HIV infection

Thana Khawcharoenporn, MD, MSc

Associate Professor of Medicine
Division of Infectious Diseases
Faculty of Medicine
Thammasat University
 !"#

The Virus
• Retroviruses
• Advantages
• Great genetic diversity $ "% &
'(%)%*+, -./0122/ 3
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• Latency $ ;4+% 79<< =485+ 8,,)%9 ;9>97> /=:

• Reducing the effectiveness of the host

immune response (CD4 cell and
macrophage) 28%%
$ (>>(7? %@ /AB C B. D - 79<< >
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 The Virus >4 ;9>97> LP
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• Two single (%>8Q9%

strands of
RNA
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• Three major
structural
genes, namely
*>4+<+<+4%
gag, pol, and
env.
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 Life cycle
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 HIV
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648( $
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circulating recombinant forms

Thailand subtypes (clades) $ )%5(J9 59]

• AE (formerly E) – 97-98% (sexual contact)

• B – 2% (IDU) :%<4+ $ 84% 48(

• Others - <1%
 End of 2018: 37.9 million $ 48(88455+

End of 2018: 1.7 million new case/yr

770,000 had died in 2018 $ 4%4<+8;
Epidemiology

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 Epidemiology
$ `4855(*+MI85?%

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 จำนวนผูป้ ่ วยที่ติดเชื้อเอชไอวีทงั ้ ผูใ้ หญ่และเด็ก
Thailand
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1990 1995 2000 2005 2012 2016 2018
 ควำมชุกของโรคติดเชื้อเอชไอวี (อำยุ 15-49 ปี )
Thailand
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1.5% ความชุกร้อยละ 1.1

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5,I8_(
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1990 1995 2000 2005 2012 2016 2018
 จำนวนผูต้ ิ ดเชื้อเอชไอวีรำยใหม่
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Epidemiology: Thailand

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 Epidemiology: Thailand
The key affected populations include:

• Commercial sex workers

• Men who have sex with men (MSM)
• People who inject drugs (PWID)
 Epidemiology: Thailand
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ชนิ ดและลักษณะของการได้ร ับหรือสัมผัสเชือ้ ่

ความเสียงต่ ้
อการติดเชือเอชไอวี
การร ับเลือด H4%>44%@5 !"#
$ 90%
้
การแพร่เชือเอชไอวี ้ ่ทารก
จากมารดาติดเชือสู 13-45%
การใช ้เข็มฉี ดยาเสพติดร่วมกับผู ้ติดเชือ้ 0.67%
เพศสัมพันธ ์ทางทวารหนัก ผู ้สัมผัสเป็ นฝ่ ายร ับ 0.5%
โดนเข็มตา 0.3%
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้
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้
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ผ่านทางเยือบุ 0.09%
้
การสัมผัสเชือเอชไอวี ่ ไม่
ผ่านทางสารคัดหลังที ่ ใช่เลือด <0.09%
เพศสัมพันธ ์ทางทวารหนัก ผู ้สัมผัสเป็ นฝ่ ายสอดใส่ 0.065%
เพศสัมพันธ ์ทางช่องคลอด ผู ้สัมผัสเป็ นฝ่ ายสอดใส่ 0.05%
เพศสัมพันธ ์ทางปาก ผู ้สัมผัสเป็ นฝ่ ายร ับ 0.01%
%55<48_5)5485)
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การสัมผัสเชือเอชไอวี ้ จากการถูกกัดหรือเป็ นผู ้กัด 0.004%
การสัมผัสเชือเอชไอวี ้ ่
ของทารกจากการดืมนมมารดาติ ดเชือ้ 0.001-0.004%
 HIV Infection via
Mucosa
• Intact mucosa ?
• R5 virus infects
dendritic cells
• Transport of virus
to regional LN
• Transmit to CD4+
T cells in regional
LN

>>4;%8
i1 *4<;9I5

Walker et al. NEJM 1998

 i1
-85 8% '5

HIV Infection
<(8);45%+Q8+79;54;<+)6
E
• Lymph nodes
LU *I **%58*%*J44%
Viremia
&

•
• Dissemination
to other organs
Brain
Spleen
Gut
Within few days

Walker et al 1998
 Natural History: Stages
• Viral acquisition jI8>4 $

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• Primary HIV infection (Acute HIV infection)

• Seroconversion $ (554<44 ZM
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• Latent period $ >;(4,5

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• AIDS JJ
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 HIV Timeline

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Acute HIV infection

4,5%(84V
• Acute HIV infection is a mononucleosis-like
syndrome.
• Differential diagnosis: infectious mononucleosis
(EBV, CMV), toxoplasmosis, rubella, syphilis
T,5
O &
• Flu-like symptoms, diarrhea, meningitis, mucosal
ulcers, lymphadenopathy C i1-K E
 Acute HIV infection
• HIV RNA (viral load) is the reference diagnostic
test.

