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Epidemiology and molecular monitoring of HIV drug resistance in Tanzania

English title Epidemiology and molecular monitoring of HIV drug resistance in Tanzania
Applicant Tanner Marcel
Number 131378
Funding scheme Resource not found: 'bd31932a-e257-46d9-9dba-079f6f2c77c6'
Research institution Swiss Tropical and Public Health Institute
Institution of higher education University of Basel - BS
Main discipline Medical Microbiology
Start/End 01.08.2010 - 31.07.2013
Approved amount 450'768.00
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All Disciplines (2)

Discipline
Medical Microbiology
Infectious Diseases

Keywords (4)

antiretroviral drug resistance; HIV cohort; rural Tanzania; molecular monitoring

Lay Summary (English)

Lead
Lay summary
The roll out of antiretroviral therapy (ART) programmes in developing countries will potentially lead to intense selection for drug resistant strains of the human immunodeficiency virus (HIV). Monitoring the prevalence and spread of drug resistance against antiretroviral drugs by using molecular tools is the primary goal of this project. The study is conducted in collaboration with the Ifakara Health Institute (IHI) in Southern Tanzania, where in 2005 a HIV treatment cohort has been initiated within the Tanzania National AIDS Control Care Programme (NACP), with currently about 5000 HIV patients enrolled. A number of defined point mutations in HIV genes are responsible for resistance against antiviral drugs. These drug resistance-associated mutations need to be identified in order to allow adequate therapeutic decisions on individual as well as population level. In this project, the HIV genes encoding the viral reverse transcriptase and protease are genotyped. Due to the limitation in affordable HIV drugs, early monitoring of the occurrence and spread of viral drug resistance is of crucial importance to low income countries. We will approach this need in three ways, (1) by establishing strictly standardized procedures for drug resistance monitoring, (2) by building up a DNA sequencing facility at the Ifakara Health Institute in Tanzania using in-house developed protocols and (3) by developing a low cost genotyping technique for HIV mutations associated with ART-failure. The molecular surveillance in samples collected in consecutive years and in cases of suspected drug resistance helps to delineate reasons for ART failure. The genotyping information is used to optimize the continued use of the current first line treatment in the Tanzanian KIULARCO cohort and helps to preserve affordable treatment options in a resource poor rural setting.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Development of a simple microarray for genotyping HIV-1 drug resistance mutations in the reverse transcriptase gene in rural Tanzania
Masimba Pax, Gare Janet, Klimkait Thomas, Tanner Marcel, Felger Ingrid (2014), Development of a simple microarray for genotyping HIV-1 drug resistance mutations in the reverse transcriptase gene in rural Tanzania, in Tropical Medicine & International Health, 19(6), 664-671.
Uptake of guidelines on prevention of mother-tochild transmission of HIV in rural Tanzania: Time for change
Gamell A, Letang E, Jullu B, Mwaigomole G, Nyamtema A, Hatz C, Battegay M, Tanner M (2013), Uptake of guidelines on prevention of mother-tochild transmission of HIV in rural Tanzania: Time for change, in Swiss Medical Weekly, 143, 1.
