Overview of HIV, Treatment, Resistance and Prospective Data - PowerPoint PPT Presentation

Overview of HIV, Treatment, Resistance and Prospective Data Collection in Tanzania Doreen Mloka Muhimbili University of Health Sciences (MUHAS) 2 nd EURESIST INTERNATIONAL MEETING BONN, GEMANY MAY 6 th 2011 MUHAS 2011 1

HIV Prevalence (15-49 yrs) by Region 2010 Kagera 7.7% Mara 1 st case 1983 - Kagera 3.4%5.6% Mwanza Arusha National Average: 5.7% 7.4% 1.6% Kili. Shinyanga Population: 42 million 1.9% Manyara 1.8% 12% Kigoma 1.5% Tanga 6.4% Pemba 0.3% 2.7% 4.8% 3.3% Tabora Singida Dodoma Unguja 0.8%% Moro- 4.9% Dar- 9.3% goro 6.7% Rukwa Iringa Pwani 9.2% 15.7% 7.0-15.7% 5.1% Mbeya Lindi 3.8% 3.1-6.9% Percent of women 5.9% 0.3-3.0% 3.6% and men age 15-49 Ruvuma who are HIV-positive Mtwara MUHAS 2011 2 NACP 2010

RESULTS HIV-1 SUBTYPE DISTRIBUTION IN COHORT HISIS (n=136) A ACD 11% 13% CD 7% AD 6% C 30% AC D 31% 2% 57 % recombinant 15% dual infections 3

Care and Treatment Services, provision of ARV’s • Wide access to ARVs initiated in October 2004 as part of the National Care and Treatment Plan • Major contributors: – Government of Tanzania – Global Fund – Governments of Canada, Sweden, Norway, Netherlands and USA – Clinton HIV/AIDS Initiative (CHAI) MUHAS 2011 4

BASE LINE TRANSMITTED DRUG RESISTANCE DATA FROM TANZANIA BEFORE NATIONAL ARV ROLL OUT 3 COHORTS – ALL ART NAIVE 1.MBEYA REGION FEMALE SEX WORKERS – 165 (HISIS) (Mloka 2008) 2. NVP COHORT (120) (Mloka 2008) 3.WOMEN ATTTENDING ANC (60) ( Somi 2008) MUHAS 2011 5

GENOTYPIC PRIMARY DRUG MUTATIONS AT BASE LINE 1. OVERALL LOW MUTATION FREQUENCY – LESS THAN 5 % 2. NO MAJOR MUTATIONS FOUND IN RT REGION 3. ONLY MINOR MUTATIONS • V179D/E ( 23.5%) • V118 I (27.8%) • K101N ( 1.3%) • A98G ( 1.3%) • K103R ( 1.3%) MUHAS 2011 6

PROTEASE REGION 1. Minor mutations K20R/M (10.5%), M36I/V (77.6%), L36P (56%), I93V (54%), V77I (7%), A71T (1.2%), L10I/V (5.8%), and D60E (5.8%) 2. Polymorphism coding for secondary resistance to protease inhibitors was detected in over 50 % of analyzed sample e.g. L63V,L63C and L63T MUHAS 2011 7

PRO REGION PRIMARY MUTATIONS : 1. L33F (1.2%) is selected by RTV, Amprenavir (APV), Lopinavir (LPV) 2. N88D (1.0%) - causes intermediate resistance to Nelfinavir (NFV) and possibly low-level resistance to (ATV) and Saquinavir (SQV). 3. L76V (1.0%) - non polymorphic mutation, that reduces susceptibility to APV, Indinavir (IDV), and LPV, while increasing susceptibility to SQV and ATV 4. L90M (3.5%) - causes resistance to SQV and NFV. When present with other mutations it also compromises the activity of IDV, RTV, APV, LPV, and ATV 5. I84V (1.2%) - causes intermediate/high-level resistance to ATV/r, FPV/r, IDV/r, NFV, and SQV/r; and low-level resistance to LPV/r, TPV/r, and DRV/r. MUHAS 2011 8

Drugs available for treatment of HIV - February, 2009 Nucleoside RTI Protease Inhibitor AZT/ Zidovudine SQV/ Saquinavir DDI/ Didanosine D4T/ Stavudine LPV/r Lopinavir - ritonavir 3TC/ Lamivudine ABC/ Abacavir TDF/ Tenofovir Non-Nucleoside RTI Other combination tablets: COMBIVIR , KALETRA NVP/ Nevirapine EFV /Efavirenz and TRIOMMUNE MUHAS 2011 9

10 MUHAS 2011

Total Number of people infected with HIV in care and treatment in CTC’s in Dar es Salaam as of end of June 2010 On Care On Treatment Adult - Males 31,123 20,335 Adult - Females 74,720 41,475 Children - Male 3,947 2,449 Children – Female 4,442 2,656 Total 114,232 66,915 Country wide 668,875 345,006 % of countrywide 17.1% 19.4% MUHAS 2011 11 NACP REPORT 2010

NEXT STEP: DATA COLLECTION FOR EURESIST NETWORK Title: Transmitted and acquired HIV drug resistance in Tanzanian patients and use of bioinformatics to predict new therapy Sponsor: EDCPT Study Site: MNH, Dar es Salaam Sample size : 250 patients Status: Proposal submitted awaiting ethical clearance MUHAS 2011 12

Data to be collected • Patient Demographics • Clinical history including OIs and underlying conditions • Patient drug history • Patient adherence records • Lab data (Viral load, CD 4 counts and Plasma for DNA genotyping and phylogenetic analysis MUHAS 2011 13

Rationale Improvement of HIV treatment and care in Tanzanian, cost effective prediction method through the Euresist data base ( HOW TO SWITCH) Rewards: 1. Molecular characterization of HIV drug resistant strains circulating. 2. Determine prevalence of transmitted and acquired HIV drug resistance in Tanzania 3. Capacity building of health care personnel in Tanzania to practice evidence based medicine through partnership and networking with international collaborators 14 MUHAS 2011

Investigators A. Muhimbili University of Health Sciences (MUHAS)- Tanzania Ferdinand Mugusi Muhammad Bakari Sabina Mugusi B. Karolinska Institute Sweden Anders Sonnerborg Irene Bontell MUHAS 2011 15

Asante Sana (Thank you very much) MUHAS 2011 16