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Tests for HIV antibody (seroconversion)

• Blood-based tests (TUH example) !8Q* 59%58>868>N 5H978J878>N
$ l FF&FFc

• ARCHITECT HIV Ag/Ab Combo (Abbott,

Germany) - a chemiluminescent microparticle
immunoassay OT =48
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dT ,544<58+
• If the HIV antibody was positive by this test, it
was then confirmed by the other 2 HIV
antibody detection assays 5H978,9% @5
$ U%5 +>>5(%48%5%+

• DetermineTM HIV-1/2 (Alere Medical,

74%J8I,
U >95> Japan) - an immunochromatographic test
• SERODIA® HIV-1/2 (FUJIREBIO, Japan)
- a passive particle agglutination test
C 2"/``/ E
h 74%J8I, 4* Ufb
• Oral fluid-based test + Blood-based tests R
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OT ,9 4)>
Rapid HIV Test: Oral Quick Test

h
Long-term nonprogressors and elite HIV
controllers %8_+%48(*>4%(5(,8(+485
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• Long-term nonprogressors FTFbFTSbT;(,

• HIV-infected individuals (~3% to 5%) who can
maintain normal CD4 counts for many years in the
absence of therapy !+8>V85%) C B.D=;((
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• Elite controllers W(% r r

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• HIV-infected individuals (~1%) who can maintain
undetectable HIV RNA level for years in the absence
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5

HIV and opportunistic infections

 (&&
4I

Natural Course of HIV Infection and Common Complications

H

1000
VL
900
CD4+ T cells Relative level of
800 Plasma HIV-RNA
CD4+ cell Count

700 TB $++S48,7.D <969<

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600
500 B.D

HZV $ DTTOfTT

400 Acute HIV Asymptomatic 4I(<*(8IN<9)?4H<(*8(

infection
syndrome OHL B. D^TT C :A# E

7(%;8;8(585<4I(<
$

300
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0
0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11
4%
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Months Years After HIV Infection H,t C K87I4M(7>9I8,
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Epidemiology of HIV-related OI in Thailand
Percent
74,,4% +*4
35
29.46
30
25
19.19
20
15 12.97

10
5
0
Tuberculosis PCP Cryptococcosis

สำนักระบำดวิทยำ กรมควบคุมโรค กระทรวงสำธำรณสุข พ.ศ. 2557

Case: Mr. A
Mr. A is a 35 year-old man who presented to a GP
clinic with fever and productive cough for 2
weeks. He noticed having night sweat and weight
loss of 5 kgs for the past month.

Physical examination revealed mildly pale

conjuctiva but otherwise unremarkable.

Chest X-ray was sent.

k9>87)<9 (<694<(I 8%J8<>I(>84% k#i u i'i

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 Tuberculosis
Outlines
• Epidemiology
• Clinical manifestations
• Diagnosis
• Treatment
• Prevention
• Timing of cART initiation
Tuberculosis: Epidemiology
%8*8
a
$ -A %4)%5 &
O

);

• Resurgence of tuberculosis after HIV epidemic

( K-/ LUbb
$ HI4>97>869 9JJ97> -A (%

• Decreased TB incidence after cART

• Higher incidence of TB in HIV-infected

individuals compared to general population in
Thailand (3,000 vs. 149 per 100,000)

WHO. Tuberculosis country profile 2013.

