HIV/AIDS RECENT ADVANCES

AIDS:PRESENT OVERVIEW AND A LOOK INTO THE FUTURE

1. HIV/AIDS RECENT ADVANCES Dr. Soumya

2. AIDS story till now   India managed to reduce its HIV count by a staggering 57 % while both Bangladesh and Sri Lanka saw an increase in HIV cases by 25 %(2001-11). This has led to various international figures praising India’s HIV/AIDS prevention model PLHIV 57 Lakh(2001) 21 lakh(2011) Adult(15-49 years) Prevalence 0.41 %(2001) 0.27%(2011) Source : NACO Dec 2013 Report

3. Still a long way to go PLHIV Estimates as of 2011 South Africa - 5.6 million Nigeria - 3.3 million India - 2.1 million Source : UNAIDS Report on the Global AIDS epidemic 2013 A mere 0.1% increase in the HIV prevalence would increase the estimated number of people living with HIV by over half a million. In India 90% of the people with an unmet need for antiretroviral treatment live

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5. C ontents AIDS Epidemiology Continuum of care HIV Testing and Counseling Anti-Retroviral Therapy (ART) HIV in Pregnancy HIV-TB co-infection HIV Vaccine NACP- IV References

6. AIDS- EPIDEMIOLOGY Concentrated HIV epidemic Generalized HIV epidemic Mixed epidemics Low-level epidemic

7. AIDS: Epidemiology Concentrated HIV epidemic : HIV has spread rapidly in one or more defined subpopulation but is not well established in the general population. Numerical proxy: HIV prevalence is consistently over 5% in at least one defined subpopulation but is less than 1 % among pregnant women. Generalized HIV epidemic : HIV is firmly established in the general population. Numerical proxy : HIV prevalence consistently exceeding 1% among pregnant women . E.g – SubSaharan Africa

8. Mixed epidemics : people are acquiring HIV infection in one or more subpopulations and in the general population. Mixed epidemics are therefore one or more concentrated epidemics within a generalized epidemic. e.g – Nigeria, Rwanda Low-level epidemic : epidemics in which the prevalence of HIV infection has not consistently exceeded 1% in the general population nationally or 5% in any subpopulation. AIDS: Epidemiology

9. ART settings acc. to uptake of ART Low-uptake ART settings – uptake less than 50% moderate- uptake ART settings - uptake 50-80% high- uptake ART settings - uptake greater than 80 % ( uptake of ART among those eligible for ART ) AIDS: Epidemiology

10. Epidemiology Concentrated HIV epidemic : HIV has spread rapidly in one or more defined subpopulation but is not well established in the general population. Numerical proxy: HIV prevalence is consistently over 5% in at least one defined subpopulation but is less than 1 % among pregnant women in urban areas. Generalized HIV epidemic : HIV is firmly established in the general population. Numerical proxy: HIV prevalence consistently exceeding 1% among pregnant women. Most generalized HIV epidemics are mixed in nature, in which certain (key) subpopulations are disproportionately affected. Mixed epidemics : people are acquiring HIV infection in one or more subpopulations and in the general population. Mixed epidemics are therefore one or more concentrated epidemics within a generalized epidemic. Low-level epidemic : epidemics in which the prevalence of HIV infection has not consistently exceeded 1% in the general population nationally or 5% in any subpopulation. Low-, moderate- and high-uptake ART settings refer to settings in which the uptake of ART among those eligible for ART is less than 50%, 50–80% and greater than 80 %, respectively . The magnitude of the problem can be assessed from the fact that for every person who gains access to anti-retroviral drugs, two people are newly infected with HIV

11. Declining Trends of HIV Epidemic in India Female: 39% of PLHIV; Children: 7% of PLHIV Source: Technical Report India HIV Estimates 2012, NACO & NIMS

12. Key terms in HIV Epidemic HIGH RISK GROUP Female Sex Worker(FSW) Men who have Sex with Men(MSM) Transgender Injecting drug users(IDU) VULNERABLE POPULATION Women having casual partners Spouses of high risk groups Youth BRIDGE POPULATION Migrant Truckers KEY POPULATION HRG Vulnerable Population PLHA

