Transcript HIV Interventions in MCH Programsm

HIV/AIDS and Maternal and
Child Health Programs in
Resource-Limited Settings
Paula E. Brentlinger, MD, MPH
Department of Global Health
January 2012
Today’s Plan
The epidemic in women and children
Antiretroviral medications for treatment and
prevention
Treatment: Other considerations in women and
children
Real-world barriers to implementation
Calls to action
HIV Epidemiology in Women and
Children: 1970s to present
Onset of AIDS Epidemic (US Data)
“Since 1981, an outbreak of acquired immune
dysfunction manifested by opportunistic
infections and neoplastic disorders such as
Kaposi’s sarcoma and malignant lymphomas
has been reported in more than 1000
homosexual men.”
Metroka CE et al. Generalized lymphadenopathy in homosexual men. Ann Int Med
1983;99:585-91.
Women, HIV, and Western Washington
“Living in Olympia I felt alone, like I was the only
woman in town with this disease [AIDS]. I got
a lot of support from all of the wonderful gay
men....I attended their support group every
week, but felt I needed another woman to talk
with, someone who could identify with having
kids.”
“Anna B.” Reflections on taking pills, being a mom, and living in a rural community. STEP
Perspective, 1998;98(2):7. (STEP: Seattle Treatment Education Program)
HIV and Women in Africa
“Antibody to human T-cell lymphotrophic virus
type III (HTLV-III) was detected in the serum of
66% of prostitutes of low socioecononomic
status............the relatively high female:male
ratio of cases of AIDS in Africa (1:1 in Zaire,
compared with 1:16 in the United
States)...raises the possibility that perinatal
transmission may result in high rates of the
infection among infants and children...”
Kreiss JK et al. AIDS virus infection in Nairobi prostitutes. N Engl J Med 1986;314:414-8.
The current numbers: 34 million living
with HIV in 2010
(WHO 2011)
Half of Adults with HIV are Women
(59% in sub-Saharan Africa)
(WHO 2011)
Likelihood of MTCT (UNICEF: Children and AIDS:
Fifth Stocktaking Report, 2010)
3.4 Million Children Under 15 Living
with HIV 2010 (90% in Africa)
(WHO 2011)
Distribution of new infections by mode of exposure
in Ghana and Swaziland, 2008
100
No risk
Medical injections
80
Blood transfusions
Injecting drug use (IDU)
Partners IDU
60
Sex workers
%
Clients
Partners of Clients
40
Men who have sex with men (MSM)
Female partners of MSM
Engaged in casual sex (CS)
20
Partners of CS
Low-risk heterosexual
0
Ghana
Swaziland 1Swaziland 2
Note: sensitivity analysis for Swaziland used different data sources.
Sources: Bosu et al. (2009) and Mngadi et al. (2009).
Figure 3
Distribution of HIV Incidence by Mode
of Exposure
Distribution of Reported HIV Infections
by Mode of Exposure
1990s & Onward: Antiretrovirals for
Treatment and Prevention!
ARV: Antiretroviral (medication)
HAART: Highly active antiretroviral therapy
(later called cART)
PMTCT: Prevention of mother-to-child
transmission
Survival and Antiretroviral Therapy
(HAART) in Adults with AIDS
Impact of HAART in South Africa
Medecins sans Frontieres project in Khayelitsha:
Of 1st 287 adult patients started on HAART,
86.3% still alive at 24 months
Median CD4 count gain 288 at 24 months
Viral load < 400 copies/ml in 69.7% of patients
at 24 months
Coetzee D, et al. AIDS 2004.
Mortality on HAART: developed vs.
developing countries (from ART-LINC)
Special Considerations re ARV use in
Women of Reproductive Age
Some ARVs are probably teratogenic (based on animal
studies) and should not be given in pregnancy or to
women at risk of pregnancy.
Some ARVs appear to have increased toxicity in pregnancy
(e.g. DDI and D4T in combination).
Some ARV side effects more common in women (e.g.
nevirapine rash and hepatotoxicity).
Drug-drug interactions involving contraception and ARVs (?)
Drug resistance risk if starting/stopping with each
pregnancy
Perinatal Infection and Survival (before
the era of treatment)
Cohort of HIV-infected children born between
1979 and 1987, Florida:
“The median survival time of all 172 children
was 38 months from the time of diagnosis.
Mortality was highest in the first year of life
(17%).....children with perinatally acquired
HIV-1 infection have a very poor prognosis.”
Scott GB et al. Survival in children with perinatally acquired human immunodeficiency virus
type-1 infection. N Engl J Med 1989;321:1791-6.
AIDS and Mortality in South African
Children
Cause-specific mortality in South Africa:
Age group
0-28 days
29 days – 1 year
1-4 years*
5-9 years*
10-14 years*
% deaths from AIDS
5.0%
34.0%
61.0%
33.0%
17.0%
* Most common cause of death in this age group
Garrib A et al, 2006.
Survival and HAART in Children:CHER
(Violari et al, NEJM 2008)
CHER, cont’d
HIV, HAART, Pediatric
Neurodevelopmental Outcomes
J of AIDS 2012;59:161-9)
(Heidari S et al.,
Special Considerations re ART in
Children
1. HIV infection progresses very rapidly (months to
a few years) to AIDS and death in infants; early
diagnosis and treatment are essential
2. Dosing is different in children because of
differences in weight and drug metabolism;
increase dose as child grows; gaps in PK data
3. Liquid formulations of ARVs for kids are harder
to acquire and handle than pill formulations for
adults
4. Importance of neurodevelopmental outcomes
5. Importance of caregivers
Antiretrovirals and Prevention: PMTCT.
