HIV in in Women Women

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HIV in Women Susan L. Koletar, MD The Ohio State University

How Many of These Women Have HIV? Answer: I don t really know Google Search: Photos of Groups of Women

Pub Med Search: HIV and Women 22,732 Results First reports 1983 focused on women as sexual partners Current publications: focus on MTCT; impact of other STDs/HPV drug regimens socioeconomic issues risk reduction strategies

Global Summary of the HIV/AIDS Epidemic Estimated Number of people living with HIV in 2009 Total Adults Women Children under 15 years 33.3 million [31.4 35.3 million] 30.8 million [29.2 32.6 million] 15.9 million [14.8 17.2 million] 2.5 million [1.6 3.4 million]

Global Summary of the HIV/AIDS Epidemic Estimated Number of people living with HIV in 2009 Total Adults Women Children under 15 years 33.3 million [31.4 35.3 million] 30.8 million [29.2 32.6 million] 15.9 million [14.8 17.2 million] 2.5 million [1.6 3.4 million]

HIV Prevalence in Women in Rural Vulindlela, South Africa Age Group (Years) HIV Prevalence (n=1237) <16 10.6% 17-18 21.3% 19-20 33.0% 21-22 22 44.3% 23-24 51.1% Abdool Karim Q, et al. AIDS 2010. Abstract TUSS0202

Young women aged 25 to 44 accounted for the majority of new HIV infections among women in 2010 in the U.S.

Risk Factors for HIV Infection in Young Women Anatomic/biologic vulnerability and sexually transmitted disease Lack of awareness Lack of recognition of partner s risk factors Feelings of less power in relationships Substance abuse Sexual abuse Socioeconomic issues Racial/ethnic differences

HIV Risks/Behaviors in Individuals >50 years Despite myths and stereotypes, older individuals remain sexually active. The availability of drugs for erectile dysfunction increases sexual activity. Compared to individuals in their 20 s, 50+ year olds are: 1/6 as likely to use condoms 1/5 as likely to have been tested for HIV Postmenopausal women may be at increased risk due to increased likelihood of thinning and dryness of vaginal mucosa.

Typical Course of Untreated HIV Infection PCP, KS, MAC, CMV & others

Characteristics and Specific Issues Relevant to HIV-Infected Infected Women

EuroSIDA: No Gender Differences in Outcomes on HAART Prospective cohort study 2547 treatment-naive patients (Male: 2036; Female: 511) Median HAART start date 1997 (range: 1995 2000) Virologic, immunologic, and clinical response to HAART No significant gender differences were found HIV RNA <500 copies/ml Outcome (% patients) All Men Women 89 89 88 Viral rebound 33 31 40 CD4 rise 83 84 80 100 cells/mm 3 AIDS 8 8 7 Death 5 5 5 Moore AL, et al. J Acquir Immune Defic Syndr. 2003;32:452 461.

Bone Loss Prospective study in HIV+ and HIV- women matched for age, BMI, race (2000 2003) 1 HIV+ women 1 >50% had osteopenia at the hip or spine 2.5 times as likely to have bone loss as HIV- women Bone density correlated with body weight Bone loss did not correlate to use of ART Incidence (%) 1 HIV+ (n=84) HIV- (n=63) Osteopenia Lumbar spine 28 14 Femoral neck 33 17 Hip total 27 8 Hip or spine 54 30 Osteoporosis Lumbar spine 6 5 Femoral neck 0 2 Hip total 1 0 Hip or spine 10 5 Risk factors for osteoporosis/osteopenia included low free testosterone, low weight, and oligomenorrhea. 2 1. Dolan S, et al. AIDS. 2004;18:475 483; 2. Dolan S, et al. 14th CROI (2007); Poster 777.

Stress, Depression, and Anxiety HIV+ Women Compared with HIV+ Men Mean Sc cores for Ps sychologic cal Well-be eing 10 9 8 7 6 5 4 3 2 1 0 P <0.001001 P <0.0101 P <0.01 P <0.05 Stress Depression Anxiety Family/Friends Emotional Support P <0.05 Partner Emotional Support HIV+ Men (n=307) HIV+ Women (n=102) Gordillo V, et al. J Behav Med. Published online June 19, 2009.

HIV+ Women Were More Likely to Have Financial Problems obe and Experience e Discrimination ato Compared With HIV+ Men (N=409) Percenta age of pat tients 100 90 80 70 60 50 40 30 20 10 0 P <0.001 P <0.001 P <0.01 Employed Financial Problems Experienced Discrimination HIV+ Men (n=307) HIV+ Women (n=102) Gordillo V, et al. J Behav Med. Published online June 19, 2009.

