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Welcome to I-TECH HIV/AIDS Clinical Seminar Series
3rd December 2009
Women and HIV
R. Scott McClelland, MD, MPH
Overview
• Introduction to HIV epidemiology in women
• HIV risk reduction for women
• Effect of male circumcision on the risk of HIV acquisition in female partners
• Gender-specific issues in selecting an antiretroviral regimen
Percentage of Adults (15+) with HIV who are Women
UNAIDS Report 2008
HIV in 15-25 year olds by sex
UNAIDS Report 2008
Case 1: HIV Prevention
• 18 y.o. HIV-negative woman recently treated for gonorrhoeae. What proven strategies can reduce her risk of acquiring HIV?– A) Abstain, Be faithful, male latex Condoms– B) ABCs and treat STIs– C) Female condom– D) Pre-exposure prophylaxis– E) All of the above
WHO Statement on HIV and STIs
WHO Fact Sheet on STI. Oct 2007 revision.
• Abstain from sexual intercourse
• Be faithful – Mutual long-term monogamy with HIV-negative partner
• Condoms
• Prompt treatment of STIs– Both in high risk and general population
UNAIDS November 2009
New HIV infections reduced 17% over the past 8 years
Condom Quiz
• How much do you know about condoms?
Question 1
• With consistent and correct use of condoms, the estimated rate of pregnancy at 12 months is closest to which range?– A. 0%– B. 1-4%– C. 5-8%– D. 9-12%– E. Over 12%
WHO Fact Sheet No234. June 2000
Question 1
• With consistent and correct use of condoms, the estimated rate of pregnancy at 12 months is closest to which range?– A. 0%– B. 1-4%– C. 5-8%– D. 9-12%– E. Over 12%
WHO Fact Sheet No234. June 2000
Question 2
• For typical condom use, the estimated rate of pregnancy at 12 months is closest to which range?– A. 5-10%– B. 10-15%– C. 15-20%– D. Over 20%
WHO Fact Sheet No234. June 2000
Question 2
• For typical condom use, the estimated rate of pregnancy at 12 months is closest to which range?– A. 5-10%– B. 10-15%– C. 15-20%– D. Over 20%
WHO Fact Sheet No234. June 2000
Question 3
• Condom failure – the device breaking or slipping off completely during intercourse – is common.– A. True– B. False
WHO Fact Sheet No234. June 2000
Condoms do not break easily
YouTube
Condoms do not break easily
YouTube
Question 4
• Longitudinal studies in men and women suggest that condoms reduce the risk of HIV infection by a rate that is closest to:– A. <50%– B. 50-65%– C. 65-80%– D. 80-95%– E. >95%
Question 4
• Longitudinal studies in men and women suggest that condoms reduce the risk of HIV infection by a rate that is closest to:– A. <50%– B. 50-65%– C. 65-80%– D. 80-95%– E. >95%
Question 5
• Longitudinal studies in women suggest that condoms reduce the risk of human papilloma virus (HPV) infection by at least:– A. 10%– B. 30%– C. 50%– D. 70%– E. 90%
Winer et al. N Engl J Med 2006
Question 5
• Longitudinal studies in women suggest that condoms reduce the risk of human papilloma virus (HPV) infection by at least:– A. 10%– B. 30%– C. 50%– D. 70%– E. 90%
Winer et al. N Engl J Med 2006
Case 1: HIV Prevention
• 18 y.o. HIV-negative woman at risk for HIV. Which microbicide has been associated with a trend towards decreased HIV risk?– A) Nonoxynol-9– B) SAVVY (C31G)– C) Cellulose Sulfate– D) Carragard– E) Buffer Gel– F) Pro 2000
Case 1: HIV Prevention
• 18 y.o. HIV-negative woman at risk for HIV. Which microbicide has been associated with a trend towards decreased HIV risk?– A) Nonoxynol-9– B) SAVVY (C31G)– C) Cellulose Sulfate– D) Carragard– E) Buffer Gel– F) Pro 2000
Microbicide
• Product that can be applied to vaginal or rectal mucosa with the intention of preventing or significantly reducing sexually transmitted infections including HIV infection– Gel– Ring– Film
Possible Targets to Prevent Transmission of HIV
McGowan. Biologicals. 2006
Pro2000 (Entry Inhibitor)
• 7 site study in Africa (6)/US (1)• 3099 women; 20.4 months; 93.6%
retention• Pro2000 vs. placebo HR 0.7 (95%CI 0.5-
1.1; p=0.10)• Pro2000 vs. no gel HR 0.7 (95%CI 0.4-
1.0; p=0.06)• Excluding time off product, Pro2000
reduced HIV incidence 36% (p=0.04)
Abdool Karim CROI 2009, LB48
Microbicides in Clinical Trials
• Pro2000 study by British Microbicide Development Program– 0.5% Pro2000 ongoing– 2% Pro2000 arm closed by DSMB 2/2008
• Microbicides containing antiretrovirals; topical Pre-Exposure Prophylaxis– Tenofovir 1% gel (HPTN 059, CAPRISA, VOICE)– TMC 120 (IPM)– UC-781 (CONRAD)
Case 1 Summary: HIV Prevention/Microbicides
• 18 y.o. HIV-seronegative woman has recently been treated for gonorrhea– ABCs and possibly other interventions such as
female condom may reduce HIV risk– Early microbicide trials with non-specific agents
generally not successful, but…– Recent experience with Pro2000 encouraging– Results of trials with antiretroviral-containing
microbicides are eagerly anticipated
Case 2: Male Circumcision and the Risk of HIV Acquisition in Women
• An HIV-seropositive man is seeking circumcision.– Will circumcision influence the risk of HIV
transmission to his wife?
