Infection with subtype C HIV-1 of lower replicative fitness as compared to subtypes A and D leads to slower disease progression in Zimbabwean and Ugandan.

Slides:

Advertisements

Similar presentations

Using longitudinal, population-based HIV surveillance to measure the real-world impacts of ART scale-up in KwaZulu- Natal, South Africa Frank Tanser Presentation.

Advertisements

1 Effect of Maternal HAART on Postnatal HIV-1 Transmission after Cessation of Extended Infant Antiretroviral Prophylaxis Taha Taha 1, Johnstone Kumwenda.

Monica Gandhi MD, MPH Associate Professor and Women’s HIV Clinic provider, HIV/AIDS Division San Francisco General Hospital/ UCSF Safe Poz Love, U.S. Positive.

The hidden HIV epidemic: what do mathematical models tell us? The case of France Virginie Supervie, Jacques Ndawinz & Dominique Costagliola U943 Inserm.

Association between STI/RTI infections and the risk of altered innate immunity protein levels among hormonal contraception users Harvard Medical School.

Virologic and immunologic response following antiretroviral therapy initiation among pregnant and postpartum women with acute HIV-1 infection: MOPDB0101.

HIV Disease in Older Patients Donna M. Gallagher, ANP The International AIDS Society–USA DM Gallagher, ANP. Presented at IAS–USA/RWCA Clinical Conference,

Predictors of HIV Transmission Risk among Patients in Care: Results from the SPNS Prevention with Positives Initiative Stephen F. Morin, PhD Principal.

A Prospective Cohort Study on the effects of Hormonal Contraception on the Natural History of HIV disease among women in Nairobi and Harare Collaborating.

Materials and Methods Abstract Conclusions Introduction 1. Korber B, et al. Br Med Bull 2001; 58: Rambaut A, et al. Nat. Rev. Genet. 2004; 5:

Module 1: Overview of HIV Infection. Lab workersHealth workersCounselors 2 Learning Objectives At the end of this module, you will be able to: Describe.

Patients in routine HIV clinical care at-risk for potentially transmitting HIV in the “test and treat” era of HIV prevention Crane, HM, Mimiaga, M, Feldman,

HIV-1 DNA levels after antiretroviral therapy in primary infection predict disease progression: the SPARTAC Trial James Williams 1,2,3, Jacob Hurst 1,2,3,

DNA methylation as an epigenetic marker in HIV-2 disease in West Africa? Alberta Davis MRC Laboratories, Gambia 18th January 2013.

Presenter : Dr T. G. Nematadzira on behalf of The IMPAACT PROMISE 1077BF/1077FF Team Efficacy and Safety of Two Strategies to Prevent Perinatal HIV Transmission.

Inputs to a case-based HIV surveillance system. Objectives  Review HIV case definitions  Understand clinical and immunologic staging  Identify the.

Biology and natural history of the virus

Perceived HIV risks, types of sexually transmitted diseases, and discordant infection status among low-tier female sex workers in China (Roundtable Presentation)

Abstract Results Objectives Results Conclusions Background Methods V-1637 Background-At the CORE center in Chicago, despite an on-site hepatitis clinic.

Reproductive Health Needs of Men and Women Enrolled in HIV Care and Treatment Services Elaine Abrams August 12, 2008 Track 1.0 Meeting.

AIDS supplement. History of HIV Originated in Africa in the late 1950’s Originally found in nonhuman primates and may have mutated First documented in.

The Influence of CCL3L1 Gene- Containing Segmental Duplications on HIV-1/AIDS Susceptibility Gonzalez et al. Mar 4, 2005 :307 Science Presenter: Braydon.

The Effect of Syphilis Co-infection on Clinical Outcomes in HIV-Infected Persons The Effect of Syphilis Co-infection on Clinical Outcomes in HIV-Infected.

Phylogenetic Insight into HIV Transmission Networks in a Southeastern US Cohort Ann Dennis 1, Stéphane Hué 2, Christopher Hurt 1, Sonia Napravnik 1, Deenan.

