 and 3.The current data are highly relevant for the developmentof future programmes for the prevention of HIV MTCT inthe developing world. The acceptability of HAART duringpregnancy was higher than that of single-dose nevirapine inprior studies [5, 6]. Even within the Mozambique healthcare system, where about 50% of women deliver at home, itwas still possible to get women tested for HIV early in thecourse of pregnancy. A surprisingly large percentage ofwomen (86%) who tested positive enrolled, and 95% (931/985) of those completed the entire protocol. The publichealth impact on vertical transmission was much higherthan previously described [1, 3–6], with a cumulativeintention-to-treat (ITT) analysis transmission rate at6 months of age of 5.3%. Among women who receivedHAART until 6 months postpartum, no transmissionsoccurred beyond 1 month of age. These results demonstratethat, in resource-limited settings, very low HIV transmis-sion rates, equivalent to those observed in developedcountries, are achievable [2]. In addition, the decision touse HAART in the postpartum period could potentiallyrender breastfeeding safe during the first 6 months of life.Table 1 Base-line parameters (993 pregnancies)Parameter Median IQ 25–75Age (years) 24.3 21.2–28.6Start of ARV therapy (week of pregnancy) 26.8 25.1–31.0Pre-ARV therapy CD4 count 489 312–692Pre-ARV therapy viral load log 4.17 3.65–4.55Pre-ARV therapy Hb 10.1 8.7–10.6Length of pregnancy (weeks) 38.5 36.1–40.2Pre-delivery days of ARV therapy 72 36–98Table 2 Risk factors for vertical transmission and multivariate analysis of HIV positive status determinants (HIV status assessed 1 month afterdelivery—forward stepwise logistic regression analysis). NVP nevirapineParameter Number HIV+ Percentage Odds ratio 95% CIViral load (c/ml) <10,000 343 4 1.2 5.6 1.9–16.4>10.000 337 22 6.1Pre-ARV therapy haemoglobin(mg/100 ml)>7 644 21 3.2 4.1 1.5–11.6<7 37 5 11.9NVP to the baby No 126 4 3.1 1.2 0.4–3.7Yes 555 22 3.8Pre-delivery length of ARV therapy <80 368 20 1.5 3.0 1.2–8.1>80 280 5 5.2Place of delivery Reference centre 386 13 3.3 1.3 0.6–2.9Others 295 13 4.2Table 3 Logistic regression analysis—independent predictors of HIV MTCTParameter B E.S. Sig. Exp(B) 95% CI per Exp (B)Viral load (c/ml) 1.605 0.556 0.004 4.979 1.766 15.321Pre-ARV therapy haemoglobin 1.164 0.544 0.032 3.204 1.103 9.306Pre-delivery length of ARV 1.107 0.512 0.030 3.026 1.110 8.2511306 Eur J Pediatr (2007) 166:1305–1307References1. Ayouba A, Tene G, Cunin P, Foupouapouognigni Y, Menu E,Kfutwah A, Thonnon J, Scarlatti G, Monny-Lobe M, Eteki N,Kouanfack C, Tardy M, Leke R, Nkam M, Nlend AE, Barre-Sinoussi F, Martin PM, Nerrienet E; Yaounde European Networkfor the Study of In Utero Transmission of HIV-1 (2003) Low rate ofmother-to-child transmission of HIV-1 after nevirapine interventionin a pilot public health program in Yaounde, Cameroon. J AcquirImmune Defic Syndr 34(3):274–2802. Dorenbaum A, Cunningham CK, Gelber RD, Culnane M,Mofenson L, Britto P, Rekacewicz C, Newell ML, Delfraissy JF,Cunningham-Schrader B, Mirochnick M, Sullivan JL; InternationalPACTG 316 Team (2002) Two-dose intrapartum/newborn nevira-pine and standard antiretroviral therapy to reduce perinatal HIV-1transmission: a randomized trial. JAMA 288(2):189–1983. Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, NakabiitoC, Sherman J, Bakaki P, Ducar C, Deseyve M, Emel L, MirochnickM, Fowler MG, Mofenson L, Miotti P, Dransfield K, Bray D,Mmiro F, Jackson JB (1999) Intrapartum and neonatal single-dosenevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012randomised trial. Lancet 354(9181):795–8024. Songok EM, Fujiyama Y, Tukei PM, Vulule JM, Kiptoo MK,Adungo NO, Kakimoto K, Kobayashi N, Genga IO, Mpoke S,Ichimura H (2003) The use of short-course zidovudine to preventperinatal transmission of human immunodeficiency virus in ruralKenya. Am J Trop Med Hyg 69(1):8–135. Stringer EM, Sinkala M, Stringer JS, Mzyece E, Makuka I,Goldenberg RL, Kwape P, Chilufya M, Vermund SH (2003)Prevention of mother-to-child transmission of HIV in Africa:successes and challenges in scaling-up a nevirapine-based programin Lusaka, Zambia. AIDS 17(9):1377–13826. Stringer JS, Sinkala M, Goldenberg RL, Kumwenda R, Acosta EP,Aldrovandi GM, Stout JP, Vermund SH (2004) Universal nevira-pine upon presentation in labor to prevent mother-to-child HIVtransmission in high prevalence settings. AIDS 18(6):939–943Eur J Pediatr (2007) 166:1305–1307 1307

English

Implementing anti-retroviral triple therapy to prevent HIV mother-to-child transmission: a public health approach in resource-limited settings

Archivio della Ricerca - Università di Roma Tor vergata

SHORT REPORT
Implementing anti-retroviral triple therapy to prevent HIV
mother-to-child transmission: a public health approach
in resource-limited settings
Cristina M. Marazzi & Paola Germano &
Giuseppe Liotta & Giovanni Guidotti &
Sandra Loureiro & Aurelio da Cruz Gomes &
Maria C. Valls Blazquez & Pasquale Narciso &
Carlo F. Perno & Sandro Mancinelli &
Annamaria Doro Altan & Karin Nielsen-Saines &
Leonardo Palombi
Received: 13 October 2006 /Accepted: 18 December 2006 / Published online: 18 January 2007
# Springer-Verlag 2007
Keywords HIVMTCT. Anti-retroviral therapy . Public
health . Resource-limited settings
We conducted a retrospective cohort study of HIV-infected
pregnant women and their infants enrolled in the DREAM
programme for prevention of HIV mother-to-child trans-
mission (MTCT) in Mozambique. All women delivering
between May 2002 and December 2005 were offered
participation. The programme consisted of the provision
of highly active anti-retroviral therapy (HAART) to
pregnant women until 6 months postpartum, and formula,
clean water, nutritional supplementation, and continuing
HAART to mothers if necessary.
In Mozambique 1,259 HIV-positive pregnant women
were offered participation: 212 (14.4%; CL95% 12.6–16.2)
refused, 54 (3.7%; CL95% 2.5–4.9) dropped out during
pregnancy, and eight women died. The remaining 985
women participated, giving birth to 958 infants, including
21 sets of twins. An additional 28 babies were stillborn.
Spontaneous abortions occurred in 20 cases. Discontinua-
tion of anti-retroviral (ARV) therapy by mothers was 3.7%
(54/1,464) before delivery, 1.5% in the first month (23/
1,464), and 1.5% (22/1,464) between the first and sixth
months after delivery. Overall drop-out rates were 5.2%
(CL95% 4.6–5.8). Approximately 80% of pregnant women
completed the treatment protocol.
Eur J Pediatr (2007) 166:1305–1307
DOI 10.1007/s00431-006-0405-8
All authors are also affiliated with the DREAM Programme (Drug
Resources Enhancement against AIDS and Malnutrition).
