Understanding Risk Factors for HIV-1 Infectiousness and Transmission

Understanding Risk Factors for HIV-1 Infectiousness and Transmission

Author: Erin M. Kahle

Publisher:

Published: 2013

Total Pages: 119

ISBN-13:

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The studies described in this dissertation focus on clinical and biologic factors associated with increased HIV-1 infectiousness among heterosexual HIV-1 serodiscordant couples. The specific aims include 1) evaluating whether specific characteristics of HIV-1 serodiscordant couples could be used to defined a higher-risk subgroup for targeted prevention research, 2) assessing the prevalence of unreported antiretroviral therapy (ART) in HIV-1 infected participants enrolling in an HIV-1 prevention trial, 3) determining whether HIV-1 subtype C is associated with increased HIV-1 transmission, and 4) assessing whether immune activation is associated with increased HIV-1 transmission. The identification of a composite set of predictors for HIV-1 transmission is applicable to the design of efficient prevention programs targeting high-risk subpopulations to maximize limited prevention resources. We developed a risk score for identifying a high-risk subpopulation of HIV-1 serodiscordant couples which will provide greater predictive ability in identifying HIV-1 transmission risk than individual risk predictors (i.e. viral load, unprotected sex). A well-developed and validated risk scoring tool, such as ours, is a valuable addition to HIV-1 prevention intervention research in order to reduce sample size, decrease cost of study and provide more efficient recruitment. Biologic factors, including both viral and host characteristics, may be associated with increased HIV-1 infectiousness. HIV-1 subtype, specifically subtype C, has been suggested as a factor in differential HIV-1 transmission between populations, although no epidemiologic evidence supports this conclusion. We compared HIV-1 subtype C and non-C subtypes and found no significant difference in risk of HIV-1 transmission in a multinational population in sub-Saharan Africa. In an analysis of cytokines as markers for immune activation, we found elevated IL-10 and IP-10 concentrations to be associated with increased HIV-1 transmission and acquisition, suggesting a potential biologic mechanism in both HIV-1 infected and susceptible partners. HIV-1 serodiscordant couples cohorts offer unique opportunities to assess correlates of HIV-1 infectiousness, as transmissions can be directly measured within partnerships. The application of our study findings will provide more efficient methods for identifying target populations and a better understanding of the virologic and immunologic mechanisms of HIV-1 infectiousness.


Individual and Couple-level Risk Factors Associated with HIV Transmission, Family Planning, and ART Initiation in an Open Cohort of Heterosexual HIV-1 Serodiscordant Couples in Rwanda

Individual and Couple-level Risk Factors Associated with HIV Transmission, Family Planning, and ART Initiation in an Open Cohort of Heterosexual HIV-1 Serodiscordant Couples in Rwanda

Author: Megan Claire Dillavou

Publisher:

Published: 2016

Total Pages: 108

ISBN-13:

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Understanding the factors of heterosexual HIV-1 serodiscordant couples that lead to risky behaviors for HIV transmission are essential in controlling the HIV epidemic in sub-Saharan Africa. Predictors of HIV transmission within stable discordant couples and trends in family planning over time, as well as predictors of ART initiation provide important information for future studies and prevention and treatment program development. This dissertation evaluates these aspects of HIV-1 serodiscordant couple transmission in an ART naive 10-year observational cohort in Kigali, Rwanda. The first study evaluated the incident HIV-1 infections and the predictors of HIV-1 transmission in ART na?ve HIV-1 heterosexual serodiscordant couples. Eighty-three partner linked incident HIV-1 infections occurred in the cohort with 37 in women (IR=2.2/100 CY; 95%CI: 1.53.299) and 46 in men (IR=2.49/100 CY; 95%CI: 1.83-3.33). In the adjusted final model of linked HIV infection in females, baseline VL (aHR 2.33; 95%CI: 1.28-4.24), female genital inflammation (cHR 4.77; 95%CI: 1.72-13.21), and having unprotected sex with study partner since last visit (cHR 3.29; 95%CI: 1.27-8.51) were significant predictors. Predictors of linked incident HIV-1 infection in males included baseline VL (aHR 2.14; 95%CI: 1.50-3.07), female genital inflammation (aHR 3.91; 95%CI: 1.71-8.94), any unprotected sex with study partner since previous visit (aHR 3.56; 95%CI: 1.48-8.56), and presence of sperm on a wet prep (aHR 3.35; 95%CI: 0.99-11.36). These findings support the need to include sexual partners in the assessment of risk and target risk reduction strategies. The second study described pregnancy and analyzed predictors of women ever using hormonal contraception (HC) by HIV status. Overall pregnancy incidence rate was 12.7/100 PY (95%CI: 11.3-14.1) while in M-F+ couples it was 13.2/100 PY (95%CI: 11.3-15.3) and 12.1/100 PY (95%CI: 10.2-14.1) in M+F- couples. 34% of HIV positive women, 26% of HIV- women who did not seroconvert, and 25% of HIV- women who seroconverted had used hormonal contraception at point during the study. In adjusted analyses, being younger (aRR 0.97; 95%CI: 0.95-0.99), ability to read Kinyarwandan easily (aRR 1.28; 95%CI: 1.06-1.55), and no STI in the past year (aRR 0.80; 95%CI: 0.67-0.95) was associated with ever HC use in HIV+ women. Among HIV negative women who did not seroconvert, HC ever use was associated with younger age (aRR 0.98; 95%CI: 0.96-1.0) and not being pregnant at baseline (aRR 0.72; 95%CI: 0.55-0.94). Across HIV groups, injectable methods were the most frequently used type of hormonal contraception at last visit and during most of study follow-up. The overall low uptake of hormonal contraception and high pregnancy rates in both HIV + and HIV- women suggest the need for more effective and widely accessible safer conception methods. The third study evaluated predictors of time to ART initiation, stratified by gender of seropositive partner. Of the 1837 couples (882 M+F- / 955 M-F+), 30% had an HIV positive partner initiate ART. Of those, 39% had a seropositive male partner (M+F-) and 61% had a seropositive female partner (M-F+). Shorter time to ART initiation in M+F- couples was predicted by baseline viral load (aHR1.54; 95%CI:1.01-2.34), while both baseline viral load (aHR1.43; 95%CI:1.02-2.02) and baseline WHO stage IV (aHR 4.85; 95%CI:1.45-16.26) predicted earlier time to ART initiation in M-F+ couples. As expected, clinical values were the main predictors of time to ART initiation. In conclusion, partner and partnership characteristics play an important in risk of HIV-1 acquisition and transmission in heterosexual serodiscordant couples. Family planning and fertility desires are particularly complex and important risk factors that may change over time for serodiscordant couples. These findings can help improve the targeted HIV prevention, safer conception and family planning services, and ART treatment programs focusing on sustained viral load suppression among heterosexual serodiscordant couples in Africa.