Manosuthi W, et al. J Infect 2007; 55: 464-9.
Latent tuberculosis $ `4*% (;5

• Asymptomatic infection =V8(4,5 %4+

O &

-)I% 8>5 (7>869 Lf

C !Y# 8% / (& Sg 9I5 E

• Increase in risk of subsequent active TB

development (15 times compared to non-HIV-
infected individuals)
9% "54%8(V8;

• INH prophylaxis decreases rate of active TB

development (62%) and mortality (26%).
_%(+I848( !"#

• Screening and treatment of latent TB is

recommended at entering care.
 "%5<5%I8 "4%5

Tuberculosis: Clinical manifestations

• Depending on CD4 level (level of inflammatory

response) B. D
"%J<(,,(>84%
B. DSbT
+4+
$ a 3

3
8%J<(,,(>84% !G/
8)4 $ a 3

3
4,58+4

4,5J;8(*+
$

• Sites of infection
• 78% pulmonary
• 15% just extrapulmonary H<9)I( 9v i1
R

• 7% pulmonary + extrapulmonary $ .8559,8%(>9; 8%J97>84%

• Fever, chronic cough, weight loss, night sweat

and fatigue
Tuberculosis: Clinical manifestations

• CXR I4+ GV <4M9

)HH9I 8%J<(,,(>84%
3

<((<+4 $

• CD4 >200: upper lobe cavities; well-formed

granulomas (%;<)+(45;4(8>(

48(%8,,,9I848%
8% C *45> ;4+% E

• CD4 <200: infiltrates in mid-lung zones

without cavities, poor granulomas
formation, or negative CXR 8%J<(,,(>84% +44 &

$ j(<59 OTS

• PPD test can be negative and does not helpful

in ruling out TB.
Tuberculosis: Clinical manifestations

• Extrapulmonary sites
• Lymph nodes
• Pleura
• Meninges
• Bone and joints
$ j'G %@ 74,,4%<N (+! !"#

• Disseminated form – a cause of fever of

unknown origin in HIV-infected patients
Latent tuberculosis: Diagnosis
• Tuberculin skin test (TST) or purified protein
derivative (PPD) test
• Cut-off level ≥5 mm is classified as positive.
• Low uptake of TST in Thailand +++&S;8+4 $

• Low sensitivity of TST

• Cross-reaction with other mycobacteria (MAC)
>95> %8
• Two visits requirement 4844,554,(,+V%5n G8++% ;8+++ 4%<N
S&
$
w
@
U & C E

• Errors during administration and measurement $ Z4I>( ".

C 9,(8< (+8;M
• The effect of BCG vaccination dT $ j(<59
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• Different cut-offs for induration

x L +(%> %4 B5,,8;+*I5I8% @5 5*4> E

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C >*M+ 24)%;5 E
 Latent tuberculosis: Diagnosis
• Interferon-gamma release assay (IGRA)
• TB specific antigen (ESAT-6, CFP-10)
<4%484%(+>;
&
,6%8+4854
• Probably more sensitive than TST $ j(<59 OTbTT *85 1+5

• The role of latent TB diagnosis in HIV-

infected patients?

- B9<< C /AB E
&
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()%>5 Yj1 O

144 $B K( r E
Tuberculosis: Diagnosis
• Compatible clinical syndromes
• CXR $ 8%J8<>I(>84%
)HH9I <)%Q

• Detection of Mycobacterium tuberculosis

• AFB staining
• PCR
$ W4<;
5>(%;(I;
• Culture (reference standard)
 "1!
HI4H*N<(]85

Latent tuberculosis: Treatment

• INH prophylaxis or preventive therapy (IPT)
• 300 mg daily for 9 months
• Low uptake of IPT in Thailand *I>*)M8<<+58)(+
$

• Inability to completely rule out active TB %%858++ $ (7>869 4845*)(4>(

• Acceptance and completion rates >4% LUSf,, w %)> ;%5) 2 5 <4> 4+

C <455 j1 589) E
• INH adverse reactions 5I9

• High rate of INH resistance [49% $

• The need for close monitoring

Latent tuberculosis: Treatment
• INH + Rifapentine C *I4,(,>%4(4; r E

• Weekly dosing for 12 week

y
;9%>%4,+<I* "1! 4)>58;9I5 <4Q45
• Daily dosing for 1 month
F
Tuberculosis: Treatment
• Empiric therapy (clinical findings, CXR, AFB)
SDbDT j455 9>7

• Standard intensive phase + continuous phase

&

• 2 months + 4 months !(%48 TSST,5 :]>9%; u P <4>4+

• 2 HRZE + 4 or X HR (± B6)
>4>(< FSbT/

• Cavitary pulmonary TB, slow response (X = 7)

