• POBLACIONES DIFICILES DE TRATAR EN LATINOAMERICA

DRA ANA PAULINA CELI HOSPITAL GENERAL DE LAS FUERZAS ARMADAS TALLER LATINOAMERICANO DE VIH

What Factors Need to Be Considered When Choosing an Initial ART

Regimen?

DHHS Guidelines. July 2016.

Pt-Specific Regimen-Specific

Baseline HIV-1 RNA Long-term tolerability and safetyChronic HBV or HCV coinfection Simplicity

Renal function Food intake requirements (and pt eating habits)

Desire to become pregnant ART interactions with comedications and lifestyle drugsIllicit drug use ART genetic barrier to resistance

HLA-B*5701 statusComorbidities and comedications

Results of genotypic drug resistance testing

Anticipated adherence

Adjusted Age Distribution(prevalent cases under control in 2013 - 2016)

20,2%

30,5%

27,4%

15,5%

5,2%

1,2%

0,0%

5,0%

10,0%

15,0%

20,0%

25,0%

30,0%

35,0%

15-29 30-39 40-49 50-59 60-69 >69

Raw data

Adjusted 1

Adjusted 2

Adjusted 3

Adjusted 1: population under control by countryAdjusted 2: population under control by country + public/private centreAdjusted 3: population under control by country + centre in the Capital/Province

Cases: 65.145 Countries: 9Centres: 41

Objetivo 2 [incidencia]

26.931 pacientes33 centros9 países2013-2016

Distribución por edadEstimación 2 (PBC)

0,0%

5,0%

10,0%

15,0%

20,0%

25,0%

30,0%

35,0%

40,0%

45,0%

50,0%

49

2013

2014

2015

2016

Aumento en jóvenes.

Objetivo 2 [incidencia]

26.931 pacientes33 centros9 países2013-2016

% edad según añoEstimación 2 (PBC)

En 2016, el grupo de jóvenes (

Causes of Treatment Failure

DHHS Guidelines. July 2016.

Poor adherence

Insufficient drug level

Viral replication in the presence of drug

Resistant virus

Social/personal issuesRegimen issues

Toxicities

Suboptimal potency

Wrong dose

Host genetics

Poor absorption

Rapid clearancePoor activation

Drug interactions

Treatment failure

Transmission

ADHERENCE

Metanalysis performed on all continents reflects heterogeneous results in adherence to ART in adolescents. in some of them adherence was insufficient to maintain virological suppression in the long term. Studies in Malawi, for example, show dose loss of ARVs in more than 50% of the population studied

• Kim MH et al. Journal of the International AIDS Society 2017, 20:21437

Tendencia de Obesidad: The Swiss HIV Cohort Study

•Nadir de CD4 La mayor influencia sobre el incremento de peso

•Contribución limitada del regimen antirretroviral

Hasse, OFID 2014

Uso de Drogas Intravenosas

Boccara, European Heart Journal (2011)

Tabaquismo

VIH No- VIH

No fumadores 34% 46%

Fumadores previos

18,7% 34,4%

Fumadores actuales

47% 19,5%

Rasmussen, CID 2015

Sedentarismo

Sedentarismo: 71,4%, mayoría mujeres (p = 0,046)

Fiengo, Rev Paul Pediatr. 2015

Risk of Resistance Is Lowest in Adherent Pts

• Adherence of 90% to 100% necessary to achieve and maintain viral suppression[1]

– HIV adherence rates may be as low as 50% to 70%[2]

– Incomplete adherence occurs in all groups of treated individuals[3]

– Lack of adherence to ART a significant predictor of progression to AIDS and death[3]

• Risk of resistance is lowest in adherent pts; lack of adherence can lead to lack of viral suppression, exertion of drug selective pressure, and expansion of resistant virus[4,5]

1. Hogg RS, et al. AIDS. 2002;16:1051-1058. 2. Jackson H. Nurs Times. 2013;109:21-23. 3. García de Olalla P, et al. J Acquir Immune Defic Syndr. 2002;30:105-110. 4. Bangsberg DR, et al. J Antimicrob Chemother. 2004;53:696-699.5. Clutter DS, et al. Infect Genet Evol. 2016;[Epub ahead of print].

