Treatment and Laboratory/ Care and Support

1. Treatment and Laboratory/Care and Support Treatment Rapporteur Presentation

2. Treatment Snapshots When and What to Start Treatment Rapporteur Presentation 7 June 2008

3. When and What to Start as First-line Therapy? (#838) Adult National Antiretroviral Treatment (ART) Guidelines (Raizes E) WHO (2006) Treatment Rapporteur Presentation 7 June 2008

4. Conclusions PEPFAR focus countries’ published guidelines are consistent with the most recent (2003 or 2006) World Health Organization (WHO) guidelines 13 of the 15 PEPFAR focus countries initiate ART in asymptomatic HIV-infected individuals below 200-250 cells/mm3 WHO guidelines: “Consider treatment [at 200-350 cells/mm3] and initiate before CD4 count drops below 200 cells/mm3.” Treatment Rapporteur Presentation 7 June 2008

5. Conclusions Since publication of the 2006 WHO guidelines, 8 countries have revised their treatment recommendations Preferred 1st line regimens now include AZT or tenofovir The dose of stavudine has been reduced 2nd line ART is consistent with the WHO guidelines; 10 countries recommend virological confirmation For six of the remaining 7 countries, first line regimens continue to include stavudine TDF and 3TC recommended in 5 countries if hepatitis B is present TDF in second line in 8 countries Treatment Rapporteur Presentation 7 June 2008

6. When and What to Start as First-line Therapy? (#838) • Botswana: Policy, Cost and Programmatic Implementation and Implications of Using a Higher CD4 cut off (Sheperd) • CD4 250 cells/ul – 20,000 additional people estimated to immediately qualify; impact on cost? • Moved from d4T/AZT to tenofovir Treatment Rapporteur Presentation

7. Transition Challenges of Tenofovir roll out in Zambia (Mwango A) Lab capacity, procurement and forecasting, changes in clinical practice, administrative preparedness, and provider trainings were necessary for implementation of new guidelines Unanticipated popularity of regimen When and What to Start as First-line Therapy? (#838) Treatment Rapporteur Presentation 7 June 2008

8. When and What to Start as First-line Therapy? (#838) Katjitae I • Namibia (2007) WHO stage 3 /4, CD4 <200 (general population), CD4 <250 (pregnant women). First line AZT/3TC/NVP (alternatives: AZT/3TC/NVP, d4T/3TC/NVP). If the CD4 threshold is raised, challenges of treating advanced patients first, increasing cost, need for improved infrastructure, and improved adherence strategies • Recently d4T to AZT (CD4<250; considering 350) • Predictable increase in anemia – cost of transfusions and EPO • Concern regarding cost of overall programme, especially with increasing > 350 Treatment Rapporteur Presentation 7 June 2008

9. When and What to Start as First-line Therapy? (#838 ) Care, Treatment and Support Rapporteur Presentation • WHO Guidelines, Cost and Implementation for Adults and Pediatrics (Gilks C) • Harmonized ART Policy Guidance for adults, adolescents, pregnant women and children • Revised WHO clinical staging of HIV for adults and children (2006) • All infants < 12 months should be treated 7 June 2008

10. When to Start ART – Infants & Children Treatment Rapporteur Presentation 7 June 2008

11. When and What to Start as First-line Therapy? (#838) Treatment Rapporteur Presentation WHO Guidelines, Cost and Implementation for Adults and Pediatrics (Gilks C) • Revised WHO clinical staging of HIV for adults and children (2006) • Issues for earlier initiation (CD4 <350): estimated 10-30% more eligible patients will lead to decrease in “coverage.” • Nevirapine (NVP) contraindicated in women with CD4>250 7 June 2008

12. When and What to Start as First-line Therapy? (#838) Treatment Rapporteur Presentation WHO Guidelines, Cost and Implementation for Adults and Pediatrics (Gilks C) • Revised WHO clinical staging of HIV for adults and children (2006) • If treat all pregnant women with combination ART, women may be on it for life given SMART data; also what to use? NVP contraindicated, use second line with PI or 3 NRTIs? • TDF not recommended in children/adolescents, in pregnancy and breastfeeding?; cost vs d4T 7 June 2008

