Download HIV/AIDS in Developing Countries

Clinical Management of
HIV/AIDS in
Resource-limited Settings
Carey Farquhar, MD, MPH
Associate Professor
Departments of Medicine,
Epidemiology and Global Health
Outline
• Special considerations
• Natural history
• Opportunistic infections
• Antiretroviral therapy
• Prevention of HIV transmission
– Heterosexual
– Mother-to-child
Kenya
A country of contrasts
Kibera slum, Nairobi
Population: ~700,000
HIV prevalence: ~8%
About 1/4 of >35 million
Kenyans earn <$1/day
Unique issues in
developing countries
Women and children
Orphans
Lack of resources
Stigma
Stigma
HIV infected persons suffer from discrimination,
abuse, rejection, and abandonment.
People often refuse HIV testing, do not disclose
HIV status, or seek care.
Discordant couple study
• Among 87 participants referred for treatment
with CD4<250 on 2 or more visits:
– Only 40 (48%) started ART within 6 months
• Factors associated with starting:
– Home ownership
• 2.5-fold more likely start if couple owned a home
– Permanent housing
• 30% more likely if not living in a slum dwelling
Guthrie B., et al. J Acquir Immune Defic Syndr. 2011 Nov; 58(3):e87-93.
Natural History
Infection
AIDS and death
1º infection
syndrome
Clinical latency
Plasma viremia
CD4+ T-cell count
6-12
weeks
Duration: 1-15+ years
Constitutional
symptoms
Opportunistic
infections
Duration: 2-3+ years
Peak viral load during acute HIV
Infection
1º infection
syndrome
Plasma viremia
CD4+ T-cell count
6-12
weeks
AIDS and death
Clinical latency
Duration: 1-15+ years
Constitutional
symptoms
Opportunistic
infections
Duration: 2-3+ years
Acute HIV
• Major contributor to transmission events
• Case definition
–
–
–
–
–
–
2-4 week febrile illness
Pharyngitis
Maculopapular rash
Lymphadenopathy
Orogenital ulcers
Meningoencephalitis
• Diagnosis more difficult in resource-limited
settings
Chronic Infection:
CDC classification (1993)
CD4 T cell
count
A
B
C
Asymptomatic Symptomatic Symptomatic
1:
>500
A1
B1
C1
2:
200-500
A2
B2
C2
3:
<200
A3
B3
C3
HIV Web Study: http://depts.washington.edu/hivaids/
AIDS defining illnesses
PCP
Esophageal candidiasis
M. avium complex
Cryptococcus
Kapsosi’s sarcoma
Cytomegalovirus
HIV dementia
Extrapulmonary TB
Cervical cancer
Recurrent bacterial pneumonia
Toxoplasmosis
Lymphoma
Invasive cervical cancer
Chronic herpes simplex
Chronic cryptosporidiosis
Histoplasmosis
Wasting
WHO staging
• Stage 1: Asymptomatic, adenopathy
• Stage 2: Weight loss, pruritic dermatitis, herpes
zoster
• Stage 3: Fever, diarrhea or cough >1 month,
pulmonary TB, candidiasis
• Stage 4 (AIDS): Kaposi’s sarcoma, cryptococcal
meningitis, CMV, lymphoma
WHO: Advanced HIV,
including AIDS
• CD4 <350 cells/μl
• Presumptive or definitive diagnosis of any
Stage 3 or 4 disease
• Children based on CD4 percent and age
– <30% - under 12 mos
– <25% - 12-35 mos
– <20% - 35-53 mos
CD4 count and
opportunistic infections
CD4 Cell Count
1,000
500
200
100
Bacterial Pneumonia, TB, HSV, Cryptosporidiosis
Thrush, lymphoma, KS
PCP
MAC, CMV, PML, PCNSL, Cryptococcus, Microsporidia, Toxo
4-8 Weeks
Up to 12 Years
2-3 Years
Common AIDS-related
conditions in Africa
•
•
•
•
•
•
•
•
Candidiasis
Tuberculosis
Malaria
Cryptococcal meningitis
Kaposi’s sarcoma
HSV/VZV
Pneumococcal pneumonia
Skin problems
– Atopic dermatitis
• Salmonellosis
Salmonella enteritis
• In Cote d’Ivoire, bacterial enteritis accounted for 7% of
admissions to ID hospital
– Salmonella typhi most common among hospitalized
patients with enteritis
• Non-typhoidal salmonella species:
– 18-20% of blood stream infections in Tanzania,
Uganda, and Malawi
– 7-12% in Kenya and Cote d’Ivoire
Less common
• Mycobacterium avium
complex (MAC)
• Pneumocystis jiroveci
pneumonia (PCP)
• Cytomegalovirus
retinitis (CMV)
Why is this?