What to Choose for Treating Pts With Adherence Concerns

• For pts with adherence concerns or for pts in whom treatment is necessary before drug resistance results available, consider[1,2]:– DRV/RTV-based regimen – DTG-based regimen

• DRV-based regimens– No approved STR at present– DRV/COBI/FTC/TAF STR currently in phase III clinical trial[3]

DTG-based regimens– If combined with ABC/3TC, contraindicated in HLA-B*5701–positive pts[4]

1. DHHS Guidelines. July 2016. 2. Günthard H, et al. JAMA. 2016;316:191-210.3. ClinicalTrials.gov. NCT02269917.4. DTG/ABC/3TC [package insert]. 2016.

Genetic Barrier to Resistance for Specific ARVs

Clutter DS, et al. Infect Genet Evol. 2016;[Epub ahead of print].

Genetic Barrier to Resistance(Approximate # Mutations Needed to Fail)

Pote

ncy

(Est

imat

ed lo

g ch

ange

in V

L)

1 log

2 log

3 log

1 2 3 4

EVGRAL

DTG

ATV/RTV

DRV/RTV

ABCTDF

RPVFTC3TC

INSTINNRTINRTIPI

Genetic Barrier to Resistance: Recommended INSTI-Based Regimens

1. DHHS Guidelines. July 2016. 2. Clutter DS, et al. Infect Genet Evol. 2016;[Epub ahead of print].

Regimen Barrier to Resistance

Comments Mutations Highly Reducing

Susceptibility*[2]

DTG/3TC/ABC

DTG + FTC/TDF or FTC/TAFHigh

Resistance to DTG emerges slowly; multiple mutations required for resistance[1,2]

DTG + FTC/TDF or FTC/TAF recommended by DHHS if must treat before resistance results available[1]

--

EVG/COBI/FTC/TDF

EVG/COBI/FTC/TAFLow/Moderate Few EVG mutations required for resistance[2]

T66I/A/KE92Q

S147GQ148H/R/K

N155H

RAL + FTC/TDF or FTC/TAF Low/Moderate Few RAL mutations required for resistance[2]Y143C/R/HQ148H/R/K

N155H*NRTI backbone mutations not shown in column: FTC/TDF, M184V/I, K65R, T69ins; ABC/3TC, M184V/I, K65R, L74V/I, T69ins, Y115F, Q151M.

Genetic Barrier to Resistance: PI- or NNRTI-Based Regimens

1. DHHS Guidelines. July 2016. 2. Clutter DS, et al. Infect Genet Evol. 2016;[Epub ahead of print].

Regimen Barrier to Resistance CommentsMutations Highly

Reducing Susceptibility[2]*

ATV/RTV + FTC/TDF or FTC/TAF High

Fewer ATV/RTV mutations required for resistance vs DRV/RTV[2]

I50LI84VN88S

DRV/RTV + FTC/TDF or FTC/TAF High

Resistance to DRV/RTV emerges slowly[1]

DRV/RTV + FTC/TDF or FTC/TAF recommended by DHHS if must treat before resistance results available[1]

--

RPV/FTC/TDF or FTC/TAF Low Few RPV mutations required for resistance[2]

L100IK101PE138KY181I/VY188L

G190E/QF227CM230L

*

Adjusted Age Distribution(prevalent cases under control in 2013 - 2016)

20,2%

30,5%

27,4%

15,5%

5,2%

1,2%

0,0%

5,0%

10,0%

15,0%

20,0%

25,0%

30,0%

35,0%

15-29 30-39 40-49 50-59 60-69 >69

Raw data

Adjusted 1

Adjusted 2

Adjusted 3

Adjusted 1: population under control by countryAdjusted 2: population under control by country + public/private centreAdjusted 3: population under control by country + centre in the Capital/Province

Cases: 65.145 Countries: 9Centres: 41

21,9%

Expected impact of HIV treatment in survival of a 20 years old person living with HIV in a high income setting (different periods)

HIV treatment prevents HIV-related illness and disability, and AIDS-related death, thereby normalizing survival

HIV-Infected Patients in the HAART Era Have a 10-Year Shorter Expected Survival than Age and Gender-Matched Controls

Adapted from Lohse N, et al. Ann Intern Med 2007;146:87-95

1

0.75

0.5

0.25

0

Prob

abili

ty o

f Sur

viva

l

Pre-HAART (1995-1996)

Early HAART (1997-1999)

25 30 35 40 45 50 55 60 65 70

Survival from age 25 years

Age, y

Late HAART (2000-2005)

Population controls

Comorbilidades en Pacientes HIV-Positivos

Guaraldi et al, CROI 2010

Co-morbidities analysed: hypertension, Type 2 diabetes mellitus, cardiovascular disease and osteoporosis

HIV-positive HIV-negative

Guaraldi et al, CROI 2010

Co-morbidities analysed: hypertension, Type 2 diabetes mellitus, cardiovascular disease and osteoporosis

Comorbilidades en Pacientes HIV-Positivos

Appay V. J Pathol 2008.

