2/20/2018

Epidemiology of HIV and AIDS

Fatima Mir
Assistant Professor
Pediatrics and Child Health

IDE Feb 20, 2018

Contents
• History
• Prevalence and trends
– global/EMR/Pakistan
• Modes of Transmission
• Epidemiological Triangle
• Transmission Models
• Natural History
• Opportunistic Infections
• Prevention Strategies

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Historical Background
• 1981 – CDC(USA)
– MMWR reporting unexplained PCP/KS in previously healthy
homosexual men in LA
– Taskforce on KS/OI to identify risk factors and develop a case
definition for national surveillance
– MMWR reporting PCP/KS in homosexual men in NY and California
– ‘gay cancer’ enters public lexicon
– 270 ‘reported’ cases; 121 dead by end of year’
– GRID (GAY RELATED IMMUNE DEFICIENCY)
• 1982-CDC (USA)
– First case definition of ‘AIDS’
– Surveillance funding to CDC and Research money to NIH
– AIDS in infant with blood transfusion

https://www.aids.gov/pdf/aidsgov-timeline.pdf

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Historical Background
• 1983
– AIDS in female sexual partners of men with AIDS
– MMWR says AIDS in homosexual men with multiple partners, IDUs,
haitians, hemophiliacs and suggests blood borne and sexual
transmission
– Francoise Barre-Sinoussi (Pasteur Institute) report a retrovirus which
could be a cause of AIDS
– The Denver Principles
– Bobby Campbell and Bobbi Hilliard (Newsweek cover)
– CDC publishes fist set of occupational exposure precautions
– CDC identifies all major routes of transmission

https://www.aids.gov/pdf/aidsgov-timeline.pdf

Historical Background
• 1984
– Robert Gallo (National Cancer Institute) discover a retrovirus (HTLV-3)
• 1985
– MMWR contains new case definition and blood screening recommendations
– New diagnostic test available
– Ryan White (hemophiliac child with HIV banned from school)
– Ronald Reagan (defends poor response of govt)
– Rock Hudson (dies and bequeaths research money)
– USPHS published first guidelines for prevention of mother to child
transmission
• 1987
– FDA approves zidovudine
– Reagan and Chirac end US-France scientific dispute. Both countries share
virus discovery credit and patents
– Princess Diana photographed shaking hands with AIDS patient

https://www.aids.gov/pdf/aidsgov-timeline.pdf

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Global HIV Statistics

People accessing ARV (June 2017) 20.9 million

People living with HIV (2016) 36.7 million
People newly infected with HIV (2016) 1.8 million
People died from AIDS-related illnesses (2016) 1 million
People have become infected with HIV since the start of the
epidemic 76.1 million
People have died from AIDS-related illnesses since the start of
the epidemic 35.0 million

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The Geographical Breakdown

Western & Eastern Europe

Central Europe & Central Asia
North America 0.2% 0.7%
0.5% East Asia
<0.1%
Middle East & North
Caribbean Africa
1% 0.1% South & South-East
Asia
Sub-Saharan Africa 0.3%
Latin America 4.7% Oceania
0.4% 0.2%

Total: 0.8% prevalence

Estimated annual number of new infections

in adults and children globally, 1990-2014
4 000 000

3 000 000
35% reduction between 2000 and 2014
Number of new infections

2 000 000

1 000 000

Source: UNAIDS/WHO estimates

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Global HIV Mortality and incidence:

2000-2014

WHO Regions

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Globally, reduction of new HIV

infections Yet, increase in some regions

HIV estimates
HIV estimates for the WHO Eastern
Mediterranean Region by the end of 2014:
• 326 000 PLHIV
– 16 000 aged 0-14 yrs;
• HIV prevalence: 0.1 %;
• 42 000 new infections;
• 15 000 AIDS deaths;

Source: UNAIDS/WHO estimates; UNAIDS MDG6 Report 2015

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Epidemic trend 2001-2014:

New infections and deaths
EM Region Global
MP4

70 000 3 500 000

60 000 3 000 000

50 000 2 500 000

40 000 2 000 000

30 000 1 500 000

20 000 1 000 000

10 000 500 000

0 0
2001 2014 2001 2014

Source: UNAIDS/WHO estimates

Where are the new infections?

