HIV-1 testing in the context of expanding PrEP modalities

Area of Science:

• Infectious Diseases
• Public Health
• Virology

Background:

• Effective antiretroviral-based pre-exposure prophylaxis (PrEP) for HIV-1 prevention is available, necessitating robust HIV-1 testing strategies for safe implementation.
• Current HIV-1 testing guidelines and algorithms for PrEP studies are diverse, employing antibody tests, nucleic acid tests, and retrospective analyses.
• Varied testing approaches pose challenges in accurately identifying rare HIV-1 acquisitions among individuals using PrEP.

Purpose of the Study:

• To summarize current and alternative HIV-1 testing approaches for effective PrEP implementation.
• To guide best practices for HIV-1 testing programs supporting PrEP use.
• To address the complexities of diagnosing HIV-1 in PrEP users, including rare breakthrough infections and modified acute HIV infection.

Main Methods:

• Review and synthesis of existing HIV-1 testing strategies, including rapid antibody tests, nucleic acid tests (qualitative and quantitative), and sensitive research assays.
• Discussion of the World Health Organization (WHO) recommendations for HIV-1 testing in PrEP users.
• Consideration of diagnostic challenges such as false-positive results and the impact of PrEP on HIV-1 presentation.

Main Results:

• Current best practices recommend rapid diagnostic tests or self-testing, aligned with national guidelines and WHO recommendations.
• Nucleic acid testing (e.g., plasma HIV-1 RNA PCR) may offer earlier detection but faces challenges in feasibility and potential for false positives.
• Sensitive assays for single-copy HIV-1 RNA and proviral DNA are valuable for resolving ambiguous diagnoses in research settings.

Conclusions:

• Diagnosing HIV-1 in PrEP users is complex due to rare breakthrough infections, PrEP's effect on acute infection, and infrastructure limitations.
• Optimal HIV-1 detection strategies for various PrEP modalities are evolving, with ongoing assessment of different tests and approaches.
• Cost, feasibility, and the positive predictive value of HIV tests are critical factors for successful PrEP programs.