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Management of HIV Infection in Women

Professor Margaret Johnson Royal Free Hospital, London, UK Romania, January 2012. Management of HIV Infection in Women. In the UK in 2010 1. 34% (22,220) of the people with diagnosed HIV were women This has quadrupled since 2000 34% (2,230) new diagnoses of HIV were in women

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Management of HIV Infection in Women

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  1. Professor Margaret Johnson Royal Free Hospital, London, UK Romania, January 2012 Management of HIV Infection in Women

  2. In the UK in 20101 • 34% (22,220) of the people with diagnosed HIV were women • This has quadrupled since 2000 • 34% (2,230) new diagnoses of HIV were in women • 95% of women living with HIV acquired the infection heterosexually 1. Health Protection Agency. HIV in the United Kingdom: 2010 Report. 2010, London

  3. Royal Free Clinic Population • Per 100 person year • # 24 weeks ART

  4. Royal Free Clinic Population (new diagnosis)

  5. Characteristics of women (>15yrs) with HIV in the UK • 61% of women are diagnosed with a CD4 cell count <350 per mm3 • Median CD4 count at HIV diagnosis • 324 cells/mm3 in pregnant women • 262 cells/mm3 in unpregnant women • 1 woman in 10 is at least 50 years old, twice as many as in 2000 Health Protection Agency. Personal communication 2010

  6. Late1 and very late2 diagnosis of HIV infection by prevention and age group 1 Diagnosed with a CD4 cell count <350 per mm3 (within 91days of diagnosis) 2 Diagnosed with a CD4 cell count <200 per mm3 (within 91days of diagnosis) Health Protection Agency Centre for Infections. HIV in the UK, CD4 Surveillance. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1287145367237. Accessed November 2011

  7. Note: There are only limited published data on testing programmes in most of these settings Beyond antenatal care: additional places to consider HIV testing for women

  8. HIV testing in termination of pregnancy service Creighton S, Reeves I. BHIVA 2009 HIV Med. 2008; 9(Suppl. 1):25(P58)

  9. CASCADE: Slower disease progression following HIV seroconversion in women n=3,414 women; n=3,509 men *Effect of sex within calendar period; †effect of sex across calendar periods Jarrin I, et aI. Am J Epidemiol 2008;168:532–40

  10. Life expectancy • Why do HIV +ve individuals on HAART not have a normal life expectancy? • Why are women more disadvantaged than men?

  11. Life expectancy ART-CC, Lancet 2000;372:293‒99

  12. Life expectancy • Patients aged >20yrs starting ART from 1996 to 2008, with >3 drugs and CD4 <350 cells/mm3(N=17,661; 25% female) • Over 91,203 person-years, 1,248 (7%) patients died May M et al. BMJ. 2011; 343:d6016

  13. COHERE: Time with CD4 ≥500 cells/mm3 Allows men, but not women, to reach similar mortality rates to general population Time spent CD4≥500 cells/mm3 Current CD4 After 1 year MALE FEMALE After 2 consecutive years After 3 consecutive years After 4 consecutive years After 5 consecutive years 0 1 2 3 Mortality ratio Adapted from Lewden C et al. 17th CROI, 2010. Poster 527. Abstract L-166

  14. Who delivers? • HIV specialist clinicians • HIV specifics • Clinicians in other specialities • e.g. obstetrics and gynecology, mental health and others • Primary care • Voluntary sector • Peer Support • Local Authorities

  15. The package Family life and relationships Prevention of onward transmission Sex-specific conditions ARV management

  16. Rates of heterosexual transmission of HIV • The likelihood of HIV transmission to women in serodiscordant couples has been reported to be more than twice that of men • 3.8 for women and 1.7 for men per 100 person-years were reported in one African study1 • A meta-analysis of studies of heterosexual discordant couples observed no incidences of transmission in patients treated with ART and with VL <400 copies/mL2 • Male circumcision can decrease the risk of male infection3,4 1. Mugo N, et al. International Microbicides Conference Pittsburgh, 2010. Abs 8 2. Attia S, et al. AIDS 2009;23:1397–1404 3. Baeten JM, et al. J Infect Dis2005;191:546–53 4. Quinn TC, et al. N Engl J Med 2000;342:921–29

  17. HIV transmission risk1 • Higher viral load and STIs increase transmission risk 1. Adapted from NONOPEP website: http://www.inmi.it/news/LineeGuida/ RecommendationsNONOCC.htm. Accessed Jan 2012

  18. Women’s vulnerability to HIV • Biological factors1,2 • Greater surface area of tissues in female sexual organs, delicate tissues that can tear easily • Ejaculate in direct contact with vaginal and cervical mucosal tissue • Ejaculate released in larger quantities with higher viral load than female secretions • Structural factors1,3 • Gender norms and inequalities (control over avoiding risk behaviour and nature of sexual interactions) • Violence3 • Forced sex may cause damage • May prevent women from safe-sex negotiations, being tested, disclosing HIV status and receiving treatment 1. Pan American Health Organization. Gender and HIV. Available from: http://www.paho.org/english/ad/ge/Gender-HIV1.pdf. Accessed March 2011 2. Larkin J, et al. MedscapeWomens Health 1996: 1(11):1. 3. WHO. Gender inequalities and HIV. Available from: http://www.who.int/gender/hiv_aids/en/. Accessed March 2011.

