This document provides an overview of recent advances in HIV/AIDS treatment. It discusses how combination antiretroviral therapy pills have simplified treatment regimens. New drug classes such as entry inhibitors and integrase inhibitors have been developed that target different parts of the viral lifecycle. Studies have also shown benefits of starting antiretroviral treatment earlier, even before symptoms develop. Vaccine research continues in an effort to develop a preventive vaccine, with some studies showing a limited level of effectiveness.

1. RECENT ADVANCE IN
HIV/AIDS TREATMENT
CHETKANT BHUSAL
MPH
NATIONAL MEDICAL COLLEGE
TU Nepal

2. CONTENTS
 Background
Global Scenario
Introduction
Structure
o Epidemiology of HIV
 HIV types, groups and subtypes
 Routes of Transmission of HIV
 WHO Clinical Staging of HIV Infection
 Diagnosis
 Methods of Prevention
 Some Key Advancement in recent Years

3. GLOBAL SCENARIO OF HIV/AIDS
 HIV is the world’s leading infectious killer
 HIV/AIDS remains one of the world's most significant
public health challenges, particularly in low- and
middle-income countries.
 Globally, an estimated 35.0 million [33.1–37.2 million]
people were living with HIV in 2013, and 3.2 million
[2.9–3.5 million] of these were children.
 The vast majority of people living with HIV are in low-and
middle-income countries. An estimated 2.1 million
[1.9–2.4 million] people were newly infected with the
virus in 2013.
http://www.who.int/features/factfiles/hiv/facts/en/

4. WHAT IS HIV/AIDS?
 HIV is retrovirus that causes acquired immune deficiency
syndrome (AIDS)
 HIV attacks and destroys white blood cells, causing a defect
in the body’s immune system.
 Previous names of HIV- Human T-lymphotropic virus –III
(HTLV-III) and lymphadenopathy associated virus (LAV)
 The immune system of an HIV-infected person becomes so
weakened that it cannot protect itself from serious
infections. When this happens, the person clinically has
AIDS.

5. ACQUIRED IMMUNE DEFICIENCY SYNDROME
 AIDS is a condition in humans in which the
immune system begins to fall leading to life
threatening opportunistic infections
 First reported in USA in 1981 and now become
pandemic
 AIDS people get life threatening diseases called
opportunistic infections (OIs)
 AIDS may manifest as early as 2 years or as late
as 10 years after infection with HIV.

6. AIDS
A “syndrome” is a group of symptoms & signs associated
with the same underlying condition

The variety of opportunistic infections & cancers cause a
variety of symptoms & signs

This group of illnesses with their symptoms & signs
makes up the syndrome “AIDS”

7. HIV/AIDS
Epidemiology of HIV/AIDS
1.Agent factor-a.
Agent-
- First identified by French scientist, known
Lymphadenipathy associated virus (LAV)
- USA’s researcher- Human T cell lymphotrophic virus III
(HTLV-III)
- HIV- By International committee on the Taxonomy in May
1986.

8. © Teaching-aoids at low cost
GP120
ENVELOPE
GLYCOPROTIENS
GP41
Lipid
Membrane
RNA
Reverse
P24
Proteins
P1
5

9. HIV/AIDS
- 1/10000th of a millimeter.
- protein capsule containing two short strands of
genetic materials (RNA) and enzymes.
- Unique ability to destroy human T4 helper cells.
- Pass through Blood Brain Barrier and can destroy
some brain cell
- This may account for certain of the neurological &
psychomotor abnormalities, observed in AIDS
patients.
- Types of HIV - HIV-1
- HIV-2

10. HIV/AIDS
- Easily killed by heat, rapidly inactivated by ether,
acetone, ethno 20% and beta-propiolactone (1:400
dilution), but relatively resistant to ionizing radiation
and UV light.
b. Reservoir of infection-
- Cases and carrier.
- Symptomless carrier can infect other lifelong

11. HIV/AIDS
c. Source of infection-
- High concentration found in blood, semen and CSF
- Lowest concentration detected in tears, saliva,
breast milk, urine & cervical and vaginal secretion.
- Also isolated in brain tissue, lymph nodes, bone
marrow cells & skin.

12. HIV/AIDS
2. Host factor-a.
Age- All but most cases occurred in sexually active age
(20-49 yrs).
b. Sex- both sexes.
c. High risk group- Sex worker (male & Female), IV drug
users, transfusion recipients of blood & their products.

13. HIV- IMMUNOLOGY
 Lymphocytes-
- T Cell
- B Cell
 Macrophage

14. HIV- IMMUNOLOGY
- Depletion in a specialized group of WBC
(Lymphocytes) called T-helper or T-4 cells. The full
name of T-helper cell is T-lymphocytes and is also
commonly known as CD4+cell. These cells play a key
role in regulating the immune response.

