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HIV / AIDS 2005. Mother To Child Transmission. - Sky R. Blue, MD. Number of people living with HIV/AIDS Total 40 million (34 - 46 million) Adults 37 million (31 - 43 million) Children under 15 years 2.5 million (2.1 - 2.9 million) People newly infected with HIV in 2003
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HIV / AIDS2005 Mother To Child Transmission - Sky R. Blue, MD
Number of people living with HIV/AIDS Total 40 million (34 - 46 million) Adults 37 million (31 - 43 million) Children under 15 years 2.5 million (2.1 - 2.9 million) People newly infected with HIV in 2003 Total 5 million (4.2 - 5.8 million) Adults 4.2 million (3.6 - 4.8 million) Children under 15 years 700 000 (590 000 - 810 000) AIDS deaths in 2003 Total 3 million (2.5 - 3.5 million) Adults 2.5 million (2.1 - 2.9 million) Children under 15 years 500 000 (420 000 - 580 000 HIV - The Numbers
Australia & New Zealand 15,000 Adults and Children Living with HIV/AIDS 2003 Eastern Europe 1 million Western Europe 550,000 N. America 950,000 210,000 21,000 44,000 Asia & Pacific 6.6 million North Africa 500,000 Caribbean 420,000 92,000 1,800,000 53,000 Sub-Saharan Africa 28.5 million Latin America 1.5 million 240,000 3,100,000 5,000 Total: 40 million Data from UNAIDS New Cases
Prevalence 15 – 30 % 5.0 - 15 % 1.0 – 5.0 % 0.5 – 1.0 % 0.1 – 0.5 % 0.0 – 0.1 % Not Available HIV Prevalence Worldwide
Men to Women Ratios • US • 14 : 1 • Haiti • 3 : 1 • Africa • 1 : 1
Estimated Incidence of AIDS, Deaths, and Prevalence by Quarter-Year of Diagnosis/Death, United States, 1985-1999* 25,000 350,000 1993 definition AIDS implementation Deaths 300,000 Prevalence 20,000 250,000 15,000 200,000 Number of Cases/Deaths Prevalence 150,000 10,000 100,000 5,000 50,000 0 0 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Quarter-Year *Adjusted for reporting delays
Epidemiology • Distribution of AIDS/HIV status1 950K 1000K 280K Undiagnosed 800K 600K 200K HIV+ but not in care 130K HIV+ 400K 200K 340K AIDS
HIV in Idaho – Prevalence HIV AIDS • District 1 50 40 • District 2 32 15 • District 3 60 36 • District 4 214 113 • District 5 48 23 • District 6 44 18 • District 7 26 15 • Total 478 260 738 (As of Dec 2003)
HIV Services Clinic – Family Medicine Residency of Idaho (FMRI) • Gender • Male 78% • Female 22% • Ethnicity • White 79% • Black 5% • Hispanic 14% • Asian 1% • Native Am 1% • Other <1%
HIV and Pregnancy • AIDS in women has risen from 7% of adult cases early in the epidemic to 27% today • 7,000-10,000 babies are born each year to HIV infected mothers • 2,000-3,000 would be born with HIV • Universal screening and perinatal treatment could reduce this to <500
HIV Testing in Pregnancy • National Recommendations • Universal voluntary testing with patient notification as a routine component of prenatal care • American Academy of Pediatrics and American College of Obstetricians and Gynecologists. Human Immunodeficiency Virus screening: joint statement of the AAP and ACOG. Pediatrics 1999;104:128. • Institute of Medicine. Reducing the odds: preventing perinatal transmission of HIV in the United States. Washington, DC: National Academy Press, 1999
HIV Testing in Pregnancy • CDC (USPHS) recommendations for HIV screening of pregnant women • Prenatal: routine HIV screening for all pregnant women using the “opt out” approach — women will be notified that they will be tested unless they decline • Labor and delivery: routine rapid testing for women whose HIV status is unknown • Postnatal: rapid testing for all infants whose mother’s status is unknown. • MMWR November 15, 2002 • Regulations, laws, & policies about HIV screening of pregnant women vary state to state
Untreated Populations • 15% of women with HIV infection have no prenatal care compared to 2% of all pregnant women (MMWR, 1998) • Risk of HIV infection at least 2- to 4-fold higher among women presenting for delivery without prenatal care E Aaron, CRNP. Presented at Clinical Pathway, August 2002.