• Meningitis (X = 7-10)
• Bone and joint (X = 4-10)
• Drug-resistant TB (H and/or R resistance)
• Second-line drugs to have at least 2 active drugs
• Fluoroquinolones (moxifloxacin, levofloxacin,
ofloxacin)
• Aminoglycosides (amikacin, kanamycin)
Tuberculosis: Drug facts
• Renal dosing adjustment: Z, E, -K ; 2) ;459 4% ( %8

fluoroquinolones, aminoglycosides
• Liver dysfunction: avoid H, R, Z )b%b)5,5*8(%+(+,8>(848 h
$

• Important adverse reactions

• Hepatitis: H, R, Z
• Cholestasis: R
k8J(,H878%
• Neuritis: H, E b ." 8)>4 9% !"#

• Drug interaction with R (enzyme inducer), esp.

protease inhibitors, nevirapine
 M(%<58+9%,8+ FUb

Tuberculosis: Timing for cART initiation

SfbbS =48
R

&

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m A(<(%79 "k"2 Z )>; ;9<(N -] u

"k"2 >
",,)%9 k974%5>8>)>84% "%J<(,,(>4IN k95H4%59
C (8*8)855*++ 8,,)%9 I8(65+>(%45*8 -4 TU %@ +44;
8%J>(,<+;+(, E

Thai AIDS Guidelines 2014.

Case 2:
A 28 year-old homosexual male who was diagnosed with
HIV in 2008, last CD4 210, VL 130,000 (no cART) who
presented to ER with shortness of breath, dry cough and
fever for 1 week. He appeared to be in acute distress with
oxygen saturation 85%. Other exam was unremarkable.
His chest x-ray is shown below.
A8<(>9I(< "%>9I5>8>8(< 8%J8<>I(>84%
Pneumocystis: Epidemiology
• P. jirovecii vs. P. carinii =;I8(<5%<+(+
*4+

• P. jiroveci vs. P. jirovecii HI4>4V4(

e &

HI4>4V4( C 88 E

• International Code of Zoological Nomenclature

vs. International Code of Botanical
Nomenclature *>4; B8E

• PCP vs. PJP

• PneumoCystis Pneumonia
Pneumocystis: Epidemiology
• Environmental fungi
• Acquisition via respiratory tract
• Community acquisition is common.
• Nosocomial acquisition has been rarely
reported.

Dohn MN, et al. Am J Respir Crit Care Med 2000; 162: 1617-21.
Choukri F, et al. Clin Infect Dis 2010; 51: 259-65.
Helweg-Larsen J, et al. QJM 1998; 91: 813-20.
Pneumocystis: Risk factors
• CD4 < 200 cells/µl
• History of previous pneumocystis infection
• CD4 < 14%
• Presence of oral candidiasis
• Recurrent bacterial pneumonia *45> !((59 B. D

• Unintentional weight loss

• High HIV viral load

Kaplan JE, et al. J Infect Dis 1998; 178: 1126–32.

Kaplan JE, et al. AIDS 2001; 15: 1831–6.
Chu SY, et al. JAMA 1995; 273: 848.
Pneumocystis: Clinical manifestations

Symptoms & Signs Frequency

Fever 79-100%
Cough 95% (70% dry)
Dyspnea 95%
Chest pain, rales, rhonchi, 7%
no symptoms
S OU/*

• Subacute onset, mostly pulmonary infection

&

• Extrapulmonary infections: lymph nodes, spleen, liver,

eyes, GI, skin, other organs

Kales CP, et al. Arch Intern Med 1987; 147: 1413-7.

Ng VL, et al. Clin Microbiol Rev 1997; 10: 401–18.
Pneumocystis: Investigations
Chest X-ray
• Diffuse, bilateral, interstitial or alveolar
infiltrates (ground glass opacity)
• Pneumothoraces
• Blebs
• Lobar or segmental infiltrates
• Cysts, nodules
• Cavities, pleural effusion
• 1/3 - normal $
%>4,5**4845(54+>8%84+
Pneumocystis: Investigations: CXR

A8<(>9I(< WI4)%; Q<(55

&

(HH9(I(%79
Pneumocystis: Investigations
Arterial blood gas
• Severity determination 3 -I9(>
5969I8>N
K/

• PaO2, Alveolar-arterial gradient (A-a)

P. jirovecii detection
• Sputum induction (sen <50-90%)
• Bronchoalveolar lavage specimen (sen 90-
99%) 7*95> ,9;
$ %4% AZi