13. Indian epidemic: Characteristics India’s highly heterogeneous epidemic is largely concentrated in only a few states — in the south and west, and in the north‐east.(AP, Maharashtra , Karnataka, TN- >55%) L ow prevalence states of Odisha , Kerala, Jharkhand, Uttarakhand , Jammu & Kashmir, Arunachal Pradesh and Meghalaya are showing rising trends in adult HIV  Adult prevalence – 0.27% (2011) Men- 61% Women -39% Children –7% Urban > Rural

14. District-wise Scenario of AIDS Category NACP-III Definition A > 1% ANC prevalence in any of the sites in the last 3 years B < 1% ANC prevalence in all the sites during last 3 years with > 5% prevalence in any HRG site (STD/FSW/MSM/IDU) C < 1% ANC prevalence in all sites during last 3 years with < 5% in all STD clinic attendees or any HRG, with known hot spots D < 1% ANC prevalence in all sites during last 3 years with < 5% in all STD clinic attendees or any HRG OR no or poor HIV data with no known hot spots Category NACP-III A 156 B 39 C 296 D 118 New Districts 30 Total 609

15. Haryana : AIDS Scenario Total Estimated HIV Positive cases – 42000 No. of AIDS cases (2012) - 2585 Maximum no. of cases (Rohtak) - 590 ART Centre - 1 No. of persons registered(upto Feb’13) -11606 Community care centre(CCC) - 1 Drop in Centres - 2

16. HIV Concentrated in HRG & Bridge Pop. Source: HIV Sentinel Surveillance 2010-11 – A Technical Brief, NACO

17. HIV TESTING AND COUNSELING LINKAGE TO CARE ENROLLMENT IN CARE RETENTION HIV PREVENTION GENERAL HIV CARE PREPARING PEOPLE FOR ART MANAGING COINFECTION AND MORBIDITIES ART INITIATION (FIRST LINE) RETENTION AND ADHERENCE MONITORING ART RESPONSE MONITORING ARV TOXICITY SECOND AND THIRD LINE ART Continuum of care

18. WHO HIV clinical stages Short, flu-like illness occurs 1-6 weeks after infection Infected person can infect other people Average- 10 years Mild symptoms HIV in blood drops to very low levels Antibodies are detectable in the blood The immune system deteriorates Opportunistic infections (OI)start to appear R apid decline in the number of CD4 + T cells Opportunistic infections become severe and cancer may develop

19. HIV Infection and Antibody Response Infection Occurs AIDS Symptoms ---Initial Stage---- ---------------Intermediate or Latent Stage-------------- ---Illness Stage--- Flu-like Symptoms Or No Symptoms Symptom-free < ---- ----

20. HIV Testing and Counselling

21. ICTC 12897 4508 8389

22. Topic Old Guidelines New Guidelines HIV Testing Initiating testing and counseling based on referrals in hospital set up Community-based HIV testing and counseling with linkage to prevention, care and treatment services is recommended, in addition to old guidelines. Couples Voluntary HIV testing and counseling HIV Testing & counselling

23. Working pattern of ICTC HIV Suspect ICTC Counselor Reason for testing Risk Assessment Pre-test COUNSELING consent BLOOD TEST HIV - ve Post test COUNSELING Change risky life pattern Preventive measures HIV + ve confirmed Post test COUNSELING ART PPTCT Drop-in Centres

24. Delivery of HIV treatment and care THREE TIER STRUCTURE

25. COE CENTRES OF EXCELLENCE Provision of second line and alternative first line ART Training, research and mentoring of ART centers linked to them ART CENTRES CD4 Testing Pre ART care and counseling ART provision Treatment of OI LINK ART CENTRES Accessible and facilitate delivery of ART Monitoring patients on ART COMMUNITY CARE CENTRES Counseling for ARV treatment preparedness and drug adherence, nutrition and prevention treatment of OI referral and outreach services for follow-up Social support services DROP IN CENTRES Psychosocial support Counseling Sharing and caring Referrals to ICTC, DOTS Needle and syringe exchange 10 380 840

26. ART PLUS CENTRES Assessment and initiate treatment for alternate first line and second line Accessible and facilitate delivery of second line ART Viral load testing Number-21 LINK ART PLUS CENTRES(LAC PLUS) ARV drug dispensing Enrolment of PLHIV in HIV care and treatment (Pre-ART Care ) Monitoring of PLHIV on ART Baseline lab tests Counseling on adherence, nutrition & prevention Delivery of HIV treatment and care

