Harvard-Brazil Collaborative Public Health Field Course January 2014 Lecture # 8 Building specialized knowledge: HIV Aluisio Segurado Department of Infectious Diseases School of Medicine, University of São Paulo Outline Biological interactions Social aspects of the epidemic Programmatic actions Current challenges Outline Biological interactions Social aspects of the epidemic Programmatic actions Current challenges Page 1
Retroviruses MIP-1 MIP-1 M-tropic HIV isolate (R5) T-tropic HIV isolate (X4) RANTES CCR2 CD4 CCR5 CD4 CXCR4 SDF1 Macrophage CD4+ T cell Cytotropism Page 2
HIV transmission SEXUAL BLOOD-BORNE VERTICAL - intrauterum - birth - breast feeding HIV genital shedding - associated factors - higher HIV plasma viral load acute infection more advanced clinical status cervicitis/ urethritis HIV genital acquisition Hu J, 2000; Deeks S, 2011; Moir S, 2011 Page 3
Immune response in HIV acute infection viral setpoint HIV infection - Natural history Moir S, 2011 Early signs and symptoms of HIV disease -Prolonged fever -Weight loss - Chronic diarrhea Page 4
Pneumocystis pneumonia Tuberculosis Cytomegalovirus retinitis Page 5
HIV and cancer Outline Biological interactions Social aspects of the epidemic Programmatic actions Current challenges CUMULATIVE GLOBAL ESTIMATE (Dec 2012) People living with HIV New HIV infections (2011) AIDS deaths (2011) Cumulative AIDS deaths 35.3 million 2.3 million 1.6 million 43.9 million UNAIDS, 2013 Page 6
ADULTS AND CHILDREN LIVING WITH HIV (Dec 2012 - estimate) 1,300,000 250,000 1,500,000 860,000 1,300,000 880,000 260,000 3,900,000 25,000,000 51,000 UNAIDS, 2013 HIV/AIDS IN BRAZIL (Nov 2012 - estimate) 718,000 people living with HIV 686,478 AIDS cases Dept. STD/AIDS/VH, Min. Health, 2013 < 1% general > 5% > 1 populational subgoup HIV/AIDS IN BRAZIL (Nov 2012 - estimate) concentrated epidemic HIV prevalence = 0.4% (15 49) 0.31% 0.52% Dept. STD/AIDS/VH, Min. Health, 2013 UNAIDS, 2013 Page 7
HIV PREVALENCE AMONG MSM - BRAZIL Malta et al. BMC Public Health 2010, 10:317 HIV PREVALENCE AMONG COMMERCIAL SEX WORKERS - BRAZIL. Malta et al. BMC Public Health 2010, 10:317 HIV PREVALENCE AMONG IDU - BRAZIL. Malta et al. BMC Public Health 2010, 10:317 Page 8
Outline Biological interactions Social aspects of the epidemic Programmatic actions Current challenges Programatic actions Primary prevention safer sex harm reduction interventions prevention of mother-to-child transmission Brazilian National ART Program universal access to medication distributed free of charge - SUS launched in 1991 zidovudine (AZT) progressively incorporated new ARVs 1997 - combined therapy (HAART) local production of generic ARVs 2008 compulsory license - efavirenz 2013 test and treat strategy Page 9
Antiretroviral therapy Reverse transcriptase inhibitors nucleoside/nucleotide analogues: AZT, 3TC, ddi, abacavir, tenofovir non-nucleoside analogues: nevirapine, efavirenz, etravirine Protease inhibitors - saquinavir, ritonavir, lopinavir, fosamprenavir, atazanavir, darunavir Fusion inhibitors - enfuvirtide, maraviroc Integrase inhibitors: raltegravir Virological and immunological outcomes of successful ART supression of blood viral replication undetectable viremia immune restoration reduction/supression of viral replication in tissues - CNS, genital tract, others remarkable reduction in HIV genital shedding Brazilian response to HIV/AIDS - main peculiar features - historical momentum legal foundations Brazilian Constitution 1988 health a right of citizens and a duty of the State SUS basic principles Berkman, 2005 Page 10
Brazilian response to HIV/AIDS - main peculiar features - historical momentum legal foundations combined interventions in prevention and care HIV testing and counseling Promoting condom use Page 11
Care responses Health service and laboratory networks Reference hospitals Day hospitals Outpatient clinics ART distribution units Labs CD4 cell counts, HIV viral loads, HIV genotyping Brazilian response to HIV/AIDS - main peculiar features - historical momentum legal issues prevention and care interventions governmental commitment Brazilian response to HIV/AIDS - main peculiar features - historical momentum legal issues prevention and care interventions governmental commitment strong civil society involvement (NGOs and private sector) Berkman, 2005; Nunn, 2012 Page 12
