HIV Guidelines. New Strategies. Santiago Moreno Hospital Universitario Ramón y Cajal Madrid
HIV Guidelines. New Strategies. Outline HIV Guidelines What is new? New strategies Treatment as Prevention
HIV Guidelines WhentoStart. Whattostart. 3
EACS Guidelines, 2014: When to Start 4
IAS-USA Guidelines, 2014: When to Start 5
GeSIDAGuidelines, 2015: When to Start ART is recommended for all HIV infected patients. CD4 count <350 cells/µl (AI) CD4 count 350-500 cells/µl (AII) CD4 count >500 cells/µl (BIII) 6
Temprano Trial: Overview Temprano ANRS Study Group. N Engl J Med. 2015;373:808-22. 7
Temprano Trial: Severe HIV morbidity Temprano ANRS Study Group. N Engl J Med. 2015;373:808-22. 8
Temprano Trial: Severe HIV morbidity Baseline CD4 500/mm 3 (n=849) Temprano ANRS Study Group. N Engl J Med. 2015;373:808-22. 9
Start: StudyDesign The INSIGHT START Study Group. N Engl J Med. 2015;373:795-807.
START: Primary Endpoint Type of event Nº de participantes Imm. ART Def. ART Serious AIDS 14 50 Serious non-aids 29 47 Total 42 96 Cumulative Percent with an event Months The INSIGHT START Study Group. N Engl J Med. 2015;373:795-807.
DHHS Guidelines, 2015: When to Start Strongly recommended for all CD4 counts: CD4 count <350 cells/µl (AI) CD4 count 350-500 cells/µl (AI) CD4 count >500 cells/µl (A1) 12
EACS Guidelines, 2014: What to Start 13
IAS-USA Guidelines, 2014: What to Start 14
DHHS Guidelines, April 2015: What to Start Recommended Regimens INSTI based PI based DTG/ABC/3TC* DTG + TDF/FTC EVG/COBI/TDF/FTC RAL + TDF/FTC DRV/r + TDF/FTC *Only for pts who are HLA-B*5701 negative. Only for pts with pre-art CrCl 70 ml/min. NNRTIs and ATV/r, previously classified as recommended, are now alternative regimens DHHS Guidelines. April 2015.
Preferred GeSIDAGuidelines, 2015: What to Start Regimens that have shown superior efficacy to their comparators in randomized clinical trials and that present a low risk of pharmacological interactions. They can be given to most patients. ABC/3TC + DTG TDF/FTC + DTG TDF/FTC + RAL Alternatives Regimens that have been inferior to the preferred regimens in randomized clinical trials or that have potential disadvantages or restrictions in their indications. They may be preferred options in some patients. 16
New Strategies. The End of AIDS? diagnose and treat prevention cure
HIV Prevention: Opportunities for biomedical interventions YEARS HOURS 36 HOURS YEARS Prior to exposure Exposure (pre-coital/coital) Exposure (post-coital) After infection Male circumcision Oral pre exposure prophylaxis (daily PrEP) Topical PrEP (daily gels or intra-vaginal rings (microbicides) Preventive Vaccines Oral pre exposure prophylaxis (intermittent PrEP) Coitally dependent topical PrEP (microbicides) Oral post exposure prophylaxis (PEP) Anti-retroviral therapy Immediate treatment of positive partners in discordant couples Treatment for prevention in all who test positive for HIV (T4P)
TasP: HIV prevention pyramid Treatment as prevention Vaccine PrEP PMTCT STI treatment Male circumcision Microbicides Testing & counselling Education Drug & alcohol treatment Condoms Harm reduction Blood screening Fauci A. IAC 2012. Abstract MOPL0101 19
Higher incidences of heterosexual transmissions with unsuppressed viral loads Mean (+SE) rate of heterosexual transmission of HIV-1 among 415 couples, according to the sex and the serum HIV-1 RNA level of the HIV-positive partner Transmission rate per 100 Person-years 35 30 25 20 15 10 5 All subjects Male-to-Female Transmission Female-to-Male Transmission 0 Quinn TC et al. N Engl J Med 2000;342:921 929. HIV-1 RNA (copies/ml) 20
Spain (Madrid) serodiscordantcouples Evidence supporting TasP as a strategy to achieve reductions in HIV transmission In serodiscordant couples with the HIV-positive partner not on ART, 9.2% of HIV-negative partners had HIV seroprevalence at enrolment, versus 0% of couples with the HIV-positive partner on ART During follow-up: Serodiscordant couple characteristics HIV-positive partner not on ARV Practicing unprotected sex (N=341) Using a condom (N=294) Estimated total acts of intercourse 11,000 42,000 Seroconversions HIV-positive partner on ARV Practicing unprotected sex (N=144) 7,000 0 Del Romero J et al. BMJ 2010;340:c2205 5 1 2 1
HIV sexual transmissibility meta-analysis: No transmission on ART below 400 copies/ml Attia S, et al.aids 2009 Jul 17;23(11):1397-404.