Infección por VIH: Estado

Proinflamatorio

Inflammation Predicts Disease in Treated HIV Infection

• Mortality[1-4]

• Cardiovascular disease[5]

• Cancer[6,7]

• Venous thromboembolism[8]

• Type II diabetes[9]

• Radiographic emphysema[10]

• Renal disease[11]

• Bacterial pneumonia[12]

• Cognitive dysfunction[13]

• Depression[14]

• Functional impairment[15]

1.Kuller LH, et al. PLoS Med. 2008;5:e203.2. Tien PC, et al. J Acquir Immune Defic Syndr. 2010;55:316-322.3. Justice AC, et al. Clin Infect Dis. 2012;54:984-994. 4. Hunt PW, et al. J Infect Dis. 2014;210:1228-1238.5. Duprez DA, et al. Atherosclerosis. 2009;207:524-529. 6. Breen EC, et al. Cancer Epidemiol Biomarkers Prev. 2011;20:1303-1314.7. Borges ÁH, et al. AIDS. 2013;27:1433-1441.8. Musselwhite LW, et al. AIDS. 2011;25:787-795.

9. Brown TT, et al. Diabetes Care. 2010;33:2244-2249.10. Attia EF, et al. Chest. 2014;146:1543-1553.11. Gupta SK, et al. HIV Med. 2015;16:591-598.12. Bjerk SM, et al. PLoS One. 2013;8:e56249.13. Burdo TH, et al. AIDS. 2013;27:1387-1395.14. Martinez P, et al. J Acquir Immune Defic Syndr. 2014;65:456-462.15. Erlandson KM, et al. J Infect Dis. 2013;208:249-2

Reduced bone mineral densityIncreased prevalence of osteoporosis or osteopenia in spine, hip or forearm:63% of HIV+ patients2

Renal dysfunction30% of HIV+ patients have abnormal kidney function1

Emerging co-morbidities in HIV+: HIV+ ~10-15 years older than HIV-

1. Gupta SK et al. Clin Infect Dis 2005;40:1559–85. 2. Brown TT et al. J Clin Endocrinol Metab 2004;89(3):1200–06.3. Clifford DB. Top HIV Med 2008;16(2):94–98. 4. Triant VA et al. J Clin Endocrinol Metab 2007;92:2506–12.5. Patel P et al. Ann Intern Med 2008;148:728–36.

Cardiovasculardisease

Neurocognitive dysfunctionNeurological impairment present in ≥50% HIV+ patients3

CancerIncreased risk of non-AIDS-defining cancerse.g. anal, vaginal, liver, lung, melanoma, leukemia, colorectal and renal5

75% increase in risk of acute MI4

FrailtyIncreased frailty phenotype if HIV infected3-14x; Associated with CD4 count

High Risk Behaviors in Persons With HIV Infection

General population[2,3]HIV-positive pts[1]

Pers

ons

(%)

Prevalence of Alcohol, Cigarette, and Illicit Drug Use Among HIV-Positive Pts vs General Population

*24% noninjection, 1.7% injection drug use in HIV-positive pts; illicit drug use for general population included marijuana, cocaine, heroin, hallucinogens, inhalants, and nonmedical use of prescription-type pain relievers, tranquilizers, stimulants, and sedatives.

100

60

40

20

0

80

Alcohol Use Cigarette Smoking Illicit Drug Use*

61.052.0

38.2

15.224.0

10.2

1. CDC.Behavioral and Clinical Characteristics of Persons Receiving Medical Care for HIV Infection–Medical Monitoring Project, United States, 2013 Cycle (June 2013-May 2014).

2. 2. CDC. Summary Health Statistics for U.S. Adults: National Health Interview Survey, 2015.3. Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health.