Missed Opportunities • Women who do not receive prenatal care • Pregnant women who seek prenatal care erratically • Non-legal residents • Injection drug users • Homeless • Women who receive prenatal care but are not offered testing E Aaron, CRNP. Presented at Clinical Pathway, August 2002.
3rd Trimester Testing • Retesting in the third trimester, preferably before 36 weeks of gestation, is recommended for women known to be at high risk for acquiring HIV: • who have a history of sexually transmitted diseases, • who exchange sex for money or drugs, • who have multiple sex partners during pregnancy, • who use illicit drugs, • who have sex partner(s) known to be HIV-positive or at high risk • who have signs and symptoms of seroconversion. CDC. Revised US Public Health Service recommendations for human immunodeficiency virus screening of pregnant women. MMWR 2001;50(No. RR-19):59--86.
Rapid Testing at Delivery • High risk of perinatal transmission in women without antenatal care and without HIV counseling and testing • Rapid testing during labor can make it possible to initiate ART prophylaxis and to refer the woman for care • ART prophylaxis should be initiated as soon as possible after a positive rapid HIV test (before confirmatory test results are available)
HIV Antibody Tests • Serum antibody (EIA) • Saliva and urine antibody tests (EIA) • Rapid tests • SUDS (Microfiltration EIA) • Laboratory-based • OraQuick • Point of care • Western blot assay • Confirmatory test
CDC criteria 1 p160, p120 AND p41 CDC criteria 2 p160, p120 OR p41 PLUS p24 p160 p120 p41 p68 p53 p32 p55 p40 p24 p18 Western Blot GAG POL ENV
HIV Direct Tests • Viral Load • Qualitative / quantitative • RNA through bDNA or PCR • p24 antigen tests
HIV care During Pregnancy • Use optimal ART for the woman’s health • Add ZDV to regimen to reduce perinatal HIV transmission • Discuss preventable risk factors • Counsel on cesarean delivery • Support decision-making by woman following discussion of known and unknown benefits and risks • Acceptance or refusal of ART or ZDV should not result in denial of care or punitive action
Pregnancy Effects on HIV • In all women, the absolute CD4 count decreases no matter whether HIV-positive or negative (pregnancy does not make HIV worse) • In HIV-positive women, percentage of CD4 cells should not change and viral load should not change because of pregnancy
Adult Treatment Guidelines Clinical Category CD4+ count HIV RNA Recommendations Any value Any value CD4+ T cells Any value <200/mm3 CD4+ T cells Any value >200/mm3 but <350 /mm3 CD4+ T cells >100,000 >350/mm3 CD4+ T cells <100,000 >350/mm3 Treat Treat Treatment should be offered Most recommend deferring treatment, but some would treat. Defer therapy Symptomatic Asymptomatic, AIDS Asymptomatic Asymptomatic Asymptomatic
Nucleoside / nucleotide analogues (NRTIs) ABC ddI FTC 3TC d4T TDF ddC ZDV/ AZT C – No studies. Concern for hypersensitivity B – Concern for lactic acidosis (do not use w/ d4T) B – No studies. C– Well tolerated. Widely used. C – Concern for lactic acidosis (do not use w/ ddI) B – No studies. Animal reports of bone abnls C – No studies. Teratogenic in animals. C – Well tolerated. The most experience. Antiretroviral Agents - 1
Non-nucleoside RT inhibitors (NNRTIs) DLV EFV NVP C – No studies. D – Teratogenic. 4/142 birth defects. Avoid in 1st trimester C – Well tolerated. Avoid initiating if CD4 >250 cells/mm3. Used as single-dose Rx in labor to prevent perinatal transmission (consider adding ZDV/3TC for 3-7 days to reduce risk of NVP resistance) . Antiretroviral Agents - 2
