Implications of the Worldwide HIV Epidemic

1
Implications of the Worldwide HIV Epidemic

• Fourth Annual Ryan White Title III/IV
• Clinical Update
• San Diego, CA
• June 2001

2
M. Keith Rawlings, MD

• President
• Integrated Minority AIDS Network, Inc.
• Chairperson, HIV/AIDS Committee
• National Medical Association

3
Adults and children estimated to be living with
HIV/AIDS as of end 1999
Eastern Europe Central Asia 420 000
Western Europe 520 000
North America 900 000
East Asia Pacific 530 000
North Africa Middle East 220 000
South South-East Asia 5.6 million
Caribbean 360 000
sub-Saharan Africa 24.5 million
Latin America 1.3 million
Australia New Zealand 15 000
Total 34.3 million
4
Of the 14,800 new HIV infections a day in 1999

• More than 95 are in developing countries
• 1 700 are in children under 15 years of age
• About 13 000 are in persons aged 15 to 49 years,
  of whom
• almost 50 are women
• about 50 are 1524 year olds

5
Regional HIV/AIDS statistics and features, end of
1999
Main mode(s) of transmission for those living
with HIV/AIDS
Adult prevalence rate
HIV-positive women
Adults children newly infected with HIV
Adults children living with HIV/AIDS
Epidemic started

• Sub-Saharan Africa
• North Africa Middle East
• South and South-East Asia
• East Asia Pacific
• Latin America
• Caribbean
• Eastern Europe Central Asia
• Western Europe
• North America
• Australia New Zealand

late 70s early 80s late 80s late 80s late
80s late 70s early 80s late 70s early
80s early 90s late 70s early 80s late
70s early 80s late 70s early 80s
24.5 million 220 000 5.6 million 530 000 1.3
million 360 000 420 000 520 000 900 000 15
000 34.3 million
8.57 0.12 0.54 0.06 0.49
2.11 0.21 0.23 0.58 0.13 1.07

55 20 35 13 25 35
25 25 20 10 47
Hetero IDU, Hetero Hetero, IDU IDU, Hetero,
MSM MSM, IDU, Hetero Hetero, MSM IDU MSM,
IDU MSM, IDU, Hetero MSM, IDU
4 million 20 000 800 000 120 000 150
000 60 000 130 000 30 000 45 000 500 5.4
million
The proportion of adults (15 to 49 years of
age) living with HIV/AIDS in 1999, Hetero
heterosexual transmission IDU transmission
through injecting drug use MSM sexual
transmission among men who have sex with men
6
Estimated number of people living with HIV/AIDS
by region, 1980 to 1999
People living with HIV/AIDS
7
Projected changes in life expectancy in selected
African countries with high HIV prevalence,
19952000
65 60 55 50 45 40 35
Average life expectancy at birth, in years
Botswana
Zimbabwe
Zambia
Uganda
Malawi
projections
1955
1960
1965
1970
1975
1980
1985
1990
1995
2000
Source United Nations Population Division, 1996
World Health Organization
UNAIDSAddisMay 1999
8
The revised Pan American Health Organization
(Caracas) AIDS case definition

• Positive HIV serologic test and the absence of
  cancer or other cause of immunosuppression plus gt
  10 cumulative points

9
The revised Pan American Health Organization
(Caracas) AIDS case definition
10
Clinical Manifestations

• Vary in different areas of the world most likely
  the result of true regional differences in the
  prevalence of specific opportunistic infections
  and malignant diseases.
• Example In Africa, severe weight loss (slims
  disease), chronic diarrhea and chronic fever are
  prominent presentations. Whereas, PCP is the
  most common OI in North America and Europe,
  though rare in Africa.