Aging With HIV: Factor Stacking

LIFESTYLE

Normal Aging Process

Low CD4Untreated HIV

HIV-Mediated Inflammation

ART Considerations in Older Pts

• Comorbidities• Polypharmacy

– Drug–drug interaction, dosing, adherence challenges• Renal or hepatic impairment

– Alterations in pharmacokinetics, potential for drug toxicity

• Challenges with single-tablet regimens– Inability to alter single component dosing– Difficulty swallowing large tablets

HIV TOXICITY

Edad (tiempo)

Traditional risk factors

Residual replication/reservoirsChronic inflamation & immuneactivation

Arvs for life

Co-morbidities in HIV patients

30 40 50 60 70 years

Co-morbidityIncidencex100 p-yrs

General populationHIV-infected persons

HIV TOXICITY

Edad (tiempo)

Traditional risk factors: Smoking, exercise,..

Productive infection: cART

Residual replication/reservoirs: II ?Chronic inflamation & immuneactivation

cART: lipids, other…

Co-morbidities in HIV patients

CVD

0

1

2

3

4

5

6

7

8

Duración del TAR

Indi

cenc

ia d

e IA

M

(por

100

0 pe

rson

as-a

ños)

Classic CVR factors common in HIV patients

Calvo M, et al. HIV Med 2013

33

Factores de Riesgo Tradicionales

• Son más prevalentes en las personas viviendo con VIH

• En algunos existe relación con la exposición a HAART y los efectos virales directos– Alteraciones del metabolismo de la glucosa– Obesidad– Dislipidemia– Hipertensión

• En otros no tanto…– Uso de drogas intravenosas– Tabaquismo– Sedentarismo– Dieta

Factores de Riesgo Tradicionales

Toxicidad Mitocondrial de los NRTIs

Efectos de HAART Sobre el Colesterol

Sawyer, HIV Clin Trials. 2009

Terapia Antirretroviral

• Los beneficios de la supresión virológica sobrepasan los efectos adversos de la medicación

• tNRTIs Elevada toxicidad mitocondrial– Progresivamente en desuso

• IPs alteran el perfil de lípidos – Diferente magnitud de acuerdo al fármaco

• Abacavir e IAM Resultados contradictorios– La mayoría recomiendan precaución

• “Amigables” TDF, FTC/3TC, NVP, ATV, RAL,DTG ,EVG

Atazanavir sin potenciar

Estudios aleatorizados de simplificación a ATV no potenciado

Estudio Estrategia Diseño Comparación

INDUMA1 Inducción-mantenimiento RCT (n=172)Mantenimiento con 2 NUC(t) + ATV vs.

continuar con 2 NUC(t) + ATV/r

ARIES2 Inducción-mantenimiento RCT (n=419)Mantenimiento con ABC/3TC + ATV vs.

continuar con ABC/3TC + ATV/r

SWAN3 Simplificación RCT (n=419) Cambio a 2 NUC(t) + ATV vs.continuar con 2 NUC(t) + IP

ASSURE4 Simplificación RCT (n=296) Cambio a ABC/3TC+ATV vs.continuar con TDF/FTC+ATV/r

SLOAT5 Simplificación RCT (n=189) Mantenimiento con 2 NUC(t) + ATV vs.continuar con 2 NUC(t) + LPV/r

1. Ghosn J, et al. Antivir Ther. 2010;15:993-1002. 2. Squires K, et al. AIDS. 2010;24:2019-27. 3. Gatell et al. Clin Infect Dis. 2007;44(11):1484-92. 4. Wohl D, et al. ICAAC 2012, San Francisco, Abstract H-885. 5. Soriano V, et al. J Antimicrob Chemother. 2008;61:200–205 4.

Atazanavir sin potenciar

Estudios aleatorizados de simplificación a ATV no potenciado: resultados de eficacia

1. Gatell JM, et al. Clin Infect Dis. 2007;44:1484-9. 2. Ghosn J, et al. Antivir Ther. 2010;15:993-1002. 3. Soriano V, et al. J Antimicrob Chemother. 2008;61:200–205 4. Squires K, et al. AIDS. 2010;24:2019-27. 5. Wohl D, et al. ICAAC 2012, San Francisco [# H-885]

ATV

+ 2

NRT

I (n=

87)

ATV/

r + 2

NR

TI (n

=85)

20

40

60

80

100

0

% d

e pa

cien

tes

con

CV

< 50

c/

mL

Sem 48

INDUMA 2 ASSURE5

TDF/

FTC

+ A

TV/r

(n=9

7)

ABC/

3TC

+ AT

V (n

=199

)

Sem 48

ARIES4SWAN 1

ABC/

3TC

+ AT

V (n

=189

)

