Identification of novel biomarkers unique to the HIV-1 latent reservoir

2019 Fiscal Year Annual Research Report

• Project/Area Number: 18K16178
• Research Institution: Kumamoto University
• Principal Investigator: MAHITI Macdonald 熊本大学, 国際先端医学研究機構, 客員講師 (50773321)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: HIV-1 / latency

Outline of Annual Research Achievements

Although the antiretroviral therapy successfully prolongs lives of HIV-infected patients, the current therapy is insufficient to eradicate infected cells. Understanding the molecular characteristic and phenotype of the cells harboring latent provirus is thus crucial for achieving cure. However, distinguishing latently-infected cells from uninfected cells remains a challenge. Taking in consideration of the HIV pandemicity in my home country Tanzania, I first tried to establish a platform to access to blood specimens of HIV-infected patients who successfully treated by antiretroviral therapy at least for 2 years. I have successfully collected whole blood from such patients (about 100), separated
PBMC, and send them to Japan after freezing. Using the collected PBMC, I then quantified the copy number of proviral DNA in a million of PBMC employing the quantitative PCR mathod I have developed. The median copy number of proviral DNA in Tanzania showed within the ranges reported in subtype B-infected patients in the developed contries. I am still trying to amplify near full length proviral genome from some of these patients' specimens. In the meanwhile, I amplified a part of proviral genome in relation to drug resistant mutations, and found that there were merely very few drug-resistant mutations in proviral genome in Tanzania despite nearly 30% of pretreatment drug resistant mutations were found in our recent study in this country.

Research Products

• [Int'l Joint Research] Muhimbili University(タンザニア)
  • Country Name: TANZANIA
  • Counterpart Institution: Muhimbili University
• [Journal Article] Circulating HIV-1 Integrase Genotypes in Tanzania: Implication on the Introduction of Integrase Inhibitors-Based Antiretroviral Therapy Regimen (2020)
  • Author(s): Masoud Salim、Kamori Doreen、Barabona Godfrey、Mahiti Macdonald、Sunguya Bruno、Lyamuya Eligius、Ueno Takamasa
  • Journal Title: AIDS Research and Human Retroviruses Volume: - Pages: -
  • DOI: 10.1089/AID.2020.0021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring (2019)
  • Author(s): Barabona Godfrey、Mahiti Macdonald、Masoud Salim、Mbelele Peter、Mgunya Amina Shaban、Minja Lilian、Sunguya Bruno、Shigemi Urara、Matsuda Masakazu、Hachiya Atsuko、Iwatani Yasumasa、Lyamuya Eligius、Ueno Takamasa
  • Journal Title: Journal of Antimicrobial Chemotherapy Volume: 74 Pages: 3016～3020
  • DOI: 10.1093/jac/dkz272
  • Peer Reviewed / Int'l Joint Research
• [Presentation] HIV drug resistance mutations in virally suppressed Tanzanians on long term ART (2019)
  • Author(s): Godfrey Barabona, Macdonald Mahiti, Salim Masoud, Doreen Kamori, George Judicate, Kyoko Yamada, Amina Shaban Mgunya, Lilian Minja, Bruno Sunguya, Eligius Lyamuya, Takamasa Ueno
  • Organizer: 第33回日本エイズ学会学術集会
• [Presentation] HIV integrase genotypes circulating in Tanzania: Implication to efficacy of integrase inhibitors containing regimen (2019)
  • Author(s): Doreen Kamori, Salim Masoud, Godfrey Barabona, Macdonald Mahiti, Bruno Sunguya, Eligius Lyamuya, Takamasa Ueno
  • Organizer: 第33回日本エイズ学会学術集会