Partner Cohort Study: HIV Transmission Risk Despite Condomless Sex International Observational Cohort Study of sero-discordant couples Analyzed transmission risk from HIV+ on ARVs with undetectable viral load from condomless sexual acts no PEP nor PREP used in HIV- Analysis of transmissions linked to partner thru phylogenetic analysis Anal sex Ten-year risk of HIV Transmission: 0 0-0.96% Receptive Anal, with 0-3.9% or without overall 0-9.2% for condomless anal sex Observed Transmissions 95% CI for 100 couple years Overall 0 0-0.4% ejaculation 0 0-1.97% Rodger A, et al. 21st CROI; Boston, MA; March 3-6, 2014. Abst. 153LB.
Treatment as prevention TasP Internationally, HIV-positive population trends are declining 1-4 For an individual, it has been demonstrated that the rate ratio of incidence of HIV infection is more favourable with the administration of ART 5 The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy 6 Cumulative probability 0.25 0.2 0.15 0.1 0.05 No. at risk Immediate Delayed 0 HPTN 052: Linked HIV transmission 0 1 2 3 4 5 Years since randomisation 893 882 658 655 Delayed Immediate 298 297 79 80 31 26 24 22 1. Wood E, et al. BMJ 2009;338:b1649; 2. Montaner JSG, et al. Lancet 2010;376:532-9; 3. Das M, et al. PLoS ONE 2010;5:e11068; 4. Henard S, et al. J Acquir Immune Defic Syndr 2012;61:400-402; 5. Anglemyer A, et al. Cochrane Database Syst Rev 2011;(8):CD009153; 6. Cohen MS, et al. N Engl J Med 2011;365:493 505 24
Community Viral Load Mirrors Reduced Rate of New HIV Cases in San Francisco Retrospective analysis of relationship between community viral load (mean of summed individual HIV-1 RNA results per yr) and new HIV diagnoses Mean Community Viral Load (copies/ml) 30,000 25,000 20,000 15,000 10,000 5000 P =.005 for association* 798 Das-Douglas M, et al. CROI 2010. Abstract 33. Mean CVL Newly diagnosed and reported HIV cases 0 2004 2005 2006 2007 2008 *Data insufficient to prove significant association with Yrreduced HIV incidence. 642 523 518 434 1200 1000 800 600 400 200 0 Number of Newly Diagnosed HIV Cases
Reduction in New HIV Diagnoses in BC: Testing, HAART, and Community VL Period of declining new HIV diagnoses in BC coincident with increased HIV testing rates, increased uptake of antiretroviral therapy, and decrease in community viral load (1996-2008) Decline in new HIV diagnoses despite increases in syphilis, gonorrhea, chlamydia Patients (n) 12,000 10,000 8000 6000 4000 2000 New HIV+ diagnoses (all) Censored at the time of death or move 1400 1200 1000 800 600 400 200 New HIV+ Diagnoses (n) HIV-1 RNA, copies/ml < 500 500-3499 3500-9999 10,000-49,999 50,000 0 0 Montaner J, et al. CROI 2010. Abstract 88LB.
Potential cost savings of different ART initiation points (South Africa) US$ (billions) 0.6 0.4 0.2 0 0.2 0.4 0.6 0.8 1 US$7.2 billion * US$17.3 billion * US$28.7 billion * Treatment initiation CD4 <200 CD4 <350 CD4 <500 All CD4 1.2 2010 2015 2020 2025 2030 2035 2040 2045 2050 * Cumulative potential cost savings from 2010 2050 Granich R et al. PLoS ONE 2012; 7:e30216 2 7
HIV Guidelines. New Strategies. Outline HIV Guidelines are evolving Earlier initiation of ART: All HIV-infected patients regardless CD4 counts to decrease morbidity and mortality, and to prevent transmission (A1) More limited preferred options: evidence supporting integrase inhibitors-based regimens New strategies Administration of ART to infected patients is at present the most efficacious strategy to prevent HIV transmission
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