Case #1
You are working in the Hope Clinic in Nairobi.
An HIV-1 infected women complains of not being
able to eat for 3 days. She has had severe pain
with swallowing.
Her last CD4 count was 250 (1 year ago)
What is your diagnosis and what are your
recommendations?
Case #2
You are spending a month at a rural hospital in
South Africa and have admitted a women with
headache, confusion, and fever. She also has a
rash. She is HIV-infected but does not know her
CD4 count and is not taking any medications.
She has been healthy up until this point.
What is your differential diagnosis?
Mandell, Atlas of Infectious Diseases
Management of cryptococcal
meningitis
• Challenging to treat
– Amphotericin B plus flucytosine best regimen
• Toxic, expensive, intravenous
– Consolidation and maintenance costly
• Threshold to stop fluconazole is CD4>100
– Early initiation of ART associated with high
mortality
• 3-fold higher among those starting ART w/in 72 hrs
– WHY?
Case #3
A man with unknown HIV status presents to the
clinic where you are working in Western Kenya.
He has skin breakdown on his penis and groin
with ulceration and purulence.
What is on your differential and what should you
offer him?
Pediatric HIV infection
The HIV epidemic in children
• 90% infected through
maternal transmission
– In utero, during delivery,
via breastfeeding
• Annual incidence of
~500,000 cases
• 3 million children living
with HIV/AIDS in Africa
Pediatric HIV infection
Two basic patterns during 1st year
• Rapid progression (15-20%)
• Slow progression (80-85%)
Risk of death without treatment:
• 45% by 2 years
• 62% by 5 years
Spira R et al. Natural history of human immunodeficiency virus type 1 infection in
children: A five year prospective study in Rwanda. Pediatrics 1999.
Clinical manifestations in children
Non-specific and variable:
Lymphadenopathy, hepatosplenomegaly
oral thrush, failure to thrive, developmental delay
Most common AIDS defining illnesses:
– Recurrent serious bacterial infections
– Herpes zoster
– PCP
– Esophageal/tracheobronchial candidiasis
Tuberculosis very common, but not AIDS-defining in
children
Characteristics of 100 children
enrolled in a Nairobi HAART study
Age (years)
4.4 (2.4, 6.0)
Baseline weight for age (z-score)
-2.45 (-4.3, -1.54)
Baseline height for age (z-score)
- 2.00 (-3.32, -1.04)
CD4 cell percent
6.3 (3.6-10.0)
Log10 HIV-1 RNA copies/ml
CD4 cell percent after HAART for 6
months
6.0 (5.4-6.6)
14.7 (8.7-20.0)
Wamalwa DC, et al. BMC Pediatr. 2010 May; 10:33.
Strategies to enhance survival
• Prophylactic drugs
– HIV+ patients receive
bactrim/septrin (trimethoprimsulfamethoxazole)
• Care by those with training
& experience in HIV/AIDS
• Highly active antiretroviral
therapy (HAART)
– Early in course of disease
Kenyatta National Hospital, Nairobi
50-75% of urban hospital beds
occupied by AIDS patients
What is HAART?