Mastro, Gayle Heyward. Epidemiology of HIV
Infection and AIDS Outside of the United States
11
Clinical Manifestations

• Mycobacterium avium, which is common in the
  developed countries is not a substantial problem
  in Africa.
• Tuberculosis is the most commonly occurring OI in
  persons infected with HIV-1 in Africa and Latin
  America. In many areas nearly half of the adult
  population aged 20-40 is infected with
  Mycobacterium tuberculosis, thus are at greater
  risk for reactivation of TB with immune
  depression.
• This also true for many countries in Asia.
• Mastro, Gayle Heyward. Epidemiology of HIV
  Infection and AIDS Outside of the United States

12
Impact of AIDS in Developing Countries

• In Botswana, 50 of households have at least 1
  member living with HIV, and an estimated 2 of
  all households will lose all income earners in 10
  years, increasing poverty by 5, and decreasing
  national household income by 8.
• Greener R. The impact of HIV/AIDS on poverty and
  inequality in Botswana. Abstract TuOrD326.

13
Impact of AIDS in Developing Countries

• The economic impact of HIV is enormous,
  particularly in the countries most affected by
  HIV. KwaZulu-Natal in South Africa is one of the
  world's worst affected areas, with more than 30
  of the population infected by HIV.
• Floyd K. The economic impact of the HIV/AIDS
  epidemic on the health sector in rural South
  Africa. Abstract WeOrD461.

14
Impact of AIDS in Developing Countries

• While, in Latin America AIDS uses to claim the
  lives of twice as many men, seven out of eight
  who now succumb to the disease are women. Many
  of the male victims are between 40 to 50 years of
  age, while female victims are younger, with those
  15 to 25 years-old most affected. Latin America
  currently has a high HIV/AIDS prevalence rate
  (0.57), closely behind Sub-Saharan Africa, the
  Caribbean, and Southeast Asia.

15
Impact of AIDS in Developing Countries

• With an estimated 4 million HIV infected people,
  India has more people living with HIV than any
  other single country in the world. According to
  Surgeon General Satcher, the number of new
  infections in India will double every 14 months.

16
Tuberculosis and HIV

• In a rural district of KwaZulu-Natal, South
  Africa rising rates of tuberculosis and HIV are
  seriously burdening hospital services. Bed
  occupancy rates jumped from 123 to 200 from
  1991 to 1998, whereas tuberculosis admissions
  rose 360 and HIV-related conditions rose
  43-fold.
• Floyd K, Reid A, Wilkinson D, Gilks C. Abstract
  WeOrD461.

17
Rapid HIV Test

• A study7 of a rapid HIV test kit reduced time
  from test to result from 17 to 2 days resulted in
  a higher uptake rate and an overall cost
  reduction of 17.5. Speed of result is an
  important factor, since the proportion returning
  for results increased from 58 to 83 in those
  tested with the faster assay.
• 7Mpairwe B. Abstract MoPeA2088.

18
HIVNET 012 (pACTG 316)

• Open Label, randomized trial of AZT vs. NVP
  AZT NVP
• labor 600 mg po then 200 mg po
• 300 mg po
• 4mg/kg X 7 days 2 mg/kg to X1
• 65/292 (22.2) 37/267(13.8)

To neonate
4/dose
preliminary data
19
HIVNET 012 (pACTG 316)

• Despite decreased rates of transmission there is
  a growing problem of drug resistance.
• Incidence of Nevirapine resistance among women
  that received single doses of the medication
  during pregnancy to reduce mother-to-child
  transmission.

20
Physician Experience

• Physician experience was a factor associated with
  cheaper costs of care in a study from Boston. The
  cost of care in the HIV clinic was approximately
  50 lower than that for patients cared for in a
  similar manner but in a non-HIV specialist
  clinic. Although no fewer hospitalizations were
  seen, time on the ward was reduced from 11.00 to
  6.92 days (Plt.001).
• Wong M, Fisher E, Thompson-Bodkins C, et al.
  Abstract MoOrB119.

21
Adherence Education on Clinical Outcome

• A study of ART naïve minorities and women treated
  with three NRTI and randomized to treatment only
  vs. treatment with education done in the US3
  showed no significant impact on the proportion of
  patients at 24 weeks to attain plasma HIV-1 RNA
  lt40 c/mL.
• 3Rawlings K, Farthing C, Brown L, et al.
  Abstract TuPeB3223.