ABC

/3TC

+ A

TV/r

(n=1

80)

Sem 144

ATV

+ 2

NRT

I (n=

278)

IP/r

+ 2

NR

TI (n

=141

)Sem 48

77 %

68 %

78 %75 % 77 %

73 %76 %

79 %

ATV

+ 2

NRT

I (n=

49)

LPV/

r + 2

NR

TI (n

=87)

SLOAT 3

89 %88 %

Sem 48

Atazanavir sin potenciar

Estudios aleatorizados de simplificación a ATV no potenciado: metaanálisis de la variación de los parámetros lipídicos

Baril J, et al. HIV Medicine 2014; 15: 301–310

Cambios en los triglicéridosDif. media IV, aleatorio, IC del 95%

Cambios en el colesterol totalDif. media IV, aleatorio, IC del 95%

1234

Total

Inferior en ATV sin potenciar IP/r inferior-100 -50 0 50 100

1234

Total

Inferior en ATV sin potenciar IP/r inferior-100 -50 0 50 100

Cambios en el colesterol LDLDif. media IV, aleatorio, IC del 95%

1234

Total

Inferior en ATV sin potenciar IP/r inferior-100 -50 0 50 100

Cambios en el colesterol HDLDif. media IV, aleatorio, IC del 95%

1234

Total

Inferior en ATV sin potenciar IP/r inferior-100 -50 0 50 100

1. InduMa 2. SLOAT 3. ARIES 4. ASSURE

Recent Switch Studies: Suppressed

Trial From To OutcomeGS-123 TDF/FTC + RAL TDF/FTC/EVG/Cobi ✔GS-264 TDF/FTC/EFV TDF/FTC/RPV ✔Strategy-NNRTI TDF/FTC + NNRTI TDF/FTC/EVG/Cobi ✔Strategy-PI TDF/FTC + PI/r TDF/FTC/EVG/Cobi ✔SPIRIT 2 NRTI + PI/r TDF/FTC/RPV ✔SPIRAL 2 NRTI + PI/r 2 NRTI + RAL ✔SWITCHMRK 2 NRTI + LPV/r 2 NRTI + RAL ✗HARNESS 2 NRTI + 3rd Agent TDF/FTC + ATV/r

ATV/r + RAL✔✗

SALT ATV/r + 2 NRTI ATV/r + 3TC ✔OLE LPV/r + 2 NRTIs LPV/r + 3TC ✔

Slide courtesy of David Wohl

Cambio en Pacientes con Supresión Virológica

• Mantener la supresión viral– 6 – 24 meses de supresión viral documentada y sostenida– Riesgo: historia de falla virológica / carga viral inicial elevada

• Conocer:– Historia previa de HAART– Resistencia previa comprobada o posible– Probabilidad de adherencia– Efectos adversos nuevos– Interacciones farmacológicas nuevas– Costo / disponibilidad

• Usar siempre la evidencia existente

Metas de Lípidos: De Acuerdo al Riesgo

Selección del Hipolipemiante

www.hiv-druginteractions.org

Manejo del Riesgo Cardiovascular en la Infección por VIH

• La modificación de los factores de riesgo debe ser temprana (recuerde el elefante silencioso)– Hábitos dietarios– Tabaquismo

• Tratamiento farmacológico– Estatinas Mejor evidencia– Escalas de riesgo– Interacciones farmacológicas

• HAART inicial en el paciente de alto riesgo cardiovascular– INSTIs, TDF, 3TC/FTC, ATV– El mejor regimen no está definido

• Siempre sopesar el riesgo / beneficio del cambio de HAART

Todo cambio / inicio de HAART debe acompañarse de intervenciones tempranas sobre los factores de riesgo cardiovascular

Reduced bone mineral densityIncreased prevalence of osteoporosis or osteopenia in spine, hip or forearm:63% of HIV+ patients2

Renal dysfunction30% of HIV+ patients have abnormal kidney function1

Emerging co-morbidities in HIV+: HIV+ ~10-15 years older than HIV-

1. Gupta SK et al. Clin Infect Dis 2005;40:1559–85. 2. Brown TT et al. J Clin Endocrinol Metab 2004;89(3):1200–06.3. Clifford DB. Top HIV Med 2008;16(2):94–98. 4. Triant VA et al. J Clin Endocrinol Metab 2007;92:2506–12.5. Patel P et al. Ann Intern Med 2008;148:728–36.

