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HIV-1 functional cure: will the dream come true?

ABSTRACT: The reservoir of human immunodeficiency virus type 1 (HIV-1), a long-lived pool of latently infected cells harboring replication-competent viruses, is the major obstacle to curing acquired immune deficiency syndrome (AIDS). Although the combination antiretroviral therapy (cART) can successfully suppress HIV-1 viremia and significantly delay the progression of the disease, it cannot eliminate the viral reservoir and the patient must continue to take anti-viral medicines for life. Currently, the appearance of the 'Berlin patient', the 'Boston patients', and the 'Mississippi baby' have inspired many therapeutic strategies for HIV-1 aimed at curing efforts. However, the specific eradication of viral latency and the recovery and optimization of the HIV-1-specific immune surveillance are major challenges to achieving such a cure. Here, we summarize recent studies addressing the mechanisms underlying the viral latency and define two categories of viral reservoir: 'shallow' and 'deep'. We also present the current strategies and recent advances in the development of a functional cure for HIV-1, focusing on full/partial replacement of the immune system, 'shock and kill', and 'permanent silencing' approaches.

SUBMITTER: Liu C

PROVIDER: S-EPMC4654816 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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HIV-1 functional cure: will the dream come true?

Liu Chao C Ma Xiancai X Liu Bingfeng B Chen Cancan C Zhang Hui H

BMC medicine 20151120

The reservoir of human immunodeficiency virus type 1 (HIV-1), a long-lived pool of latently infected cells harboring replication-competent viruses, is the major obstacle to curing acquired immune deficiency syndrome (AIDS). Although the combination antiretroviral therapy (cART) can successfully suppress HIV-1 viremia and significantly delay the progression of the disease, it cannot eliminate the viral reservoir and the patient must continue to take anti-viral medicines for life. Currently, the a ...[more]

PMID: 26588898

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Project description:BACKGROUND:Long-acting injectable antiretroviral therapy (LA ART) was found to be non-inferior to daily oral ART in Phase 3 clinical trials. LA ART may offer an important alternative for people living with HIV with challenges adhering to daily oral ART or preferences for non-pill-based regimens. METHODS:Using a mixed methods approach integrating survey, in-depth interview and biological data from female sex workers (FSW) living with HIV in Tanzania (N = 208) and the Dominican Republic (DR) (N = 201), we assessed factors associated with the potential likelihood of LA ART use if it were available. We conducted multivariate logistic regression and thematic content analysis. RESULTS:Likelihood of LA ART use was high with 84.92% of FSW from the DR and 92.27% of FSW from Tanzania reporting they would be "likely" or "very likely" to use LA ART if available (p = 0.02). In Tanzania better HIV-related patient-provider communication (AOR 4.58; 95% CI 1.90-11.05) and quality of HIV clinical care (AOR 3.68; 95% CI 1.05-12.86) were positively associated with the high likelihood of LA ART use. In the DR, easier clinic access was associated with a higher likelihood of LA ART use (AOR 3.04; 95% CI 1.41-6.56), as was greater monthly income from sex work (AOR 2.37; 95% CI 1.27-4.41). In both settings, years on ART was significantly associated with a strong likelihood of LA ART use (TZ: AOR 1.16 per year; 95% CI 1.00-1.34/DR: AOR 1.07 per year; 95% CI 1.00-1.14). Qualitative findings underscored enthusiasm for LA ART and reinforced its potential to address sex work-specific barriers to daily oral ART adherence including work-related schedules and substance use. CONCLUSIONS:We found a high likelihood of LA ART use if available among FSW in two diverse settings and documented barriers to future uptake. Community-driven approaches which include tailored health education and improved patient-provider communication and quality of care, as well as strategies to facilitate appointment adherence are needed to optimize LA ART use among FSW.

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HIV-1 functional cure: will the dream come true?

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HIV-1 functional cure: will the dream come true?

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