Brazilian response to HIV/AIDS - main peculiar features - historical momentum legal issues prevention and care interventions government/civil society commitment human rights perspective Page 13
Brazilian HIV epidemic - trends territorial spread Brazilian HIV epidemic - trends territorial spread changes in the proportional distribution of different exposure categories Page 14
Distribution of AIDS cases in men aged 13 and over, according to exposure categories and year of diagnosis. Brazil, 1983-2009* Dept. STD/AIDS/VH, Min. Health, 2011 Brazilian HIV epidemic - trends territorial spread changes in the proportional distribution of different exposure categories male-female ratios AIDS male-female ratios, Brazil Male-female ratios in AIDS cases according to year of diagnosis, Brazil, 1986-2008 Male-female ratios in AIDS cases in individuals aged 13-19, according to year of diagnosis, Brazil, 1986-2008 16,0 15,1 Razão de sexo (M:F) 14,0 12,0 10,0 8,0 6,0 4,0 2,0 0,0 1986 9 6,5 6 5,4 4,7 3,9 3,5 3,2 2,7 2,4 2,1 1,9 1,8 1,7 1,6 1,5 1,5 1,5 1,5 1,5 1,5 1,5 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Ano de diagnóstico Razão de sexo (M:F) 7,0 6,1 6,4 6,0 5,0 4,6 4,3 4 4,0 3,1 3,0 2,4 2,2 1,9 2,0 1,5 1,2 1 0,8 0,7 0,6 0,6 0,7 0,7 0,6 0,6 0,6 0,7 0,8 1,0 0,0 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Ano de diagnóstico Dept. STD/AIDS/VH, Min. Health, 2010 Page 15
AIDS male-female ratios, Brazil Dept. STD/AIDS/VH, Min. Health, 2013 Clinical outcomes Reduced morbidity incidence of opportunistic infections Dept. STD/AIDS/VH, Min. Health, 2005 Clinical outcomes Reduced morbidity progression to AIDS hospital admissions day hospital use Page 16
Clinical outcomes Reduced mortality (AIDS-related deaths) RJ Grinsztejn B, 2013 MDGs and HIV/AIDS UNAIDS, 2013 Global HIV epidemic - trends UNAIDS, 2013 Page 17
Global HIV epidemic - trends UNAIDS, 2013 Global HIV epidemic - trends UNAIDS strategy 2011-2015 Page 18
Outline Biological interactions Social aspects of the epidemic Programmatic actions Current challenges Current challenges - 1 regional discrepancies local epidemics late diagnosis uptake and retention in care Global new HIV infections Page 19
AIDS incidence in Brazil (Dec 2012 - estimate) Dept. STD/AIDS/VH, Min. Health, 2013 AIDS incidence in Brazil Dept. STD/AIDS/VH, Min. Health, 2013 AIDS incidence in Brazil (aged 15-24) Dept. STD/AIDS/VH, Min. Health, 2013 Page 20
AIDS mortality in Brazil Dept. STD/AIDS/VH, Min. Health, 2013 Global AIDS-related deaths Late entry into HIV care Grangeiro A, 2011 Page 21
HIV/AIDS care cascade - Brazil Dept. STD/AIDS/VH, Min. Health, 2013 HIV/AIDS care cascade sub-saharan Africa UNAIDS, 2013 Current challenges - 2 ART sustainability highly vulnerable populations adherence to ART Page 22
Number of people on ART Dept. STD/AIDS/VH, Min. Health, 2013 Number of people on ART Current challenges - 3 coinfections HCV, HPV comorbidities mental health HIV drug resistance chronic AIDS lypodistrophy, cardiovascular risk Page 23
Outcomes of chronic ART Deeks S, 2011 Current challenges - 4 Stigma and discrimination need to address more vulnerable populations targeted prevention and care initiatives need to face structural dimensions of vulnerabiliy to HIV acquisition and disease development recent retrenchment in human rights-based response in Brazil Malta C, 2013; Reis RK, 2013 HIV stigma and discrimination UNAIDS, 2013 Page 24
Important strategies scaling up HIV testing scaling up early ART test and treat use of combined HIV prevention technologies behavioral, structural and biomedical approaches integrating HIV care and other health care programs STD detection and treatment Microbicides Cervical barriers vaginal diaphragms HIV testing and counseling PREVENTION OF HIV SEXUAL TRANSMISSION Male voluntary circumcision Immunization HIV vaccine HSV-2 therapy ART prophylaxis PEP PrEP TaP HIV integration Tuberculosis care Sexual and reproductive health care Primary care Antenatal and child care Non-communicable diseases Page 25
segurado@usp.br Page 26