HIV, Liver Fibroses, Metabolic Syndrome, Osteopenia, Osteoporosis, Renal Impairment, Vitamin D Deficiency
Conditions
Brief summary
With the availability of effective anti-retroviral therapy, HIV-infected individuals are expected not to die of AIDS and have longer life expectancy. But at the same time, HIV-associated non-AIDS (HANA) conditions are becoming more important in their clinical management. It is currently uncertain whether patients started on different anti-retroviral regimens will have different incidence of HANA conditions. This study aims to evaluate the incidence of various HANA conditions in a cohort of newly diagnosed HIV-infected individuals in Hong Kong initiating anti-retroviral treatment. The incidence of various HANA conditions will be evaluated for those receiving INSTI versus other non-INSTI-based regimens. The HANA conditions evaluated will include 1. Hypertension 2. Diabetes and insulin resistance 3. Dyslipidemia 4. Lipodystrophy 5. Metabolic syndrome 6. Osteopenia and osteoporosis 7. Vitamin D deficiency 8. Renal impairment and kidney tubular dysfunction and 9. Liver fibrosis. Patients will be assessed prior to initiation of anti-retroviral therapy, and 48 weeks and 96 weeks after initiation of treatment. The incidence of development of each HANA condition will be determined and compared between those initiated different anti-retroviral regimens.
Detailed description
This is a prospective, longitudinal, cohort study. 150 newly diagnosed HIV-infected individuals attending HIV clinics in Hong Kong will be recruited. Clinical assessment, and laboratory and imaging studies will be performed at baseline prior to initiation of anti-retroviral regimen, then annually thereafter for 5 years. Choice of anti-retroviral regimen will be decided by the in-charge HIV physician. Incidence of development of various HANA will be determined in those initiated INSTI-based regimens and other anti-retroviral regimens. An electronic platform will be used to formulate risk prediction for various clinical outcomes, and serve as a clinical decision support tool. Statistical analysis; 1. The incidence rate of each HANA defined as above will be calculated as: 2. The incidence rate of each HANA will be determined for subjects started INSTI-based regimens and other non-INSTI-anti-retroviral regimens. 3. Variables, including demographic, clinical, treatment-related, and laboratory parameters, will be evaluated for association with development of various HANA, in univariate and multivariate analyses. Analyses will be performed for the whole cohort, and subgroup analyses will be performed in those initiated INSTI-based regimens and other non-INSTI-based regimens.
Interventions
None listed
Sponsors
Chinese University of Hong Kong
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed HIV infection by HIV antibody or RNA test 2. Age ≥18 years old 3. Anti-retroviral treatment naïve 4. Agree to initiate anti-retroviral therapy (ART) as determined by in-charge HIV physician
Exclusion criteria
1. Pregnancy 2. Unable to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Baseline | Participants who were assessed at baseline and at least one of follow-up visits were included in the data analysis for prevalence of HIV-associated non-AIDS conditions (HANA) Prevalences of the following HIV-associated non-AIDS conditions (HANA) were assessed at baseline. * hypertension * diabetes mellitus * insulin resistance * dyslipidemia * metabolic syndrome * osteoporosis * osteopenia * vitamin D deficiency * renal disease * kidney tubular dysfunction * intermediate or advanced fibrosis (FIB-4 \>1.3) * advanced fibrosis (FIB-4 \>2.67) |
| Incidence Rates of HANA Conditions for At-risk Groups | Enrollment to 2 years | Participants who were assessed at baseline and at least one of follow-up visits were included in the data analysis for incidence rates of HANA Incidence rates of following HANA conditions were reported among at-risk INSTI and non-INSTI-based antiretroviral therapy at 2 years. * hypertension * diabetes mellitus * insulin resistance * dyslipidemia * metabolic syndrome * osteopenia * osteoporosis * vitamin D deficiency * renal disease * kidney tubular dysfunction * intermediate or advanced fibrosis (FIB-4 \> 1.3) * advanced fibrosis (FIB-4 \>2.67) |
Countries
Hong Kong
Participant flow
Recruitment details
During the study period, a prospective and longitudinal cohort study involving People living with HIV (PLWH) recruited from the Infectious Diseases Clinic of the Prince of Wales Hospital, Hong Kong SAR, from April 2018 to May 2022. PLWH initiating or switching to a new ART regimen within 6 months were enrolled. Participants were assessed at baseline and followed up annually for 2 years to assess for the presence of various HANA conditions.