Cardiovasculardisease

Neurocognitive dysfunctionNeurological impairment present in ≥50% HIV+ patients3

CancerIncreased risk of non-AIDS-defining cancerse.g. anal, vaginal, liver, lung, melanoma, leukemia, colorectal and renal5

75% increase in risk of acute MI4

FrailtyIncreased frailty phenotype if HIV infected3-14x; Associated with CD4 count

K Althoff. 20TH CROI 2013. #59.

HIV TOXICITY

Edad (tiempo)

Traditional risk factors: Hypertension, diabetes, drugs, HCV…

Productive infection: HIV nephropaty

Residual replication/reservoirs: Chronic inflamation & immuneactivation

cART: TDFIndinavirATV/rCobi, DTG

Co-morbidities in HIV patientsHIV nephropaty

CKD

HIV & KIDNEY

Tenofovir fumarate (TDF)*

Proximal tubulopathy (Fanconi sd.)

* Metabolismo renal (85%)

HIV & KIDNEYProximal tubulopathy (Fanconi sd.)

Aminoaciduria Glucosuria. Poliuria. Polidypsia Phosfaturia – Hypophosphatemia. Bone Hiponatremia, hipokalemia Renal tubular acidosis type II Tubular proteinuria Hypercalciuria

53

Change in eGFR (Cockcroft-Gault)Studies 104 and 111: Week 48 Combined Analysis

54*Cockroft-Gault (mL/min).

0 12 24 36 48

0

10

20 E/C/F/TAF

E/C/F/TDF

Time (Weeks)

Mea

n (S

D) c

hang

e fro

m b

asel

ine

eGFR

Coc

krof

t-Gau

lt (m

L/m

in)

-10

-20

-6.6

-11.2p

Proximal Tubule Cell

For illustrative purposes only.For illustrative purposes only.

Urinary Space

Lepist EI, et al. ICAAC 2011. Abstract A1-1724German P, et al. J Acquir Immune Defic Syndr. 2012;61:32-40

Lepist EI, Ray AS. Exper Opin Drug Metab Toxicol. 2012;8:433-448

Blood Vessel

SCr ≈ 1.0 mg/dLSCr ≈ 1.14 mg/dL

CobicistatCreatinine

• COBI blocks a transport pathway used for creatinine secretion from the proximal tubule by inhibiting a transport protein called MATE1

• THIS IS NOT TOXICITY

Cobicistat inhibits tubular secretion of creatinine

Proximal Tubule Cell

For illustrative purposes only.For illustrative purposes only.

Urinary Space

Lepist EI, et al. ICAAC 2011. Abstract A1-1724German P, et al. J Acquir Immune Defic Syndr. 2012;61:32-40

Lepist EI, Ray AS. Exper Opin Drug Metab Toxicol. 2012;8:433-448

Blood Vessel

SCr ≈ 1.0 mg/dLSCr ≈ 1.14 mg/dL

DTGCreatinine

• DTG blocks a transport pathway used for creatinine secretion from the proximal tubule by inhibiting a transport protein called OCT2

• THIS IS NOT TOXICITY

DTG inhibits tubular secretion of creatinine

EFFECT OF DTG ON SERUM CREATITINE

1. Spring: Raffi F et al. Lancet 2013;381:735–43 2. Single . Walmsley S. y cols. N Engl J Med 2013; 369:1807-18. 3.Sailing: Cahn P, y cols. Lancet 2013;382(9893):700-708 4. Viking 3: Vavro et al. EUDRW 2014; Barcelona, Spain. Abstract O_10.

DTG 50 mg qd

RAL 400 mg bid

Months

Mea

n ch

ange

from

bas

elin

e

(μm

ol/L

)

Gráfico1

007.727.727.827.82

227.647.648.988.98

448.288.287.487.48

888.528.527.687.68

12128.268.2610.5810.58

16169.969.967.677.67

24248.398.397.537.53

32328.918.917.717.71

40409.029.028.348.34

4848

DTG

ATRIPLA

0

0

11.6

1

11.1

0.2

11.6

0.7

13.4

1.3

12.3

2.1

13

0.5

11.6

0.2

11.3

-0.6

10.2

-0.7

Sheet1

X-ValuesDTGATRIPLADTG sdA sd

000

211.617.727.82

411.10.27.648.98

811.60.78.287.48

1213.41.38.527.68

1612.32.18.2610.58

24130.59.967.67

3211.60.28.397.53

4011.3-0.68.917.71

4810.2-0.79.028.34

To resize chart data range, drag lower right corner of range.

