Targeted Clinical Strategies and Low Level Viraemia (LLV) in Boosted Protease Inhibitor Therapy

Phase of Study: Non-Drug Study

Objectives:

1. Primary To investigate the causes of low level viraemia (LLV) in HIV-infected individuals with no PI resistance associated mutations (RAMs) on conventional genotyping who have a detectable plasma HIV viral load (pVL) and report >95% adherence* to their ARV regimens containing a boosted protease inhibitor.

   *in case the questionnaire cannot be performed, clinical documentation of adherence will be used for interpretation of adherence level.

2. Secondary To observe the evolution in virologic and immunologic responses following routine clinical intervention in HIV-infected individuals with no primary protease inhibitor mutations (IAS, USA) on conventional genotyping who have a detectable plasma HIV viral load (pVL) and report >95% adherence* to antiretroviral regimens containing a boosted protease inhibitor.

   • in case the questionnaire cannot be performed, clinical documentation of adherence will be used for interpretation of adherence level.

Study Design: A multi-centre, non-drug, observational cohort study.

Methodology: HIV-infected individuals attending three selected HIV clinics at the Chelsea and Westminster Hospital, St Mary's Hospital and Guy's and St Thomas' Hospital over the duration of the study will be identified at weekly viral resistance meetings and routine clinic appointments if they demonstrate the following HIV pVL criteria:

1. An HIV pVL of 41-2000 copies/ml (c/ml) on two consecutive tests after being \<40 c/ml on at least two occasions on a bPI-containing regimen
2. An HIV pVL of 41-2000 c/ml on two consecutive tests having never achieved \<40 c/ml on a bPI-containing regimen after more than six months of treatment.

Eligible patients will be provided with a patient information sheet and a written consent form. Following consent:

1. Virologic and immunologic assessments will be collected from the clinical records available
2. Viral resistance test (VRT) (using VircoTYPE HIV-1 Virtual PhenotypeTM-LM for conventional genotyping and Ilumina MiSeq as next generation sequencing, NGS for minority species testing) will be performed on the first detectable HIV pVL(>40 c/mL) found in clinic and at 3 to 6 and 12 months later, if HIV pVL is still >40 c/mL.

Planned Sample Size: 120 to 240 samples over the one-year study period, with each centre providing 40 to 80 samples.

Summary of Eligibility Criteria: HIV-infected individuals with no primary protease inhibitor mutations (IAS, USA) on standard VRTs who have a detectable pVL and report >95% adherence* ARV regimens containing a boosted protease inhibitor with HIV VL criteria as detailed above. Individuals who have a detectable HIV VL after stopping ARV or having an 8-item Morisky score of above 2 (or \<95% reported adherence will not be eligible.

*in case the questionnaire cannot be performed, clinical documentation of adherence will be used for interpretation of adherence level.

Number of Study Centres: Three

Duration of Study: One year from study approval. Samples for resistance testing will be collected over the duration of the study.

Criteria for Evaluation:

1. Emergence of new primary protease inhibitor mutations (IAS, USA) using NGS will be described.
2. Comparison of respective parameters (HIV VL and CD4 count) between different clinical interventions. The latter will not be dictated by the protocol but will be conducted as routine clinical practice.

Primary Endpoint:

Development of primary protease inhibitor mutations (IAS, USA) on NGS in HIV-infected patients with primary protease inhibitor mutations (IAS, USA) on standard VRTs who demonstrate LLV on ARV regimens containing a bPI.

Secondary Endpoints:

1. Proportion of patients achieving an undetectable HIV VL following an intervention during periods of LLV on ARV regimens containing a bPI
2. Evolution of CD4 cell count following an intervention during periods of LLV on ARV regimens containing a bPI.

Note: This is a non-drug study and no interventions will be dictated by this protocol.