Afghanist Other
an 5%
Egypt 2%

2014
3%
Morocco
Pakistan
8%
38%
Somalia Others
9% Afghanistan
5%
Egypt 2%
3%
Morocco
5%
Sudan
14% Somalia
Iran
6%
Pakistan
21% Sudan 49%
11%
2013

WHO estimates
Number of adults and children with
HIV/AIDS in Pakistan at the end of 2013 Iran
19%
97400 estimated cases

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Slide 15

MP4 Update with Global

PARRY, Dr Matti, 10/11/2015
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Pakistan
• First cases dominated by returning
workers from UAE and elsewhere
Shah SA, et al. Int J STD AIDS 1999;10: 812

• Explosion in epidemic correlated with

– Increases in injection drug use
– Increased availability of heroin from
Afghanistan
– Continued neglect of IDUs in government
HIV/AIDS control efforts

Pakistan

Till 2005, Pakistan defined as a

‘low prevalence – high risk country’

Country with a ‘Concentrated epidemic’

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HIV in Pakistan
2012
• Number of people living with HIV
– 87,000 [50,000 - 160,000]
• Adults aged 15 to 49 prevalence rate
– <0.1% [<0.1% - 0.2%]
• Deaths due to AIDS
– 3,500 [2,100 - 6,600]

Pakistan Perspective
• Driver of epidemic
– PWIDs 104,804 to 420,000
– Prevalence above 40% in multiple cities
• Faisalabad, DG Khan, Gujrat, Karachi, Sargodha
– Harm reduction service delivery
• Nai-Zindagi and NACP through funding from
Global Fund

Bergenstrom et al. Harm Reduction Journal (2015) 12:43 Drug related HIV epidemic in Pakistan: a
review of current situation and response and the way forward beyond 2015

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Which fluids are potentially

infectious for HIV?
• blood • semen

• saliva • vaginal fluid

• sweat • breast milk

• feces • urine

Which fluids are potentially

infectious for HIV?
• blood • semen

• saliva • vaginal fluid

• sweat • breast milk

• feces • urine

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Modes of transmission
• Parenteral
– Contaminated injection equipment
– Unscreened blood
• Sexual
– Genital-genital
– Genital-oral
– Genital-anal
• Vertical
Bergenstrom et al. Harm Reduction Journal (2015) 12:43 Drug related HIV epidemic in Pakistan:
a review of current situation and response and the way forward beyond 2015

Exposure Risks
(average, per episode)
Type of Contact Risk
Percutaneous (blood) 0.3%
Mucocutaneous (blood) 0.09%
Receptive anal intercourse 1%
Insertive anal intercourse 0.06%
Receptive vaginal intercourse 0.1 – 0.2%
Insertive vaginal intercourse 0.03 – 0.14%
Receptive oral (male) 0.06%
Female-female orogenital 4 case reports
IDU needle sharing 0.67%
Vertical (no prophylaxis) 24%

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Epidemiological Triad

Causal Pie

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Risk groups in Pakistan

• In order of frequency
– IV Drug Users
– Hijras
– Male Commercial Sex Workers
– Female Commercial Sex Workers
• New risk groups
– Infants of above
– Frequent transfusion recepients
– Contaminated needles

Risk Factors for HIV Transmission

through sexual or parenteral mode
• Host
– Acute primary HIV infection
– Advanced clinical stage of HIV
– Sexually transmitted diseases
– Receptive anal intercourse
– Menstruation
– Vitamin A deficiency
– Race
• Pathogen
– HIV-1 versus HIV-2
• Environment
– Lack of male circumcision
– Multiple sexual partners without condom use
– Needle sharing during drug use
– Lack of information sharing with key populations
Amon. The political epidemiology of HIV. J Intl AIDS Society 2014 17:1932
Morris. Concurrent partnerships and HIV prevalence disparities by race. Am J Public Health 2009 99:1023-31

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Risk Factors for vertical

transmission of HIV
Maternal Factors Fetal Factors
• HLA homozygosity • Low birth weight
• Advanced HIV disease • Premature delivery
• Upregulation of CCR5 • Birth order
• Maternal age<30
• Innate immunity/β-defensin
• Poor health-seeking behaviour polymorphism
• Non compliance with HAART
• Feeding Practices
• Obstetric interventions
• Breast feeding and mixed
• Chorioamnionitis and genital
infections
feeding
• Prolonged rupture of membranes
• Mode of Delivery