HIV-1 evolution in response to immune selection pressures

Population-based impact of ART in high HIV prevalence settings Marie-Louise Newell Professor of Global Health Faculty of Medicine, Faculty of Social and.

Examining Subjects of HIV-1 With Possible Predominant Viral Strains Samantha Hurndon Isaiah Castaneda.

HIV/renal studies (CHIC) Baseline renal function as predictor of HIV/renal disease progression –Death, opportunistic infection –Severe chronic kidney disease.

Edward Mills PhD, Associate Professor, Faculty of Health Sciences University of Ottawa AIDS Mortality Among Men in Africa: An overview of the evidence.

Ad5 expressing Gag, Pol and Nef Immune responses in control of HIV replication non-human primates // SIV extrapolated to humans // HIV Prospects for.

TREATMENT OF SERO-DISCORDANT COUPLES: IMPLICATIONS FOR YOUNG PEOPLE JJ KUMWENDA (FRCP-UK)

AIDS Epidemic Update December /06 e. AIDS Epidemic Update December /06 e TOTAL North America Eastern Europe & Central Asia Latin America.

Phenotypic properties influencing HIV-1 transmission fitness IAS Conference on HIV Pathogenesis, Treatment & Prevention Vancouver July 21 st 2015 Katja.

Kow-Tong Chen, M.D., Ph.D., Hsiao-Ling Chang, Ph.D., Chu-Tzu Chen, M.P.H., and Ying-An Chen, M.P.H. Volume 23, Number 3, 2009 AIDS PATIENT CARE and STDs.

HIV and STI Department, Health Protection Agency - Colindale HIV and AIDS Reporting System The threshold for an ART secondary prevention effect on HIV.

Alison Drake International AIDS Society Conference July 18, 2011 Valacyclovir suppression reduces breast milk and plasma HIV-1 RNA postpartum: results.

Prevalence and risk factors for self-reported sexually transmitted infections among adults in the Diepsloot informal settlement, Johannesburg, South Africa.

Mean HIV viral load among resident cases and undiagnosed in Oregon Jeff Capizzi, Epidemiologist Sean Schafer, HIV/STD/TB Medical Epidemiologist Lea Bush,

Can early antiretroviral therapy fully restore health? Workshop on Pathogeneses and Management of Long-Term Complications of ART IAS Conference, Rome July.

Human Immune Deficiency Virus Infection Dr Huda Taha Sep 2015.

Conclusions Materials and Methods Background Objectives HIV-1 RNA is the most significant determinant of cervical HIV-1 shedding. Shedding has also been.

Where services are needed The number of women and girls who were newly infected with HIV in Note: For Botswana and Zimbabwe, the number of women.

HIV and AIDS Data Hub for Asia-Pacific HIV and AIDS Data Hub for Asia-Pacific Review in slides Thailand.

Serologic markers and molecular epidemiology of HBV from an HIV infected cohort from Cameroon Tshifhiwa Magoro 1, Emmaculate Nongpang 2, Lufuno Mavhandu.

Effect of ART on malaria parasitaemia and clinical episodes in adults in rural Uganda: A population-based cohort study Billy N. Mayanja 1, Kathy Baisley.

HIV Prevalence and Incidence Estimates Among Women with High Risk Indicators in Addis Ababa, Ethiopia Asfawesen G-Yohanes 1, Stephanie Combes 2, Abraham.

Herpes Simplex Virus Type 2 infection among U.S. military service members: Public Health Implications and Opportunities for HIV Prevention Christian T.

Impact of immune-driven sequence variation in HIV- 1 subtype C Gag-protease on viral fitness and clinical outcome Thumbi Ndung’u, BVM, PhD HIV Pathogenesis.

HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Slideset on: Hecht FM, Wang L, Collier A, et al. A.

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection The INSIGHT START Study Group Ben Andres Oct 15, 2015.

Do Adolescents Equally Utilize PMTCT Services as Adult Women? Data from Patient Tracking Database in Zimbabwe 18 th ICASA, Harare 3 December 2015 Reuben.

Provider Initiated HIV Counseling and Testing Unit 1: Introduction to HIV/AIDS.