C. M. Marazzi
LUMSA University,
Rome, Italy
P. Germano
Community of Sant’Egidio—DREAM programme,
Rome, Italy
G. Liotta :C. F. Perno : S. Mancinelli :A. D. Altan : L. Palombi
University of Tor Vergata,
Rome, Italy
G. Guidotti
National Institute of Health,
Rome, Italy
S. Loureiro :M. C. V. Blazquez
DREAM Programme,
Maputo, Mozambique
A. d. Gomes
Catholic University of Beira,
Beira, Mozambique
P. Narciso
National Institute of Infectious Disease “L. Spallanzani”,
Rome, Italy
K. Nielsen-Saines (*)
Department of Pediatrics,
David Geffen UCLA School of Medicine,
MDCC 22-442 10833 LeConte,
Los Angeles, CA, USA
e-mail: knielsen@mednet.ucla.edu
Anti-retroviral treatment induced a significant reduction
in virus load, with the percentage of women with fewer
than 1,000 viral copies per millilitre (c/ml) rising from 17%
at baseline to 90% by the time of delivery. A total of 707
children were tested at 1 month of age, and 467 were re-
tested at 6 months. The HIV incidence rate was 3.8%
(CL95% 3.1–4.5) at 1 month, with an additional 1.5%
(CL95%: 0.9–2.1) of babies testing positive at 6 months.
The cumulative intention-to-treat incidence rate was 5.3%
at 6 months. When data for women who stayed on
treatment for the full duration of the protocol were analysed
separately, vertical transmission rates dropped to 1.4% at
6 months. Maternal mortality was 0.8% (eight deaths in 993
pregnancies). The incidence rate of significant hepatic,
dermatological and haematological adverse reactions to
anti-retroviral agents on a sub-sample of 778 pregnant
women was 6.1% (CL95% 4.2–8.0), 3.2% (CL95% 2.0–
3.4) and 14.1% (CL95% 11.6–16.6), respectively.
Base-line parameters, risk factors for vertical transmis-
sion, and multivariate analysis of the determinants of HIV
positive status are shown in Tables 1, 2 and 3.
The current data are highly relevant for the development
of future programmes for the prevention of HIV MTCT in
the developing world. The acceptability of HAART during
pregnancy was higher than that of single-dose nevirapine in
prior studies [5, 6]. Even within the Mozambique health
care system, where about 50% of women deliver at home, it
was still possible to get women tested for HIV early in the
course of pregnancy. A surprisingly large percentage of
women (86%) who tested positive enrolled, and 95% (931/
985) of those completed the entire protocol. The public
health impact on vertical transmission was much higher
than previously described [1, 3–6], with a cumulative
intention-to-treat (ITT) analysis transmission rate at
6 months of age of 5.3%. Among women who received
HAART until 6 months postpartum, no transmissions
occurred beyond 1 month of age. These results demonstrate
that, in resource-limited settings, very low HIV transmis-
sion rates, equivalent to those observed in developed
countries, are achievable [2]. In addition, the decision to
use HAART in the postpartum period could potentially
render breastfeeding safe during the first 6 months of life.