13. Side Effects and Toxicity Treatment Rapporteur Presentation 7 June 2008

14. Renal Dysfunction Renal disease – very high baseline renal insufficiency, mortality on ART strongly correlated (especially early) - routine renal screening? – warning signal (Bolton, session B7, Wed morning) Women, age, WHO ¾, Hb<8 Renal dysfunction pre-ART common and carries a very high mortality, even with mild dysfunction Treatment Rapporteur Presentation 7 June 2008

15. Mortality by Baseline Renal Function25,249 patients initiating ART in Lusaka, Zambia Creatinine clearance calculated by Cockroft-Gault equation Treatment Rapporteur Presentation 7 June 2008

16. Resistance in Patients on ART Nigeria: Cross sectional analysis of patients with detectable viral load and history of ART prior to entry Almost 2 years on unmonitored therapy Gentoyped – multiple nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) Treatment Rapporteur Presentation 7 June 2008

17. Number of Drug Resistance Mutations (DRMs) in the Reverse Transcriptase Gene NNRTI DRMs NRTIDRMs Treatment Rapporteur Presentation 7 June 2008

18. ART Response Post Single-dose Nevirapine (sdNVP) (McConnell) Follow-on from CROI Reassuring that NNRTI suppressive regimens are potent beyond 6 months But what about the ones who need treatment? Treatment Rapporteur Presentation 7 June 2008

19. 87% 82% 86% 64%* (n = 450) (n = 106) (n = 51) (n = 153) * P < 0.001 vs unexposed Treatment Rapporteur Presentation 7 June 2008

20. Community Based and Other Methods for Reducing Patient Default Treatment Rapporteur Presentation Good adherence can be achieved using trained antiretroviral drug (ARV) clients and other devoted community members; Planned and consistent home visits as well as social support are crucial for both the client and family members Peer educators for default tracking can be successful in rural districts to return patients to care and support ART initiation and support. Pharmacy refill records are a useful adherence assessment tool. An analysis comparing pharmacy refill rate and self-reported adherence and barriers to adherence is in progress. 7 June 2008

21. Community Based and Other Methods for Reducing Patient Default Treatment Rapporteur Presentation A community-based adherence model utilizing patient Community Health Volunteers and local religious leaders may help improve adherence and retention in care. Interventions delivered by community volunteers offer an attractive opportunity to supplement formal health services. Community program activities need to be routinely validated and information collected must be simple. A low-cost,“real time” default tracing system is feasible to maintain retention in treatment and care using a mobile phone follow-up system. 7 June 2008

22. Challenges in Delivery of Care and Treatment to Most-at-Risk Populations (MARPs) Treatment Rapporteur Presentation • Building HIV/TB Care for Detained Injecting Drug Users (IDU), Jakarta, Indonesia (Magnani R, #1282) • IDUs responsible for 55-60% HIV infections nationally, 1/4-1/3 of inmates are IDUs, HIV prevalence among inmates 10-17%, higher among IDUs (40-50%) • Inmate release and transfer leads to formidable challenges, especially for treatment adherence • Increase in number of inmate deaths suspected to be related to HIV/AIDS led to call for help 6 June 2008

23. Challenges in Delivery of Care and Treatment to MARPs Treatment Rapporteur Presentation • Building HIV/TB Care for Detained IDUs, Jakarta, Indonesia (Magnani R, #1282) • Intervention package: diagnostic and clinical services, condoms, adherence counseling and support, addiction counselng, post-release coordination with community-based non-governmental organizations working with IDUs and people living with HIV/AIDS (PLWHA) • 19% screened were TB +, of those TB +, 31% were HIV + • Use of NGOs crucial to undertake “sensitive” activities government may not want to address 6 June 2008

24. Population prevalence 1.3% (2006 DHS, people in prostitution 35.3 % (ISBS ‘06), people in prostitution condom use 95% with clients, 51% with boyfriends Median age 29, 34 out of 53 had other girlfriends, fiancées or spouses. 26 out of 53 were financially supported by girlfriend Risk perceptions inversely related to trust in partner, people in prostitution unwillingness to use condoms was most frequently cited barrier BF willing to get tested, however few have Knowledge, Attitudes and Condom Use Practices Among boyfriends of people in prostitution, Bamako, Mali (Fofana F, #1703) Treatment Rapporteur Presentation 7 June 2008

