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La terapia antiretrovirale nella donna
e la nascita di un bambino non infetto
Andrea Antinori
INMI Lazzaro Spallanzani IRCCS, Roma
ART for HIV Prevention: The Hypothesis
• Initiation of ART results in early
and sustained reductions in plasma
and genital HIV levels
• Led to the hypothesis that ART use
would result in decreased
infectiousness
1. Quinn TC, et al. N Engl J Med. 2000;342:921-929.
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Transmission Rate per 100 Person-Yrs
• The quantity of HIV in plasma (and
genital secretions) is the prime
determinant of whether someone
with HIV will transmit the virus to a
sexual partner[1]
30
25
20
15
10
5
0
HIV-1 RNA (copies/mL)
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402 mother–infant pairs, the rate of transmission
of HIV-1 was 7.6% (95% CI, 4.3 to 12.3 percent)
with zidovudine treatment and 22.6% (95% CI,
17.0 to 29.0 percent) with placebo (P <0.001).
Sperling RS, et al. N Engl J Med, 1996
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Prevalence of HIV infection, by population
group in Italy
Suligoi B, et al. Ann Ist Super Sanità, 46;1,2010
Percent of women receiving ARV medicines to
prevent vertical transmission, by region, 2010–2015
Source: 2016 Global AIDS Response Progress Reporting and UNAIDS 2016 estimates.
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Trends of reported HIV diagnosis by transmission
mode and year of diagnosis, adjusted for reporting
delay (EU/EEA, 2006-2012)
Number of cases
10,000
Heterosexual, excluding cases originating
from Sub-Saharan
African countries
8,000
6,000
Heterosexual cases originating
from Sub-Saharan African countries
4,000
MSM
IDU
2,000
Mother-to-child transmission
Other/undetermined
0
2006
2007
2008
2009
2010
2011
2012
Year of diagnosis
•
•
Despite multiple efforts to reduce new HIV infections, the number of new diagnoses remains stable
In MSM subgroup, the number of HIV diagnosis increased by 11% from 2006 to 2012
IDU, injection drug users; MSM, men who have sex with men
European Centre for Disease Prevention and Control/WHO Regional Office for Europe: HIV/AIDS surveillance in Europe 2012
MTCT rates in diagnosed women
UK & Ireland 2000-2011
2,5%
MTCT rate 3000
2012-14 0.43%
2.1%
MTCT rate
1.4%
1,5%
2000
1.1%
1500
0.72%
1,0%
0.60%
0.46%
0,5%
Live births
(data reported to2500
end June 2016)
2,0%
1000
500
0,0%
2000-01
2002-03
2004-05
2006-07
0
2008-092010-11 (incomplete)
Year of birth
~12,500 singleton births; significant decline in MTCT over time (p<0.001)
Graph derived from data in Townsend et al. Earlier initiation of ART and further
decline in mother-to-child HIV transmission rates, 2000-2011. AIDS 2014; 28:1049–57
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New HIV infections among children (aged 0–14 years) with
and without the provision of antiretroviral medicines to
prevent mother-to-child transmission, global, 1995–2015
Source: UNAIDS 2016 estimates.
Antenatal HIV screening strategies
EU/EEA, 2013 survey
The most common strategy (15/24) of
antenatal screening for HIV in EU/EEA
countries is opt-out screening, where
pregnant women are tested as part of
routine antenatal care unless they explicitly
decline.
Opt-in screening is the chosen strategy in
six countries, where pregnant women are
offered testing and must provide explicit
consent.
The Czech Republic, Slovakia and Spain
reported universal screening for HIV with
systematic testing of all pregnant women.
Romania and Slovenia reported that they
operated targeted antenatal HIV screening
among women who inject drugs.
European Centre for Disease Prevention and Control. Antenatal screening for HIV, hepatitis B, syphilis and rubella susceptibility in the
EU/EEA. Stockholm: ECDC; 2016.
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Pregnant women living with HIV
In 5,700 deliveries to diagnosed women in UK and Ireland NSHPC, 2009-2014
HIV diagnosis known
but untreated at
conception
HIV diagnosis known
at conception, on ART
51%
28%
HIV diagnosed via
antenatal screening
Undiagnosed at
delivery
21%
HIV antenatal screening uptake >97% since 2011
French et al, HIV Medicine 2016
• Icona cohort: 158 of 2,862 women
experienced 169 pregnancies (88 in naives and
81 in 70 ART-experienced women)
• VL was detectable in 35.6% of women at
delivery
• This was less likely with increasing calendar
periods (adjusted OR per 1-year longer: 0.8,
95% CI 0.7 to 0.9, P = 0.007)
D’Arminio Monforte A, et al. J Acquir Immune Defic Syndr, 2014
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MTCT: Impact of duration of treatment and
baseline HIV viral load
Sub-group analysis: women on cART with
VL<1000
Townsend et al. AIDS, 2014
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MTCT rates in Europe
Country
MTCT rate
Time period
France
0.7%
2000-2011
Italy
1.0%
2005-2010
Denmark
0.5%
2000-2008
Sweden
0.6%
1999-2003
Spain
1.6%
2000-2007
UK
0.57%
2007-2011
UK
0.4%
2009-2014
Ukraine
2.2%
2013
Russia
3.5%
2013
Mandelbrot et al 2015, von Linstow et al 2010, Naver et al 2006, Chiappini et al 2011, Prieto et al 2012, personal
comm. Inga Latysheva, Townsend et al 2014, French et al 2016
European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord
Migrant women were more likely to be diagnosed in late
pregnancy
Adjusted OR for HIV diagnosis
at ≥20 gest. weeks in women
with unknown HIV status at
conception
• Ref. group: native women
• Adjusted for factors including
parity, time period, age, cohort
• 33% diagnosed late in migrant women vs 24% in native women
• % with late HIV diagnosis declined significantly over study period
Favarato G, et al. Eur J Public Health, 2017
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Linee-guida SIMIT 2016
Terapia antiretrovirale di combinazione (cART)
• L’indicazione al trattamento delle donne in gravidanza non deve discostarsi da quella al di fuori della gravidanza
[AIII].