Guía Fecha Criterio de inicio de TAR por CD4 o condiciones clínicas

Edad como criterio de

inicio

Recomendación de ARVs

específicos por criterio de edad

OMS Sep, 2015 TAR universal, prioridad en pacientes con enfermedad avanzada o CD4+ ≤ 350 céls/mm3

No No

DHHS Abril, 2015 Todos, independiente de CD4, igual nivel de evidencia y fuerza de recomendación para todos (A1)

No No

IAS Julio, 2014 Todos (A1a – BIII, según niveles de CD4+) No No

EACS Octubre, 2015

50 años No

México 2015 Todos (A1) >55 años (considerar)

No

Chile 2016 Todos >50 años (A) No (Sí RCV)Colombia Nov, 2014 Infección sintomática, < 500 céls/mm3 o la

presencia de varias condiciones que priorizan su inicio

>60 años No

Venezuela 2014 Infección sintomática o CD4+ 50 años No

Ecuador 2012 Infección sintomática o CD4+

Comorbilidad o FR en > 50 años

Recomendación de 1ª línea

No se recomienda(n) Observaciones

Sano, sin comorbilidades ni uso de medicamentos

INIsATV/r, DRV/r, RPV coformulado

Efavirenz EFV se asocia a mayor depresión, trastornos del sueño y neurocognitivos en la población de mayor edad y tiene impacto metabólico negativo

Riesgo cardiovascular elevado o muy elevado

Inhibidor de integrasa (RAL o DTG), RPV coformulado

Abacavir, EVG/Cobi, lopinavir/ritonavir, fosamprenavir/ritonavirDRV/r?....

Aún controversial por falta de evidencia definitiva del riesgo mayor reportado de infarto agudo de miocardio y trombosis cerebral.

Hipercolesterolemiao Hipertrigliceridemia

Tenofovir/emtricitabina + RPV o RAL o DTG; alternativa: maraviroc

EFV, IP/r y formulaciones con cobicistat

Uso de ritonavir y cobicistat incrementan colesterol y limitan uso óptimo de estatinas

Diabetes mellitus Raltegravir + TDF/FTC o ABC/3TCo rilpivirinacoformulado

Vigilar incremento de concentración de metformina por dolutegravir.

IP/r se asocian a resistencia a la insulina, con menor efecto en ATV y DRV reforzados con 100 mg de ritonavir

Comorbilidad o FR en > 50 años

Recomendación de 1ª línea

No se recomienda(n) Observaciones

Insuficiencia renal RAL + ABC + 3TC -TDF, coformulaciones fijas de TDF/FTC/EFV -TDF/FTC/RPV con CrCl

HIV y Mujer

• Globalmente, en 2015 se estimaba que 17.8 millones de mujeres viven con HIV HIV (>15), correspondiendo al 51 %de los adultos que viven con HIV

• La mujer jóven y adolescente de 15 a 24 años son particularmente afectadas por el HIV. En 2015 se estimaba que 2.3 millones de mujeres adolescentes y mujeres jóvenes viven con HIV, lo que represeta el 60% de todos los jóvenes que viven con HIV(15-24)

• In 2015, de las nuevas infecciones, globalmente, el 47% fueron en mujeres

• En Latin America, las mujeres representan el 29 % de las nuevas infecciones, mientras que las mujeres jóvenes entre 15 y 24 años, constituyen el 36% de esas nuevas infecciones

UNAIDS, 2015

http://www.unwomen.org/en

Age Distribution at Diagnosis according to Gender

n= 17.988N= 30 centresCountries= 82013-2015

4,8%

15,9%

19,3%

26,5%

18,3%

9,0%

2,9%

0,7%

5,8%

12,4%

14,4%

27,7%

19,5%

11,0%

2,9%

0,6%

0,0%

5,0%

10,0%

15,0%

20,0%

25,0%

30,0%

35,0%

15-19 20-24 25-29 30-39 40-49 50-59 60-69 >69

Hombres

Mujeres

• Anticonceptivos:– Orales-Inyectables– Interacción de drogas

• Menopausia:– Mal entendidos acerca de los riesgos de cotraer HIV en los adultos

mayores– Actividad sexual no protegida– Falta de prevención, mensajes dirigidos a la población jóven– Los médicos, en general, no consideran a los adultos mayores como

una población sexualmente activa

Luther VP, et al. Clin Geriatr Med. 2007;23:567-583. Jama 2013,April 3 Num 13

Interacciones de anticonceptivoshormonales y ARVs

WHO Guidelines. June 2016.

