Taking medicines
properly ?
95％…?

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Introduction
When you start HIV treatment, health care providers
might tell you "You have to take medicines properly","If you fail, HIV virus will develop Resistance thatmeans the treatment won't work effectively"
Also, we sometimes hear from patients:"I skipped a dose every other day
until the next appointment because
I was running out of medicines."「きちんとのむ」ってどんなこと？
＜英語訳＞
Contents■ Drugs are Effective ? ………………………………………… 2
Not Effective?

■ How do the drug-resistant viruses emerge ? ………… 3■ When you take medicines properly… ………………… 4■ When you don’t take medicines properly… ………… 5■ "Following Properly ? ……………………………………… 6
4 major principles for adherence."■ Mind drug-drug interaction ……………………………… 9"I've heard that HIV treatment
loses effectiveness because of
Resistance in the future when
I take it for long term""My doctor advised me to change medicines
to better one, but I'm worried whether
I lose treatment options when drug
resistant viruses appear in the future."
The purpose of this booklet is to achieve your correctunderstanding on Adherence and drug-resistant viruses.
We personalize HIV for your better understanding.

■ The goal is 100%
■ Reinfection…………………………………………… 10…………………………………………………… 12■ Cross-resistance ……………………………………………… 13■Q&A…………………………………………………………… 14■ Which type you are in ? …………………………………… 16
Tips to avoid forgetting to take medicine

Drugs are Effective ?
Not Effective ?

There are 3 types of viruses based on drug resistance degrees.
Viruses which drugs are effective(drug-sensitive viruses)
strength… drug > virusest5IFZDBOSFQMJDBUFSBQJEMZ
t5IFZBSFBMTPDBMMFEXJMEUZQFWJSVTFT
t5IFZDBOUSFQMJDBUFXIFOZPVUBLFNFEJDJOFTQSPQFSMZWhen compared to military, they are unarmed infantry in a large number
and try to fight stronger enemy.

How do the drug-resistantviruses selected ?
tHIV replicates by making copies of themselves in human body.
Anti-HIV drugs can prevent HIV from making copies.
tSincedrug-sensitive viruses replicate and make many copies, theysometimes produce defective viruses.
tCandidate for drug-resistant viruses has an ability to evolve
JOUPUIFESVHSFTJTUBOUWJSVTFTXIJDIESVHTBSFOPUFGGFDUJWF
(Become resistant)tWe can prevent selecting
drug-resistant virus seeds by taking medicines
properly, because anti-HIV drugs are still effective against.

strength… drug > virusest5IFZBSFEFGFDUJWFQSPEVDUTPGPSJHJOBM
drug-sensitive viruses.
t5IFZBSFGSBHJMFBOEDBOUSFQMJDBUFFGåDJFOUMZ
t5IFWJSVTXIJDITVSWJWFEUIFESVHBUUBDLDBOFWPMWF
intodrug-resistant viruses.
t5IFZDBOUSFQMJDBUFXIFOZPVUBLFNFEJDJOFTQSPQFSMZThey are spies who collect information of enemy in an unguarded moment..

Viruses which drugs are not effective(drug-resistance viruses)
strength… drug < virusest5IFZIBWFBDRVJSFESFTJTUBODFBHBJOTUESVHT
t$BOEJEBUFGPSESVHSFTJTUBOUWJSVTFTFWPMWFE
into drug-resistant viruses.
t5IFZDBOSFQMJDBUFFWFOJGESVHTBSFBENJOJTUFSFEQSPQFSMZThey are special units sniping enemies using information strategically2

Drug-sensitive
viruses
Replicate rapidly
Mistake in copying

Candidate fordrug-resistantviruses

Evolution

Drug-resistantviruses

BecomeresistantDrugs are noteffective(candidate for drug-resistant viruses)

Drugs are effective

Viruses which drugs are less effective

Once drug-resistant viruses emerge, it is difficult to prevent
them from replicating even if you take medicines properly.
3When you takemedicines properly…
t/PXJNBHJOFZPVUBLFBTFUPGESVHT UBCMFUTBTTIPXO UXJDFEBJMZ UBCMFUTBEBZ ×2(Morning,
Evening)t8IFOZPVUBLFNFEJDJOF UIFESVHDPODFOUSBUJPOJOCMPPE CMPPEDPODFOUSBUJPO JODSFBTFTBUåSTU BOEEFDSFBTFTBGUFSXBSETXIJMFESVHTCFJOHSFTPMWFEBOENFUBCPMJ[FEt:PVIBWFUPUBLFBOFYUEPTFQVODUVBMMZUPLFFQUIFCMPPE
DPODFOUSBUJPOBSPVOEUIFFGGFDUJWFMFWFM

When you fail to take anti-HIV drugs, the bloodconcentration of gets lower than the therapeutic level.
Then, how do viruses behave?
8IFOZPVUBLF
NFEJDJOFTQSPQFSMZy

7JSVTFTXBOUUPSFQMJDBUF
5IFZDBOhUSFQMJDBUFXIFOESVHTXPSLFGGFDUJWFMZ
They try to find weaknessof the drug to overcome
and multiply.