Evaluating Individual and Couple-level Risk Factors Associated with HIV Acquisition in HIV Serodiscordant Couples in Zambia: Alcohol Use, Fertility Desire, and HIV Acquisition from Outside Partners in an Open Cohort in Zambia

Evaluating Individual and Couple-level Risk Factors Associated with HIV Acquisition in HIV Serodiscordant Couples in Zambia: Alcohol Use, Fertility Desire, and HIV Acquisition from Outside Partners in an Open Cohort in Zambia

Author: Dvora Leah Davey

Publisher:

Published: 2016

Total Pages: 93

ISBN-13:

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The high prevalence of serodiscordant relationships coupled with the high risk of transmission within those relationships across sub-Saharan African countries makes these couples a target for HIV prevention efforts. The development of appropriate and effective interventions for HIV prevention in serodiscordant couples must be based on accurate assessments of sexual risk behaviors, substance use, and fertility desires. My dissertation evaluates HIV acquisition and transmission in heterosexual HIV serodiscordant couples in Lusaka, Zambia. My first study analyzed the role that alcohol use plays on sexual behavior and HIV acquisition in Zambian serodiscordant couples. Men who reported heavy drinking was associated with increased odds of having =>1 outside sexual partnership (adjusted odds ratio [aOR]=2.02; 95% CI=1.58, 2.57), and condomless sex with main partner in the past 3-months (aOR=1.61; 95% CI=1.28, 2.04). Women's heavy drinking was associated with increased odds of having =>1 outside partner (aOR=1.89, 95% CI=1.35, 2.64), and condomless sex with main partner in past 3-months (aOR=1.54; 95% CI=1.31, 1.82). Women who reported being drunk daily or almost daily was associated with increased HIV acquisition (aHR=3.71; 95% CI=0.90, 15.25). Men who reported being drunk weekly or daily/almost daily was associated with increased HIV acquisition (aHR=1.72; 95% CI= 1.01, 2.93), and transmission (aHR=1.42; 95% CI=0.97, 2.10). My second study evaluated the incidence and predictors of HIV acquisition from an outside partner in serodiscordant couples in Zambia. Forty-five unlinked HIV infections occurred among women (1.85 per 100-couple-years [CY]) and 55 unlinked HIV infections occurred among men (1.82 per 100 CY). Risk of female unlinked infection was associated with baseline female alcohol consumption (aHR=5.44; 95% CI: 1.03, 28.73), recent genital ulcers and/or genital inflammation (aHR=6.09; 95% CI: 2.72, 13.64 and aHR=11.92; 95% CI: 5.60, 25.37, respectively). Risk of male unlinked HIV infection was associated with reporting being drunk weekly or daily/almost daily at baseline (aHR=3.52; 95% CI=1.19, 10.46), recent genital inflammation (aHR=8.52; 95% CI: 3.82, 19.03), genital ulceration (aHR=4.27; 95% CI: 2.05, 8.89), self-reporting =>1 outside partner (aHR=3.36; 95% CI: 1.53, 7.37). My third study evaluated the effect of fertility desires on HIV acquisition among HIV serodiscordant couples in Zambia. Among a sub-set of 1,029 serodiscordant couples, 311 agreed that they wanted a child in the future (30.4%), and 368 agreed they did not want a child or did not know (36.0%), and 344 couples disagreed about having a child (33.6%), of which in 212 couples (61.6% of disagreeing couples) the man wanted a child but the woman did not, and in 132 couples (38.3% of disagreeing couples) the woman wanted a child but the man did not. The adjusted risk ratio for woman's HIV acquisition was 2.06 (95% CI=1.40, 3.03) among women who wanted a child, 1.75 (95% CI=1.07, 2.87) for men who wanted a child in the next 12-months, and 2.55 (95% CI=1.32, 4.93) among couples who agreed that they wanted a child compared to couples who agreed they did not want a child. In conclusion, heavy alcohol use plays an important role in linked and unlinked HIV acquisition and transmission in serodiscordant couples. The strongest predictors of unlinked infection in serodiscordant relationships were alcohol use, genital inflammation and ulceration prior to infection. Further, women were particularly vulnerable when they or their partner wanted to have a child. These findings will help improve the implementation of HIV prevention and safer conception services among heterosexual serodiscordant couples in Southern Africa and beyond.


