HIV (Human Immunodeficiency Virus) infects cells of the immune system and destroys or impairs their function. Infection progressive deterioration of the immune system breaking down the body's ability to fight out infections & diseases by opportunistic bacteria, viruses and fungi. AIDS (Acquired Immune Deficiency Syndrome) refers to the most advanced stages of HIV infection and a collection of signs and symptoms caused by more than 20 opportunistic infections or related cancers.

1. HIV/AIDS:Prevention & ControlDr PrabirRanjanMoharana Assistant Professor Community Medicine aaaa

2. Know the FACTS of HIV/AIDS

3. Fact 1 HIV (Human Immunodeficiency Virus) infects cells of the immune system and destroys or impairs their function. Infection progressive deterioration of the immune system breaking down the body's ability to fight out infections & diseases by opportunistic bacteria, viruses and fungi. AIDS (Acquired Immune Deficiency Syndrome) refers to the most advanced stages of HIV infection and a collection of signs and symptoms caused by more than 20 opportunistic infections or related cancers.

4. CD4 facts What CD4 cells do CD4 cells/T-cells/T-helper cells : Organize the immune system’s response to bacterial, fungal and viral infections. CD4 cell counts in people without HIV HIV-negative man : 400-1600/ml of blood HIV-negative women : 500-1700/ml of blood. Menstruation: Women’s CD4 cell counts go up and down during the menstrual cycle. OCP: Oral contraceptives lowers woman’s CD4 cell count. Smoking: Smokers tend to have higher CD4 cell counts (by about 140). Sleep: A lower CD4 cell count in the early morning which rises in the afternoon.

5. Fact 2Modes of transmission Vaginal, oral or anal sex withan infected person. Transfusion of infected blood. Sharing unclean needles or syringes to take drugs. Unsterilized needles for tattooing, skin piercing or acupuncture. From mother to baby in uterus during Pregnancy, childbirth (vertical transmission) or through breastfeeding. occupational exposure in health care settings.

6. Fact 3 33 million people live with HIV/AIDS worldwide, the vast majority of whom are in low & middle-income countries. An estimated 2.7 million people were newly infected with the virus in 2007.

7. Fact 4 HIV/AIDS is the world’s leading infectious killer. Claiming—to date—more than 25 million lives. 2 million people die every year from HIV/AIDS.

8. Disease Burden World Population:7124 million People Living with HIV/AIDS(PLHA): 33 million(0.46%) Sub-Saharan Africa remained the most heavily affected by HIV, accounting for 68% of all people living with HIV and for 76% of AIDS deaths 2.7 million new infections every year. India Population: 1210 million. PLHA: 2.4 million(0.19%) . India 2nd to South Africa in absolute number of HIV cases.

9. Adults and Children Estimated to Be Living with HIV, 2007(UNAIDS, 2007 @ www.unaids.org) Eastern Europe & Central Asia 1.5 million [1.1 – 1.9 million] Western & Central Europe 730 000 [580 000 – 1.0 million] North America 1.2 million [760 000 – 2.0 million] East Asia 740 000 [480 000 – 1.1 million] Middle East & North Africa 380 000 [280 000 – 510 000] Caribbean 230 000 [210 000 – 270 000] South & South-East Asia 4.2 million [3.5 – 5.3 million] Sub-Saharan Africa 22.0 million [20.5 – 23.6 million] Latin America 1.7 million [1.5 – 2.1 million] Oceania 74 000 [66 000 – 93 000] Total: 33 million (30 – 36 million)

10. Fact 5 Combination antiretroviral therapy (ART) prevents the HIV virus from multiplying in the body. If the reproduction of the HIV virus stops, then the body's immune cells are able to live longer and provide the body with protection from infections.

11. Fact 6 About 4million HIV-positive people had access to antiretroviral therapy (ART) in low- and middle-income countries in 2008. This is a 36% increase in treatment coverage compared to 2007 and a 10-fold increase over 5 years. Global coverage of ART is still low, reaching only 42% of the estimated 9.5 million people who need it.

12. Fact 7 More than 2 million children are living with HIV/AIDS, according to 2007 figures. Most of the children live in sub-Saharan Africa & were infected by their HIV-positive mothers during pregnancy, childbirth or breastfeeding. 1000 children become newly infected with HIV each day. The number of children receiving ART increased from about 75,000 in 2005 to 2,76,000 in 2008.

13. Fact 8 Mother-to-child-transmission is almost entirely avoidable,. Access to preventive interventions remains low in most developing low- & middle-income countries. However, progress has been made. In 2008, 45% of pregnant women living with HIV received anti-retroviralsto prevent mother-to-child transmission of the virus, up from 10% in 2004.