Hormonal Contraceptive

NRTI PI NNRTI INSTIAny* ATV LPV DRV RTV EFV NVP ETR RPV DTG RAL EVG/c

Combined oral contraceptives

Etonogestrel or levonorgestrel implant

Transdermal ethinyl estradiol

Norethisterone (norethindrone)

DMPAinjectable

No clinically significant interaction or interaction unlikelyPotential interaction that may require monitoring or regimen alteration

*Includes 3TC, ABC, ddI, d4T, FTC, TDF, ZDV.

Inh nucleósido/tido de TI Inhibidor de proteasa Inhibidor de integrasa

ABC/3TCTDF/FTC ó 3TCAZT/3TC

LPV/rATV/rDRV/r

Raltegravir

Inh nucleósido/tido de TI Inh No nucleósido de TIEfavirenzRilpivirina*

No está recomendada la administración de DRV/r y LPV/r una vez por día

Rilpivirina no recomendado con menos de 200 cél cd47mm3, y con cargas virales mayores a 100.000 c/ml

Esquema alternativo como 3ra droga

Esquemas preferidos

Insuficientes datos con DTG, EVG, Maraviroc, FosamprenavirNo recomentados: d4T, ddI, ETV, Enfuvirtide

Modif DHHS Perinatal Guidelines. 2016.

TAR en la mujer

Esquemas preferidos Esquemas alternativos

ABC/3TC+DTGTDF/FTC ó 3TC+DTGTDF/FTC+EVG/cobi

TDF/FTC+RAL

TDF/FTC+ATV/rABC/3TC-ATV/r

TDF/FTC ó 3TC+EFVABC/3TC+EFV

TDF/FTC ó 3TC+DRV/rABC/3TC+DRV/r

Dianummer 1What Factors Need to Be Considered When Choosing an Initial ART Regimen?Dianummer 3Dianummer 4Dianummer 5Causes of Treatment FailureADHERENCE Tendencia de Obesidad: The Swiss HIV Cohort StudyUso de Drogas IntravenosasTabaquismoSedentarismoRisk of Resistance Is Lowest in Adherent PtsWhat to Choose for Treating Pts With Adherence ConcernsGenetic Barrier to Resistance for Specific ARVsGenetic Barrier to Resistance: Recommended INSTI-Based RegimensGenetic Barrier to Resistance: PI- or NNRTI-Based RegimensDianummer 17HIV treatment prevents HIV-related illness and disability, and AIDS-related death, thereby normalizing survivalHIV-Infected Patients in the HAART Era Have a 10-Year Shorter Expected Survival than Age and Gender-Matched Controls Comorbilidades en Pacientes HIV-Positivos Dianummer 21Infección por VIH: Estado ProinflamatorioInflammation Predicts Disease in Treated HIV InfectionEmerging co-morbidities in HIV+: �HIV+ ~10-15 years older than HIV-High Risk Behaviors in Persons With HIV InfectionAging With HIV: Factor Stacking ART Considerations in Older PtsDianummer 28Dianummer 29Dianummer 30Dianummer 31Classic CVR factors common in HIV patientsDianummer 33Factores de Riesgo TradicionalesFactores de Riesgo TradicionalesToxicidad Mitocondrial de los NRTIsEfectos de HAART Sobre el ColesterolTerapia AntirretroviralAtazanavir sin potenciarAtazanavir sin potenciarAtazanavir sin potenciarRecent Switch Studies: SuppressedCambio en Pacientes con Supresión VirológicaMetas de Lípidos: De Acuerdo al RiesgoSelección del HipolipemianteManejo del Riesgo Cardiovascular en la Infección por VIHEmerging co-morbidities in HIV+: �HIV+ ~10-15 years older than HIV-Dianummer 48Dianummer 49Dianummer 50Dianummer 51Dianummer 52Dianummer 53Change in eGFR (Cockcroft-Gault)�Studies 104 and 111: Week 48 Combined Analysis Dianummer 55Dianummer 56EFFECT OF DTG ON SERUM CREATITINEDianummer 58Dianummer 59Dianummer 60HIV y MujerDianummer 62Dianummer 63Interacciones de anticonceptivos hormonales y ARVsDianummer 65TAR en la mujer