  19. Aspiration: timely diagnosis • Reduce late presentation in women • Identify barriers and opportunities for HIV testing for women • Expand HIV testing into existing women's services • Enhance the visibility of women who are not pregnant or who are older 1. BHIVA. National HIV Testing Guidelines. 2008 2. NICE. HIV Testing Guidelines 2011

  20. Note: There are only limited published data on testing programmes in most of these settings Beyond antenatal care: additional places to consider HIV testing for women

  21. Women: Demographics in Europe • New HIV diagnoses in women by mode of transmission (%); by WHO European geographic area in 2006 ECDC and WHO HIV/AIDS Surveillance Report in Europe. 2007 Joint United Nations Programme on HIV/AIDS (UNAIDS), United Nations Population Fund (UNFPA), UNIFEMWomen and HIV/AIDS: Confronting the crisis. 2004

  22. BHIVA Audit & Standards Sub-Committee. HIV testing and diagnosis. 2008 Tests offered at time of indicator condition

  23. Physician barriers to HIV testing • HIV testing was offered to 4,111 age-eligible patients in emergency units or acute care units within the UK Rayment et al. HINTS Study Group. Available at www.bhiva.org/documents/Conferences/TimeToTest2010/Presentations/AnnSullivan.pdf

  24. Patient AR • 24 yr old HIV-positive woman • CD4 370,VL89,000 • Partner HIV -ve • BMI 21

  25. What are the problems she faces? • Disclosure • Losing her job • Contraception - Pregnancy • Starting Treatment • Anxiety and Depression • Anaemia • Trip around the world • Am I going to die?

  26. For women newly diagnosed with HIV • Engaging in HIV care with a comprehensive multidisciplinary team which includes peer support • Identification of each woman’s coping strategies and support networks • Undertaking appropriate baseline assessment and investigations • Supporting women through disclosure

  27. The HIV factor.... • The impact of HIV on: • Existing relationships • Formation of new relationships • Sero-different relationships • Contraceptive options • Fertility and getting pregnant • The management of pregnancy

  28. After the test: telling others • Disclosure – difficulties and dilemmas for women • Telling men • Telling children • Reckless transmission Vyavaharkar M et al. AIDS Educ Prev. 2011; 23:78–90

  29. Disclosure • 2‒67% women do not disclose to anyone1–4 • Positive outcomes of disclosure reported5 • Less anxiety • Fewer symptoms of depression • Increased social support, acceptance • No need to hide treatment • Easier to plan for future, discuss prevention • Not associated with break up of relationship5 • Important to identify those at risk of violence2 1.Gielen AC et al. Women’s Health. 1997; 25:19–31 2.Kilmarx P et al. Sexually Transmitted Diseases. 1998; 25:28–37. 3.Simoni J et al. AIDS and Behaviour. 2000 4:147–58 3.Lester P et al. JAIDS and HR. 1995; 10:341–9 4.WHO. Gender Dimensions of HIV Status Disclosure to Sexual Partners: Rates, Barriers and Outcomes. 2004

  30. Current treatment guidelines: when to start ART? ‡ Treat in specific circumstances, including pregnancy, coinfection, HIV-AN or other deficiency, VL > 105 copies/mL, CD4 decline > 50-100 cells/mm3 per year, age > 50 years, high cardiovascular risk or malignancy *Generally defer treatment; closer follow up if VL > 105 copies/mL † ART should be considered unless patient is an elite controller (HIV-1 RNA 50 copies/mL) or has stable CD4 cell count and low-level viremia in the absence of ART 1. EACS Guidelines 2011. Available at http://www.europeanaidsclinicalsociety.org/guidelinespdf/EACS-EuroGuidelines_FullVersion.pdf. Accessed April 2011. 2. DHHS Guidelines 2011. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed April 2011 3. Thompson MA et al., JAMA 2010;304:321–333

  31. EACS recommendations for initiation of ART in HIV-positive persons

  32. Is there a preferred first line regimen for women • Safe among women with CD4 >350 cells/mm3 • No interactions with hormonal contraception • Safe in pregnancy • Not associated with weight gain or increases in body fat • Associated with few adverse events

  33. Aspiring to... effective ARV therapy • EFFICACY • Equivalent efficacy between sexes in RCTS but numbers are small1 • There is substantial variability within the data • EFFECTIVENESS • Tolerability differences2 • Discontinuation and switch rates higher in women3,4 1.Struble K.16th Conference on Retroviruses and Opportunistic Infections, February 8–11, 2009 2. Ofotokun. Top HIV Infect. 2005;13:79 3. Barber TJ et al. Antiviral Ther. 2011 (in press) 4. Currier et al. Ann Intern Med. 2010;153:349–57

  34. EACS Treatment Guidelines 2011

  35. Initial combination regimen for antiretroviral-naïve adult patients Select one drug in column A and one NRTI combination in column B (*) * Generic HIV drugs are becoming more available and can be used as long as they replace the same drug and do not break recommended fixed dose combinations. ** Only drugs currently licensed for initiation of therapy by the European EMA are taken into consideration.