14. Fact 9 In 2007, more than 4,50,000 deaths from tuberculosis occurred among people living with HIV. This is equal to nearly a quarter of the estimated 2 million deaths from HIV in that year. Majority of people living with both HIV & TB reside in sub-Saharan Africa (about 80% of cases worldwide), of whom around 1 quarter are in South Africa.

15. Fact 10 Some key ways to prevent HIV transmission: Abstaining from high risk sex or practice safe sexual behaviors like using condoms. Getting tested & treated for sexually transmitted infections, including HIV. Avoiding injecting drugs, or if someone does, should always use new & disposable needles & syringes. Ensuring Safe Blood: Any blood or blood products that some one might need are tested for HIV.

16. Clades (viral subtypes) of HIV(Harrison’s Principles of Internal Medicine, 17th edition, 2008) HIV has genetic diversity and varies in different geographic regions HIV: 3 strains: M, N, 0 (M responsible for most infections worldwide) Main subtype in North America is subtype B Subtype C is most common worldwide AE, AG, AB are circulating recombinant forms (CRF) greatest diversity occurs in sub-Saharan Africa  A key concern for AIDS vaccine researchers is the tremendous genetic diversity of HIV

17. History of the Disease: African green monkeys Haiti Carribean countries USA Whole world. 1981 Los Angeles cases of Kaposi sarcoma and P. jiroveci pneumonia in young homosexual males and IV drug abusers. 1986 Chennai- first HIV positive case 1987 Mumbai - first AIDS patient

18. Life cycle of HIV (AIDSInfo) Binding and fusion Reverse transcription Integration Transcription Assembly 6. Budding

20. Transmission modes of HIV in India

21. Key populations at risk of HIV: Heterosexuals (developing countries) Men who have sex with men (MSM in developed countries)/Bisexuals. Injection drug users (IDU). Commercial sex workers (CSW), Migrants, Truck drivers. Newborns of infected mothers. Prisoners, transfusion recipients, professionals. Sexually transmitted infections (STI) clinic attendees. Adolescents.

22. A.Predominant Routes B.Effective Route of transmission of Transmission 1. Sexual contact: 84.53% 1. Blood transfusion: 90-95% 2. Bloodand 2. Perinatal: 20-40% Blood products: 3.37% 3. IDUs : 3.36% 3. Sexual intercourse: 0.1-1.0% 4. Perinatal transmission : 2.14% 5. Others: 6.7% 4. Mucous membrane: 0.09%

24. Insect bites

25. Touching, hugging

26. Water, food

27. Kissing

28. Public baths

29. Handshakes

30. Work or school contact

31. Using telephones

33. Clinical Spectrum of HIV/AIDS Initial Infection: Acute Retroviral Syndrome Asymptomatic(2-6 weeks upto 36 weeks) 50% have symptoms of acute viral fever like- fever, rash, joint pain, sore throat, diarrhea, swollen lymph nodes. HIV antibodies: not detectable. Window Period but viral multiplication present. Patient is highly infective.

34. Clinical Spectrum of HIV/AIDS Asymptomatic Carrier State: (Clinical Stage I) Early Asymptomatic Disease(CD4 count>500/ml) & no overt signs. Progressive deterioration in immune system. Some remain Asymptomatic & don’t seek T/t(5-7 years). Signs & symptoms of Persistent GeneralisedLymphadenopathy(PGL) HIV antigen & antibodies: Both detectable. Patient is highly infective.

35. Clinical Spectrum of HIV/AIDS AIDS Related Complex(ARC) State: (Clinical Stage II) Intermediate HIV Infection(CD4 count: 200-500/ml) No Opportunistic Infection. Early signs & symptoms of Recurrent Oral Ulcers, Moderate weight loss(<10% of body weight), Recurrent RTI(Sinusitis, Pharyngitis, Tonsilitis, Otitis Media) Herpes zoster infection, Seborrhoic Dermatitis/pruritus. Herpes zoster Angular Chelitis Pulmonary tuberculosis.

36. Clinical Spectrum of HIV/AIDS AIDS State: Late Stage HIV Disease/(Clinical Stage III) Signs & symptoms of Opportunistic Infections(CD4 count: 50-200/ml) Unexplained Intermittent/Persistent fever, night sweat, Unexplained chronic diarrhoea (>1 month), Unexplained Severe weight loss(>10% of body weight) Unexplained Anemia, Leucopenia, Thrombocytopenia. Oral Hairy Leukoplakia Severe Infection(empyema, meningitis, pneumonia) OIs: Pneumocystisjeroveci pneumonia, Cerebral Toxoplasmosis, Pulmonary/disseminated Tuberculosis, Cryptococcal Meningitis/ Severe OropharyngealCandidiasis.