22
Impact of Antiretrovirals

• The impact of HAART treatment in Canada was
  assessed by considering changes between 1985 and
  1999. An estimated 6420 deaths were avoided
  saving 490 million, representing the balance
  between the high costs of antiretroviral therapy
  and the 115.4 million indirect cost savings per
  year.
• McMurchy D, Palmer R. Abstract MoPeC2474.

23
Impact of Antiretrovirals

• However being an active injecting drug user and
  having a lower CD4 cell count were associated
  with poorer uptake of available treatment,
  suggesting that financial issues may not always
  be a prime determinant of use.
• Anis A, Guh D, Skippen, Schechter M,
  O'Shaughnessy M. Abstract ThPe5276

24
Vaccines

• The economic issues around vaccine acceptance
  were studied in 900 randomly selected Kenyans in
  Nairobi.16 Four of 10 were not willing to
  receive a vaccine that was less than 50
  effective, whereas most would not or could not
  pay more than 2 for the vaccine were it
  available.
• 16 Forsythe S, Arthur G, Mutemi R, Gilks C.
  Abstract MoOrC127.

25
AIDS Will Hit Economy Hard

• National wealth in the countries hit hardest by
  HIV/AIDS will be reduced by 15 to 20 over the
  next 10 years because of the HIV pandemic,
  according to new research published by UNAIDS and
  the World Bank.
• The Independent, Durban South Africa, Saturday
  July 8, 2000

26
AIDS Will Hit Economy Hard

• In South Africa, where an estimated 20 of the
  people are infected with HIV, researchers
  forecast that the gross domestic product (GNP)
  will be 17 lower by 2010 than it would have been
  without AIDS.
• The Independent, Durban South Africa, Saturday
  July 8, 2000

27
Workplace Cost

• The effect of HIV on the economics of the
  workplace was evaluated in a 7 year study from
  South Africa, using estimated HIV-related costs
  from insurance, clinic, hospital, and human
  resource databases with regard to 400
  agricultural workers, 26.8 of whom were
  infected.19
• 19 Morris C, Cheevers EJ, Stein Z. Abstract
  MoPpE1065.

28
Workplace Cost

• The most significant costs to industry were lost
  work, replacement workers, and lost productivity.
  The estimated cost per worker in the last 2 years
  of employment was 9673 Rand (1612) per annum.

29
Ambulatory Cost

• An Italian study examined the costs of care in an
  ambulatory setting showed that 74.7 of costs
  were attributable to antiretroviral medication
  expense, 10.1 to hospitalization, and 15.2 to
  diagnostics. The costs for day care and
  hospitalizations dropped significantly during the
  follow-up, which offset the additional costs of
  drug therapy.
• Cassetti I, Vanzulli C, Bugarin G, et al..
  Abstract MoPeD2567.

30
Social Costs

• A survey of 332 households in Mumbai, India,17
  showed that as the male members of the society
  lose earning capacity, women have a limited
  ability to take on this role because of their own
  infection status and caring responsibilities for
  the family. The decline in income adversely
  affected child education to a significant extent.
  
• 17 Shah S. Abstract MoPeD2528.

31
Household Income

• A study that compared 300 HIV-affected households
  with a similar number of non-affected households
  in Thailand showed a 71 reduction in total
  income.18
• 18 Kongsin S, Sirinirund P, Jiamton S, Boonthum
  A. Abstract TuOrD379.

32
Impact of HIV/AIDS on urban households, Côte
dIvoire
General population
Families living with AIDS
30 000 Francs CFA
25 000
Monthly income per capita
20 000
15 000
Monthly consumption per capita
10 000
5 000
Savings/Disavings
0
5 000
Source Simulation-based on data from Bechu,
Delcroix and Guillaume, 1997
UNAIDSAddisMay 1999
33
The World Bank is to spend 500 Million on a
comprehensive AIDS program for Africa

• The multi-sector AIDS program, developed in
  coordination with the UNAIDS international
  program, will help countries implement nationwide
  HIV/AIDS programs. AIDS is, above all, an
  issue of commitment. The sobering reality is
  that AIDS is not a health problem, but a serious
  development issue.
• Callisto Madavo,
• Vice President World Banks Africa Region
• Daily News, Durban South Africa, Monday July 10,
  2000