&OFNJFT %SVHT BSF
BMXBZTPOUIFJSHVBSEBOE
OFWFSTIPXUIFJSXFBLOFTTUIFHSBQIPOUIFQSFWJPVTQBHF

When you don’t take medicines properly…

Takingmedicine&OFNJFT %SVHT ESPQHVBSE
JUhTBCJHDIBODFGPSWJSVTFTUPMFBSOFOFNJFThDIBSBDUFSJTUJDTSide Effects Level (Too high)
4JEFFGGFDUTFBTJMZEFWFMPQTherapeutic Level (Good)#MPPE$PODFOUSBUJPOWhen you don’t takemedicines properly…

&GGFDUJWFFOPVHIUPTVQQSFTTWJSVTFT
4JEFFGGFDUTBSFMFTTMJLFMZUPEFWFMPQ

Unguarded :Chance to learn
about enemies
Unguarded~ Special Lecture ~#FBESVHSFTJTUBOUWJSVT

Unguarded

Targeted Trough Level(The lowest)

The lowest blood concentrationof therapeutic level

Ineffective Level (Too low)
/PUFGGFDUJWFFOPVHIUPTVQQSFTTWJSVTFT%SVHSFTJTUBOUWJSVTFTDBOFNFSHFFBTJMZt:PVNVTULFFQZPVSCMPPEDPODFOUSBUJPOIJHIFSUIBOUIFMPXFTUMFWFM
(5BSHFUFE5SPVHI-FWFM UPQSFWFOU)*7GSPNNVMUJQMZJOHBOEHFUUJOHSFTJTUBODF
t5PLFFQZPVSCMPPEDPODFOUSBUJPOIJHIFSUIBOUIF5BSHFUFE5SPVHI-FWFM ZPVOFFEUBLFNFEJDJOFTSFHVMBSMZBOEQVODUVBMMZ
4

3FQFBUFEVOHVBSEFENPNFOUTFOBCMFWJSVTFT
UPMFBSOESVHTXFBLOFTT BOEUIFZBDRVJSFUIFSFTJTUBODFBHBJOTUESVHT

%SVHSFTJTUBOUWJSVTFTBSFOPMPOHFSEFGFBUFECZUIFESVHTUIBUZPVUBLFOPX
5

"Following Properly ?
4 major principles
for adherence."

You must take medicine properly
to avoid drug-resistant viruses
What is the exact meaning of taking
medicines properly in the first place ?

Never forget. Never skip.
t8IFOZPVGBJMUPUBLFBOUJ)*7ESVHTBTQSFTDSJCFE UIFCMPPE
DPODFOUSBUJPOPGESVHTFBTJMZHFUTMPXFSUIBOUIFUIFSBQFVUJDMFWFM XIJDINFBOTESVHSFTJTUBOUWJSVTFTDBOFNFSHF

Don’t spare your pills!
t*GZPVSFEVDFUIFEPTFPSUIFUZQFTPGBOUJ)*7ESVHTPOZPVSEFDJTJPOGPSSFBTPOTTVDIBTTJEFFGGFDUTPSTIPSUBHFPGUIFESVHT UIFCMPPEDPODFOUSBUJPOHFUTMPXFSUIBOUIFUIFSBQFVUJDMFWFMFBTJMZ
5IFOESVHSFTJTUBOUWJSVTFTDBOFNFSHF
I’ll takea half dose
today