• Lung biopsy (sen 95-100%) 5>(%;(I; $ W4<; C >44 8%6(5869 E

Pneumocystis: Diagnosis
Special staining
• Giemsa or Wright (cyst and trophozoite)
• Gomori Methanamine Silver (GMS) (cyst)
AI45 R C 5>);895 79<< +(<< 48<
Pneumocystis: Treatment
Antipneumocystis Duration 21 days
Preferred "% rr
V
&
Trimethoprim-sulfamethoxazole (TMP-SMX) IV or po
K85*9(I; o
$^
(15 mg/kg of TMP per day) USUc
C jb*I & E

Alternative 1 Clindamycin 600 mg IV q 8 hrs or 300-450 mg po

q.i.d. PLUS
Primaquine 15-30 mg/kg/day po
Alternative 2 Pentamidine 4 mg/kg/day IV

Corticosteroid therapy: benefits

• Decrease mortality at 1 and 3-4 months
• Decrease rate of respiratory failure

Corticosteroid therapy: indications

• ABG: PaO2 ≤ 70 mmHg >)5>9I48;
• ABG: A-a gradient ≥ 35 mmHg C 95H&<) !"# H(>89%>
%8LU!6!V6v E
Pneumocystis: Treatment
Antipneumocystis Duration 21 days
Preferred Trimethoprim-sulfamethoxazole (TMP-SMX) IV or po
(15 mg/kg of TMP per day)

Alternative 1 Clindamycin 600 mg IV q 8 hrs or 300-450 mg po

q.i.d. PLUS
Primaquine 15-30 mg/kg/day po
Alternative 2 Pentamidine 4 mg/kg/day IV

$ V8555

UU `/!""-':1XBX
Pneumocystis: Prevention
Type of prophylaxis Indication Duration
Primary =(88%)8++ CD4 < 200 cells/µl Until CD4 becomes ≥
Secondary $z %'L'L+!`U After infection 200 cells/µl after ART

Drug Administration
TMP-SMX 800/160 mg po daily $XBXl -4]4H<(5,4585 <I>458+M>I85;5
C A(7>I8, E 400/80 mg po daily $X7X 4%<N
800/160 mg po 3 times/week $XBX 4%<N
Dapsone 100 mg po daily
Dapsone + D 100 mg po daily + P 75 mg po daily + leucovorin 25
Pyrimethamine mg po daily
 % &
85+48+%488+

Pneumocystis: Timing for cART initiation

XBX":/ 9%488+>488()

"k"2 >;+4 $ a
d 5>9I48; "% h( "k"2! )4>5485+ 3 *89%488+>4884V

Thai AIDS Guidelines 2014.

CASE 3:
27 year-old male with AIDS (CD4 17 VL 105,000)
diagnosed 1 month ago, no cART, brought to the ED
with headache for 7 days, progressively getting
worse, with N/V and subjective fever. This morning,
he became less responsive. j((5 $

$
B)5*8%Q I9J<9] C KBX E

PE: T 39 °C, BP 150/80 mmHg, HR 60/min RR 12-

26/min F"BX

HEENT: papilledema both eyes

Chest, CVS, Abdomen – unremarkable
Neuro: not cooperative, no nuchal rigidity, moved all
extremities equally
 $ "%;8(% 8%? C =+ ;4+%5<8;9 E

$ ;8<(>9 69%>I87<9 %H>45

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R 7(H5)<9 >4+%
Cryptococcosis: Epidemiology
fLS/ j;( &

• Environmental fungi
+%58(+

• Pigeon nests and droppings (neoformans var.

grubii, neoformans)
• Eucalyptus trees (neoformans var. gattii)
• Africa, South Asia and Southeast Asia (HIV)
• Thailand: C. neoformans var. grubii (96%) and
C. neoformans var. gattii (4%)

Khawcharoenporn T, et al. Infection 2007; 35: 51-8.

Park BJ, et al. AIDS 2009; 23: 525-30.
Poonwan N, et al. Eur J Epidemiol 1997; 13: 335-40.
Cryptococcosis: Epidemiology
$
%48<;4)<+;44>;49< B12

• Acquisition via respiratory route

• Low immunity leads to disseminated infection
(esp. central nervous system)
• Mainly community acquisition
• Nosocomial transmission has been rarely
reported but associated with use of
contaminated medical instruments.
• Risk factors: CD4 < 100 cells/µl

Krcmery V Jr, et al. Infection 1997; 25: 130.