S Selvaraj and E Paintsil. Virologic and Host Risk Factors for Mother-to-Child Transmission of
HIV. Current HIV Research 2013, 11, 93-101

Risk Factors for vertical

transmission of HIV
Viral Risk Factor Reason for Enhanced Time of Transmission
Transmission

HIV RNA Load Increased viral burden In utero/intrapartum/postpartum

HIV Subtypes Increased viral burden In utero/intrapartum/postpartum

Resistant Viral Strains Increased viral burden In utero/intrapartum/postpartum

Replication fitness Increased viral burden In utero/intrapartum/postpartum

Facilitator Pathogens Increased viral burden In utero/intrapartum/postpartum

S Selvaraj and E Paintsil. Virologic and Host Risk Factors for Mother-to-Child Transmission of HIV. Current HIV
Research 2013, 11, 93-101

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Transmission Models
• Mathematical Model
– Transmission dynamics in gays, IDUs etc
• Networks
– Patient zero cluster
• Sociogeographic models
– Wallace et al (disintegration of neighbourhood
residents--urban burnout—violent death,
AIDS related mortality)

MacQueen. The epidemiology of HIV transmission: trends, structure and dynamics. Ann Rev Anthropol
(1994) 23: 509-526

Natural History
• Consists of 3 distinct phases
– Acute Retroviral Syndrome
– Period of Clinical Latency
– AIDS

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Natural History

hdch

Natural History of HIV Infection

• Rapid Progressors
– 5– 10%, AIDS 1-2 years

• Intermediate Progressors
– 80-90%, Asymptomatic 5-8 years

• Slow Progressors
– 5-10%,Good immune responses, 10-15
years, Rare

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Who to Test and Where

Who to test When to test Where to test

Children with signs and

symptoms of HIV infection
Integrate with healthcare encounter In all health settings
or who have a family
member living with HIV

Adolescents from key

Youth-friendly services STI clinics, outreach
populations

ART clinics, maternal and

As soon as possible after the family member is child health and antenatal
Families with index cases
diagnosed care settings homes,
community outreach

When husband is a PWID.

Pregnant women and HIV- Husband is known HIV positive.

Antenatal care
exposed infants
In areas where there is evidence of high
number of PLHIV in the general population

Who to test
• Clinical Stage 1
– Asymptomatic
– Persistent generalized lymphadenopathy

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Who to test
• Clinical Stage 2
– Moderate unexplained weight loss
– Recurrent respiratory tract infections
– Herpes zoster
– Angular cheilitis
– Recurrent oral ulcerations
– Papular pruritic eruptions
– Seborrhoeic dermatitis
– Fungal nail infections

Who to test
• Clinical Stage 3
– Unexplained severe – Pulmonary TB
weight loss – Severe bacterial
– Unexplained chronic infections
diarrhea (>1 month) – Acute necrotizing
– Unexplained persistent ulcerative stomatitis,
fever (>1 month) gingivitis or
– Persistent oral periodontitis
candidiasis – Unexplained anemia,
– Oral hairy leukoplakia neutropenia and/or
chronic
thrombocytopenia

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Who to test
• Clinical Stage 4
– HIV wasting syndrome – CMV
– PJP – CNS toxoplasmosis
– Recurrent severe – HIV encephalopathy
bacterial pneumonia – Extrapulmonary
– Chronic herpes cryptococcosis
simplex infection – Disseminated NTM
– Oesophageal – PML
candidiasis – Chronic
– Extrapulmonary TB cryptosporidiosis
– Kaposi sarcoma – Chronic isosporiasis

Who to test
• Clinical Stage 4 (cont)
– Disseminated mycosis Recurrent septicaemia
(including nontyphoidal Salmonella)
– Lymphoma
– Cervical carcinoma
– Atypical disseminated leishmaniasis
– HIV nephropathy or cardiomyopathy

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How to test adults and older

children
• Serology
– HIV antibody

• False negative results:

– Window period
– Immunosuppression from malignancy or medication
– Agammaglobulinemia
– Type N or O strains, or HIV 2

• False positive results:

– Autoimmune diseases (SLE)
– Recent immunization (influenza, rabies, Hep B, HIV)
– Pregnancy
– Multiple myeloma
– Error or factitious

How to test in younger children

• Early Infant Diagnosis (EID) at 4-6mo
– NAT
• HIV TNA PCR
– Xpert on DBS
• HIV RNA PCR
– Serum
• HIV DNA PCR
– Serum

• Serology at time of end of risk period

– Positive confirmed with VL

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Pre and Post Test counseling

• Pre Test counseling should include
– Information about the test
– Information of how HIV is transmitted and how
to prevent acquiring HIV
– Information about confidentiality
– Information about what a positive and
negative test means

Pre and Post Test counseling

• Post Test counseling should include
– Information about what the test means
– Information of how to prevent HIV if the test is
negative
– Information about confirmation of a positive
test and linking to care

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When to start
Age WHO Clinical stage CD4 Counts

less than 5 years

Regardless
Regardless

5-10 years • stage 3 or 4

• active TB
≤500 cells/mm3

Adolescents Regardless of ≤500 cells/mm3

(10-19 years) • active TB
• HBV/HIV with CAH
• HIV+ Pregnant and
breastfeeding women
• HIV+ in a sero-discordant
partnership

What to start
Age Preferred regimen

NRTI NRTI NNRTI PI

<3 years Abacavir Lamivudine - Lopinavir/ritonavir

3-10 Abacavir Lamivudine Efavirenz

years

>10 Tenofovir Lamivudine Efavirenz

years

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What to start
Key messages
• AZT: Anemia
• TDF: Nephrotoxicity, decreased bone
density

• NVP: Rash and hepatotoxicity

• EFV: CNS and teratogenicity

Opportunistic infections (OIs)

• OIs are associated with major HIV related

morbidity and mortality
• Most are readily treatable and/or
preventable

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OIs
• STDs
• Tuberculosis
• Stage 4 conditions
• Helminths
• Malaria
• HCV
• HBV

How to monitor
• T helper cell absolute values (surrogate for
immune status)
– CD4
• Viral titers (surrogate for treatment
success and progression of disease)
– HIV RNA PCR
– HIV DNA PCR

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Clinical criteria: TF in children

• Adolescents
– New or recurrent clinical event indicating
severe immunodeficiency (WHO Stage 4)
• after 6 months of effective treatment
• Children
– New or recurrent clinical event indicating
severe immunodeficiency (WHO Stage 3-4)
• after 6 months of effective treatment

Immunologic criteria: TF in
children
• Children younger than 5 years
– Persistent CD4 levels below 200 cells/mm³
• Children 5-10 years
– Persistent CD4 levels below 100 cells/mm³
• Adolescents
– CD4 count falls to the baseline (or below)
OR
– Persistent CD4 level below 100 cells/mm³

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Virologic criteria: TF in children

• Plasma viral load above 1000 copies/ml
– based on two consecutive viral loads
• within 3mo with adherence support
• after at least six months of using ARV drugs

General Care Principles

• Nutritional assessment
• Increased calories
• Deworming
• Vitamin A and D
• CTXp

Guidelines for an Integrated Approach to the Nutritional care of HIV-infected

children (6 months-14 years) Handbook. WHO 2009

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Improving Adherence
• No single intervention will help improve
adherence
• Disclosure and Psychosocial support
becomes important as we approach
adolescence

Vreeman et al. The Perceived Impact of Disclosure of Pediatric HIV Status on Pediatric Antiretroviral
Therapy Adherence, Child Well-Being, and Social Relationships in a Resource-Limited Setting. AIDS
Patient Care and STDs 2010: 24 (10).