Combination therapy to avoid resistance
–
–
–
–
–
Nucleoside/nucleotide reverse transcriptase inhibiters (NRTI)
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Protease inhibitors (PI)
Entry inhibitors
Integrase inhibitors
Three drugs from at least 2 different classes
Keys to success are compliance and monitoring
HIV life cycle
PEPFAR
• $18.8 billion commitment over 5 years
• 15 Focus Countries, 12 in sub-Saharan Africa, ~
50% of world’s HIV
• Reauthorization for next 5 years @ $50 billion for
HIV, TB, malaria
When to Start?
• Prevent Immune system destruction
• More effective when started early
• Preserve HIV directed CTL
Early
• Toxicities of treatment
• Increased risk of resistance
• Low rate of disease progression
• Cost
Later
WHO: Advanced HIV,
including AIDS
• CD4 <350 cells/μl
• Stage 3 or 4 disease
• Other specific situations at higher CD4
– Pregnancy
– Discordant couples
• Children based on age and CD4 percent
– All children < 1 year
– Children > 1 year CD4%<25
Case #4
A 27 year women with a CD4 count of 72
begins nevirapine, lamivudine and
zidovudine. At the time she has no
complaints except fatigue.
She presents 4 weeks later with chest pain,
dry cough and fevers. What is on your
differential?
Chest Radiographs
Initial
3 weeks later
Immune reconstitution and HAART

Worsening of signs and symptoms due to known
infections OR occult infections

Results from improvement in immune function after
the initiation of ARVs

Most common with:
– Mycobacterial infections (MTb, MAC)
– Cryptococcal infection
– HHV-8 (Kaposi’s sarcoma)
– CMV, Hepatitis B and C
– Histoplasmosis
Tuberculosis
Paradoxical Reaction %
50
40
36
30
graph
20
10
7
3
0
HIV+/HAART
HIV+
HIV-
Median duration of TB treatment - 109 d, HAART - 15 d
Median CD4 at time of IR syndrome - 92 cells
Narita, Am J Resp and Crit Care Med, 1998
ARVs with Pulmonary TB
WHO recommendations: November 2009
– Start TB treatment first
– Use Efavirenz as preferred NNRTI
– Treat with ART immediately if CD4<50
– Treat within 2-4 weeks if CD4>50
– Start ART within 8 weeks
Prevention
Couple treatment with strong
message about preventing
transmission
–
–
–
–
–
Condoms & “safe” sex
Treatment of STDs
Circumcision
Future vaccines & microbicides
Interventions to prevent mother-to-child HIV-1
transmission
– Treatment as prevention
– Pre-exposure prophylaxis (PrEP
Case #5
A 23 year old Kenyan woman presents with
her first pregnancy for antenatal care at
24 weeks gestation and is found to be
positive for HIV by rapid ELISA testing.
She is counseled regarding interventions
to prevent HIV transmission.
Is a CD4 count and HIV viral load indicated?
If so, how will this change management?
Case #5
Her CD4 count is 360 cells/ul and no HIV
viral load is performed. She is
asymptomatic with respect to her HIV
infection.
What regimen will she be prescribed to
prevent MTCT? Is there an alternative
regimen?
Case #5
She tells you her sister also has HIV and
her baby died. She wants to do
everything she can to prevent her baby
from becoming infected and is interested
in formula feeding.
One problem she sees with formula
feeding is that she is reluctant to tell her
husband that she has HIV.
Case #5
She delivers a healthy infant and decides to
breastfeed because she still hasn’t told her
partner. She wants to know if the baby is
infected and plans to stop breastfeeding
early.
What additional counseling will she
need regarding infant feeding?
Case #5
She successfully weans at 6 months, returns
at 15 months for an HIV ELISA, and is told
that her baby is not infected.
How should you advise her now regarding
follow-up care?
Resources
• CDC guidelines and educational materials (domestic)
– http://aidsinfo.nih.gov/guidelines
– http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf
• UNAIDS/WHO recommendations and updates
(international)
– http://www.who.int/hiv/pub/en/
• Country-specific guidelines for everything, including:
– ARV therapy – adults, children
– HIV testing (couple counseling and testing; homebased testing)
– Prevention of mother-to-child transmission
Asante sana