Cross-Cultural Perspectives on Couples with Mixed HIV Status: Beyond Positive/Negative

Cross-Cultural Perspectives on Couples with Mixed HIV Status: Beyond Positive/Negative

Author: Asha Persson

Publisher: Springer

Published: 2016-10-24

Total Pages: 285

ISBN-13: 3319427253

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This edited volume presents a detailed portrait of couples living with mixed HIV status, where one partner is HIV-positive and the other negative. Readers will come to understand the various and complex ways in which these mixed-status, or serodiscordant couples build a life together within the shadow of HIV-related stigma. Spanning the globe, coverage explores serodiscordance as a negotiated practice and process, inseparable from the social context in which it is situated. The book shows how couples draw on diverse and sometimes contradictory cultural discourses of medicine, romance, and “normality” to make sense of and manage their mixed HIV status and any perceived risks, not uncommonly in ways that depart from prevailing HIV prevention messages. Throughout, compelling personal stories accompany the empirical research, sharing the firsthand experiences of men and women in serodiscordant relationships. Bringing together research from diverse disciplines and geographical regions, this book contributes important insights for future HIV health promotion as well as offers new knowledge to scholarship on the cultural intersections of illness and intimacy. It will appeal to a broad audience working across the fields of HIV, health, gender, sexuality, development, and human rights.


Heterosexual Transmission of AIDS

Heterosexual Transmission of AIDS

Author: Contraceptive Research and Development Program. International Workshop

Publisher: Wiley-Liss

Published: 1990-03-19

Total Pages: 464

ISBN-13:

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Since the HIV virus was first identified as the cause of AIDS, basic research and epidemiological data have accumulated dramatically and rapidly. Yet, with all that is known about the virus, surprisingly little is known about precisely how it is actually transmitted. Focusing on the sexual transmission, prevention, and control of the HIV virus in heterosexuals, Heterosexual Transmission of AIDS examines the sexual mechanisms of transmission, including HIV interactions with sperm, semen, and cervical and vaginal secretions. Exploring the principle risk factors in heterosexual transmission of HIV, the book offers authoritative information on routes of transmission and discusses the impact of specific contraceptive methods in controlling the spread of the disease. Includes an overview of the biology of retroviruses and their pathogenicity and describes animal models for investigating HIV infection mechanisms and transmission prevention.


Disease Control Priorities, Third Edition (Volume 6)

Disease Control Priorities, Third Edition (Volume 6)

Author: King K. Holmes

Publisher: World Bank Publications

Published: 2017-11-06

Total Pages: 1027

ISBN-13: 1464805253

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Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases. The volume emphasizes the need to effectively address emerging antimicrobial resistance, strengthen health systems, and increase access to care. The attainable goals are to reduce incidence, develop innovative approaches, and optimize existing tools in resource-constrained settings.


Modeling the AIDS Epidemic

Modeling the AIDS Epidemic

Author: Margaret L. Brandeau

Publisher: Raven Press (ID)

Published: 1994

Total Pages: 664

ISBN-13:

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Emerging from the 34th Joint National Meeting of the Operations Research Society of America and The Institute of Management Sciences, held in San Francisco, November 1992, this volume presents AIDS modeling research that can directly or indirectly improve decision making for planning, resource allocation, and public health policy. The volume is divided into four sections: AIDS policy modeling; models for AIDS backcasting and forecasting; modeling infectivity and disease progression; and modeling the social organization of risky behavior. Annotation copyright by Book News, Inc., Portland, OR