Dr. William P. Howlett Matthew P. Rubach, MD Dr. Neema W. Minja Department of Internal Medicine, KCMC KCMC/Duke Collaboration HIV in Tanzania: Current Epidemiology and Learned Lessons from the Early Epidemic KCMC CLINICAL CONFERENCE 1 ST JUNE 2016

EPIDEMIOLOGY TANZANIA/ SUB-SAHARAN AFRICA

THMIS SURVEY 2011/2 Tanzanian HIV Prevalence 5.1 % 2007/82011/2 Prevalence (15 – 49 yrs) 5.7%5.1% Women*6.6%6.2% Men4.6%3.8% * Not statistically significant Tanzania HIV /AIDS & Malaria Indicator Survey 2011/1

Global AIDS Response Country Progress Report 2014

TANZANIA (2011/2)SSA (2013) TOTAL #1.4 million24,7 million (71% of Global) Prevalence5.1%4.7 % New infections68, 4471,5 million Deaths79, million Adults on ARVs37.5%39% Regional variations Njombe 14.8% Manyara 1.5% Swaziland (27.4%) South Africa 5.9 mil PLWHIV (25% of SSA) Senegal 0.5% Global AIDS Response Country Progress Report 2014 UNAIDS GAP Report

HIV prevalence n general has decreased regions report an increase: Ruvuma, Kagera, Kigoma, Rukwa, Mtwara, Kilimanjaro, Singida, & Arusha TACAIDS National Response Report 2012

High risk groups GroupPrevalence of HIV FWS31.4% MSM22.2% Prev. estimates (12.3 – 41%) PWIDS16% Prev. estimates (34.8 – 42%) Global AIDS Response Country Progress Report 2014

Global AIDS Progress Report 2013 UNAIDS

UGANDA The HIV/AIDS Uganda country Progress Report 2014

The role of anti-retroviral agents in prevention of HIV

Prevention Efforts Behavorial interventions: sex education/safe sex practices, counseling, safe infant feeding Structural interventions: address gender and social inequality, needle exchange programs Biomedical interventions: Male circumcision Microbicides ARV: Pre-Exposure Prophylaxis (PrEP) Treatment as Prevention (TAP)

Pre-Exposure Prophylaxis Indication: for high-risk populations who may be repeatedly exposed to HIV Sero-discordant couples Sex workers Men who have sex with men (MSM) IV drug users Approach: Step 1: confirm person is HIV-negative Step 2: prescribe ARV (usually 1-2 agents, e.g., Tenofovir/Emtricitabine or Tenofovir alone) Step 3: HIV test every 3 months

Data Supporting Use of PrEP

Trials with No Benefit to PrEP FEM-PrEP 1,951 women aged years Kenya, South Africa and Tanzania ‘High risk:’ >/=1 vaginal sex acts in previous 2 weeks or > 1 sex partner in previous month Randomized to TDF/FTC vs. placebo: Adherence self-report 95% Pill count adherence 88% Detection of TDF in patient plasma was 15-26%!!! VOICE 5,029 women aged years South Africa, Uganda and Zimbabwe Randomized to oral TDF vs. TDF/FTC vs. TDF gel vs. placebo: Adherence self-report or pill count 84-91% Detection was 29-40%!!! Van Damme et al, N Engl J Med 2012;367:411 Marazzo et al, N Engl J Med 2015;372:509

PrEP & Guidelines WHO Oral pre-exposure prophylaxis with TDF or TDF/FTC for Serodiscordant couples MSM Recommendation in place since 2012 TZ MoH No recommendations for or against PrEP in 2015 NACP guidelines WHO, Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, 2013 Guidance on oral PrEP for serodiscordant couples and MSM at high risk of HIV, 2012

PrEP  TAP Role for PrEP in the era of Treatment as Prevention??? HPTN 052: randomized serodiscordant couples to early ART vs. standard of care Early ART group: hazard of 0.04 (95% CI ) of transmitting HIV to the HIV-negative partner Cohen et al, N Engl J Med 2011;365:493

When to Start ART Risk:benefit ratio of medications & costs of medications  WHO GL CD4 threshold < 200 Severe et randomized 816 Haitian adults with CD to early ART vs. Deferred until CD4 < vs. 36 incident cases of TB (HR 2.0 [95% CI ], p=0.01) 6 vs. 23 deaths in early vs. deferred (HR 4.0 [95% CI ] p=0.001) Absolute Risk Reduction (ARR): 5.6%-1.5% = 4.1% Number needed to treat (NNT): 1/ARR = 1/0.041 = 24 WHO 2010 CHANGED GUIDELINE ON ART INITIATION TO CD4 < 350 Severe et al, N Engl J Med 2010;363:3

INSIGHT START Study 4865 adults with CD4 > 500 randomized to immediate ART vs. ART once CD4 < 350 Composite endpoint: serious AIDS-related event, non-AIDS related event or death from any cause Endpoint events: 42 (1.8%) of immediate group and 96 (4.1%) of delayed group Hazard Ratio 0.43 (95% CI ) p< START Team, N Engl J Med 2015;373:795

14 vs. 50 events HR 0.28 p < vs. 21 events HR 0.58 p= 0.13

TEMPRANO DESIGN 2056 patients from Ivory Coast, 2x2 factorial design to assess Early ART vs. Waiting for WHO criteria for ART Isoniazid Preventive Therapy Endpoint: AIDS-defining event, other serious complications (cancer, bacterial infections, TB) or death Results: TB & invasive bacterial disease: 42% and 27% of the primary endpoint events Endpoint HR 0.56 (95% CI ) early ART vs. deferred ART TEMPRANO ANRS, N Engl J Med 2015;373:808

PrEP in the Era of HIV-TAP Evolution of WHO guidance on CD4 thresholds for initiating ART: Start ART AdultsCD4 < 200CD4 < 350CD4 < 500All PLHIV regardless of CD4 Current TZ NACP 2015 Guidance: CD4 < 500 or Clinical Stage 3 or 4 AIDS Initiate ART regardless of Clinical Stage or CD4 count in following scenarios: –TB co-infection (Stage 3 criterion) –Hepatitis B co-infection –High risk population: MSM, IVDU, sex worker, prisoner –Serodiscordant couples

Lessons learnt from the early epidemic

Biomarker of HIV Testing Programs: CD4 at Diagnosis Siedner et al, Clin Infect Dis 2015;60:1120 Temporal trends in CD4 count at presentation to care in sub- Saharan Africa

References The third Tanzania HIV and Malaria Indicator Survey 2011 – 2012 (THMIS III) Global AIDS Response country progress report The United Republic of Tanzania. The GAP. UNAIDS. Beginning of the end of the AIDS epidemic The HIV and AIDS Uganda country progress report 2014 National HIV and AIDS Response report Tanzania Mainland. TACAIDS Global AIDS Response Country Progress Report 2014 Boerma et al. Spread of HIV infection in a rural area in Tanzania. AIDS Vol 13. No. 10. pg 1233 – 1240 Fact Sheet: Njombe adolescents at a glance regional survey results DHSTHMIS Adolescent