Participants by arm
| Arm | Count |
|---|---|
| INSTI INSTI-based antiretroviral therapy | 183 |
| Non-INSTI non-INSTI-based antiretroviral therapy | 32 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 40 | 7 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | INSTI | Non-INSTI | Total |
|---|---|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 14.5 | 48.8 years STANDARD_DEVIATION 12.7 | 46.7 years STANDARD_DEVIATION 14.2 |
| Duration of HIV diagnosis | 0.8 years | 7.7 years | 1.0 years |
| Race/Ethnicity, Customized Chinese | 174 Participants | 30 Participants | 204 Participants |
| Race/Ethnicity, Customized Non-Chinese | 9 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Female | 23 Participants | 4 Participants | 27 Participants |
| Sex: Female, Male Male | 160 Participants | 28 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 139 | 0 / 24 |
| other Total, other adverse events | 0 / 139 | 0 / 24 |
| serious Total, serious adverse events | 0 / 139 | 0 / 24 |
Outcome results
Primary
Incidence Rates of HANA Conditions for At-risk Groups
Participants who were assessed at baseline and at least one of follow-up visits were included in the data analysis for incidence rates of HANA Incidence rates of following HANA conditions were reported among at-risk INSTI and non-INSTI-based antiretroviral therapy at 2 years. * hypertension * diabetes mellitus * insulin resistance * dyslipidemia * metabolic syndrome * osteopenia * osteoporosis * vitamin D deficiency * renal disease * kidney tubular dysfunction * intermediate or advanced fibrosis (FIB-4 \> 1.3) * advanced fibrosis (FIB-4 \>2.67)
Time frame: Enrollment to 2 years
Population: At risk participants who had baseline and at least one follow-up study visits during the two-year period were included in the analysis. Incidence rates of HANA-conditions were reported in INSTI and non-INSTI groups. A person-year is a unit expressing the cumulative observation time during which the population is at risk for HANA conditions. Incidence rates are expressed as the number of new cases developing HANA conditions per 100 at-risk person-years during the study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of metabolic syndrome | 9.9 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of osteopenia | 5.1 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of osteoporosis | 1.1 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of vitamin D deficiency | 16.7 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of renal diseases | 20.1 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of hypertension | 14.7 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of kidney tubular dysfunction | 16.3 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of intermediate or advanced fibrosis (FIB-4 >1.3) | 6.7 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rate of diabetes mellitus | 3.3 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of insulin resistance | 31.6 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of dyslipidemia | 16.5 cases per 100-persons years |
| INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of advanced fibrosis (FIB-4 >2.67) | 1.9 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of advanced fibrosis (FIB-4 >2.67) | 0 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of intermediate or advanced fibrosis (FIB-4 >1.3) | 11.5 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of osteopenia | 3.4 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of hypertension | 10.5 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of osteoporosis | 0 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of dyslipidemia | 14.3 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of vitamin D deficiency | 7.1 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rate of diabetes mellitus | 9.5 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of metabolic syndrome | 11.8 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of renal diseases | 17.2 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of insulin resistance | 41.9 cases per 100-persons years |
| non-INSTI | Incidence Rates of HANA Conditions for At-risk Groups | Incidence rates of kidney tubular dysfunction | 13.3 cases per 100-persons years |
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing hypertension in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.352, 6.45]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing hypertension in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.251, 14.919]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing diabetes mellitus in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.099, 1.155]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing diabetes mellitus in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.132, 1.948]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing insulin resistance in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.395, 1.397]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing insulin resistance in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.444, 1.759]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing dyslipidemia in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.274, 5.139]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing dyslipidemia in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.257, 5.688]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing metabolic syndrome in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.196, 3.739]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing metabolic syndrome in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.108, 2.631]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing osteopenia in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.172, 11.35]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing osteopenia in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.119, 9.317]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing osteoporosis in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0, 0]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing osteoporosis in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0, 0]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing vitamin D deficiency in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.679, 7.122]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing vitamin D deficiency in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.85, 14.833]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing renal diseases in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.465, 3.077]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing renal diseases in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.51, 4.638]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing kidney tubular dysfunction in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.408, 3.331]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing kidney tubular dysfunction in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.615, 7.18]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing intermediate or advanced fibrosis (FIB-4 \> 1.3) in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0.159, 1.995]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing intermediate or advanced fibrosis (FIB-4 \> 1.3) in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0.244, 3.493]
Comparison: Crude incidence rate ratio (IRR) was expressed as a ratio of incidence rates of developing advanced fibrosis (FIB-4 \>2.67) in INSTI group compared with non-INSTI group as reference group at 2 years.95% CI: [0, 0]
Comparison: Adjusted Incidence rate ratio (IRR) was expressed as a ratio of incidence rate of developing advanced fibrosis (FIB-4 \> 2.67) in INSTI group compared with non-INSTI group at 2 years after adjusted by age, sex, treatment-naive or experienced, duration of HIV diagnosis, baseline body weight and CD4 count.95% CI: [0, 0]
Primary
Prevalences of HIV-associated Non-AIDS Conditions (HANA)
Participants who were assessed at baseline and at least one of follow-up visits were included in the data analysis for prevalence of HIV-associated non-AIDS conditions (HANA) Prevalences of the following HIV-associated non-AIDS conditions (HANA) were assessed at baseline. * hypertension * diabetes mellitus * insulin resistance * dyslipidemia * metabolic syndrome * osteoporosis * osteopenia * vitamin D deficiency * renal disease * kidney tubular dysfunction * intermediate or advanced fibrosis (FIB-4 \>1.3) * advanced fibrosis (FIB-4 \>2.67)
Time frame: Baseline
Population: Participants who had baseline and at least one follow-up study visits were included in the analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of diabetes mellitus | 30 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of osteoporosis | 6 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of dyslipidemia | 85 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of vitamin D deficiency | 27 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of hypertension | 69 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of renal diseases | 58 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of metabolic syndrome | 60 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of kidney tubular dysfunction | 55 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of insulin resistance | 79 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of intermediate or advanced fibrosis (FIB-4 >1.3) | 42 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of advanced fibrosis (FIB-4 >2.67) | 5 Participants |
| INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of osteopenia | 72 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of advanced fibrosis (FIB-4 >2.67) | 1 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of hypertension | 15 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of diabetes mellitus | 4 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of insulin resistance | 9 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of dyslipidemia | 17 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of metabolic syndrome | 16 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of osteopenia | 9 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of osteoporosis | 1 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of vitamin D deficiency | 3 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of renal diseases | 9 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of kidney tubular dysfunction | 9 Participants |
| non-INSTI | Prevalences of HIV-associated Non-AIDS Conditions (HANA) | Prevalence of intermediate or advanced fibrosis (FIB-4 >1.3) | 10 Participants |
p-value: 0.244Chi-squared
p-value: 0.584Chi-squared
p-value: 0.067Chi-squared
p-value: 0.365Chi-squared
p-value: 0.033Chi-squared
p-value: 0.196Chi-squared
Comparison: Chi square test is used to detect the difference in prevalence of osteoporosis between INSTI and non-INSTI groups.p-value: 1Fisher Exact
Comparison: Chi square test is used to detect the difference in prevalence of vitamin D deficiency between INSTI and non-INSTI groups.p-value: 0.572Fisher Exact
Comparison: Chi square test is used to detect the difference in prevalence in renal disease between INSTI and non-INSTI groups.p-value: 0.698Chi-squared
p-value: 0.848Chi-squared
p-value: 0.274Chi-squared
p-value: 1Fisher Exact