34
Spread of HIV over time in Latin America and the
Caribbean, 1984 to 1999
Estimated percentage of adults (1549) infected
with HIV
2.0 6.0 1.0 2.0 0.5 1.0 0.1
0.5 0.0 0.1 trend data unavailable outside
region
35
Spread of HIV over timein sub-Saharan Africa,
1984 to 1999
Estimated percentage of adults (1549) infected
with HIV
20.0 36.0 10.0 20.0 5.0 10.0 1.0
5.0 0.0 1.0 trend data
unavailable outside region
36
Spread of HIV over time in Asia, 1984 to 1999
2.0 5.0 1.0 2.0 0.5 1.0
0.1 0.5 0.0 0.1 trend data
unavailable outside region
37
Impact of Global Epidemic on the United States

• Global Economy
• Regional Upheaval
• Resource Allocation
• 2000 Census

38
Practice Example

• 33 yo white female with undetectable viral load
  for 4 years having never been on anti-retroviral
  medications. CD4 initially 630 with a 50 cell
  decline annually.
• History reveals that husband works for
  multi-national corporation that is stationed in
  Southeast Asia.

39
US Census Data

• Fifty-eight percent growth among Hispanic
  population in the 1990s. Mostly in the form of
  immigration.
• Increasing immigration by people native to Asia
  and Africa.
• Community data showing that the locations for
  residence in the United States is varied and not
  limited to prior epicenters.

40
Multiple HIV Subspecies

• Currently there are Clades A N with numerous
  combinations
• United States and Western Europe Clade B
• Africa and Asia Clade C
• Multiple Clades through out the world
• Limitations of detection of non-clade B with
  present testing

41
Implications for Monitoring Effectiveness

• Limitations of detection of non-clade B with
  present testing
• Are not picked up by Roche Amplicor 1.0
• Requires version 1.5 or bDNA testing to monitor
  viral load

42
Relationship of HIV Groups, Subtypes
HIV
HIV-2
HIV-1
Group N
Group M
Group O
Subtype A
Subtype B
Subtype A
Subtype C
Subtype G
Subtype B
Subtype D
Subtype H
Subtype E
Subtype I
Subtype F
Subtype J
43
Why is HIV Subtype Important?

• Diagnosis (?)
• Apetrei C, AIDS 1996 Dec10(14)F57-60
• Monitoring
• Loussert-Ajaka I et al. Lancet 1995 Sep
  30346(8979)912-3
• Response to therapy (?)
• Palmer S et al. AIDS Res Hum Retroviruses 1998
  Jan 2014(2)157-62
• Prognosis (?)
• Kanki P et al, J Infect Dis 1999 Jan179(1)68-73
• Vaccine development
• Girard M et al, AIDS Res Hum Retroviruses 1998
  Jan 2014(2)157-62
• Transmissibility (?)

44

• CDC efforts to characterize strain diversity

• National serosurveillance for HIV-1 group O
• Pau et al, Transfusion 1996 36398-400.
• National AIDS surveillance for HIV-1 group O
• Sullivan PS et al, JID 2000 181463-469
• Sentinel hospital surveillance for subtypes
• Irwin et al, JID 1997 1761629-1633.
• Viral strain and resistance study (ASD based)
• following slide
• Sentinel strain and viral resistance survey
• following slide
• Seronegative AIDS surveillance
• Sullivan PS et al, AIDS 1999 Jan 1413(1)89-96
• Ad Hoc surveillance for "unusual" strains

45

• Group O Prevalence, Africa

0.2
1
lt0.1
1
2
6-8
lt0.1
46

• Surveillance for HIV-1 Group O Infections

• Country of birth strategy used to select patients
  who are reported with HIV infection or AIDS,
  alive, and born in an African country where HIV-1
  group O has been reported, or in a country
  bordering Cameroon
• Countries included are Gabon, Nigeria, Niger,
  Senegal, Togo, Cameroon, Equatorial Guinea,
  Congo, Chad, and Central African Republic
• Followup included interview and collection of
  specimen for typing of HIV strain.