Effects of Alcohol and Crack Cocaine Use on Virological and Immunological Disease Progression in a Cohort of U.S. Women with HIV/AIDS Judith A. Cook, Ph.D.

Mycoplasma genitalium and risk of HIV acquisition among women in Zimbabwe Sue Napierala 1, Barbara Van Der Pol 2, Cynthia Kwok 3, Helen Weiss 1, Tsungai.

04/19/ Projected effectiveness of mass HIV vaccination with multi-dose regimens to be tested in South Africa Peter Gilbert Dobromir Dimitrov Christian.

Boston University Slideshow Title Goes Here Eliminating CD4 thresholds in South Africa will not lead to large increases in persons receiving ART without.

ART was initiated when indicated by WHO and national guidelines

Overview of the trends in reducing HIV transmission and incidence

EVALUATING STABILIZATION TUBES FOR STORAGE OF CD4 HIV POSITIVE SAMPLES AT KILIFI DISTRICT HOSPITAL, KENYA Nella Raphael Kalama.

Acceptability of early HIV treatment among South Africa women N Garrett, E Norman, V Asari, N Naicker, N Majola, K Leask, Q Abdool Karim and SS Abdool.

STIs and susceptibility to HIV infection

Conclusions & Implications

Introduction Results Objectives Methods Conclusion Funding

AIDS supplement.

Meningitis Surveillance and investigation of causes of altered mental status among Kamuzu Central Hospital admissions, Lilongwe, Malawi Charles Kyriakos.

Co-infection of STIs with HIV among men who have sex with men (MSM) in Beijing, China Xiaoyan Zhang State Key Laboratory for Infectious Disease Prevention.

Engagement in methadone maintenance therapy associated with less time with plasma HIV-1 RNA viral load above 1500 copies/mL among a cohort of HIV-positive.

Predicting the Onset of AIDS

Andreas D. Haas, PhD Postdoctoral fellow, ICAP at Columbia University

MSM Attending STD Clinics HIV Testing More Frequently: Implications for HIV Prevention and Surveillance D Helms1, H Weinstock1, K Mahle1, A Shahkolahi1,2,

Presentation transcript:

Infection with subtype C HIV-1 of lower replicative fitness as compared to subtypes A and D leads to slower disease progression in Zimbabwean and Ugandan women Overview HIV-1 diversity in global epidemicOverview HIV-1 diversity in global epidemic Compare the replicative fitness of HIV-1 subtype A, C, and DCompare the replicative fitness of HIV-1 subtype A, C, and D Determine if disease progression differs among subtypes in a natural history cohortDetermine if disease progression differs among subtypes in a natural history cohort

x Gao et al., Nature, 1999 Santiago et al., Science, 2002 Corbet, J Virol, 2000 Foley & Korber HIV Database, LANL 50% 35% ~15-25% Diversity of primate lentiviruses

HIV-1 subtype and recombinant prevalence in the world Subtype C is dominating the epidemic

Has HIV-1 subtype C prevalence increased over time as compared to other HIV-1 subtypes in regional epidemics? Vidal et al J. AIDS Rainwater et al ARHR Li et al Li et al Zhonghua Liu Xing. Bing. Xue. Za Zhi Li et al ARHR Infected population based WHO/UNAIDS reports Soares et al AIDS Van Harmelen et al ARHR

Is there a difference between subtype fitness?

Measurement of viral fitness Ball et al, 2003 Relative fitness: virus production in dual infection/proportion in the inoculum Fitness difference: ratio of relative fitness values = More fit/less fit

B vs. B C vs. C Paired T test, p > 0.5 Y axis wins X axis wins Ball et al., J. Virol C vs. B Paired T test, p < B wins C wins No significant differences in intrasubtype B or C fitness Subtype C NSI/R5 HIV-1 are less fit than subtype B NSI/R5 HIV-1

C wins A, B, or D wins Competitions between: NSI/R5 primary HIV-1 isolates of subtypes A, B, C, and D SI/X4 primary HIV-1 isolates of subtypes A, B, C, and D Subtype C isolates are less fit than any other group M isolates, regardless of subtype Possible order in group M fitness: B = D > A >> C

How does subtype C fitness relate with other human lentiviruses?

