Of Mothers, Orphans and the HIV Pandemic

Karen P. Beckerman, MDAssociate Professor of Obstetrics

and GynecologyNew York UniversityDirector of ObstetricsBellevue Hospital Center

25 October 2002

New slides needed:CSx data: 367, 316, Models of HIV Rx in dev worldTb Rx and dev worldAsk Ester if she might consider a picture of herself and her daughterRupert and his son.

HIV disease in the U.S.Pediatric AIDS incidenceReproductive Health and HIVPrinciples of care: universal

developed world

Preconceptional and early pregnancy counseling

Vertical TransmissionPrinciples of care during pregnancyThe global epidemic

December 2001:> 40 million infected>8,000 deaths per day600 new infections per houra child dies every minuteOctober 2002:5 million new infections in 2001800,000 children infected44 million orphans by 2010

Reproductive Health & HIV Pregnancy does not alter the course of HIV

disease in the west. Data do not exist examining the effect of

pregnancy on HIV progression in the developing world.

Prospective studies show that a pregnant HIV infected mother has a 3% chance dying before her baby’s first birthday and an 11% chance of dying before the second birthday.

HIV in Africa DATA are VERY

SCARCE ! The epidemic is

heterosexual. After infection, rapid

progress to AIDS. Less than half will remain

symptom-free at 3 years. Median survival is 9 years. Survival with AIDS is

“short.”

HIV and African Women 55% of infected individuals are

women. Male to female transmission is 10x

more efficient that female to male. Women are infected early in their

reproductive lives, Ususally by older men. Rates of pregnancy and nursing are

high among African women with asymptomatic HIV.

“The Population Chimney”

HIV mortality will produce population pyramids that have never been seen before.

By 2010, men will outnumber women in each 5-year cohort between 15 and 49.

USAID, “Children on the Brink”

Largescale orphaning:• Historically, sporadic and short term.HIV orphaning: • Long term and chronic.• Will worsen in coming decades.• Most will be uninfected.• All will face extraordinary risks: Inadequate nutrition, housing and health care. Servitude, harshness & abuse Acquisition of HIV

Proposed Solutions to the Orphan Crisis:

Strengthen coping capacities of families Protection of property and inheritance rights District AIDS committees Community day-care centres Waiving school fees Support youth expression Encourage political will Reduction of stigma Promote the rights of women and children Encourage partnership and leadership

-USAID, 2001

Principles of care of the HIV-1 infected pregnant mother

First things first:

Safe shelter Adequate nutrition Transportation Self-determination

Self Determination:

Reproductive choice

OI Prophylaxis

Treatment

Delivery plan

Principles of care of the HIV-1 infected pregnant motherProtection of mothers from mono- and dual therapies likely to induce ART resistance:

Low Fidelity HIV-1 Replication

•Two polymerases without proofreading activityHIV-1 reverse transcriptaseCellular RNA polymerase

•Two RNA copies per virionInsertions and deletions are common

•RNA strand breaks force template switching

•Uracil incorporation into proviral DNAEspecially in resting cells

Pregnancy and ART resistance in Uganda

NVP single dose prophylaxis:HIVNET 006 & 012Single dose to mother + single dose to infantTransmission fell from 25 to 13%

10 of 46 mothers studied 6 weeks to 6 months later had detectable resistance

Of the 36 infected infants, 8 had detectable nnRTI resistance at 6 weeks of age.

Pregnancy and ART resistance in the developed world

Principles of care of the HIV-1 infected pregnant motherProtection of mothers from mono- and dual- therapies likely to induce resistance:

•Nevirapine prophylaxis (even one dose) is highly likely to result in nnRTI resistance if not given in a safe combination.

•In the U.S., nevirapine prophylaxis given in addition to standard ART resulted in no benefit to mother or baby, but did cause significant induction of nnRTI resistance.(Dorenbaum, PACTG 316, CROI, 2001)

Pregnancy and ART resistance in the developed world

•Zidovudine/lamivudine (AZT/3TC) induces resistance (M184V) at same frequencies in pregnant women as in men

•In one study, 4 of 5 mothers developed M184V (Clark, J Med Virol.59:364)

•M184V can be transmitted to neonates

Pregnancy and ART resistance in the U.S. and England:

Are these data relevant to us today?

Unfortunately, YES.

ACTG 185: late 1990s

86% received ZDV 14% received ZDV/3TC

30% of mothers had nRTI resistance by delivery

These mothers were 3 times more likely to transmit virus to their infant

(p=0.03)

Principles of care of the HIV-1 infected pregnant motherProtection of mothers from mono- and dual- therapies likely to induce resistance:

•Women refusing 3 medications should be offered zidovudine prophylaxis, never Combivir alone.

Combivir Alone

Priniciples of care of the HIV-1 infected pregnant motherAggressive use of combination antiretroviral therapy to achieve durable suppression of maternal HIV replication and to protect mother from induction of antiretroviral resistance:

Offer 3 or more medications Twice daily dosing