Viral hepatitis and rapid diagnostic test based screening for HBsAg in HIV-infected patients in rural Tanzania.
Franzeck Fabian C, Ngwale Ramadhani, Msongole Bernadeta, Hamisi Marian, Abdul Omary, Henning Lars, Letang Emilio, Mwaigomole Geoffrey, Battegay Manuel, Hatz Christoph, Tanner Marcel (2013), Viral hepatitis and rapid diagnostic test based screening for HBsAg in HIV-infected patients in rural Tanzania., in PloS one, 8(3), 58468-58468.
Prevalence of Drug Resistance Mutations and HIV Type 1 Subtypes in an HIV Type 1-Infected Cohort in Rural Tanzania.
Masimba Pax, Kituma Elimsaada, Klimkait Thomas, Horvath Edit, Stoeckle Marcel, Hatz Christoph, Mossdorf Erick, Mwaigomole Emmanuel, Khamis Salim, Jullu Boniphace, Abdulla Salim, Tanner Marcel, Felger Ingrid (2013), Prevalence of Drug Resistance Mutations and HIV Type 1 Subtypes in an HIV Type 1-Infected Cohort in Rural Tanzania., in AIDS research and human retroviruses, 29(9), 1229-1236.
Uptake of guidelines on prevention of mother-to-child transmission of HIV in rural Tanzania: time for change
Gamell A, Letang E, Jullu B, Mwaigomole G, Nyamtema A, Hatz C, Battegay M, Tanner M (2013), Uptake of guidelines on prevention of mother-to-child transmission of HIV in rural Tanzania: time for change, in Swiss Medical Weekly, 143, w13775.
A case-control study of factors associated with non-adherent to antiretroviral therapy among HIV infected people in Pwani Region, eastern Tanzania
Idindili B, Jullu B, Mugusi F, Tanner M (2012), A case-control study of factors associated with non-adherent to antiretroviral therapy among HIV infected people in Pwani Region, eastern Tanzania, in Tanzania Journal of Health Research, 14(3), 194-203.
Improved antiretroviral treatment outcome in a rural African setting is associated with cART initiation at higher CD4 cell counts and better general health condition.
Mossdorf Erik, Stoeckle Marcel, Mwaigomole Emmanuel G, Chiweka Evarist, Kibatala Patience L, Geubbels Eveline, Urassa Honoraty, Abdulla Salim, Elzi Luigia, Tanner Marcel, Furrer Hansjakob, Hatz Christoph, Battegay Manuel (2011), Improved antiretroviral treatment outcome in a rural African setting is associated with cART initiation at higher CD4 cell counts and better general health condition., in BMC infectious diseases, 11, 98-98.
HIV and parasitic co-infections among patients seeking care at health facilities in Tanzania
Idindili B, Jullu B, Hattendorf J, Mugusi F, Antelman G, Tanner M (2011), HIV and parasitic co-infections among patients seeking care at health facilities in Tanzania, in Tanzania Journal of Health Research, 13(4), 75-85.
Management of HIV and AIDS at lower primary health care facility in Chalinze, eastern Tanzania
IDINDILI BONIPHACE, JULLU BONIFACE, MUGUSI FERDNAND, TANNERMARCEL (2011), Management of HIV and AIDS at lower primary health care facility in Chalinze, eastern Tanzania, in Tanzania Journal of Health Research, 13(3), 1-12.
HIV/AIDS clinical manifestations and their implication for patient clinical staging in resource limited settings in Tanzania
Boniphace Idindili, Omari M, Fred RS, Ferdinand Mugisi, Marcel Tanner (2011), HIV/AIDS clinical manifestations and their implication for patient clinical staging in resource limited settings in Tanzania, in Open AIDS Journal, 5, 9-16.