37. Clinical Spectrum of HIV/AIDS Advanced State of HIV/AIDS: (Clinical Stage IV) Signs of HIV wasting syndrome(CD4 count:< 50/ml) Neurological manifestations of motor abnormality, cognitive impairement, behavior changes, various types of malabsorption, wasting of muscles. Extra-Pulmonary TB/Milliary TB MAIC infection Kaposi’s Sarcoma/CNS Lymphoma Histoplasmosis OesophagealCandidiasis(Candidiasis of trachea, bronchi, lungs) Chronic cryptosporidiosis, cryptococcosis, isosporiasis.

38. Initial Evaluation of the Patient Full medical and sexual history Addiction history History of sexually transmitted diseases (STDs) History of Blood Transfusion Immunization history Previous HIV test Current state of health including assessment of clinical manifestations of infection Conditions that may interfere with HIV management (eg. heart disease) Systems review including other illnesses/ opportunistic infections Complete physical exam

39. Opportunistic Infections Associated With AIDS Categories of Opportunistic Infections or Diseases • Bacterial & Mycobacterial • Fungal • Malignancies or cancers • Protozoal • Viral • Neurological conditions

40. Course of HIV Disease (Untreated Infection)

41. HIV Counseling Three time testing of blood to know the HIV status of a person. Tests are available at Integrated Counseling and Testing Center(ICTC). HIV Counseling: Pre-test & Post-test Type. Tremendous social, physical, mental implication on being +ve. Unethical to do testing without informed consent. Privacy of the patient history is maintained Adequate time is given for counseling.

42. Post-test Counseling Acceptance of sero-status. Education about risks of transmission/high risk behavior(“NO” to : donate blood, share needle, do unsafe sex, have pregnancy). Prevention of Parent-to-Child Transmission (PPCT). Plan for future orphans/wills. Early management of Opportunistic Infections. Preventive therapy like TB prophylaxis, Contraception etc. Improvement in quality of life by ART. Reference to Social Support.

44. Detects viral core protein p-24 & gp-41.Rapid tests (CDC, 2008) HIV antibody alternate screening tests that produce results within ~20 minutes. FDA-approved tests that use blood or oral fluid, approved since 2002.

46. FDA-Approved Rapid HIV Antibody Screening Tests CDC, 2008 OraQuick Rapid HIV-1/2 Antibody Test Reveal G3 Rapid HIV-1 Antibody Test Uni-Gold Recombigen HIV Test Multispot HIV-1/HIV-2 Rapid Test Clearview HIV 1/2 Stat Pak Clearview Complete HIV 1/2

47. Testing in Pregnancy opt-in testing, person cannot be given an HIV test unless specifically requested. opt-out testing, health care providers must inform pregnant women that an HIV test will be included in the standard group of tests pregnant women receive. A woman will receive that HIV test unless she specifically refuses. The CDC currently recommends that health care providers adopt an opt-out approach to perinatal HIV testing .

48. Prevention & Control of AIDS: Elimination of Reservoir: ART/HAART Treatment is life long but not curative but supportive. Reduce HIV-related morbidity and prolong survival. Improve quality of life & delay onset of AIDS. Restore and preserve immunological functions. Maximally suppress viral load (HIV-RNA). Prevent vertical HIV transmission. Newer regimens are potent, durable, less toxic, and have simplified regimens (simpler regimens improve adherence). Non-Nucleoside Reverse Transcriptase Inhibitors, Protease Inhibitors, Nucleoside Analogues.

49. Clinical Guidelines WHO: 2010 Recent guidelines support earlier treatment and recommend that a CD4 count of 350/μL is the lowest count to begin ART(WHO-2010) Symptomatic Asymptomatic CD4 < 350/μL CD4 > 350/μL Individualized treatment ● High viral load (>1,00,000 copies/mL) ● Rapid CD4 decline (>100/μL per yr) ● Hepatitis B or C coinfection ● HIV-associated nephropathy ● Risk factors for non-AIDS diseases (eg. cardiovascular disease) ART recommended

50. Treatment Nucleoside Reverse Transcriptase Inhibitors (NRTI's)-Zidovudine, Lamivudine, Stavudine, Abacavir. Non-Nucleosides Reverse Transcriptase Inhibitors (NNRTI's)-Etravirine,Efavirenz, Nevaripine, Delaviridine. Protease Inhibitors(PI's)-Indinavir, Ritonavir, Saquinavir. Nucleotide Analogs-Tenofovir, Emtricitabine. Integrase Inhibitors-Raltegravir. Entry/Fusion Inhibitors-Enfuviritide, Celsentri - CCR5 Inhibitor Combination Medications-lamivudine + abacavir, lopinavir + norvir

51. Challenges to Disease Management Toxicities or adverse effects. Drug interactions. Clinical manifestations related to the drugs and the HIV infection itself. Maintenance of adherence. Threat of drug resistance. Co-morbid conditions. Pregnancy.

