Adverse Effects and Treatment
Strategies During Long Term ART
Clinical and Research Center of Infectious Diseases
Beijing DiTan Hospital, Capital Medical University
Prof. FuJie Zhang
Outline
Grand goals and limited ARVs01
Adverse effects: a common problem faced by physicians and patients
02
Integrase inhibitors: a new era of HARRT
03
Common adverse effects of ARVs and treatment strategies
04
An ambitious treatment target to help end the AIDS epidemic: 2030 UNAIDS target
• Model indicates, if all these targets can be achieved by 2020, it could forecast AIDS
elimination by 2030 worldwide
• This achievement would create profound healthcare and economic benefit
UNAIDS. 90–90–90: An ambitious treatment target to help end the AIDS epidemic. October 2014; pp 1. Available at:
http://www.unaids.org/sites/default/files/media_asset/90-90-90_en_0.pdf (Accessed August 2015).
90%
Diagnosed
73% treated patients were suppressed
90%
Treated
90%
Virally
suppressed
Compared with 2014 suppressed
rate, a 3-fold increase in 2015
Goals of Antiretroviral Therapy
Maintain or restore the health of people living
with HIV-1 (PLWHIV) through suppression of
HIV-1 replication
Minimize or eliminate short and long-term
adverse effects of the therapy
Have therapies that are accessible to all
PLWHIV
Prevent transmission of HIV-1 to others via any
route of exposure
1
2
3
4
Main transmission route of new reported HIV/AIDS cases
National Health and Family Planning Commission of the People’s Republic of China: China AIDS Response Progress Report, May 2015.
Available at: http://www.unaids.org/sites/default/files/country/documents/CHN_narrative_report_2015.pdf (accessed August 2016)
CHINA
Sexual transmission rate 94.5%
100
80
60
40
20
0
≤2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
HETER
OHOMO IDU BLOOD MTCT UNKNOWN
Perc
en
tag
e (
%)
11.3
44.2
0.330.6
34.1
2.5
38.9
29.2
3.4
40.9
27.9
6.1
48.3
25.2
9.1
58.4
19.1
12.0
65.7
14.2
14.7
68.0
10.0
19.1
69.4
7.7
21.4
66.4
6.0
25.8
66.25
4.34
28.25
Drug categories Commonly used drugs Marketing status
NRTIsZidovudine, lamivudine, abacavir, tenofovir,
emtricitabine, etc.
marketedNNRTIs Efavirenz, etravirine, rilpivirine
PIs Ritonavir, tipranavir, atazanavir, etc.
INTIs Raltegravir, dolutegravir
FIsnot yet marketed
CCR5 inhibitors
Nearly 20 ARVs of four categories have come into the domestic market at present
NRTI: nucleoside reverse-transcriptase inhibitor; NNRTI: non-nucleoside reverse-transcriptase inhibitor; PI: protease inhibitor; FI: fusion Inhibitor;
INTI: integrase inhibitor; CCR5: chemokine receptor 5
Society of infectious diseases, Chinese Medical Association. Third edition of the guidelines for diagnosis and treatment of HIV/AIDS (2015). Chinese
Journal of clinical infectious diseases 2015; 8(5):385-401.
Limited treatment options
7
3rd Agent– PIs
2nd line
LPV/r
3rd Agent– NNRTIs
1st line
EFV (generic)
NVP (generic)
NRTI DUAL BACKBONE
3TC (generic)+/ AZT (generic)TDF
NRTI: nucleoside reverse-transcriptase inhibitor; TDF: enofovir disoproxil fumarate; 3TC: lamivudine; NNRTI: non-nucleoside reverse-transcriptase inhibitor;
PI: protease inhibitor; EFV: efavirenz; NVP: nevirapine; LPV/r: lopinavir/ritonavir.
ART: antiretroviral therapy; NRTIs: nucleoside reverse-transcriptase inhibitors; NNRTIs: non-nucleoside reverse-transcriptase inhibitors; PIs: protease inhibitors; INIs: integrase inhibitors.