• Analogamente agli uomini, le donne HIV positive devono iniziare un regime di terapia ARV al riscontro della
positività per HIV, indipendentemente da conta di cellule CD4 e carica virale [AI].
• In caso di riscontro di HIV durante la gravidanza si deve accelerare il più possibile l’inizio della terapia.
• Gli obiettivi del trattamento sono:
• Ottenere una soppressione virale stabile (HIV-RNA non rilevabile).
• Mantenere la carica virale non rilevabile nelle donne che si trovano già in questa condizione all’inizio della gravidanza.
• Realizzare il più rapidamente possibile una soppressione virale dell’HIV fino a livelli non rilevabili nelle donne che iniziano il
trattamento in gravidanza.
• Ottenere HIV-RNA non rilevabile al 3° trimestre, e in particolare a 34-36 settimane e al momento del parto [1-6, 10].
• Il Test di resistenza è raccomandabile in tutte le donne non ancora in trattamento ed in quelle in trattamento con
HIV-RNA rilevabile. Laddove i tempi siano limitati va avviata empiricamente la terapia.
• Il TDM non è raccomandato di routine.
• Solo in caso di tossicità grave si può prendere inconsiderazione la interruzione della cART.
• Gli schemi terapeutici consigliati si basano su studi clinici effettuati in gravidanza che ne hanno dimostrato
l’efficacia (anche a lungo termine), la tossicità accettabile e la facilità nell’uso.
Antenatal ART resulted in significantly lower rates of
early HIV transmission than zidovudine alone
Fowler MG, et al. N Engl J Med, 2016
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Antiretroviral medicine regimen used in preventing
mother-to-child transmission, global, 2010–2015
Source: 2016 Global AIDS Response Progress Reporting and UNAIDS 2016 estimates.
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DHHS Recommendations: Initial ART in
Pregnant Women
Guideline
Status
NRTIs
PIs
Integrase
Inhibitors
Preferred
3TC/ABC
FTC/TDF
3TC + TDF
Atazanavir/RTV*
Darunavir/RTV*†
Raltegravir*§
Alternative
3TC/ZDV
Lopinavir/RTV*
Insufficient
data to
recommend
FTC/TAF
Fosamprenavir
NNRTIs
Efavirenz*
Rilpivirine*‡
Dolutegravir
EVG/COBI
EVG/COBI
*In addition to 2-NRTI backbone. †Must be used twice daily in pregnancy. ‡Only if pretreatment
HIV-1 RNA ≤ 100,000 copies/mL and CD4+ cell count ≥ 200 cells/mm3. §If adherence concerns or
potential for ART discontinuation postpartum, a PI is preferred over INSTI to reduce resistance
risk.
DHHS Perinatal Guidelines. October 2016.
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Linee-guida SIMIT 2016
Gravidanza. Come iniziare (Considerazioni sulla
scelta dei farmaci/Farmaci consigliati).
Raltegravir can be used in standard dosages in
HIV-infected pregnant women
Geometric mean (with upper 95% confidence interval) raltegravir
concentration–time profiles during the third trimester of pregnancy
(open squares) and postpartum (filled circles).
Blonk MI, et al. Clin Infect Dis, 2015
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PROMISE: Efficacy and Safety
 Between treatment arms, no significant difference in primary safety or efficacy endpoints;
continuing ART associated with lower HIV event rate
Outcome, n (Rate/100 PY)
Continue ART (n = 827)
Stop ART (n = 825)
HR (95% CI)
Primary efficacy composite
endpoint events
4 (0.21)
6 (0.31)
0.68 (0.19-2.40)*
 AIDS-defining events
2 (0.10)
3 (0.15)
0.67 (0.11-4.02)
0
0
--
2 (0.10)
4 (0.20)
0.52 (0.09-2.81)
Primary safety composite
endpoint events†
260 (18.4)
232 (15.4)‡
--
Composite of HIV/AIDS-related or
WHO stage 2/3 events
57 (3.09)
99 (5.49)
0.56 (0.41-0.78)
WHO stage 2/3 events
39 (2.02)
80 (4.36)
0.47 (0.32-0.68)§
 Serious non-AIDS event
 Death
*P = .54. †Time to first grade 3/4 sign or symptom or grade 2-4 chemistry or hematology result. ‡P = .08.
§P < .001.

189 (23%) pts in Continue ART arm experienced virologic failure; in pts with virologic failure
who had resistance testing, 52/155 (34%) had evidence of resistance
Currier J, et al. AIDS 2016. Abstract THAB0103LB.
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