Preventive Strategies
• Antiretroviral Therapy
– 2 NRTIs + 1 NNRTI
– 2 NRTIs + 1 PI
– 3 NRTIs
• PPTCT
• PEP
• PrEP

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Rates of PTCT
100 infants born to HIV-infected 55–80 infants will
women who breastfeed, without not be HIV-
any interventions infected

5-10 10-15 5-20

infants infants infants
infected infected infected
during during during
pregnancy labour breast-
and feeding
delivery

20-45 infants will be HIV-infected

WHO Module 3: Specific Interventions for the Prevention of Mother-to-Child Transmission of

HIV (PMTCT)

Impact of PPTCT Interventions on

Parent to Child Transmission
• Without any intervention
– 20-45%
• With interventions in breastfeeding infants
– 5%
• With interventions in non-breastfeeding
infants
– <2%

World Health Organization 2010: PMTCT strategic vision 2010–2015 : preventing mother-to-child transmission of HIV to
reach the UNGASS and Millennium Development Goals.
http://www.who.int/bulletin/volumes/86/1/07-043117/en/#

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Component 1
• Identify pregnant women with HIV
• Testing and counselling during ANC, labour,
delivery and postpartum
– Main bottleneck in Pakistan

Component 2

• Provide HIV-infected pregnant women with

interventions for PMTCT
• ART DURING PREGNANCY
• Safer delivery practices
– C-SEC
– PLANNED VAGINAL

• Breast feeding (AFASS) vs Formula Feeding

• NVP prophylaxis to infant

PMTCT Generic Training Package

Module 2, Slide 60

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Intervention 1
• ARV for pregnant women
– FDC (TDF+3TC+EFV)

Intervention 2
• Safer Delivery Practices
– Planned Vaginal
– C-section
• Preferred if mum not virally suppressed at 36
weeks

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Intervention 3
• Infant Feeding
– Formula feed if AFASS
• NVP prophylaxis for 6 weeks
• Discontinue at 6 weeks if VL negative
– If VL cannot be done
» Can discontinue at 6 weeks if mother is on ARV and
was virally suppressed at 36weeks

Intervention 3
• Infant Feeding
– Breast feed
• NVP prophylaxis for 6 weeks
• Discontinue at 6 weeks if VL negative and mother
on ARV and virally suppressed at 36 months
• If VL cannot be done and mother has discontinued
ARV for any reason, can discontinue at 12 weeks
• CPT till HIV VL possible

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Intervention 4
• ARV to HIV exposed infant
– Breast fed
• NVP for 6 weeks if mother is ARV compliant
• NVP for 12 weeks if mother discontinues ARV
– CPT till VL possible
– Formula fed
• NVP for 6 weeks
• CPT till VL possible

Component 3

• Linkages to long-term treatment, care, support

services are critical. Such services include:
– ARV therapy
– Symptom management
– Prevention and treatment of HIV-related conditions
– Reproductive health care: family planning and
contraception counselling
– Nutritional support
– Psychosocial and community support
– Palliative care, if indicated
PMTCT Generic Training Package

Module 2, Slide 66

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Component 4

• Regular follow-up care, especially

during the first two years of life
– Immunizations
– Prophylaxis for Pneumocystis pneumonia,
other common infections
– HIV testing
– Monitoring of feeding, nutrition, growth and
development

PMTCT Generic Training Package

Module 2, Slide 67

Preventive Strategies
• Behavorial Change
• Condoms
• Male circumcision
• ART
• PrEP
• PPTCT
• Harm Reduction

Lancet 2014 384:272-79

Jones et al. Transformation of HIV from pandemic to low endemic level.

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Pakistan Perspective
• 0.04% prevalence in general population
• Concentrated epidemic in HRGs
– IDUs (36.4%)
– FSW (28%)
– MSW (12%)
– TGSW (17.5%)
• Range of services required for comprehensive care
– Needle and syringe exchange programs
– OST for IDUs or outreach and engagement of patients
– Linking services with VCT, testing and ART

Revitalizing the HIV response in Pakistan: a systematic review and its implications.
Singh et al. Intl J Drug Pol 25 (2014): 26-33

Attributable Risk

Revitalizing the HIV response in Pakistan: a systematic review and its implications.
Singh et al. Intl J Drug Pol 25 (2014): 26-33

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Revitalizing the HIV response in Pakistan: a systematic review and its implications.
Singh et al. Intl J Drug Pol 25 (2014): 26-33

Integrated model for HIV services delivery

for HIV prevention, treatment and care in
Pakistan

Revitalizing the HIV response in Pakistan: a systematic review and its implications. Singh
et al. Intl J Drug Pol 25 (2014): 26-33

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