Circumcision and HIV Transmission To Women
Quinn N Engl J Med 2000
Circumcision of HIV-positive Men
Wawer. CROI 2008, 33LB
• Rakai study of 124 discordant couples with uninfected female partner
• Female partners tested every 6 months
Circumcision in HIV-positive Men
• Reduced wound healing at 30 days compared to HIV-negative (73% vs. 83%, P<0.001)
• Less GUD in circumcised vs. uncircumcised arm of study (RR 0.48, 95% CI 0.3-0.8)
• Incidence in female partners; 14.4/100p-y in circumcised vs. 9.1/100p-y in uncircumcised (RR 1.59, 95%CI 0.7-4.3)
Transmission by Timing of Wound Healing and Resumption of Sex
When sex resumed Intervention Arm
Transmitted/N
%
Before complete healing 5/18 27.8%
At or after complete healing
6/63 9.5%
Early vs. later RR=2.92 (1.01-8.46)
P=0.06
Case 2 Summary: Male Circumcision and Risk of HIV Acquisition in Women
• An HIV-seropositive man is seeking circumcision. Will circumcision influence the risk of HIV transmission to his wife?– Transmission from an HIV-positive man to an
HIV-negative woman may be increased if sex is resumed before full wound healing
– Condom use must be promoted, especially during the period of wound healing
Case 3: ART in Women
• 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. On Depo Provera since first post-partum visit.– What other considerations should guide our decision about
the first-line ART regimen for this patient?
Case 3: ART in Women
• 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. On Depo Provera since first post-partum visit. She received single-dose nevirapine one year ago to reduce the risk of mother-to-child transmission of HIV during her first pregnancy.
Case 3: ART in Women
• 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. Started Depo Provera since first post-partum visit. She received single-dose nevirapine one year ago to reduce the risk of mother-to-child transmission of HIV during her first pregnancy. Which first-line ART regimen would you recommend:– A) Lopinavir/ritonavir + 2NRTI– B) Efavirenz or Nevirapine + 2NRTI– C) 3NRTI
Case 3: ART in Women
• 22 y.o. woman diagnosed with HIV during prior pregnancy. CD4=224cells/μL, HB=10g/dL, Ccreat = 100cc/min, other labs normal. Started Depo Provera since first post-partum visit. She received single-dose nevirapine one year ago to reduce the risk of mother-to-child transmission of HIV during her first pregnancy. Which first-line ART regimen would you recommend:– A) Lopinavir/ritonavir + 2NRTI– B) Efavirenz or Nevirapine + 2NRTI BUT…– C) 3NRTI
Consider Women’s History of Receiving Single Dose Nevirapine
No
Yes
No
* If no reproductive potential
Yes
Response to Nevirapine Containing ART after sd-NVP for PMTCT
• 218 women starting ART after participation in a trial of NVP vs. placebo for PMTCT– 106 placebo and 112 sd-NVP women
• 6 months post ART initiation, virologic failure 5% in placebo vs. 18.4% in sd-NVP; p=0.002
• Within 6 months of sd-NVP– Failure 0% placebo vs. 41.7% sd-NVP; p<0.001
• Over 6 months after sd-NVP– Failure 7.8% placebo vs. 12% sd-NVP; p=0.39
Lockman NEJM 2007;356:135
Time to Virologic Failure when ART Started <6 Months Post Partum
Lockman NEJM 2007;356:135
Time to Virologic Failure when ART Started >6 Months Post Partum
Lockman NEJM 2007;356:135
Time to Virologic Failure when ART Started >6 Months Post Partum
Lockman NEJM 2007;356:135
Archived Resistance after PMTCT Regimens
• SD NVP leads to archiving of resistant HIV in latent CD4+ cells in >8% of women1
• Use of additional drugs reduces but doesn’t eliminate development of NVP resistance2,3
• Resistance to other components of regimen– Postpartum 3TC resistance (15% of exposed
women) associated with ~7-fold increased odds of 12-month virological failure in Cote d’Ivoire3
1. Wind-Rotolo. JID 20092. Lehman. JAIDS 20093. Coffie CID 2008.
First-line Regimen Choice After SD Nevirapine
Aliv
e w
ithou
t V
irolo
gic
Fai
lure
0 25 50 75 100 125 150
Week
LPVr
NVP
Lockman. CROI Montreal February 2009
Case 3 Summary: ART In Women
• Consider history of sd-NVP when selecting first-line ART regimen in women– If women received sd-NVP within past 6 months,
avoid all NNRTIs in first-line regimen– If women received sd-NVP >6 months prior to
ART initiation, okay include NNRTI in 1st line• Recommendations evolving with emerging data• Lamivudine resistance may also be an issue
– Higher adherence independently associated with improved outcome regardless of regimen1
1. Coffie CID 2008
UNAIDS Report 2008
Welcome to I-TECH HIV/AIDS Clinical Seminar Series
Next session: December 17, 2009
Devika Singh
HIV and STIs, Part 4