Sullivan PS et al, J Infect Dis 2000 181463-469
47

• Outcome of Investigations (n155)

Sullivan PS et al, J Infect Dis 2000 181463-469
48

• Distribution of HIV-1 Types (n37)

Sullivan PS et al, J Infect Dis 2000 181463-469
49

• Group O Surveillance -- Conclusions

• Retrospective strain surveillance may have poor
  rates of location of subjects, and non-US born
  subjects may have high refusal rates
• Even among persons at highest risk for infection
  with HIV-1 group O, only 2 cases have been
  identified in the US
• Patients living with HIV or AIDS in the US have
  HIV-1 strains typical of their countries of birth
• Subtype A was the most common HIV-1 subtype among
  African-born persons with HIV infection in the US
• There is a need for continued population-based
  and ad hoc surveillance for group O in the US

50

• Prevalence studies

• Viral strain and resistance study
• Seattle, Los Angeles
• 98/98 subtype B
• New York City, 1993-1995
• S. Beatrice et al, 5th Conference on Retroviruses
  and OIs
• 27/32 HIV-1 infections in African-born clients
  were non-B subtypes
• Sentinel Surveillance for viral strain and
  resistance
• Houston, New Orleans, Miami, Newark, New York
  City, Denver, Detroit, San Diego, San Francisco

51

• Non-B Subtype Surveillance

• Performed in a Bronx hospital which serves a
  culturally diverse population
• Enrollment criteria included aged 18-44, not
  known HIV, not admitted for HIV-related illness
• HIV serology, followed by subtype specific
  peptide serology, followed by sequencing and
  phylogenetic analysis
• Collected information on country of birth,
  travel, and sexual contact with foreign-born
  persons

Reference Irwin KL et al, J Infect Dis 1997
1761629-33.
52

• Results -- Subtype Surveillance

1749 patients 828 HIV tested
43 (5.2) HIV seropositive
8 not serotype B-MN
35 serotype B-MN
Reference Irwin KL et al, J Infect Dis 1997
1761629-33.
53
Results -- Subtype Surveillance
Reference Irwin KL et al, J Infect Dis 1997
1761629-33.
54

• Conclusions - Subtype Surveillance

• Non-B subtypes of HIV-1 are present in patients
  admitted to US hospitals with new HIV
  serodiagnoses
• Local transmission of subtype A HIV-1 occurred in
  at least one case
• Peptide serology provides a useful means of
  screening samples for unusual serotypes
  sensitivity may be better than specificity

Reference Irwin KL et al, J Infect Dis 1997
1761629-33.
55

• Important Questions

• What are sensitivity and specificity of currently
  FDA-licensed EIA tests for non-B subtypes?
• Panel of 250 samples from African-born
  surveillance -- no failures except one (LAC)
  group O specimen, 1 clade B, 1 untypable sample
  (J Clin Microbiol 2001 Mar39(3)1017-20)
• Are there variations in inherent
  (pre-antiretroviral treatment) genotypic
  resistance which are correlated with subtype?
• Two CDC studies ongoing
• Group O resistant to NNRTI (J Virol 1997
  8893-8898)
• Subtype G less sensitive to PI (5th retroviral
  conf, Abstract 404)

56

• Important Questions

• What are the sensitivity and specificity of
  screening serology for non-B subtypes?
• PPV good for A and E low sensitivity for D low
  PPV for A and C (Plantier et al, 5th Retroviral
  Conf Abtract 115)
• Are there differences in the natural history or
  transmissability of non-B subtypes?
• Sweden -- all subtypes A-J (except I), standard
  medical care, no difference in CD4 slope (J.
  Albert, Abbott Group O meeting, Paris 1997)
• Hu et al AIDS 1999 13 873-881 -- no consistent
  association with transmission
• How prevalent are non-B subtypes in the US?
• Ongoing CDC studies

57

• Important Questions

• What are the implications of recombinant viruses
  for HIV diagnostics and viral load monitoring?
• What is an adequate standard of diagnostics to
  identify recombinant viruses?
• Is it important for clinicians to know HIV
  subtype for clinical management?
• How will subtype diagnostic services be provided
  in the future?