27. Highly Active Anti Retroviral Therapy(HAART)

28. HAART Regimens H FIRST LINE 2NRTI+ 1NNRTI PREFFERED REGIMEN TDF + 3TC (or FTC) + EFV SECOND LINE 2NRTI+ RITONAVIR BOOSTED PI PREFFERED REGIMEN TDF + 3TC (or FTC) +  ATV/RTV THIRD LINE INTEGRASE INHIBITOR+2 ND GENERATION NNRTI+ PI PREFFERED REGIMEN RAL   +ETV+RTV/DRV

29. Goals of ARV Therapy R educe HIV-associated morbidity and prolong the duration and quality of survival, R estore and preserve immunologic function Maximally suppress plasma HIV viral load P revent HIV transmission

30. Overview of WHO 2013 guidelines The 2013 consolidated guidelines compile new , existing recommendations and other guidance across the continuum of HIV care. Includes guidance on HIV diagnosis, general HIV care and the strategic use of ARV drugs. Developed in accordance with procedures outlined by the WHO Guidelines Review Committee and are based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system.

31. Recommendations: When to Start TARGET POPULATION (ARV-NAIVE) 2010 ART GUIDELINES 2013 ART GUIDELINES STRENGTH OF RECOMMENDATION & QUALITY OF EVIDENCE HIV+ ASYMPTOMATIC C D4 ≤350 cells/mm 3 CD4 ≤500 cells/mm 3 (CD4 ≤ 350 cells/mm 3 as a priority) Strong , moderate-quality evidence HIV+ SYMPTOMATIC WHO clinical stage 3 or 4 regardless of CD4 cell count No change Strong, moderate-quality evidence PREGNANT AND BREASTFEEDING WOMEN WITH HIV CD4 ≤350 cells/mm 3 or WHO clinical stage 3 or 4 Regardless of CD4 cell count or WHO clinical stage Strong , moderate-quality evidence HIV/TB CO-INFECTION Presence of active TB disease, regardless of CD4 cell count No change Strong, low-quality evidence HIV/HBV CO-INFECTION Evidence of chronic active HBV disease, regardless of CD4 cell count Evidence of severe chronic HBV liver disease, regardless of CD4 cell count Strong, low-quality evidence HIV+ PARTNERS IN SD COUPLE No recommendation established Regardless of CD4 cell count or WHO clinical stage   Strong, high-quality evidence

32. Populations With No Specific Recommendations Insufficient evidence and/or favorable risk-benefit profile for ART initiation at CD4 > 500 cells/mm 3 (or regardless of CD4 count) in the following situations: Individuals with HIV who are 50 years of age and older Individuals co-infected with HIV and HCV Individuals with HIV-2 Key populations with a high risk of HIV transmission (e.g.: MSM, sex workers, IDU) These populations should follow the same principles and recommendations as for other adults with HIV

33. Lab monitoring before starting ART Phase of HIV management Recommended Desirable (if feasible) HIV diagnosis HIV serology, CD4 TB screening HBV (HBsAg) serology Cryptococcus antigen if CD4 ≤100 Screening for STIs Assessment for major NCD’s and comorbidities F/U before ART CD4 cell count (every 6–12 mths) ART initiation CD4 cell count Hemoglobin for AZT Pregnancy test Blood pressure Urine dipsticks for glycosuria and serum creatinine for TDF LFT for NVP

34. Receiving ART CD4 (every 6 months) HIV viral load (at 6months after initiating ART and every 12 months ) Serum creatinine for TDF Treatment failure CD4 (Persistent CD4<100) HIV viral load (>1000) Lab monitoring during ART Phase of HIV management Recommended Desirable (if feasible)

35. ART Regimens :NACO

36. ART Scale up for PLHIV in India, 2005 - 2012

37. HIV-TB Co-infection A setting with a high burden of TB and HIV refers to settings with adult HIV prevalence ≥1% or HIV prevalence among people with TB ≥5 % Among PLHA, TB is the most frequent life-threatening opportunistic infection and a leading cause of death(25%). HIV care settings should implement the WHO Three I’s strategy : Intensified TB case-finding , I soniazid preventive therapy (IPT) I nfection control at all clinical encounters

38. DIAGNOSIS OF TB IN HIV Frequently negative sputum smears Atypical radiographic findings Resemblance to other opportunistic pulmonary infections like pneumonia WHY is it difficult to diagnose TB in HIV infected patient Arrow points to cavity in patient's right upper lobe --typical finding in patient with TB