  36. Representation of women in randomised controlled trials in naïve patients

  37. FDA meta-analysis: Similar efficacy of HAART in women versus men • FDA review of trials from 2000–2008 • Results • 22,411 HIV+ subjects in 43 RCTs for 16 ARVs; 20% women • No significant gender differences in treatment response at week 48, discontinuations for AEs, lost to follow-up or death • Higher rate of discontinuations for virological failure in males (8.15%) than females (4.25%) Soon G, et al. 50th ICAAC 2010. Abstract H-1812

  38. FDA meta-analysis: Similar efficacy of HAART in women versus men Favours male (n=6) Total Soon G, et al. 50th ICAAC 2010. Abstract H-1812 -100% -50% 0% 50% 100%

  39. Efficacy and Safety analysis of LPV/r in HIV-infected women • Meta-analysis of seven randomized clinical trials • VL <50; similar between women and men through 48 weeks Intention to treat; non-completers = failures • No gender differences in CD4 increases, treatment related moderate/severe AE’s. Increased rates of discontinuation in ARV naïve women but similar in experienced women

  40. Virological outcome RPV versus EFV in combination with TDF/FTC (TLOVR)

  41. ACTG 5202: Association of race/ethnicity and sex with outcomes Female (n=322) Male (n=1535) • Virological failures by gender and treatment group • Study not specifically powered for gender/race comparisons • Black race was associated with increased risk of VF, possibly related to lower adherence and higher rate of third drug tolerability endpoints Virological failure events Number at risk Smith K, et al. CROI 2011. Poster 536

  42. ACTG 5202: Association of race/ethnicity and sex with outcomes Smith K, et al. CROI 2011. Poster 536 Smith K, et al. CROI 2011. Poster 536

  43. GRACE study design GRACE n=287 womenn=142 men • Study criteria • ≥18 years of age • Viral load ≥1000 copies/mL • Previous therapy consisting of a PI- or NNRTI-based HAART regimen of ≥12 weeksa • No prior use of DRV/r, ETR, ENF or TPV 4-weekfollow up 48 weeks DRV/r 600/100 mg BD + investigator-selected OBRb 287 women; 142 men a Patients were allowed to enter the study on treatment interruption of ≥4 weeksb Investigator-selected NRTIs and NNRTIs were allowed; ENF, TPV, or agents from novel classes were not allowed Currier J, et al. Ann Intern Med. 2010;153:349–57

  44. GRACE: Virological response not significantly different in women versus men at 48 weeks Women (ITT-LOVR), Men (ITT-LOVR) 100 Women (TLOVR-non-VF) Men (TLOVR-non-VF) 90 80 73.5% 70 73.0% 60 58.5% Patients with HIV-1 RNA<50 copies/mL, % 50 50.9% 40 30 20 10 0 0 8 16 24 32 40 48 Time, weeks Women (ITT-LOVR), N 287 287 287 287 287 287 287 Women (TLOVR-non-VF), n 266 252 244 236 222 212 200 Men (ITT-LOVR), N 142 142 142 142 142 142 142 Men (TLOVR-non-VF), n 136 132 131 128 122 117 113 The 95% CI crossed zero for both ITT and non-VF censored analyses; The 95% CI only included 15% in the ITT–TLOVR analysis Currier J, et al. Ann Intern Med. 2010;153:349–57 48

  45. ARVs, women and adverse events • Different adverse event profiles between women and men1,2 • Rates similar but the events differ1 • Women with nausea, men with diarrhea3 • Discontinuation rates are consistently higher in women compared to men clinical trials3‒7 • Discontinuation in randomised controlled trials due to pregnancy 1. Tedaldi E et al. JAIDS. 2008; 47:441–8; 2. Ofotokun I. Top HIV Infect. 2005; 13:79–83; 3. Squires K et al. J Antimicrob Chemother. 2011; 66:363–70; 4.Murri R et al. JAIDS. 2003; 34:184–90; 5. Spire B et al. AIDS Care. 2004; 16:558–64; 6. Currier J et al. Ann Intern Med. 2010; 153:349–57; 7. Pirkle CM et al. HIV Med. 2009; 10:152–6

  46. UK cohort: clinical outcomes Barber TJ et al. Antivir Ther. 2011; 16(6):805–14. Time to first treatment modification Women were more likely than men to discontinue treatment for reasons other than virologic failure Adjusted relative hazard (men vs. women): 0.72 [0.63, 0.83]

  47. A Meta-Analysis Evaluating the Effects of Body Mass Index on Efficacy, Safety and Tolerability of LPV/r in Women from 7 Randomised Clinical Trials through 48 weeks of Treatment Hermes el al 2nd International Workshop HIV & Women Bethesda Jan 2012

  48. Subjects meeting meta-analysis criteria Total Subjects N= 2022 Total Women W = 492 Women with BMI data N=485 BMI <25 n=258 25 < BMI <30 N=130 BMI >30 N=97

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