1. Montessori V, et al. CMAJ. 2004; 170(2):229-238. 2. Burgoyne RW, et al. J Antimicrob Chemother. 2008;b61(3):469-473.
3. Margolis AM, et al. J Med Toxicol. 2014;b10(1):26-39. 4. Lennox JL, et al. Ann Intern Med. 2014;161(7):461-471.
5. Erlandson KM1, et al. PLoS One. 2014; 9(12):e114166. 6. Raines C, et al. Assoc Nurses AIDS Care. 2005; 16(5):35-48.
7. Protopopescu C, et al. J Antimicrob Chemother. 2009; 64(3):599-606. 8. Tozzi V, et al. Antivir Ther. 2006; 11(5):553-560.
Most of ARVs have prominent side effects leading to decline in the quality of life and treatment adherence of
patients with HIV
• Adverse effects such as diarrhoea,
anaemia, lipodystrophy syndrome,
etc. are associated with decreased
quality of life among patients2,5
• Central nervous system adverse
effect is one factor that affects
patients' quality of life6
• Side effect is an independent risk
factor associated with non-
adherence to ART7
NRTIsnephrotoxicity8
NNRTIs
CNS6
(central nervous
system)
PIscardiovascular disease
dyslipidemia
hyperglycemia3,4
INIsdiarrhea,
nausea, fever4
ARV related adverse effects are widely distributed1-4
Challenges with treatment outcome
• Discontinuation of EFV as first line treatment
• Prescribing information1
1.7% discontinued due to rash
2.1% discontinued EFV due to nervous system symptoms
1% discontinued EFV due to psychiatric disorders
• Study information2
20% discontinue EFV in a study conducted in 2012
CNS toxicity is the major reason
• Switch to 2nd line treatment too early3
1Atripla® Prescribing Information. Bristol-Myers Squibb and Gilead, 20102A. Scourfield. et al. AIDS 2012; 26(11):1399-401.
3Patients number distribution, sources from NCAIDS
89% 87% 83% 79% 75% 71%
11% 13% 17% 21% 25% 29%
1 2 3 4 5 6
Reeks1 Reeks2
Outline
Grand goals and limited ARVs
Adverse effects: a common problem faced by physicians and patients
Integrase inhibitors: a new era of HARRT
03
Common adverse effects of ARVs and treatment strategies
04
02
01
China: nonadherence to ART is mainly due to drug’s side effects
Li H, et al. Chin J Epidemiol 2005; 26(7):507-510.
66,96%10,43%
7,83%
8,69%
4,35%1,74%
1 2 3 4 5 6
The constituent ratio of causes of treatment discontinuation during HAART
To understand the interrelated factors that influence the treatment compliance of patients with HIV
infection in China, this study investigated drug adherence, side effect and clinical manifestation of
the patients who have or not have received ART for 2-12 months in AIDS high incidence areas.
Meta-analysis: adverse drug events had a serious impact on treatment adherence
AEs: adverse events.
Al-Dakka I, et al. AIDS Care 2013; 25(4):400-414.
The effects of sensory AEs on adherence
OR = 0.67
The effects of general AEs on adherence
OR = 0.72
The effects of gastrointestinal AEs on adherence
OR = 0.49
The effects of mental health AEs on adherence
OR = 0.65
Adverse drug reactions significantly decreased quality of life in patients with HIV/AIDS
Guo MT, et al. Chinese General Practice 2015; 18(2):138-143.
It indicated that adverse drug reaction is becoming
an important factor influencing patientsˊ QOL
This study aims to explore the medication status
of AIDS patients and the factors influencing their
quality of life (QOL). From March to August 2013,
in some designated AIDS medical institutions of
Harbin, by random sampling method, a self-
made questionnaire and WHO QOL- HIV- BREF
were used to investigate the medication status
of patients taking antiviral drugs, their QOL and
its influencing factors.
Adverse n Physiology Psychology Independence Social Environment Spiritual pillar/ General Total QOL score
reactions relationship Belief health
t value
VariableRegression
coefficient
P value
Severe
Adverse drug
reactions
Std regression
coefficient
Mild
t value P value
Cost of treating adverse event is a great economic burden for HIV patients
AE: adverse event; ARV: antiretroviral (drug).
Dong XP, et al. Chinese Health Economics 2008; 27(10):39-41.