15. HIV TYPES
 Highly variable virus because of very readily mutation
 Even within the body of a single infected person,
there are many different strains of HIV
Two types
 HIV-1
 HIV-2
 Both are transmitted by similar methods and cause
clinically indistinguishable AIDS
 HIV-1 is worldwide predominant
 HIV-2 is less easily transmitted, relatively uncommon
and concentrated in west Africa

16. 16
HIV TRANSMISSION
 HIV enters the bloodstream through
 Open cuts
 Breaks in the skin
 Mucous membranes
 Direct injection

17. 17
 Common fluids that are a means of transmission
 Blood
 Semen
 Vaginal secretions
 Breast milk

18. 18
HIV IN BODY FLUIDS
Semen
11,000 Vaginal
Fluid
7,000
Blood
18,000
Amniotic
Fluid
4,000 Saliva
1
Average number of HIV particles in 1 ml of these body fluids

19. 19
ROUTES OF TRANSMISSION OF HIV
Sexual Contact: Male-to-male
Male-to-female or vice versa
Female-to-female
Blood Exposure: Injecting drug use/needle sharing
Occupational exposure
Transfusion of blood products
Perinatal: Transmission from mother to baby
Breastfeeding

20. 20

21. 21
HISTORY OF HIV/AIDS PREVENTION
EFFORTS
1988 National AIDS Prevention and Control Program
initiated
1993 National Policy on Blood Safety
1995 National Policy on AIDS
2003 HIV/AIDS operational plan
2007–2011 Second National HIV/AIDS Strategy
2006–2008 National Action Plan
2010 National Policy on HIV and STI

22. HIV/AIDS PREVENTION: WHAT WORKS?
Prevention of:
 Sexual transmission
 Prenatal transmission
 Mother-to-child-transmission

23. AIDS can be PREVENTED by
Being mutually
faithful to your
partner

24. AIDS can be PREVENTED by
Using a
condom for
safer sex

25. AIDS can be PREVENTED by
Using only HIV
screened blood
or
blood products
when required

26. AIDS can be PREVENTED by
Always using new
- Needles
- Syringes
- Blades
- Razor

27. AIDS can be PREVENTED by
Avoiding
injectable
drugs and
needle sharing

28. AIDS can be PREVENTED by
seeks advice
before planning
a baby

29. 29
DIAGNOSIS
 4-6 weeks window period and difficult to diagnose
 After 13 weeks, antibody test is positive
Diagnostic methods
1. Hematological findings- CD4 cell count, TC, DC
2. Microbiological findings- OI diagnosis, PCR, RT-PCR
3. Serological findings
 ELISA (Enzyme Link Immune Sorbant Assay)
 Western blotting
 Viral load
 IFA
 Tri dot method

30. RECENT ADVANCEMENT IN HIV/AIDS
 For all of the progress made against HIV/AIDS over the
years, the push for still better treatments is far from over.
 Until a cure is discovered, doctors and researchers will
continue to look for new and more effective ways to
control the disease and save lives.
 While HIV medications can attack the virus and keep
the disease in check for several years or more, the side
effects can be severe, the medications can be difficult to
take, and they don't always work for everyone.

31. SOME KEY ADVANCES IN RECENT YEARS
2006
 In 2006, the agency in USA
simplified treatment for many
patients by approving Atripla
tablets, which combine three
common HIV drugs (efavirenz,
emtricitabine, and tenofovir
disoproxil fumarate) into one
pill.

32.  A study lasting just under one year showed that the
combination pill reduced the virus and enhanced
the immune system of 80 percent of HIV patients.
 Unfortunately, the pills can also cause mental
problems, including suicidal thoughts, confusion,
hallucinations, memory loss, aberrant(abnormal )
thinking, paranoia(fear), and depression.
 Patients should also watch out for warning signs
that the drug is damaging the liver or the muscles.
 Other common side effects include joint pain,
muscle pain, shortness of breath, dizziness,
stomach pain along with nausea or vomiting, loss of
appetite, yellow-colored skin, pale stools, or dark
urine.

33. ADVANCEMENT ….
2007
 Researchers are developing drugs that work in entirely
different ways from the first generation of HIV
medications.
 In 2007, the U.S. Food and Drug Administration (FDA)
approved maraviroc (Selzentry), a drug known as an
"entry inhibitor." Doctors also call it a CCR-5 co-receptor
antagonist.

34. ADVANCEMENT ……
 Unlike earlier HIV medications that keep the virus from
dividing after it enters a white blood cell, maraviroc can stop
the virus from entering the cells in the first place.
 The drug blocks the main entryway into cells. Because
different strains of HIV use different entryways, the drug will
not work in all cases.
 Blood tests can show if your particular strain of HIV will
respond to this drug.