Do HIV-1 subtype C infected individuals showed different rates of disease progression than those infected with subtype A or D? Newly infected HIV-1 women were enrolled from a cohort of 4,439 women from family planning sites from Uganda and Zimbabwe evaluating the effect of hormonal contraception on HIV-1 acquisition (quarterly HIV-1 testing) This analyses includes women recruited within three months of infection (62 Ugandan and 88 Zimbabwean). This represents a sub-set analyses of the total 275 recruited HIV-1 infected women.

Based on this slope of CD4 cell decline and a starting CD4 cell count of 680/ml for Uganda and 520/ml for Zimbabwe, a y intercept of 200 CD4 cells/ml would require: A mean of 8 yrs for progression to AIDS in Ugandan women 20 yrs in Zimbabwean women Analyses of CD4 cell decline following acute/early HIV-1 infection in Ugandan and Zimbabwean women

Mean and slope of CD4 cells per week 1 VariableNo. of women/Total N (%) No. of visits/Total N (%) Mean CD4 cells (95% CI) Slope of CD4 Cells (per week) (95% CI) Time-invariant variable Uganda62/150 (41.3)906/2048 (44.2) (629.90, )-1.09 (-1.35, -0.84) Zimbabwe88/150 (58.7)1142/2048 (55.8) (481.76, )-0.28 (-0.50, -0.06) < 25 years old at SV63/150 (42.0)851/2048 (41.6) (593.78, )-0.60 (-0.86, -0.34) ≤ 9 years education at HC Screening 76/150 (50.7)1054/2048 (51.5) (539.30, )-0.78 (-1.01, -0.55) HSV at SV128/146 (87.7)1746/2006 (87.0) (548.71, )-0.64 (-0.85, -0.43) HIV Subtype: A27/87 (31.0)423/1233 (34.3) (631.43, )-1.07 (-1.42, -0.72) C44/87 (50.6)571/1233 (46.3) (439.91, )-0.48 (-0.79, -0.16) D16/87 (18.4)239/1233 (19.4) (524.13, )-1.29 (-1.74, -0.84) 1 By GEE approach Following calculation of the CD4 decline slopes per patient and then measuring the mean (GEE approach), we estimate again that: Ugandan women will progress to AIDS in a mean of weeks or 8.0 yrs Zimbabwean women will progress to AIDS in a mean of weeks or 21.8 yrs p < p < 0.01

Conclusions Ex vivo observations Subtype C “stands alone” as a less fit subtype in PBMC competitions (regardless of the ethnic source of the PBMCs) Subtype C and other group M subtypes show similar fitness in Langerhan cells, a model for HIV-1 transmission In vivo observations Women, recruited at acute/early HIV-1 infection, progress more rapidly to AIDS in Uganda than in Zimbabwe as indicated by CD4 cell decline This slower progression is not associated with age, opportunistic infections, STDs, sexual habits, and other characterized parameters Preliminary data suggest that this difference is not associated with host genetics, e.g. co- receptor genetic polymorphisms Viral load set points and viral loads at 6 and 12 months were not significantly different in Uganda and Zimbabwean women (poster MOPE0275, Morrison et al.) The only predictor of slow disease progression was infection with HIV-1 subtype C. Is this related to low subtype C virulence?

Acknowledgements CWRU Immaculate Nankya Korey Demers Sarah Ball Andre Marozsan Dawn Moore Courtney Walker Eric Arts Robert Salata Makerere University/JCRC Francis Mmiro Roy D. Mugerwa Peter Mugyenyi Sandra Rwambuya Fred Kyeyune Stanley Bulime University of Washington Barbra Richardson FHCRC-SCHARP Peter Cornelisse UCSF Nancy Padian IUPUI Barbara van der Pol University of Zimbabwe Tsungai Chipato Marshall Munjoma Family Health International Charles Morrison Cynthia Kwok Pai-Lien Chen NICHD, NIH Joanne Luoto Patricia Reichelderfer The entire GS/VF/HC-HIV Study Team in Uganda, Zimbabwe, Thailand, and US