When you reduce
the types of pills…

When you fail to takemedicines which you aresupposed to take at night

Takingmedicine

Skip

When you reducethe dose of pills…

67

Remind Drug-druginteraction
Never take too much.
Never take a several dose at a time.
t8IFOZPVUBLFUIFESVHTBUPODFXIJDIBSFTVQQPTFEUPCFUBLFOJOTFWFSBMUJNFTJOBEBZ PSUBLFBEPVCMFEPTFPGBNFEJDJOFTUPNBLFVQGPSBNJTTFEEPTF UIFCMPPEDPODFOUSBUJPOPGESVHHFUTIJHIFSUIBOUIF4JEF&GGFDUT-FWFM
t*UJTEBOHFSPVTCFDBVTFUIFIJHIFSCMPPEDPODFOUSBUJPOMFBETTJEFFGGFDUTFBTJMZ
t5BLJOHUPPNVDINFEJDJOFTBUPODFEPFTOhUSFTVMUJOIJHIFSFGGFDUJWFOFTTt4PNFUZQFTPGESVHTXIJDIBSFTVQQPTFEUPCFUBLFOTFWFSBMUJNFTBEBZ
BSFNFUBCPMJ[FEJOTIPSUFSUJNF
&WFOJGZPVUBLFTFWFSBMEPTFBUPODF UIFJSFGåDBDZEPFTOhUMBTUMPOHFS

t8IFOUBLJOHUXPPSNPSFESVHTSFHVMBSMZ NBUUFSPGDIFNJTUSZ %SVHESVHJOUFSBDUJPO NVTUCFDPOTJEFSFE
t6OGBWPSBCMFESVHJOUFSBDUJPONBZSFTVMUJOMFTTFGGFDUJWFOFTTPSTJEFFGGFDUT
t/PUPOMZESVHTQSFTDSJCFECZBEPDUPS CVUBMTPTPNFPWFSUIFDPVOUFSESVHTPSTVQQMFNFOUTXIJDIBSFTPMEBUBQIBSNBDZPSBDPOWFOJFODFTUPSF
DPVMEDBVTFUIFESVHJOUFSBDUJPO
t4PNFPGUIFNBKPSBOUJ)*7ESVHTIBWFTUSPOHESVHESVH
JOUFSBDUJPOTXJUIWBSJPVTESVHT
t:PVTIPVMEJOGPSNIFBMUIDBSFQSPWJEFSTUPDIFDLUIFESVHESVH
JOUFSBDUJPOJGZPVUBLFNFEJDJOFTPSTVQQMFNFOUTSFHVMBSMZPSJOUFOEUPTUBSUUBLJOHUIFNNever quit, but continue.
t*UJTOFDFTTBSZUPUBLFBOUJ)*7ESVHTGPSMJGF:PVNBZOPURVJUUBLJOH
UIFNFWFOJGZPVSTZNQUPNTPSUIFSFTVMUPGNFEJDBMUFTUBSFJNQSPWFE
t8IFOZPVGFFMVODPNGPSUBCMFUPUBLFNFEJDJOFTCFDBVTFPGQPTTJCMFTJEF
FGGFDUTPSNPPEDIBOHF ZPVTIPVMEJOGPSNIFBMUIDBSFQSPWJEFSTåSTU*UJTEBOHFSPVTUPRVJU PSJOUFSSVQU UBLJOHBOUJ)*7NFEJDJOFTPOZPVSEFDJTJPO
t5PLFFQBMMZPVSNFEJDBMBQQPJOUNFOUTJTJNQPSUBOUUPLFFQBOFZF
PVSGPSBOZDIBOHFPGZPVQIZTJDBMDPOEJUJPO
8

9

The goal is 100%,
which means..
t1SPQFSNFBOT>95% adherence!
t5IFTUVEZTIPXFEUIBUNPSFESVHSFTJTUBOUWJSVTFTXFSFTFMFDUFE
with bad adhrence less than 95% (ref)How many missed doses in a month (30 days)
could be allowed to keep "95%" adherence ?
◆ Those who are prescribed once-daily regimen take 30 times a month.
If…
you forget once, it means taking medicines
29 times a month (29 ÷ 30 = 96.6%).
you forget twice, it means taking medicines
28 times a month (28 ÷ 30 = 93.3%).
Therefore, forgetting only twice makes the adherence less than 95%.

100%

Rate of patients who developed drug-resistant viruses

How properly should patientstake medicines to avoid
drug-resistant viruses.