53. Having a faithful and uninfected sexual partner.

54. Safe Sex Practice: no sex with unknown partner.

55. Use of condoms in sex with a unknown partner.

56. Use of condom between married couple if one of them has multiple partners.

57. Use of condoms by HIV +ve couple.(Gender Disparity)

59. Strict Sterilisation practice in health care facilities.

60. Discouraging tatooing, sharing of razors, shaving brushes, bathing brushes,nail cutters.

62. Zidovudine-600 mg every day Lamivudine-150 mg twice a day Indinavir-800 mg every 8 hours Nelfinavir-750 mg three times a day Post-Exposure Prophylaxis

63. Treatment Recommendations A large number of antiretroviral drugs are now available:  Nucleoside and nucleotide analogues (NRTIs)  Non-nucleoside reverse transcriptase inhibitors (NNRTIs)  Protease inhibitors (PIs) and boosted protease inhibitors (PI/r) CCR5 antagonists  Integrase inhibitors ART for initial therapy in treatment- naïve patients (Hammer et al., 2008)  Two NRTIs plus either efavirenz (NNRTI) or a ritonovir-boosted protease inhibitor (eg. lopinavir/r) ART available for patients with drug-resistant HIV Prophylaxis for some opportunistic infections: Toxo, PCP, TB, MAC

64. Medical Complications of ARThttp://aidsinfo.nih.gov/contentfiles/HIVandItsTreatment_cbrochure_en.pdf Cardiovascular disease- eg. abacavir Hyperlipidemia- increased triglycerides/cholesterol Hepatotoxicity- liver damage Hyperglycemia and diabetes Lactic acidosis Lipodystrophy Osteonecrosis, osteopenia, osteoporosis- bone disease Skin rash eg. Stevens-Johnson syndrome eg. Toxic epidermal necrolysis Pancreatitis Renal or kidney failure Bleeding events Suppression of bone marrow

65. WHO’s HIV/AIDS work for the period 2006-2010 is structured around five strategic directions:

66. Testing and Counseling: Voluntary HIV counseling and testing (VCT) Infant HIV diagnosis and family testing and counseling 2. Maximizing the health sector’s contribution to HIV prevention. 3. Accelerating the scale-up of HIV/AIDS treatment and care. 4. Strengthening decentralization and expanding health systems. 5. Investing in strategic information to guide a more effective response. 1. Enabling people to know their status through confidential HIV testing and counseling.

67. NEEDS Continuous surveillance Awareness programmes Increased health care allocations Identification of high risk groups Access to treatment for all Removal of stigma and discrimination Developing appropriate guidelines

68. The Red Ribbon Express has seven coaches equipped with educational material, primarily on HIV/AIDS, interactive touch screens and 3D models, PPTCT services in the context of RCH II, HIV-TB co-infection, an LCD projector and platform for folk performances, counseling cabins and two doctors’ cabins for providing counselling and syndromic treatment for STI and RTI cases, an office, dining area and pantry. Red Ribbon Express

72. Premature Development of Complications from HIVDeeks et al., 2009

73. Non-AIDS Related Complications That May Be More Common Patients With HIV Hypertension (high blood pressure) Diabetes mellitus and insulin resistance Cardiovascular disease Pulmonary hypertension (increased pressure in the pulmonary artery) Cancer Osteopenia and osteoporosis (decreased bone mineral density) Liver failure Kidney failure Peripheral neuropathy Frailty Cognitive decline and dementia

74. Conclusions HIV destroys immune function leading to immune deficiency and the development of opportunistic infections, leading to the development of AIDS There is currently no cure for AIDS and no vaccine, although with good adherence to treatment, ART can prevent progression to AIDS indefinitely (ART Cohort Collaboration, 2008) In addition to side effects from ART, HIV itself can result in non-AIDS related complications Guidelines and recommendations for HIV management by the CDC and other professional organizations exist and are routinely updated