Wang CY, et al. N Engl J Med 2005; 352: 1271-2.
Khawcharoenporn T, et al. Infection 2007; 35: 51-8.
Cryptococcosis: Clinical manifestations
Asymptomatic infection
(%>8Q9% F

• Isolated cryptococcal antigenemia I84nJ;(4,4

• Screening in patients with CD4 < 100 cells/µl

• Increased risk of subsequent disseminated infection

CNS infection (meningitis, cryptococcoma)

• Fever, headache (subacute)
• Meningeal irritation signs (25-33%)
• Blurred vision, altered mental status
• Localized neurological deficits
Cryptococcosis: Clinical manifestations
Pulmonary infection (pneumonia, abscess)
• Fever
• Cough
• Dyspnea

Cutaneous infection
• Papules
• Molluscum-like lesions

C
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Cryptococcosis: Diagnosis
• History
• Physical examination – non-specific
• CT brain (mass, hydrocephalus) 69%>I87<9 J4I

• CSF examination
- High opening pressure
- Mononuclear predominance
- High protein, low sugar
- Indian ink
- Cryptococcal antigen
Cryptococcosis: Diagnosis
• Fungal culture from infected specimen
• Special staining
'8+485) 7(H5)<9

$ 7(H5)<9 >4+% !(5

GMS Mucicarmine
Cryptococcosis: Treatment
Isolated cryptococcal antigenemia 8<;54%,5

• Evaluation to exclude disseminated infection, CNS

infection 4I%)%);8I5(4,5
• Cryptococcemia or serum cryptococcal antigen ≥ 1:512
(treat as CNS infection)
• Fluconazole 400 mg/day oral for 6-12 months or until
CD4 becomes more than 100 cells/µl for at least 3
months "54<(>9;
&

Perfect JR, et al. Clin Infect Dis 2010; 50: 291-322.

Cryptococcosis: Treatment
CNS infection $^ H*(59 -]

Phase Timing Regimen

Induction 2 weeks Amphotericin B (1.0 mg/kg/day)
Amphotericin B (0.7-1.0 mg/kg/day) +
Fluconazole (800-1,200 mg/day)
Liposomal amphotericin B (3-4 mg/kg/day)
Amphotericin B (1.0 mg/kg/day) + U

Flucytosine 100 mg/kg/day for 2 weeks

then Fluconazole (1,200 mg/day) for 1
week
Cryptococcosis: Treatment
CNS infection
Phase Timing Regimen
Consolidation 8-10 weeks Fluconazole 400-800 mg/day
C Q9(I5 8%8>8(< E
Cryptococcosis: Treatment
CNS infection

Phase Timing Regimen

Maintenance Until CD4 > Fluconazole (200 mg/day)
(2° prophylaxis) 100 cells/µl for Amphotericin B (1.0 mg/kg/week)
≥ 3 months on
ART Itraconazole (200 mg/day)
Cryptococcosis: Treatment
$
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Maintenance of normal CSF pressure

95H &

• During the first 2 weeks – associated with survival

• CSF drainage daily iX ;I(8% %H

• Neurosurgery consultation for VP shunt placement if

no response in 2 weeks
• Acetazolamide, corticosteroid and mannitol are not
effective and can cause significant adverse effects.
$ 9%((4+45)5+J;8+((
B5J HI955)I9 h

Graybill JR, et al. Clin Infect Dis 2000; 30: 47-54.

Perfect JR, et al. Clin Infect Dis 2010; 50: 291-322.
Cryptococcosis: Treatment
Pulmonary infection
• ARDS and severe infection treat as CNS infection
• Mild to moderate symptoms with localized infection
Fluconazole 400 mg/day for 6-12 months depending on
the response

Others $ J;>8 H)<,4%(IN R

B12

• Multi-site and severe infection, concomitant

cryptococcemia treat as CNS infection
• Mild to moderate symptoms with localized infection
Fluconazole 400 mg/day for 6-12 months depending on
the response

Perfect JR, et al. Clin Infect Dis 2010; 50: 291-322.