25. Challenges in Delivery of Care and Treatment to MARPs Treatment Rapporteur Presentation • Why IDUs are still not receiving healthcare, Ukraine (Kurpita V) • HIV prevalence 1.64% concentrated epidemic IDUs (up to 60%), people in prostitution (up to 32%), men who have sex with men (MSM) (up to 8%) • Of those on ART <2% are IDUs, 85% of those lost to follow-up (LTFU) are IDUs • Multiple obstacles: political, financial, limited access to care, geographic separation of care sites, high stigmatization • High prevalence of co-morbidities in IDUs (85% hepatitis C co-infected), psychiatric illness, lack of knowledge of HIV and drug addiction in medical professionals • Increasing number of non-opiod users, need more evidence re interaction of ARVs and other drugs 6 June 2008

26. Challenges in Delivery of Care and Treatment to MARPs Treatment Rapporteur Presentation 6 June 2008

27. Prevention and Sexually Transmitted Infection (STI) Management with High-Risk Populations, India (avahan) (Menon H) Challenges to scale up: geographic spread, mobile/hidden nature of populations, Rapid roll out of infrastructure, by end of year 4, 280,000 covered (people in prostitution, MSM, IDU), $58/person/year Three staged approach to achieve scale (establish infrastructure, intensify coverage and quality, maintain coverage) Strategy of microplanning to know population peer deals with Flexible management: different contexts require different solutions Lessons learned: focus on scale, define standards but promote innovation, use data, quality is critical, listen to the beneficiaries Challenges in Uganda (Madraa, E) MSM population not well studied, still marginalized, difficult to reach population People in prostitution still face obstacles such as stigma Treatment Rapporteur Presentation 7 June 2008

28. Ethiopia: Retention and Mortality During Six Months of ART Retrospective n= 321, 59% female, average age 34 years; At 6/12: 72% still in care; 18% died (linked to CD4/ mobility/weight); 8% LTFU, 1% transfer: Distance from facility linked to being male, advanced disease, higher age Decentralization important – deal with distance, earlier diagnosis intra-facility linkages Treatment Rapporteur Presentation 7 June 2008

29. Gender and HIV and Outcomes on ART South African study; Retrospective, n = 6 500 ART adults over 3 years; 66% female (ratio changed slightly over time) Women were younger, higher CD4 (80 vs 95), better body mass index (BMI), lower WHO Treatment Rapporteur Presentation 7 June 2008

30. Survival to Death or Loss to Follow Up Adjusted analysis showed survival advantage for women [HR =1.22 (1.06 - 1.39) p=0.004] Male Female Log rank test p=0.0033 Treatment Rapporteur Presentation 7 June 2008

31. Gender and HIV and Outcomes on ART Time to 100 cell increase – again, women more likely and faster (clinical significance?) Women more likely to get viral load suppression at 10/12 (no difference at 4/12) Men access treatment later and sicker; worse virological and immunological data Suggest: focus men on men as a vulnerable group?; workplace voluntary counseling and testing, ‘male friendly’ clinics; Pick up drugs at post office Treatment Rapporteur Presentation 7 June 2008

32. ART-LINC: Effectiveness of cotrimoxizole (CTX) prophylaxis on survival and program retention in African highly active antiretroviral therapy (HAART)-treated adults with baseline Cd4>200 cells/ul Data from ART-LINC collaboration, survival model Outcome: Death or LTFU (gone for 6 months) CTX, CTX before or during CTX,vs CTX after ART, followed up (ART and CTX considered equal across arms); retention 75% Multivariable analysis: Mortality not different ART – LINC Collaboration Treatment Rapporteur Presentation 7 June 2008

33. Session L9 Rwanda (Tene): Clinical and immunological outcomes in children in a decentralized programme 1988 children on ART (55%>5 years); 11%<1 year Median follow-up – 14.6/12; Higher lost to follow up if not started on ART (OR 3.3) Treatment Rapporteur Presentation 7 June 2008

34. Uganda (Musiime): Response of children to ART: urban vs. rural 24 and 48 week data; Similar outcomes, rural presented sicker Treatment Rapporteur Presentation 7 June 2008

35. Treatment Rapporteur Presentation 7 June 2008

36. Outline: Laboratory data Laboratory Infrastructure Quality Systems Early Infant Diagnosis Training Treatment Rapporteur Presentation 7 June 2008

37. Laboratory Strategy Maputo Declaration National governments to support laboratory systems as a priority by developing a national laboratory policy within the national health development plan that will guide the implementation of a national strategic laboratory plan Develop national strategic laboratory plans that integrate laboratory support for the major diseases of public health importance including HIV, tuberculosis, and malaria Treatment Rapporteur Presentation 7 June 2008