The 1st PMTCT Trial (PACTG 076)
Monotherapy with zidovudine (AZT) in late
pregnancy reduced HIV transmission during
pregnancy and childbirth by 67% (25.5% with
placebo vs. 8.3% with zidovudine) in PACTG
076 trial.
Connor E, N Engl J Med 1994.
MTCT at Age 6 Weeks by ARV Regimen
Botswana National Data Oct 2006-Nov 2007
Tlale J et al. IAS Mexico City Aug 2008 (Abs ThAC04), quoted in Mofenson L
2008
15%
Most Women Formula Feed Their Infants
12.3%
10%
5%
7.0%
4.7%
0.7%
0%
3.3%
5.5%
3.1%
2.3%
HAART HAART AZT
AZT
AZT sdNVP No
AZT
ART
pre-preg during >4 wk >4wk <4 wk <4 wk
preg +sdNVP alone +sdNVP alone
6 Month vs. 6 Week NVP (Coovadia HM et al,
Lancet 2012;379:221-8)
Earlier vs. Later Maternal HAART
(Chibwesha CA et al, J of AIDS 2011;58:224-8)
Infant Mortality, Maternal HAART,
Breast-feeding (Homsy et al, JAIDS Jan 2010)
WHO Policy, 2009: The Radical
Changes
Mothers known to be HIV-infected should be
provided with lifelong antiretroviral therapy or
antiretroviral prophylaxis interventions to reduce
HIV transmission through breastfeeding
according to WHO recommendations.
Mothers known to be HIV-infected should
exclusively breast feed their infants for the first 6
months of life, introducing appropriate
complementary foods thereafter, and continue
breast-feeding for the first 12 months of life.
Antiretrovirals and Prevention: Sexual
Transmission
(Celum&Baeten, Curr Opin Infect Dis 2012;25(51-7)
Prevention: Microbicides (2) Tenofovir gel
PrEP: Aspects Specific to Women
Vaginal vs. blood concentrations of drug
Female-controlled (unlike condom use)
Drug interactions involving oral PrEP and
hormonal contraceptives (?????)
In the pipeline: drug-eluting vaginal rings?
HIV Prevention: Other Considerations
in Women and/or Children
Other Considerations in PMTCT (1)
Prevention of unwanted pregnancies is the first
step in PMTCT!
Other Considerations in PMTCT (2):
Obstetrical Interventions
An incomplete list of obstetrical interventions or choices
that increase likelihood of vertical transmission:
o Choosing prolonged labor over caesarean delivery
(especially with prolonged rupture of membranes)
o Episiotomy
o Placement of internal monitors
o Artificial rupture of membranes
o Forceps deliveries
o Transfusions with unscreened/infected blood
Other Considerations in PMTCT (3):
Vertical HIV Transmission and
Placental Malaria (Brahmbhatt 2008)
Prevention: Male Circumcision
Male circumcision prevents sexual transmission
of HIV to uninfected men, but:
In Uganda, serodiscordant (husband HIV+, wife
HIV-) randomized to circumcision vs none:
HIV transmission to wives
13.8/100 py in circumcision group
9.6/100py in non-circumcision group
Wawer et al, CROI abstract 33 LB, 2008
Prevention: Condoms work if used
Some successful targeted condom programs:
• Targeted condom promotion (condom distribution plus
individual and group counseling) in female commercial sex
workers in Kenya. Condom use associated with threefold
reduction of risk of HIV seroconversion.
• Condom use and HIV education in female sex workers in India
led to decreased HIV incidence (by about 67%) in intervention
group.
• Targeted condom distribution and HIV education in male army
conscripts in Thailand led to 50% reduction in HIV incidence.
Merson M, et al. AIDS 2000.
Prevention: Voluntary Counseling &
Testing for HIV (VCT)
Some aftermath of VCT: For women who were
HIV+ and disclosed their status to a partner:
14% reported break-up of marriage, 26%
breakup of sexual relationship, 7% physical
abuse, 3% neglected or disowned by family
(vs. 1%, 14%, 4%, and 2% if HIV-negative and
disclosed).
Grinstead O, et al. AIDS 2001.
“Cheap Solutions Cut AIDS Toll for Poor
Kenyan Youths” (NYT, 6 Aug 2006)
“....when girls were given free school uniforms
instead of having to pay $6 for them – the
principal remaining economic barrier to
education in Kenya – they were significantly
less likely to drop out and become pregnant...”
“...classroom debates and essay-writing contests
on whether students should be taught about
condoms to prevent HIV increased the use of
condoms without increasing sexual activity...”
HIV/AIDS Treatment: Other
Considerations in Women and Children
Growth and HIV exposure (Filteau et al)
Orphans and school attendance (from
UNICEF, 2010)
Infant growth vs water supply (Patel et
al.)
Real-World Barriers to Coverage of
Prevention and Treatment
ART Coverage
The PMTCT cascade (Braun et al)
Pediatric early diagnosis in
Mozambique (Cook et al.)
Calls to Action
The Call to Action (UNICEF, 2010)
1. Change the PMTCT focus from coverage of ARV
prophylaxis to the health of mothers and the
HIV-free survival of children.
2. Make exclusive breast-feeding safe and
sustainable.
3. Identify HIV positive newborns, children and
young people without delay and provide rapid
access to ART for those eligible.
4. Make children and adolescents central to the
development and implementation of promising
new prevention strategies.
5. Redress low levels of knowledge about HIV.
6. Increase access of children and adolescents
living on the margins of society to health,
education, and social welfare services.
7. Provide economic support to poor and
vulnerable women, children and adolescents.
8. Prevent violence and abuse of women and
girls and enforce laws against it.
Integrate Services
Harmonize the MDGs (Waage et al
2010)
Thank you!
Questions????