Protease inhibitors (PIs) APV ATV FPV IDV LP/r NFV RTV SQV TPV C – No studies. Oral solution contraindicated. B – No studies. Concern hyperbilirubinemia C – No studies C– Unboosted: poor blood levels in preg C – No studies B – Registry data shows no incr in birth def B –Not used alone due to GI side effects B – Well tolerated, used boosted C – No studies Antiretroviral Agents - 3
NRTI Toxicity • Bone marrow suppression ZDV (AZT) • Anemia(1%- severe, 50%-mild) • Mitochondrial toxicity • Related to inhibition of DNA polymerase • ddC > ddI > d4T > ZDV > 3TC > ABC > TDF • Peripheral neuropathy(15-35%) • ddC > ddI > d4T • Pancreatitis (6-10%) • ddI > ddC > 3TC • Hypersensitivity rash (3-5%) • Abacavir • Not related to mitochondria
NRTI Toxicity During Pregnancy • Symptoms may be subtle, insidious, and non-specific • Fatigue, nausea, anorexia, abdominal pain, weakness • May be synergistic with maternal changes seen during pregnancy • Overlaps with other complications of pregnancy • Acute fatty liver of pregnancy • HELLP syndrome
Lactic Acidosis • Lactic acidosis is a rare life-threatening complication of antiretroviral therapy • Nucleoside analogue therapy-induced mitochondrial toxicity appears to be the cause of this syndrome • Diagnosis is difficult because symptoms are vague and non-specific • Routine monitoring of lactate levels is not recommended in asymptomatic patients; however, lactate should be measured in patients with unexplained weight loss, nausea, or abdominal pain • Treatment includes discontinuing NRTIs, followed by supportive care measures
Symptoms Nausea and vomiting Abdominal pain Weight loss Malaise Dyspnea/tachypnea Laboratory Findings Increased anion gap Increased lactic acid levels Increased lactate/pyruvate Lactic Acidosis Adapted from: Boxwell DE, Styrt BA. 39th ICAAC, San Francisco, CA, 1999. Abstract 1284.
NNRTI Toxicities • Rash 5-20% • Delavirdine > nevirapine > efavirenz • CNS 5% • Dizziness, vivid dreams, psychiatric • Efavirenz >> nevirapine • Nausea/diarrhea • Any • Liver toxicity 2-5% • Nevirapine (400mg QD > 200mg BID; risk greater if CD4 count before initiation of NVP in women is >250 cells/mm3) • Fetal abnormalities • Efavirenz
PI Toxicities • Lipodystrophy (up to 84%, severe in 12%) • Glucose intolerance (up to 23%) • Dyslipidemia (up to 90%) • Cutaneous changes, e.g., dry skin
Glucose Metabolism • Abnormalities of glucose homeostasis (primarily insulin resistance) are common in patients on ART • Higher incidence in patients receiving PIs • Mechanisms remain unclear at this time • Treatment with insulin-sensitizing agents may be beneficial
Insulin Resistance • Increased insulin levels found • Blood sugars normal • State of compensated insulin resistance
Antiretroviral Pregnancy Registry • Collaborative project managed by PharmaResearch Corporation on behalf of an advisory committee (specialists in OB/GYN, ID, teratology, epidemiology, and CDC and NIH members) and sponsored by: • Abbott Laboratories, Agouron Pharmaceuticals, Inc., Boehringer Ingelheim Company, Bristol-Myers Squibb, Co., Gilead Sciences, Inc., GlaxoSmithKline, F. Hoffmann-LaRoche Ltd., Merck & Co., Inc. and PharmaResearch. • Purpose: To assess safety of ARVs during pregnancy • Telephone: (800) 258-4263 Fax: (800) 800-1052 available at http://www.apregistry.com
Antiretroviral Pregnancy Registry • Through January 31, 2004 there were 5010 voluntarily reported prospective cases www.apregistry.com