Cryptococcosis: Prevention

Type of prophylaxis Indication Duration

Primary CD4 < 100 cells/µl Until CD4 becomes ≥

100 cells/µl after ART

Drug Administration
Fluconazole 400 mg po per week
Itraconazole
{ ,+?8<48
200 mg po daily
Cryptococcosis: Timing for cART initiation

$ Z;5 .9<(N C BINH>47477)5 8% ( "k"2 f/ E

l L/ 5?)<< 4* 68( "k"2 (>

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Thai AIDS Guidelines 2014.

 HIV infection treatment
• Antiretroviral therapy
• Combination regimen of 3 active drugs
<(>9
• Inhibit CD4 destruction by the HIV
• Increase CD4 count level and immunity

%4+

| (%>8
Classes
1) CCR5/CXCR4
Inhibitors
2) Entry inhibitors 2
3) Nucleoside reverse 1
6
transcriptase
inhibitors (NRTI)
3 4
4) Non-nucleoside
reverse
transcriptase 5
inhibitors (NNRTI)
5) Integrase inhibitors
6) Protease Inhibitors
(PI)
 Available Antiretroviral Agents

Nucleoside RTIs Nonnucleoside RTIs Protease Inhibitors

• Zidovudine (ZDV) • Nevirapine (NVP) • Saquinavir (SQV)
• Didanosine (ddI) • Delavirdine (DLV) • Ritonavir (RTV)
• Zalcitabine (ddC) • Efavirenz (EFV) • Indinavir (IDV)
• Stavudine (d4T) • Etravirine (ETR) • Nelfinavir (NFV)
• Lamivudine (3TC) • Rilpivirine (RPV) • Amprenavir (APV)
• Abacavir (ABC) • Doravirine (DOR) • Lopinavir/r (LPV/r)
• Emtricitabine (FTC) • Atazanavir (ATV)
• Tenofovir DF (TDF) Integrase Inhibitors • Fosamprenavir (FPV)
• Raltegravir (RAL) • Tipranavir (TPV)
• Dolutegravir (DTG) • Darunavir (DRV)
Boosters • Elvitegravir (EVG)
• Ritonavir (RTV) • Bictegravir (BIC) Fusion Inhibitor
• Cobicistat (cobi) • Enfuvirtide (T-20)

CCR5 Antagonist
• Maraviroc (MVC)
 Available Antiretroviral Agents
(Thailand)
Nucleoside RTIs Nonnucleoside RTIs Protease Inhibitors
• Zidovudine (ZDV) • Nevirapine (NVP) • Saquinavir (SQV)
• Didanosine (ddI) • Delavirdine (DLV) • Ritonavir (RTV)
• Zalcitabine (ddC) • Efavirenz (EFV) • Indinavir (IDV)
• Stavudine (d4T) • Etravirine (ETR) • Nelfinavir (NFV)
• Lamivudine (3TC) • Rilpivirine (RPV) • Amprenavir (APV)
• Abacavir (ABC) • Doravirine (DOR) • Lopinavir/r (LPV/r)
• Emtricitabine (FTC) • Atazanavir (ATV)
• Tenofovir DF (TDF) Integrase Inhibitors • Fosamprenavir (FPV)
• Raltegravir (RAL) • Tipranavir (TPV)
• Dolutegravir (DTG) • Darunavir (DRV)
Boosters • Elvitegravir (EVG)
• Ritonavir (RTV) • Bictegravir (BIC) Fusion Inhibitor
• Cobicistat (cobi) • Enfuvirtide (T-20)

CCR5 Antagonist
• Maraviroc (MVC)
 Available Antiretroviral Agents on the
National Essential Drug List (Thailand)

Nucleoside RTIs Nonnucleoside RTIs Protease Inhibitors

• Zidovudine (ZDV) • Nevirapine (NVP) • Saquinavir (SQV)
• Didanosine (ddI) • Delavirdine (DLV) • Ritonavir (RTV)
• Zalcitabine (ddC) • Efavirenz (EFV) • Indinavir (IDV)
• Stavudine (d4T) • Etravirine (ETR) • Nelfinavir (NFV)
• Lamivudine (3TC) • Rilpivirine (RPV) • Amprenavir (APV)
• Abacavir (ABC) • Doravirine (DOR) • Lopinavir/r (LPV/r)
• Emtricitabine (FTC) • Atazanavir (ATV)
• Tenofovir DF (TDF) Integrase Inhibitors • Fosamprenavir (FPV)
• Raltegravir (RAL) • Tipranavir (TPV)
• Dolutegravir (DTG) • Darunavir (DRV)
Boosters • Elvitegravir (EVG)
• Ritonavir (RTV) • Bictegravir (BIC) Fusion Inhibitor
• Cobicistat (cobi) • Enfuvirtide (T-20)

b*f^ GK1
CCR5 Antagonist
• Maraviroc (MVC)
When to start antiretroviral
therapy
Important considerations for initiating ART
(+>I+44+ 3 849%94>( r