This study recruited 100 patients with HIV/AIDS receiving HAART in Shanxi. Safety and efficacy
monitoring was conducted at the end of weeks 1, 2, 4, 8, 12, 24, 36, 48 and 52 during a one-year
follow-up period. Related adverse reactions in patients were treated by the physicians and the data
on direct costs of HAART were collected.
Cost composition for AE treatment
of 100 subjects
In rural areas, cost of treating AE
is about 30% of each farmer’s
net income per year.
Item Cost (Yuan) Ratio (%)
Antiretroviral drugs
Efficacy monitoring
Safety monitoring
AE treatment
Total
Composition of total cost for
treatment of patientsCategory Cost (Yuan) Comp. (%) Avg.
(Yuan per person)
Property of AE: ARVs related
opportunistic infection
(prevention & cure)
others
subtotal
AE cost: drugs
nursing
hospitalization
laboratory test
diagnosis and treatment
examination
medical supplies
transfusion
subtotal
0 10 20 30 40
1
2
3
The incidence rates of adverse events and drug switches during 2-year treatment (%)
Reeks2 Reeks1
P<0.001
P<0.001
P<0.001
Subjects:adult patients with HIV Infection in homosexual who started ART using AZT/TDF+3TC+EFV
as initial therapy from 2012
10.5
23.5
30.5
23.3
16.56.2
Fujie Zhang unpublished.
Drug switch
(except switch due to
pregnancy)
Adverse events occurred
Switch because of AEs
(except switch due to
pregnancy)
Outline
Grand goals and limited ARVs
Adverse effects: a common problem faced by physicians and patients
Integrase inhibitors: a new era of HARRT
Common adverse effects of ARVs and treatment strategies
04
01
02
03
Integrase inhibitors: a new era of HAART
Integrase inhibitors have gained a leading role in HIV
antiretroviral therapy (ART) because of favourable clinic
characteristics: high antiviral potency with rapid HIV
RNA declines, good tolerability, a favourable safety
profile and absence of significant drug-drug
interactions as well as targeting a new mode of action
hence lacking cross-resistance to other drug classes3
Considerations of new drugs
for HIV treatment at present1,2
Fewer drug interactionsimprove the efficiency of concomitant medications
Improved tolerability facilitates adherence
Improved safety reduces long-term toxicity
Improved efficacy reduces the risk of failure and drug resistance
1. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Last updated April 8, 2015; last reviewed April 8, 2015.
2. Geretti AM, et al. Curr Opin Infect Dis. 2014;27(6):545-553.
3. Blanco JL, et al. Expert Opin Pharmacother. 2015;16(9):1313-1324.
Shift To Integrase Inhibitor-based TherapyInitial Antiretroviral Therapy
Courtesy of Thibaut Davy and Sonia Napravnik
1,773 patients
initiating ART
between 1996 and
2014 in the UCHCC,
follow-up through
2015
比例
不同年份起始抗病毒治疗方案的类型
UCHCC: UNC CFAR HIV Clinical Cohort
bPI = LPV/r, DRV/r or ATV/r therapy
Other = includes unboosted PI and other bPI combinations
Outline
Grand goals and limited ARVs
Adverse effects: a common problem faced by physicians and patients
Integrase inhibitors: a new era of HARRT
Common adverse effects of ARVs and treatment strategies
01
02
03
04
Cause of non-accidental death for HIV patients
Categories Causes of death No. %
AIDS related infections(N = 4250, 27.8%)
Other AIDS related diseases and syndromes 1038 6.8
Pneumocystis pneumonia (PCP) 893 5.8
Recurrent bacterial pneumonia 677 4.4
Acute HIV infection syndrome 509 3.3
Candidiasis 269 1.8
HIV encephalopathy 255 1.7
Cryptococcosis 171 1.1
Herpes simplex virus infection 96 0.6
Chronic cryptosporidiosis (intestinal tract with diarrhea for >1 months)
67 0.4
Diffuse or extrapulmonary infection, toxoplasmosis encephalopathy
58 , 54 0.4 , 0.4
Cytomegalovirus infection, visceral herpes simplex virus infection 35 , 30 0.2, 0.2
Others (disseminated non tuberculous mycobacteria, chronic cryptosporidiosis, progressive multifocal leukoencephalopathy)
98 0.6
Respiratory diseases 2987 19.5
Cardiovascular diseases 2028 13.3
Malignant tumors 1916 12.5