Table 1 Base-line parameters (993 pregnancies)
Parameter Median IQ 25–75
Age (years) 24.3 21.2–28.6
Start of ARV therapy (week of pregnancy) 26.8 25.1–31.0
Pre-ARV therapy CD4 count 489 312–692
Pre-ARV therapy viral load log 4.17 3.65–4.55
Pre-ARV therapy Hb 10.1 8.7–10.6
Length of pregnancy (weeks) 38.5 36.1–40.2
Pre-delivery days of ARV therapy 72 36–98
Table 2 Risk factors for vertical transmission and multivariate analysis of HIV positive status determinants (HIV status assessed 1 month after
delivery—forward stepwise logistic regression analysis). NVP nevirapine
Parameter Number HIV+ Percentage Odds ratio 95% CI
Viral load (c/ml) <10,000 343 4 1.2 5.6 1.9–16.4
>10.000 337 22 6.1
Pre-ARV therapy haemoglobin
(mg/100 ml)
>7 644 21 3.2 4.1 1.5–11.6
<7 37 5 11.9
NVP to the baby No 126 4 3.1 1.2 0.4–3.7
Yes 555 22 3.8
Pre-delivery length of ARV therapy <80 368 20 1.5 3.0 1.2–8.1
>80 280 5 5.2
Place of delivery Reference centre 386 13 3.3 1.3 0.6–2.9
Others 295 13 4.2
Table 3 Logistic regression analysis—independent predictors of HIV MTCT
Parameter B E.S. Sig. Exp(B) 95% CI per Exp (B)
Viral load (c/ml) 1.605 0.556 0.004 4.979 1.766 15.321
Pre-ARV therapy haemoglobin 1.164 0.544 0.032 3.204 1.103 9.306
Pre-delivery length of ARV 1.107 0.512 0.030 3.026 1.110 8.251
1306 Eur J Pediatr (2007) 166:1305–1307
References
1. Ayouba A, Tene G, Cunin P, Foupouapouognigni Y, Menu E,
Kfutwah A, Thonnon J, Scarlatti G, Monny-Lobe M, Eteki N,
Kouanfack C, Tardy M, Leke R, Nkam M, Nlend AE, Barre-
Sinoussi F, Martin PM, Nerrienet E; Yaounde European Network
for the Study of In Utero Transmission of HIV-1 (2003) Low rate of
mother-to-child transmission of HIV-1 after nevirapine intervention
in a pilot public health program in Yaounde, Cameroon. J Acquir
Immune Defic Syndr 34(3):274–280
2. Dorenbaum A, Cunningham CK, Gelber RD, Culnane M,
Mofenson L, Britto P, Rekacewicz C, Newell ML, Delfraissy JF,
Cunningham-Schrader B, Mirochnick M, Sullivan JL; International
PACTG 316 Team (2002) Two-dose intrapartum/newborn nevira-
pine and standard antiretroviral therapy to reduce perinatal HIV-1
transmission: a randomized trial. JAMA 288(2):189–198
3. Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito
C, Sherman J, Bakaki P, Ducar C, Deseyve M, Emel L, Mirochnick
M, Fowler MG, Mofenson L, Miotti P, Dransfield K, Bray D,
Mmiro F, Jackson JB (1999) Intrapartum and neonatal single-dose
nevirapine compared with zidovudine for prevention of mother-to-
child transmission of HIV-1 in Kampala, Uganda: HIVNET 012
randomised trial. Lancet 354(9181):795–802
4. Songok EM, Fujiyama Y, Tukei PM, Vulule JM, Kiptoo MK,
Adungo NO, Kakimoto K, Kobayashi N, Genga IO, Mpoke S,
Ichimura H (2003) The use of short-course zidovudine to prevent
perinatal transmission of human immunodeficiency virus in rural
Kenya. Am J Trop Med Hyg 69(1):8–13
5. Stringer EM, Sinkala M, Stringer JS, Mzyece E, Makuka I,
Goldenberg RL, Kwape P, Chilufya M, Vermund SH (2003)
Prevention of mother-to-child transmission of HIV in Africa:
successes and challenges in scaling-up a nevirapine-based program
in Lusaka, Zambia. AIDS 17(9):1377–1382
6. Stringer JS, Sinkala M, Goldenberg RL, Kumwenda R, Acosta EP,
Aldrovandi GM, Stout JP, Vermund SH (2004) Universal nevira-
pine upon presentation in labor to prevent mother-to-child HIV
transmission in high prevalence settings. AIDS 18(6):939–943
Eur J Pediatr (2007) 166:1305–1307 1307


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Implementing anti-retroviral triple therapy to prevent HIV mother-to-child transmission: a public health approach in resource-limited settings

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