Post on 28-Aug-2019
• 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