Tuberculosis, hepatitides 907 , 420 5.9 , 2.7
Others(n = 1710, 11.2%)
HIV wasting syndrome 507 3.3
Other digestive system diseases 860 5.6
Endocrine and metabolic diseases 282 1.8
Histoplasmosis / interstitial pneumonia, drug side effects 28 , 21 0.2 , 0.1
Other non-AIDS related deaths 1095 7.2
The epidemic reports of HIV/AIDS deaths 2013 (n = 15271)
The number of accidental deaths (10.6%) increased year by year
0
5000
10000
15000
20000
25000
1 2 3 4 5 6 7 8
Year of death
Reeks4 Reeks3 Reeks2 Reeks1
Other non disease external causes of deaths (injury, etc.), N = 1286 (1.1%)
Drug overdose, N = 8657 (7.2%)
Suicides, N = 2178 (2.3%)
Non-accidental deaths, N = 107081
(89.4%)
Increased risk of suicide in patients receiving EFV-containing regimens
• EFV treatment was associated
with increased risk of suicide
low absolute risk
• The incidence of attempted/completed suicide was
associated with EFV (HR: 2.58; 95% CI: 0.94 to 7.06; P = .06)
• Treatment with EFV was also associated with increased risk
of death due to injury, drug dependence, or unknown causes
Mollan K, et al. IDWeek 2013. Abstract 40032.Reproduced with permission.
Multivariate Analysis of Factors Associated With Suicidality in ACTG Clinical Trials
Variable HR (95% CI) P 值
Randomly assigned EFV 2.15 (1.20-3.87) .01
Age category, yrs< 3030-44≥ 45
2.82 (1.25-6.34) 1.69 (0.81-3.55) 1.00 (reference)
.04
Hx IDU 2.18 (1.11 -4.30) .02
Psychiatric hx or psychoactive rx 3.90 (2.23 -6.82) < .001
47 events/5817 PY (8.08/1000 PY)
15 events/4099 PY (3.66/1000 PY)
EFVEFV-free
HR: 2.28 (95% CI 1.27-4.10; P = .006)
0.05
0.04
0.03
0.02
0.01
0
Pro
ba
bili
ty
1920 24 48 72 96 120 144 168
Wks to Suicidality
EFV, efavirenz; Hx, history; IDU, injection drug use; PY, person-years; rx, medication.
1. Digestive system adverse reactions and
treatment strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment strategies
An immediate switch to alternative medicine is required for serious adverse reactions in the digestive
system
AZT: zidovudine; PI: protease inhibitor
1. Han D, et al. Chin Hosp Pham J 2015; 35(22):2038-2041. 2. Ma XP. Chinese Community Doctors 2015; 31(113):19-20.
3. Wang H, Zhou BP. Infect Dis Info. 2014; 27(6):369-372. 4. Cao J, Wang M. National Medical Frontiers of China 2013; 8(7):39-40.
Treatment strategies• Co-administration with food can decrease some adverse reactions of digestive system (EFV should be taken
on an empty stomach)
• Symptomatic treatment should be provided for patients with serious side effects3
• When metoclopramide, loperamide or other symptomatic treatments have no effect on severe gastrointestinal
symptoms such as nausea, vomiting and diarrhea, switch to other medicines4
28,30%
19,27%
16,40%
5,96%
0%
10%
20%
30%
1 2 3 4
Incid
en
ce o
f d
ige
stive
syste
m
ad
ve
rse e
ve
nts
1,2
• AZT and PIs are the most common adverse reactions of gastrointestinal tract3
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment
strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment strategies
The regimens containing AZT induced high incidence of bone marrow suppression1-3
Treatment strategies
• Monitor routine blood test before treatment and treatment intervals2
• Avoid co-administration with drugs that induce bone marrow suppression2
• Symptomatic treatment; switch to alternative medicine when Hb < 75g/L or decreased
by 25% compared to the baseline
AZT: zidovudine; EFV: efavirenz; NVP: nevirapine
1. Yao ST, et al. Chin J Viral Dis. 2011; 1(2):128-134. 2. Wang H, Zhou BP. Infect Dis Info. 2014; 27(6):369-372.
3. Cao J, Wang M. National Medical Frontiers of China 2013; 8(7):39-40.
32,0%
23,6%
10,5%
0%
7%
14%
21%
28%
35%
1 2 3
Th
e in
cid
en
ce
ra
tes
of
bo
ne
ma
rro
w s
up
pre
ss
ion
1
This was a retrospective analysis from patients with AIDS (n=3014) in Dehong, Yunnan province
who received national free antiretroviral treatment from July 1st, 2004 to December 31th, 2009.