35. ADVANCEMENT ……
 Studies have found that the drug was able to
reduce levels of HIV and boost the immune system
of patients who weren't responding to other drugs.
 Over time, however, it may cause liver damage and
raise the risk of heart trouble.
 Less serious side effects can include cough, fever,
colds, rash, abdominal pain, dizziness, and muscle
pain.

36.  The year 2007 saw many firsts in HIV
treatment. It was the year the FDA
approved raltegravir (Isentress), the first
drug in a class known as integrase
inhibitors.
 It works by keeping the HIV virus from
inserting its genetic material into white
blood cells.
 Like maraviroc, the drug can reduce virus
levels and increase immune system cells in
patients who aren't responding to other
drugs.
 The most common side effects seen during
studies include headache, fever, diarrhea,
and nausea.
Tables of Isentress
(raltegravir), an integrase
inhibitor used for HIV
treatment

37. ADVANCEMENT ……
 In addition to creating whole new classes of drugs,
researchers continue to improve on old types.
 In 2007, the FDA approved etravirine (Intelence),
a non-nucleoside reverse transcriptase inhibitor that
blocks an enzyme the virus needs to copy itself.
 When used in combination with other HIV drugs,
etravirine can reduce levels of HIV in the blood
while boosting levels of germ-fighting white blood
cells.

38. ADVANCEMENT ……
 One major downside to the drug is that it can cause
mild to severe skin rashes.
 Other common side effects include nausea, nerve
pain, diarrhea, stomach pain, vomiting, fatigue,
headache, and high blood pressure.

39. ADVANCEMENT ……
2008
 Another study published in January 2008 pointed
toward even more potential benefits from early
therapy.
 As reported in the Journal of Acquired Immune
Deficiency Syndrome, starting treatment when the
CD4+ count is above 350 seems to reduce the risk
of anemia and painful nerve damage (neuropathy).

40.  The ultimate goal for many HIV researchers is
finding a way to stop the infection before it starts.
 Ever since the early days of the epidemic, doctors
have envision a vaccine that could make people
invincible to the virus.
 Just as vaccines rid the world of smallpox and
nearly erased polio, it was hoped that a simple shot
could make HIV a thing of the past.

41. ADVANCEMENT ……
 Researchers continue to pursue a vaccine for HIV,
but the goal remains elusive.
 Vaccines work by preparing a person's natural
immune system to fight a particular germ.
 As noted in a 2008 issue of the New England Journal
of Medicine (NEJM), the search for an HIV vaccine is
greatly complicated by the fact that the human
immune system has very few defenses against the
virus.
 Still, researchers have recently completed testing a
two-vaccine regimen in Thailand.

42. 2009
 On September 24, 2009, a team of U.S. and Thai
researchers announced that their investigational
vaccine regimen was safe and 31 percent effective in
preventing HIV infection
 New drugs are just one part of the ongoing fight against
HIV. Researchers are also continually looking for the
best ways to put current drugs to use.
 A major study published in the New England Journal of
Medicine (NEJM) in 2009 may change the approach to
treating HIV.
 The study followed more than 17,500 patients with HIV
infections that had not yet caused any symptoms.

43. ADVANCEMENT ……
 Researchers used a measurement called a "CD4+" count
to classify each patient based on the strength of his or
her immune system.
 Patients were then divided into two different groups:
those with CD4+ counts of 351 to 500, and those with
counts higher than 500.
 Within each of the two groups, patients either began
early treatment with antiretroviral drugs or deferred
treatment until their CD4+ counts dropped below 350 or
500, respectively.
 The researchers found that those who received early
treatment had a significantly better survival rate.

44. ADVANCEMENT ……
 The study suggests that patients with a CD4+ count
between 351 and 500 and even higher should get
treatment right away.
 Compared with patients who got treatment immediately,
patients who waited until their count dropped below 350
to start taking medications -- the usual approach -- had a
69 percent greater mortality risk.
 Patients who received treatment while their CD4+ count
was still above 500 fared even better.
 Compared with these early starters, patients who
followed the usual treatment plan had a 94 percent
greater mortality risk.

45. ADVANCEMENT ……
 NEJM report suggested a successful vaccination may
only be able to slow the spread of the virus once it enters
the body but never be possible to completely prevent HIV
infection with a vaccine. Even that, of course, could be a
life-saving advance.
 Nevertheless, scientists continue to look for new
modalities to develop the elusive vaccine.

46. ADVANCEMENT ……
2010
 In 2010, at least eight human antibodies were
discovered that can stop the HIV virus from infecting
cells in a laboratory.
 Scientists at the National Institute of Allergy and
Infectious Diseases discovered that two of these
antibodies can block more than 90% of known global
strains of the virus.
 Learning how the structure of the antibody binds to the
virus will take the team one step closer to designing a
vaccine that could stimulate healthy people to make
these antibodies as protection against HIV infection.