39. HIV infection increases the likelihood that new infection with M . tuberculosis (due to immune suppression) will progress rapidly to TB disease. Among HIV-infected individuals, lifetime risk of developing active TB is 50%, compared to 5-10% in persons who are not HIV-infected. In a person infected with HIV, the presence of other infections, including TB, allows HIV to multiply more quickly. This may result in more rapid progression of HIV infection HIV infected persons have approximately an 8‐times greater risk of TB than persons without HIV infection HIV-TB Co-infection

40. CD4 Cell count ART Regimen ATT Regimen CD4 < 50/ mm 3 Start immediately Start immediately CD4 < 250/ mm 3 Start as soon as ATT tolerated (2-4 wks ) Start immediately CD4 250 -350/ mm 3 Start after the initial phase(8 wks ) of TB treatment completed Start immediately CD4 >350/ mm 3 Re-evaluate with repeat CD4 count after TB treatment Start immediately

41. PPTCT :4 Pronged approach

42. PPTCT (Cont.) Without any intervention risk of transmission of HIV from infected mother to her child is between 20-45 %. SD-NVP is highly effective in reducing risk of transmission from about 45% to less than 10 % Multiple drugs for PPTCT can reduce transmission to less than 5% if started early in pregnancy and continued throughout period of delivery and breast feeding . Adults 57 % Children 35%

43. PMTCT program option Pregnant and breastfeeding women with HIV HIV-exposed infant Use lifelong ART for all pregnant and breastfeeding women (“Option B+”) Regardless of WHO clinical stage or CD4 Breastfeeding Replacement feeding Initiate ART and maintain after delivery & cessation of breastfeeding 6 weeks of infant prophylaxis with once-daily NVP 6 weeks of infant prophylaxis with once-daily NVP Use lifelong ART only for pregnant and breastfeeding women eligible for treatment (“Option B”) Eligible for Treatment (CD4 Count) Not eligible for treatment Initiate ART and maintain after delivery and cessation of breastfeeding Initiate ART and stop after delivery and cessation of Breastfeeding

44. Establish HIV Status of Pregnant Women HIV - ve newly detected HIV infection Continue ART From ICTC collect the blood Sample for CD4 and sent it to ART center and refer women to there ART Center : Initiate ART to HIV + ve pregnant mother regardless of WHO Clinical Stage and CD4counts Preferred Regimen : TDF+3TC+EFV ART center will collect sample for baseline and other investigations Repeat HIV as per guidelines for window period &h/o risk factor Known HIV infected case and already receiving ART

45. Mother :Continue ART during labour and delivery( intrapartum ) Mother: Continue ART(Postpartum) Infant: Daily NVP from birth until 6 weeks of age then stop (Irrespective of choice of infant feeding) Exclusive BF/RF Continue ART Continued

46. D uration of BF in HIV Breastfeeding should only stop once a nutritionally adequate and safe diet without breast-milk can be provided.( AFASS Criteria) Acceptable Feasible Affordable Sustainable Safe

47. HIV in Body Fluids Semen 11,000 Vaginal Fluid 7,000 Blood 18,000 Amniotic Fluid 4,000 Saliva 1 50 Semen 11,000 Vaginal Fluid 7,000 Amniotic Fluid 4,000 Saliva 1 Average number of HIV particles in 1 ml of these body fluids

48. AIDS: modes of spread 1.7 5

49. Routes of HIV Transmission

50. HIV: Prophylaxis Standard Precautions : Hand washing Use of protective barriers e.g - gloves,masks,goggles,gowns Safe handling and safe disposal of sharps Respiratory hygiene and cough etiquettes Safe decontamination and disposal of contaminated waste

51. Post-exposure Prophylaxis C omprehensive management given to minimize the risk of infection following potential exposure to blood-borne pathogens e.g. HIV. This includes: 1. First aid 2. Counseling 3. Risk assessment 4. Relevant laboratory investigations based on informed consent of the exposed person. 5. Depending on the risk assessment, the provision of short term (4 weeks ) of ART. 6. Follow up and support

52. Post-exposure prophylaxis (PEP) has its greatest effect if begun within 2 hours of exposure. There is little benefit if started >72 hours. The prophylaxis needs to be continued for 4 weeks (28 days ). Preferred PEP regimen : Initially: 2 drug regimen ( Zidovudine + Lamivudine ) then 3 drug regimen : after expert opinion ( AZT + 3TC + NVP) Clinical follow-up: the exposed person must be monitored for the eventual appearance of signs indicating an HIV. These symptoms almost always appears within 3 to 6 weeks after exposure. Laboratory follow-up : after exposure testing at 3 months and 6 months is recommended . Post-exposure Prophylaxis