The incidence rates of related adverse drug events 90 days after ART were assessed.
• AZT+EFV caused a high rate of anemia1
• AZT+NVP induced high incidence of leukopenia1
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment strategies
Skin side effects due to NNRTIs can affect patients' quality of life and prognosis
• A rash is the most common manifestation of ART. The eruptions range from mild and transient to life-
threatening, with 2%–10% of cases associated with an interruption or termination of therapy1
• NNRTIs cause cutaneous reactions in 10%–17% of all those who start taking them1
Oral ulcers and facial rash induced by NVP2
Stevense-Johnson syndrome caused by NVP2
NNRTIs: non-nucleoside reverse transcriptase inhibitors
1. Isaacs T, et al. J Antimicrob Chemother. 2013; 68(12):2871-2874.
2. Introcaso CE, et al. J Am Acad Dermatol. 2010; 63(4):563-9; quiz 569-570.
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and
treatment strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment strategies
EFV and AZT are most commonly associated withneurological, psychiatric symptoms
EFV: efavirenz; AZT: zidovudine; NRTI: nucleoside reverse-transcriptase inhibitor; CNS: central nervous system
Abers MS, et al. CNS Drugs 2014; 28:131-145.
Antiretroviral Adverse event
Common(>10%)
Efavirenz Dizziness, insomnia, vivid dreams, impaired
concentration, lightheadedness, headache,
aggression, anxiety
Zidovudine Myopathy
NRTIs Peripheral neuropathy
Ritonavir Circumoral paraesthesias
Occasional(1-<10%)
Efavirenz Memory loss, hallucinations, depression
Ritonavir Peripheral neuropathy, dysgeusia
Enfuvirtide Peripheral neuropathy
Rare(<1%)
Efavirenz Mania
NRTIs Mitochondriopathy syndromes
Selected neuropsychiatric adverse events associated with antiretrovirals
Treatment strategies for neuropsychiatric side effects
EFV: efavirenz; CNS: central nervous system; AZT: zidovudine; RTV: ritonavir; DTG: dolutegravir; RAL: raltegravir; EVG: elvitegravir
1. Wang H, Zhou BP. Infect Dis Info. 2014; 27(6):369-372. 2. Abers MS, et al. CNS Drugs2014; 28:131-145.
3. GLASGOW 2016:http://chuansong.me/n/1095679052451 4. Cao J, Wang M. National Medical Frontiers of China 2013; 8(7):39-40.
ARV Treatment strategies
EFV • Patients with mental illness should avoid the use of EFV before taking
medicine1
• Administration on an empty stomach can reduce the blood concentration:
take the medicine 2-3 hours before sleep1
• Avoid mechanical operation 2-4 weeks before taking medicine1
• The stepwise dose increase (W1: 20mg/d, W2: 400mg/d, W3: 600mg/d)
could lead to a significant reduction in CNS toxicity2
AZT • Dose reduction or discontinuation2
RTV2 • Boosted PI at lower doses with less common side effects
• Discontinuation results in complete resolution of the symptoms
Kaletra®2 • Symptoms generally resolved after discontinuation
DTG3 • Discontinuation
RAL2 • Generally mild and rarely warrant discontinuation
• When serious dizziness or insomnia occurs and affects normal life or psychiatric symptoms of patients, switch to
alternative medicine4
• A switch is needed for patients with limb weakness, sensory loss or reduction of fingertips, or mild hereditary ataxia4
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment
strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment strategies
Most of ARVs have the potential to casue liver damage
Kovari H, et al. Open Forum Infect Dis. 2016 Jan
21;3(1):ofw009.
Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study. Among 21485 participants receiving ART, 6368 developed chronic liver enzyme elevation.
Co-infections
Zhang F, et al. Lancet ID. 2014;14(11):1065-72
69.8%
18.2%
8.7%3.3%
HIV infection
HCV-HIV co-infection
HBV-HIV co-infection
Triple infection
Retrospective observational cohort study in China recruited patients in 2010-2011
Switch to other kind of ARV after recovery of liver fucntion
Wang H, Zhou BP. Infect Dis Info. 2014; 27(6):369-372.
01
02
03
04
05
High risk patients
• Monitoring of liver function
Hepatoprotective
therapy
Criterion for
discontinuation• Consider discontinuation
when transaminase
exceeds 5-10 times than
normal level
Avoid to use
similar liver
damaging
drugs
After recovery of
liver fucntion
• Switch to other drugs
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment strategies
Many ARVs may lead to renal injury
Renal abnormality ARV Management
• Proximal tubulopathy (proteinuria,
progressive decline in eGFR,
phosphaturia)
TDF • Progressive decline in eGFR and no
other cause
• Confirmed hypophosphataemia of
renal origin and no other cause
• Osteopenia/osteoporosis in the
presence of increased urine
phosphate leak
• Nephrolithiasis (crystalluria,
haematuria, leucocyturia, loin pain,
acute renal insufficiency
IDV、ATV(DRV)
• Confirmed renal stones
• Recurrent loin pain +/- haematuria
• Interstitial nephritis (progressive
decline in eGFR, tubular
proteinuria/ haematuria,
eosinophiluria, leucocyte casts
IDV、ATV
• Progressive decline in eGFR and no
other cause
• Progressive decline in eGFR TDF、PI/r
EACS Guidelines 2016 V8:P47.
Symptomatic treatment for
serious patients
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment
strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment strategies
PIs are the major drugs leading to uneven distribution of fat1-3
1. Su H J. Jilin Medicine, 2012; 33(21):4541-4542.
2. Wang H, Zhou BP. Infect Dis Info. 2014; 27(6):369-372.
3. Cao J, Wang M. National Medical Frontiers of China 2013; 8(7):39-40.
The uneven
distribution
of fat
• Fat atrophy2
• AZT caused a loss of fat
• EFV can cause fat atrophy
• Fat deposition2
• Taking PIs and NNRTIs can induce fat deposition
• Switch to the same class of drugs can't
reduce fat deposition
• Treatment strategy: switch to alternative
medcine
• The incidence of fat redistribution was 8.6%11
2
3
4
5
RAL has little effect on blood fats
Synergized action
TDF: tenofovir; NVR: nevirapine; RAL: raltegravir; DTG: dolutegravir; RPV: rilpivirine; ETV: etravirine; ABC: abacavir; TAF: tenofovir alafenamide; EFV: efavirenz;
ATV: atazanavir; RTV: ritonavir; COBI: cobicistat; DRV: darunavir; EVG: Elvitegravir
Alejos B, et al. Presented at AIDS 2016; Poster #WEPDB0105.
TDF and NVR could reduce blood fats, but
whether they can decrease cardiovascular risk
remains to be further studied
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and
treatment strategies
9. Abnormal bone metabolism and treatment strategies
CVD is the fourth leading cause of death in patients with AIDS
47%
11% 11%
7%
0%
10%
20%
30%
40%
50%
1 2 3 4
AIDS-related death
Th
e p
rop
ort
ion
of
de
ath
s in
pa
tie
nts
wit
h A
IDS
CVD: cardiovascular disease.
Huang SJ. International Journal of Pharmaceutical Research 2007; 34(4):301-303.
ABC and PIs could induce higher risk of CVD
ABC: abacavir; PI: protein inhibitor
CVD: cardiovascular disease; MI: myocardial infarction
Huang SJ. International Journal of Pharmaceutical Research 2007; 34(4):301-303.
3-6/1000• The incidence of MI or CVD after taking ABC
and PIs was 3-6/1000
5.1/1000• The incidence of MI in PI group was 5.1/1000
26%• The first 4~6 years of ART were accompanied
with an annual increase of 26% MI
2.06• The relative risk of MI in treatment group
versus in the untreated group was 2.06
High risk patients with CVD should select ABC and PIs cautiously
ABC: abacavir; PI: protein inhibitor
CVD: cardiovascular disease; MI: myocardial infarction
Wang H, Zhou BP. Infect Dis Info. 2014; 27(6):369-372.