38. Laboratory Strategy Treatment Rapporteur Presentation • There is a need to integrate laboratory services instead of having program specific laboratory services (John Nkengasong) • There is a need for a laboratory coordinating mechanism for stakeholder collaboration and commitment to strengthen national level efforts to improve laboratory services (Jack Nyamongo #756) 7 June 2008

39. High proportion of pulmonary tuberculosis (PTB) cases are not identified by the health system, most of HIV+ cases are eligible for ARVs Majority of identified PTB cases are smear-negative Creative approaches such as TB screening during home-based HIV testing initiatives should be considered, and the need to strengthen laboratories for more culture back up in TB diagnostic process (Laserson K.F et al; abstract #358) Routine measurement of standardized indicators is useful to maintaining quality of mycobacterial culture system (Patama Monkongdee #1238) Concentration of sputum improves detection of mycobacterium tuberculosis (MTb) by about 31% Fluorescent microscopy reduces reading time four fold (Girmachew Mamo #784) TB/HIV Treatment Rapporteur Presentation 7 June 2008

40. HIV Incidence Countries should strongly consider application of incidence assays in HIV surveillance systems to monitor incidence in populations over time However, BED incidence must be adjusted using published data, or preferably local adjustments to correct HIV incidence for assay misclassification (Andrea Kim #383) Treatment Rapporteur Presentation 7 June 2008

41. Early Infant Diagnosis (EID) Utilize a pilot phase to develop vital in-country technical skills, laboratory capacity, and development and testing of systems A coordinated multi-partner effort is useful in rolling out the service Integration of services into existing health systems with strengthening of linkages to care and treatment centers facilitates sustainability and maximizes coverage of the program Engage national and facility authorities in each step of implementation (John Gamaliel #1567) Treatment Rapporteur Presentation 7 June 2008

42. Early Infant Diagnosis Creation of a laboratory QA program during development of EID program allows for detection/correction of testing errors and ensures accurate results returned for infant treatment The appointment of Lab project coordinator with a specific responsibility to review laboratory data and perform site visits facilitated the timely reporting and quality of the EID diagnostics. (John Gamaliel #1567) Treatment Rapporteur Presentation 7 June 2008

43. Quality Assurance Treatment Rapporteur Presentation • Must identify appropriate authority at national level to run QA programs • Important to encourage participants to use external quality assurance (EQA) results to improve their performance • QA program and quality management systems (QMS) complement one another to support quality laboratory testing (Wilai Chalermchan) • Require dedicated quality officers at labs 7 June 2008

44. CARE AND SUPPORT Care and Support Rapporteur Presentation 7 June 2008

45. Outline • Adult care • Palliative care • Pediatric care • Counseling & Testing (CT) • Tuberculosis and HIV (TB/HIV) • Food and Nutrition • Orphans and Vulnerable Children (OVC) • Key observations Care and Support Rapporteur Presentation 7 June 2008

46. Adult Care Care and Support Rapporteur Presentation 7 June 2008

47. Retention in care: pre-ART Care and Support Rapporteur Presentation Everyone recognizes retention as problem, but little attention at this conference. 119 HIV+ patients enrolled in 5 health centers (HCs), 99% referred to antiretroviral treatment (ART) site for staging, but only 33 (28%) went within 3 months (Ubarijoro, S, # 727) Piloted clinical staging and CD4 testing at 3 HCs in 2007; 39 patients enrolled, only 3 ART-eligible, and all successfully referred (Ubarijoro, S, # 727) 7 June 2008

48. Pregnant Women and CD4 Testing & ART Initiation: Jose Macamo Hospital(El-Sadr, W, Session F11) Care and Support Rapporteur Presentation 7 June 2008

49. Quality Improvement pilot results: HIV Quality Improvement (HIVQUAL) in 12 hospitals in Thailand, 2002-2005Session E9(Fox, K, #1352) Care and Support Rapporteur Presentation 7 June 2008

50. Documents for Scaling-up HIV Prevention, Care and ART at Primary Health Centers • WHO/PEPFAR (Ellerbrock, T, Session G3) • imaimail@who.int beginning June 20, 2008 Care and Support Rapporteur Presentation 7 June 2008