Collaboration

Group / person Country
Types of collaboration
Ifakara Health Institute Tanzania (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
International AIDS conference July 2012, Poster Supply Chain Management in peripheral Care and Treatment Centres (CTCs) in rural Tanzania: situational assessment 01.07.2012 Washington , United States of America Tanner Marcel; Nyogea Daniel Simon;


Associated projects

Number Title Start Funding scheme
144717 Comprendre les freins à la baisse de la fécondité en Afrique du sud du Sahara 01.09.2013 SNSF Professorships

Abstract

Project title: Epidemiology and molecular monitoring of HIV drug resistance in TanzaniaBackground: Genetic mutations in the target genes of anti-HIV drugs associated with viral drug resistance threaten the integrity of any combination antiretroviral treatment, today the standard of care for HIV patients. Therefore key mutations need to be identified early-on in order to maintain the combined pressure of several drugs and to enable adequate therapeutic decisions on an individual as well as population level.In resource poor settings accessibility to and preservation of inexpensive drugs for antiretroviral treatment (ART) is most needed. Active drug combinations can only be preserved when treatment programmes are tightly linked to a careful and effective resistance testing that also allows capturing the resistance dynamics in patients’ cohorts. However, the current costs for standard testing by nucleotide sequencing of viral genes involved in drug resistance are prohibitive for resources constraint settings. Unfortunately and due to the currently less than perfect drug supply and treatment monitoring particularly for those settings resistance testing is of highest priority. Moreover, the current molecular typing techniques are still mainly designed and optimized for HIV subtype B, the prevailing type in Europe and US. In contrast, subtype B is absent in Tanzanian HIV isolates and in neighboring high HIV endemic areas. Thus, specific, effective and cost-saving methods are required for targeting the local strains that govern resistance dynamics.Approach Due to the limitation in affordable HIV drugs, early monitoring the occurrence and spread of viral drug resistance is of crucial importance to low income countries. We will approach this need in three ways, (1) by building up state-of-the-art sequencing technology at IHI using in-house developed protocols and by establishing strictly standardized procedures for drug resistance monitoring. Prior to treatment samples of patients with suspected resistance will be genotyped as well as collected for archiving. (2) As sustainability critically depends on personnel with good expertise in molecular biology and epidemiology, we propose to establish a training center for ART resistance monitoring at the currently existing and well equipped molecular biology laboratory at IHI. Furthermore, also the regional and a great proportion of the countrywide demand will benefit from laboratory personnel able to perform HIV molecular testing. (3) A cheaper but very robust genotyping technology, as an alternative to sequencing, is urgently needed for rural settings in Africa. So far, most approaches to HIV genotyping were complicated by the extensive genetic diversity of HIV. To overcome this problem we have devised a tailor-made genotyping technique adapted to local genotypes and custom-designed to particularly monitor the drugs actually used in our study area and greater region in Tanzania. Therefore, the overall goal of this three-pronged approach is to establish a peripheral research and resource centre will be established to become an East-African focal point for HIV resistance monitoring and surveillance (in analogy to our previous achievements for molecular research on malaria) with the aim to generate evidence for guiding the design of treatment regimes in areas where only a limited number of drugs against HIV are available.Specific objectives •Provide HIV genotypes from 500 treatment naïve participants enrolled in KIULARCO. •Establish standard operating procedures for genotyping cases of suspected resistance.•Design and initiate a 12-18 months training programme for young university graduates (MSc level; one enrollment every 6 months) to learn and routinely apply the skills required for sequencing and data analysis. •Investigate dynamics of resistance patterns before, during and after introduction of treatment at IHI, as example for a representative rural setting. •Use SNP data for mathematical modelling of the evolution and spread of drug resistance to predict and possibly extend the therapeutic life span of local drugs. •Build up epidemiological expertise and data base management skills necessary to guide public health planning for further ART roll out in Tanzania with the National AIDS Control Programme (NACP) supported by the Global Fund against AIDS, TB and Malaria.•Review in collaboration with the NACP the local HIV treatment policies in the light of observed and predicted resistance dynamics. Provide feedback for national guidelines.Expected outcomes •Affordable and sustainable technique specifically addressing urgent medical needs of countries where costs of established laboratory techniques are beyond the current capabilities of local health facilities.•Development of laboratory skills in Tanzania by technology transfer of quality controlled, standard HIV Resistance-Testing by sequencing to the IHI.•Surveillance and prediction of HIV drug resistance by characterizing circulating virus strains.•Properly calibrated and validated analyses of evolution and spread of drug resistance and therapeutic life span in rural Africa. •Gain in basic knowledge on primary versus secondary transmission of resistance. •This research will assist in improving the efficacy and preservation of viable treatment options by providing information for evidence-based public health decisions and by contributing to the minimal essential data needs for scaling-up and monitoring ART.•The parallel build-up of a resistance database and sample cohort will directly assist a national treatment guideline system in Tanzania.
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