• It should be cautious for high risk
patients with CVD to select drugs such
as ABC and PIs that have great effects
on lipid metabolism.
01
02
03
04
• Regular blood lipid and blood
glucose monitoring
• Change of lifestyle
• Symptomatic treatment
1. Digestive system adverse reactions and treatment
strategies
2. Bone marrow suppression and treatment strategies
3. Skin toxicity and treatment strategies
4. Nervous system adverse reactions and treatment
strategies
5. Liver function damage and treatment strategies
6. Renal injury and treatment strategies
7. Lipid metabolic disorders and treatment strategies
8. Cardiovascular system adverse reactions and treatment
strategies
9. Abnormal bone metabolism and treatment
strategies
TDF and PIs may cause osteoporosis1-3
TDF: tenofovir; PIs: protein inhibitors; BMD: bone mineral density
1. JJ, Zhang Q. Chin J Exp Clin Infect Dis(Electronic Edition) 2015; 9(4):454-457.
2. McComsey GA, et al. The Journal of Infectious Diseases 2011; 203:1791-1801.
3. Wang H, Zhou BP. Infect Dis Info. 2014; 27(6):369-372.
4. He MQ, Ke TY. China Medicine and Pharmacy 2016; 6(8):34-37.
BMD was
decreased by
2%~6%1,2
after 2-year
ART treatment 01
Bone mass loss
in ART group
was 2.5 times
than that in non
treatment group1 02
• TDF and PIs may cause osteoporosis• Osteoporosis increases the risk of fracture
Treatment strategies
• Patients with high risk of osteoporosis (low birth weight, women, elderly,
smoking, drinking, hypogonadism, hyperthyroidism, using hormone) select TDF
and PIs with caution1
• Monitoring BMD regularly4
• Nutritional support treatment4
PopulationPreferred first-line regimens
Alternative first-line regimens1,2
Adults TDF + 3TC (or FTC) + EFV
AZT + 3TC + EFV (or NVP)
TDF + 3TC (or FTC) + DTG3,4
TDF + 3TC (or FTC) + EFV4003,4,5
TDF + 3TC (or FTC) + NVP
Pregnant or breastfeeding women
TDF + 3TC (or FTC) + EFV AZT + 3TC + EF V (or NVP)
TDF + 3TC (or FTC) + NVP
Adolescents TDF + 3TC (or FTC) + EFV
AZT + 3TC + EF V (or NVP)
TDF (or ABC) + 3TC (or FTC) + DTG3,4
TDF (or ABC) + 3TC (or FTC) + EFV4003,4,5
TDF (or ABC) + 3TC (or FTC) + NVP
Children 3 years to less than 10 years
ABC + 3TC + EFV
ABC + 3TC + NVP
AZT + 3TC + EFV (or NVP)
TDF + 3TC (or FTC) + EFV (or NVP)
Children less than 3 years
ABC (or AZT) + 3TC + LPV/r ABC (or AZT) + 3TC + NVP
WHO 2015: initial treatment (first-line regimens)
1. For adults and adolescents d4T should be discontinued as an option in first-line treatment.2. ABC or boosted protease inhibitors (PIs) (ATV/r, DRV/r, LPV/r) can be used in special circumstances.3. Safety and efficacy data on use of DTG and EFV400 in pregnant women, people with HIV/TB co-infection and children and adolescents younger than 12 years of age are not yet
available.4. Conditional recommendation, moderate quality evidence. Refer to full guideline for more detail.5. EFV at lower dose (400 mg/day).
1
Brief summary
Since patients with AIDS need
combination therapy for ART, it
is difficult to avoid adverse
reactions 23 4
Adverse reactions have a great
influence on the curative
efficacy, prognosis, quality of life
and medical expenses of
patients
Treat with adverse effects
immediately during ART
ISENTRESS®, a representative
INSTI with proved safety and
efficacy, can be used as the
preferred HAART drug
THANK YOU
Top Related