Trends in Standardized Incident Rates of AIDS-Defining and Non-AIDS Cancers Patel et al. Ann Int Med 2008 148:728

Recommendations for Routine Screening and Care Testing Recommended by CDC 1 : All patients aged 13-64 years of age should receive an HIV test as part of routine healthcare Individuals considered high risk for HIV infection should be tested annually All pregnant women should be screened for HIV infection All HIV+ women of childbearing potential should be offered preconception counseling and care as a component of routine primary medical care 2 Annual cervical cancer screening is recommended for HIV+ women 3 1 Branson BM, et al. MMWR. 2006;55:1-17. 2 Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services December 2013. 3. American Cancer Society Guidelines for the Early Detection of Cancer. www.cancer.org.

Treatment

Currently Available Antiretroviral Medications NRTI Abacavir (ABC) Didanosine (ddi) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4t) Tenofovir (TDF) Zidovudine (AZT) NNRTI Delavirdine ea e( (DLV) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RLP) PI Integrase Inhibitor (II) Atazanavir (ATV) Raltegravir (RAL) Darunavir au a (DRV) [elvitegravir (EVT)] Fosamprenavir (FPV) Fusion Inhibitor Indinavir (IDV) Enfuvirtide (ENF, T-20) Lopinavir (LPV) CCR5 Antagonist Nelfinavir (NFV) Maraviroc (MVC) Ritonavir (RTV) Saquinavir (SQV) Fixed Dose Combinations Tipranavir (TPV) TDF/FTC/EFV (Atripla) TDF/FTC/RLP (Complera) TDF/FTC/EVT/cbc (Stribild)

Treatment as Prevention

PACTG 076 & USPHS ZDV Recs CDC Recommends Routine HIV screening

Partners PrEP Study: Serodiscordant Heterosexual Couples Double-Blind Randomization 1:1 Tenofovir DF qd (n=1584) Phase 3, Double-Blind Study Kenya, Uganda Serodiscordant, heterosexual couples (n=4758) (HIV-positive partner not yet eligible for ART) Primary Endpoints HIV infection in HIV-negative partner Safety l ( 4758) Emtricitabine/Tenofovir DF qd (n=1579) Normal liver, renal, hematologic values/function Follow-Up Up to 36 months (median 23 months; 7830 person-years) Placebo (n=1584) All patients received comprehensive HIV prevention services. 26 Baeten J, et a. N Engl J Med. 2012;367:399-410. Murnane P, et al. 20 th CROI. Atlanta, 2013. Abstract 1000.

Partners PrEP Study: Subsets of High-Risk Women HIV Incidence HIV In ncidence (per 100-p person-yea ars) 6.5 75% 74% Reduction Reduction (P=0.03) (P=0.037) 1.60 1.60 5.49 84% Reduction (P=0.016) 016) 72% Reduction (P=0.027) 1.7 Placebo Tenofovir DF Emtricitabine/tenofovir DF 4.6 79% Reduction (P=0.043) 78% Reduction (P=0.046) 090 0.90 0.8 09 0.9 Unprotected Sex Prior 3 Months (n=329/314/319) Partner HIV RNA >50K Copies/mL (n=154/144/146) Male Partner >10 Years Older (n=143/149/136) 27 Murnane P, et al. 20 th CROI. Atlanta, 2013. Abstract 1000.

Prevention Hopes for the Future Effective microbicide(s) Effective vaccine(s)

Very Early Triple-Drug ART Elicits Functional Cure in HIV-Infected I Child Infant born to untreated HIV-infected mother at 35 wks gestation via spontaneous vaginal delivery [1] Maternal HIV infection identified during labor via ELISA and Western blot Infant HIV infection confirmed via HIV-1 DNA PCR, HIV-1 RNA analysis of 2 separate samples at 30 and 31 hrs of age [2] ZDV/3TC + NVP (at therapeutic ti dose) initiated iti t at 31 hrs of age, continued for 7 days ZDV/3TC + LPV/RTV continued from 7 days to 18 mos of age HIV-1 RNA undetectable by Day 30 Mother removed patient from care at 18 mos of age 1. Persaud D, et al. CROI 2013. Abstract 48LB. 2. DHHS Pediatric Guidelines. 2012.

Functional Cure Child: Standard HIV-1 Assays Undetectable to Age 26 Mos ART regimens: ZDV/3TC + NVP Assessments at Mos 24 and 26 (31 hours 7 days) Western blot negative ZDV/3TC + LPV/RTV (7 days No HIV-specific CD8+ or CD4+ 18 months) T-cell responses Plasma VL on ART displayed typical biphasic decay from baseline VL 19,812 c/ml VL undetectable by < 30d of age VL remained undetectable though > 80d of age Persaud D, et al. CROI 2013. Abstract 48LB. Standard HIV-1 RNA and HIV-1 DNA undetectable By ultrasensitive assays Mo 24: HIV-1 RNA 1 c/ml; HIV-1 DNA < 2.7 c/million PBMCs Mo 26: HIV-1 DNA 4 c/million PBMCs Clinical trials of exposed infants treated with ART recommended