82.1%
80%

66.7%

71.4%

54.6%

60%

40%

21.7%

◆ Those who are prescribed twice-daily regimen take 60 times a month.
If…
you forget once, it means taking medicines
59 times a month (59 ÷ 60 = 98.3%).
you forget twice, it means taking medicines
58 times a month (58 ÷ 60 = 96.6%).
you forget twice, it means taking medicines
57 times a month (57 ÷ 60 = 95%).
Therefore, forgetting 3 times still keeps the adherence more than 95%.

t3PVHIMZTQFBLJOH UIFMFTTUJNFTZPVUBLFNFEJDJOFTBEBZ 
the easier the adherence gets lower.
tIt is more and more important to take medicines properly as more once-daily
NFEJDJOFTBSFBWBJMBCMF XIJDIBSFCBTJDBMMZFBTZBOECFUUFSNFEJDBUJPOT

20%

0%
≧ 95%

90 –
94.9%

80 –
89.9%

70 –
79.9%

＜ 70%

January

February

March

Rate of Adherence
Paterson DL et al.Ann Intern Med. 133: 21-30(2000)

It is important to take 100% of doses
to avoid emerge of drug-resistant viruses.
1011

Reinfection.
t3FJOGFDUJPONFBOTCFJOHJOGFDUFECZ)*7BHBJO)PXFWFSQSPQFSMZZPVUBLFNFEJDJOF BOUJ)*7ESVHTDBOFOUJSFMZMPTFFGGFDUJWFOFTT XIFOUIFJOGFDUFEWJSVTFTBSFESVHSFTJTUBOU
t&WFOJGZPVUBLFNFEJDJOFT ZPVIBWFQPTTJCJMJUZUPCFSFJOGFDUFEBOEUPJOGFDUPUIFSTCross-resistancet:PVIBWFUPDIBOHFNFEJDJOFTJGPOFPGUIFESVHTMPTFTFGGFDUJWFOFTTCFDBVTFPGESVHSFTJTUBOUWJSVTFT
t6TVBMMZUIFOFXESVHJTFGGFDUJWFBHBJOTUUIFESVHSFTJTUBOUWJSVTFT
CVUJGJUIBTUIFTJNJMBSDIBSBDUFSJTUJDTUPUIFQSFWJPVTESVH JUNJHIUOPUXPSLFGGFDUJWFMZt*OPUIFSXPSET TPNFPGESVHSFTJTUBOUWJSVTFTTIPXSFTJTUBODFBHBJOTUESVHTZPVIBWFOFWFSUBLFOBOEJUJTDBMMFE$SPTT3FTJTUBODF

3FJOGFDUJPOSimilarity.

5SZOPUUPUBLFSJTLZBDUJPOTQVUUJOHPUIFSTBOEZPVSTFMWFT
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13

Q&A
Q 1 I take them for a long time ?
AWill drugs lose effectiveness when
No. Drugs remain effective even though you take for a long time,
unless drug-resistant viruses appear.

doctor recommended me to change my medicines
Q 2 Myto better ones with fewer side effects, but I'm worried
that once I change current medicines, I will lose future
treatment options when drug-resistant viruses appear.

A
Q3

You won't lose your options. The number of options will notdecrease when you change your medicines for reasons of side
effects, size of tablets, or frequency of taking medicine.

Can I change back to previous drugs when the new drugs
result in severer side effects ?

A

Yes, you can. Previous drugs remain effective if the reasonof change is not because of drug-resistant viruses.
Since you have to take side effects into account in the long-term
treatment, it is important to discuss with your doctor.

can I find out whether
Q 4 How
I have drug-resistant viruses or not ?
A

A blood examination called "Drug Resistance Test"
reveals the emergence of drug-resistant viruses.
This test can be covered by health insurance.

case that my current drugs lose effectiveness,
Q 5 Indoestheany
drug I've never taken is effective against HIV ?
A

Not always. Anti-HIV drugs with the similar characteristics
to the ones which lose effectiveness are
You can find out which drugs are effective by drug resistance tests.

14

Q 6 What if I realize that I forget to take medicines ?
A

There are several ways to handle dependingon the time you realize it.
① If you have still some time before the next pills( when you realize just after the previous turn)t5BLFNFEJDJOFTBTTPPOBTQPTTJCMF
t5BLFZPVSOFYUEPTFBTTDIFEVMFEt:PVEPOhUIBWFUPEFMBZUIFOFYUEPTF
② If the next turn is coming soon(you were late in recognizing that you forgot)t4LJQUIFEPTFZPVGPSHFU
t5BLFZPVSOFYUEPTFBTTDIFEVMFEt%POPUUBLFBEPVCMFEPTF
t*OGPSNZPVSEPDUPSIPXNBOZUJNFTZPVGBJMUPUBLFNFEJDJOF 
when you see the doctor next time.