• Patients should be willing and able to commit

to treatment and understand the benefits and
risks of therapy and the importance of
adherence.
When to start antiretroviral therapy
Asymptomatic patients (CD4 criteria: cells/µl)

DHHS WHO Thai

(2017) (2017) 2017
Any Any Any
When to start antiretroviral therapy
Asymptomatic patients
 K ;9>97> a
\, >I(%5,85584%
R

Treatment as Prevention
$ %V8;458+>;%+58*8(%
• Prenatal transmission prevention
• Heterosexual and homosexual transmission
prevention
• Prevention of transmission via blood (among
IDU)
What to start antiretroviral
therapy
What to start: Initial combination regimens
for naïve patients (TAS 2017 recommended)
UfPT
 What to start: Initial combination regimens: @

Thai national guidelines 2020? W<<)+ &

Regimen WHO 2019 TAS 2020?

Preferred first-line TDF + 3TC or FTC + DTG TXF + XTC + DTG
Alternative first- TDF + 3TC + EFV 400 mg NRTIs: ABC + 3TC
line .4<)>9QI(68I NNRTI: EFV
"%>9QI( 8%*8M8>4I
59 RPV
C 4>%5> :j# E

TXF = TDF or TAF

XTC = 3TC or FTC
What to start: Initial combination regimens for
naïve patients (recommended)
:)I4H9 $
"%>9QI( 59 8%*8M8>4I C .-W E *>+)%>%

DHHS 2019 (AI) EACS 2018

BIC/TAF/FTC (AI) DTG/ABC/3TC

DTG/ABC/3TC(AI) DTG + TDF/FTC or TAF/FTC
if HLA-B*5701 negative
DTG plus tenofovir/FTC BIC/TAF/FTC
(AI for both TAF/FTC and TDF/FTC)

RAL plus tenofovir/FTC RAL + TDF/FTC or TAF/FTC

(BI for TDF/FTC, BII for TAF/FTC)
DTG + 3TC DRV/r or DRV/c + TDF/FTC or
TAF/FTC

RPV + TDF/FTC or TAF/FTC

 2":

ARV and common adverse reactions

&

ARV Adverse reactions

AZT Rashes, fever, anemia, N/V
3TC/FTC Rashes, anemia (rare)
TDF Cr rising, proximal RTA, osteopenia
NVP Rashes, hepatitis, dyslipidemia
EFV Dizziness, nightmare, hepatitis, rashes,
dyslipidemia
LPV/r Diarrhea, N/V, hepatitis, dyslipidemia
Goal of HIV treatment
( .(%%85 %44% 5?8% (,%84%

• Reconstitution of the patient’s immunity

• Immunological response
• An increase in CD4 count of ≥50 cells/µl at four to
eight weeks followed by slower incremental
increases of 50 to 100 cells/µl per year
• Factors influencing the increase of CD4 (nadir, age,
type of ARV, concomitant drugs)
• Virologic response
• Viral load suppression below the limits of assay
detection

Thompson MA, et al. JAMA 2010;304:321.

Le Moing V, et al. J Infect Dis 2002;185:471.
General knowledge
What are the facts?
• HIV transmission via a mosquito bite
• HIV transmission via saliva (kissing, eating
together)
• Substance use with sex increases risk?
• HIV free test available?
• What is the lifespan of an HIV-infected patient?
• Other available HIV tests?
• Screening for sexually-transmitted infections
and partners’ HIV status
HIV cure: is it possible?
k9H4I> L +(%> /AK >I(%5H<(%>
• Sterile cure?
• Long term functional cure and no need for
combined antiretroviral therapy
• Long term functional cure but still need
combined antiretroviral therapy
*89%4*+84,%
• Immune reconstitution (partial functional cure)
" E

and need for combined antiretroviral therapy

 Worldwide goals for
HIV/AIDS control
• No death
• No new case
• No stigmatization
Q&A