47. ADVANCEMENT ……
 Two other milestones emerged in 2010, advancing the
hope of effective prevention.
 While neither milestone falls into the category of a single
shot vaccine, both show promise towards controlling the
pandemic.
 One study, published in the November 23, 2010 issue of
the NEJM, found that among men having sex with men,
a daily dose of an oral antiviral drug reduced the risk of
HIV infection by 44%.

48. ADVANCEMENT ……
 For those participants who strictly followed the daily
regimen, their risk shrunk even further.
 Close adherence to the daily dosing schedule was
73% effective in reducing the risk of HIV infection.
 There's new hope that a germ-killing gel could
protect women from HIV.

49.  In 2010, researchers with the National Institutes of
Health reported that a study conducted by the Centre
for the AIDS Programme of Research in South Africa
(CAPRISA) found that women who regularly used a
vaginal microbicide gel made from the antiretroviral
drug Tenofovir lowered their risk of contracting HIV
through sex by about 40 percent compared with women
using a placebo gel.
 The gel is much less effective than a condom, but not
all men are willing to use condoms.
 Researchers hope that an improved version of the gel
could someday give women the chance to put real
protection in their own hands.

50. 2011
 FDA in US approved the drug NNRTI Rilpivirine in May 2011
but which caused serious life –threatening side effects. These
includes depression, mood changes, suicidal thoughts and
liver problems.
 Rilpivirine + FTC + TDF (Complera) - Aug. 2011 Complera
tablets are composed of three antiviral compounds that are
indicated for use as complete regimen for treatment of HIV-1
infection in adults that have had no prior antiviral treatments.
 Side effects include new or worsening renal impairment,
depressive disorders, and decrease bone density. Serious side
effects signs of liver damage, nausea, upper stomach pain,
itching, loss of appetite, dark urine, clay-colored stools,
jaundice, unusual thoughts and behavior, suicidal thoughts
.Other common side effects are headache, isomina, rash, and
depression.Complera will harm unborn children in pregnant
woman.

51. ADVANCEMENT ……
2012
 FDA in Aug. 2012 approved Fixed Dose Combination
(FDC)Elvitegravir + Cobicistat + FTC + TDF (Stribild)
 It is used treat adults who have never taken HIV medications
before.
 Side effects include worsening kidney problems, including
kidney failure ,bone problems; changes in fat such as an
increased amount of fat in head and neck , changes in the
immune reconstitution syndrome.

52. ADVANCEMENT ……
2013
 In August 2013 FDA approved Integrase inhibitor
Dolutegravir
 Serious life-threatening side effects which include
allergic reactions, fever, general ill feeling, extreme
tiredness, muscle or joint aches, blisters or sores in
mouth, blisters or peeling skin, redness or swelling of
your eyes, swelling of your mouth, face, lips ,or tounge,
trouble in breathing etc.
 Fixed Dose Combination (FDC) Quad (boosted integrase
inhibitor + Truvada) - Submitted for approval

53.  As a result of recent advances in access to antiretroviral
therapy (ART), HIV-positive people now live longer and
healthier lives.
 In addition, it has been confirmed that ART prevents
onward transmission of HIV.
 At the end of 2013, 11.7 million people were receiving
ART in low- and middle-income countries; this
represents 36% [34–38%] of the 32.6 million [30.7–34.8
million] people living with HIV in low- and middle-income
countries.

54. ADVANCEMENT ……
 Progress has also been made in preventing mother-to-
child transmission and keeping mothers alive.
 In 2013, close to 7 out of 10 pregnant women living
with HIV – 970 000 women – received antiretroviral
(ARVs).
 WHO has released a set of normative guidelines and
provides support to countries in formulating and
implementing policies and programmes to improve
and scale up HIV prevention, treatment, care and
support services for all people in need.

55. REFERENCES
 http://www.webmd.com/hiv-aids/guide/sexual-health-aids
 http://www.who.int/
 http://www.who.int/features/factfiles/hiv/facts/en/
 : http://www.avert.org/hiv-drugs-development.
htm#sthash.mUrN4qwi.dpuf
 http://consumer.healthday.com/encyclopedia/infecti
ous-diseases
 http://www.authorstream.com/
 www.fda.gov/../ucm317oo4.htm
 www.vaccines.org
 www.rxlist.com>home>drugs az list
 Aidsinfo.nih.gov.home.drugs

56.  National Institute of Allergy and Infectious
Diseases. NIAID Media Availability. Landmark
Discoveries Characterize NIH HIV/AIDS Research
in 2010. November 29, 2010
 Kitahata, M.M. et al. Effect of early vs deferred
antiretroviral therapy for HIV on survival. New
England Journal of Medicine. April 1, 2009
 U.S. Department of Health and Human Services. Anti-
HIV gel shows promise in large-scale study in women.
February 9, 2009.

57. THANK YOU