If you have any questions, let's ask health care providers.

if I'm running out of medicines because of natural
Q 7 Whatdisasters or troubles during travels.
A

In emergency, the ways of coping are different dependingon the drugs. Be prepared in advance to handle the situation
properly even in emergency.
For emergencyt"TLIFBMUIDBSFQSPWJEFSTJOBEWBODFUIFXBZTPGDPQJOH
and contact information in emergency.
t,FFQBTFWFSBMEBZCBDLVQTVQQMZPGZPVSNFEJDJOFT
with you always.
t3FNFNCFSOBNFTBOEBNPVOUPGESVHT
It is recommended to write down these information ona piece of paper and put it in your wallet.
t8SJUFEPXOQIPOFOVNCFSTPGUIFIPTQJUBMPOBQJFDFPG
paper in case your mobile phone gets out of work.

Do not forget to confirm with your health care providers
the way of coping every time you change or add medicines.
15

Which type are you in ?
Tips to avoid forgetting
to take medicines"Taking anti-HIV medicines properly" means
taking everyday,
taking exact dosage,
types of medicines,
taking exact types, and keep taking.

A variety of strategies to maintain adherence according to your type.
Type A: who forgets to take medicines carelesslyt6TFBMBSNGVODUJPOPGNPCJMFQIPOFTBOEPUIFSFMFDUSPOJDEFWJDFT
t6TFBOBQQPGTNBSUQIPOFTXIJDISFNJOETUBLJOHNFEJDJOFT
→:PVDBOåOETPNFBQQTXJUIXPSETNFEJDJOFT3FNJOEFS
t6TFFNBJMUPPMUIBUBWPJEGPSHFUUJOH

Any of them can't be missed.

Don't to forget mail（忘れちゃだメール）
http://www.da-mail.jp/
1SPWJEFECZUIF.JOJTUSZPG)FBMUI -BCPSBOE8FMGBSF
GSFFPGDIBSHFBOPOZNPVTt"TLZPVSIPVTFIPMENFNCFSTUPSFNJOEZPVUPUBLFNFEJDJOFTBUUIFTDIFEVMFEUJNF

Type B who forgets to carry medicines.
t1VUZPVSNFEJDJOFTJOBQJMMCPYBOECSJOHJUXJUIZPV
t,FFQBCBDLVQTVQQMZPGNFEJDJOFTBUXPSL
8FBQQSFDJBUFBMMUIFQBUJFOUTBOEIFBMUIDBSFQSPWJEFSTXIPHBWFVTOVNFSPVTTVQQPSUTUPNBLFUIJTCPPLMFU

Type C: who forgets whether you took medicines or not.
t6TFBEBZQJMMCPY→*UJTVTFGVMUIBUZPVDBOUFMMCZKVTUMPPLJOH

「きちんとのむ」ってどんなこと？ ＜英語訳＞
Type D: who falls asleep without taking medicinesand realizes in the morning.

平成26年度 厚生労働省科学研究費補助金エイズ対策研究事業「HIV感染症の医療体制の整備に関する研究」班

作

成t$POåSNXJUIZPVSIFBMUIDBSFQSPWJEFSTUIFXBZPGDPQJOHJOBEWBODF

Type E: who couldn't take medicines because
he couldn't eat anything. who couldn't take medicines
because the time of meal has changed so much.
(medicines which should be taken with food)t"TLBOEDPOåSNIPXNVDIGPPEZPVTIPVMEFBUXIFOZPVUBLF
NFEJDJOFTXJUIZPVSIFBMUIDBSFQSPWJEFSTJOBEWBODF
t"TLBOEDPOåSNIPXMBUFZPVDBOUBLFNFEJDJOFTBGUFSNFBMXJUIZPVSIFBMUIDBSFQSPWJEFST

16

2015年3月発行

杉浦 亙 [研究分担者] 名古屋医療センター
宮崎菜穂子 [研究協力者] 東京大学医科学研究所

翻 訳 古川龍太郎（東京大学医科学研究所）、Shin.T
イラスト 知野見美紀
連絡先（独）国立病院機構 名古屋医療センター 臨床研究センター 感染・免疫研究部〒460-0001 名古屋市中区三の丸四丁目1番1号 Tel：052-951-1111（代）発行者

伊藤俊広 [研究代表者]

お問合せ(contact us)（独）国立病院機構 仙台医療センター

http://www.hiv-resistance.jp/contact/

Drug-resistant HIV Information Center薬剤耐性)*7インフォメーションセンター

http://www.hiv-resistance.jp/
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the reproduction of contents, the illustration of booklet.

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