53. Oral pre-exposure prophylaxis Serodiscordant couples daily oral PrEP ( TDF or TDF + FTC) Men and transgender women daily oral PrEP (Specifically TDF + Emtricitabine ) ART for prevention among serodiscordant couples PLHIV in serodiscordant couples who start ART for their own health, ART is also recommended to reduce HIV transmission to the uninfected partner. HIV-positive partners with a CD4 count ≥350 cells/mm3. HIV prevention based on ARV drugs

54. Post-exposure prophylaxis for occupational and non-occupational exposure to HIV Post-exposure prophylaxis for women within 72 hours of a sexual assault Recommended duration of PoEP is 28 days , First dose as soon as possible within 72 hours The choice based on first-line ART regimen.

55. HIV Vaccine Need Despite the remarkable achievements in development of anti-retroviral therapies and recent advances in new prevention technologies, the rate of new HIV infections continues to outpace efforts on prevention and control. Challenges H.I.V . mutates rapidly ; H.I.V. mutates in one day as much as influenza viruses do in a year . The virus has developed multiple mechanisms to evade the body’s defenses T argets the very cells (CD4) that coordinate the immune response to viral infections . Broadly neutralising antibodies usually appear between 2-- 4 years but by that time the antibodies cannot save them because they are overwhelmed by the mutating virus.

56. HIV Vaccine:the new hope AIDSVax R ecombinant protein (HIV gp120) adjuvant with alum Recombinant adeno associated virus vaccine( rAAV ) R ecombinant adenovirus type-5 vaccine containing HIV gag , pol and nef genes RV144 C anarypox vector prime + monomeric gp120 boost Failed in Phase II trials Failed in MSM Paradoxically increased the risk of infection among uncircumcised men with exposure to the virus used in the vaccine . vaccine with the greatest promise till date. 31% efficacy in Phase III trials

57. NACP – IV: Priorities Preventing new infections Preventing of Parent to child transmission Focusing on IEC strategies for behaviour change in HRG, awareness among general population and demand generation for HIV services Providing comprehensive care, support and treatment to eligible PLHIV Integrating HIV services with health systems in a phased manner Reducing stigma and discrimination through greater involvement of people living with HIV( GIPA )

58. Needle-Syringe Exchange Programme and Opioid Substitution Therapy for IDUs Targeted Interventions for High Risk Groups (FSW, MSM, IDU, Truckers & Migrants) Link Worker Scheme for rural population Prevention & Control of Sexually Transmitted Infections IEC, Social Mobilization & Mainstreaming Condom promotion Blood safety Counselling & Testing Services (ICTC, PPTCT, HIV/TB ) First line & second line ART Care &Support Centres HIV-TB Coordination Focus on PPTCT Treatment of Opportunistic Infections Prevention is the main stay High risk populations Low risk populations People living with HIV/AIDS Care, Support and Treatment NACP IV Strategies Capacity Building Strategic Information Management

59. References Joint United Nations Programme on HIV/AIDS (UNAIDS). Report on the global AIDS epidemic .UNAIDS 2013 National AIDS Control Organisation. About NACO;NACO 2013. Available from: http://www.nacoonline.org/About_NACO / . Chawla S, Sahoo SS, Jain RB, Khanna P, Mehta B, Singh I.HIV-Is a vaccine the answer? Hum Vaccin Immunother 2013;10(1). www.ncbi.nlm.nih.gov/pubmed/15817963 medind.nic.in/ nac /t03/i3/nact03i3p11.pdf World Health Organization. Global HIV/AIDS Response– Epidemic update and health sector progress towards Universal Access – Progress Report 2013.

60. References WHO. Antiretroviral Therapy for HIV infection in Adults and Adolescents in Resource-limited settings: Towards Universal Access . Recommendations for a public health approach. 2006 revision . medind.nic.in/ nac /t03/i3/nact03i3p11.pdf Guidelines for the Use of Antiretroviral Agents in HIV Infected Adults and Adolescents,2013.Available from: ( http://aidsinfo.nih.gov/guidelines ) International AIDS committee(IAS);Kualalumpur,Malaysia,30 June – 3July 2013