Viviane D. Lima

Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study

BACKGROUND Results of cohort studies and mathematical models have suggested that increased coverage with highly active antiretroviral therapy (HAART) could reduce HIV transmission. We aimed to estimate the association between plasma HIV-1 viral load, HAART coverage, and number of new cases of HIV in the population of a Canadian province. METHODS We undertook a population-based study of HAART coverage and HIV transmission in British Columbia, Canada. Data for number of HIV tests done and new HIV diagnoses were obtained from the British Columbia Centre for Disease Control. Data for viral load, CD4 cell count, and HAART use were extracted from the British Columbia Centre for Excellence in HIV/AIDS population-based registries. We modelled trends of new HIV-positive tests and number of individuals on HAART using generalised additive models. Poisson log-linear regression models were used to estimate the association between new HIV diagnoses and viral load, year, and number of individuals on HAART. FINDINGS Between 1996 and 2009, the number of individuals actively receiving HAART increased from 837 to 5413 (547% increase; p=0.002), and the number of new HIV diagnoses fell from 702 to 338 per year (52% decrease; p=0.001). The overall correlation between number of individuals on HAART and number of individuals newly testing positive for HIV per year was -0.89 (p<0.0001). For every 100 additional individuals on HAART, the number of new HIV cases decreased by a factor of 0.97 (95% CI 0.96-0.98), and per 1 log(10) decrease in viral load, the number of new HIV cases decreased by a factor of 0.86 (0.75-0.98). INTERPRETATION We have shown a strong population-level association between increasing HAART coverage, decreased viral load, and decreased number of new HIV diagnoses per year. Our results support the proposed secondary benefit of HAART used within existing medical guidelines to reduce HIV transmission. FUNDING Ministry of Health Services and Ministry of Healthy Living and Sport, Province of British Columbia; US National Institute on Drug Abuse; US National Institutes of Health; Canadian Institutes of Health Research.

Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals.

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon‐free direct‐acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three‐quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale‐up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2‐, 13‐, and 15‐fold increases, respectively). Scale‐up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three‐quarters within 15 years. Less impact occurs with delayed scale‐up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US

HCV treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals.

3.2 million in Edinburgh and approximately

Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy.

50 million in Melbourne and Vancouver. Conclusion: Interferon‐free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale‐up, and should be addressed. (Hepatology 2013;58:1598–1609)

Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon‐free direct‐acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three‐quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale‐up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2‐, 13‐, and 15‐fold increases, respectively). Scale‐up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three‐quarters within 15 years. Less impact occurs with delayed scale‐up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US

The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time.

3.2 million in Edinburgh and approximately

The effect of adherence on the association between depressive symptoms and mortality among HIV-infected individuals first initiating HAART.

50 million in Melbourne and Vancouver. Conclusion: Interferon‐free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale‐up, and should be addressed. (Hepatology 2013;58:1598–1609)

Validating a Shortened Depression Scale (10 Item CES-D) among HIV-Positive People in British Columbia, Canada

Objective: To characterize the temporal changes in mortality and life expectancy among HIV-positive individuals initiating antiretroviral therapy in British Columbia, Canada, from 1993 to 2004. Methods: This analysis was restricted to 2238 antiretroviral-naive HIV-positive individuals who started antiretroviral therapy between January 1993 and September 2004. The primary analysis endpoint was all-cause mortality stratified by four time periods: 1993–1995, 1996–1998, 1999–2001, and 2002–2004. Cox proportional hazard models, with associated 95% confidence intervals (CI), were used to estimate the hazard of death. Abridged life tables were constructed to compare life expectancies at the age of 20 years. Results: Product limit estimates of the cumulative mortality rate at 12 months after therapy initiation decreased from 15.8% (± 1.6%) in 1993–1995 to 6.1% (± 1.1%) in 2002–2004. Life expectancy at the age of 20 years has increased from 9.1 years (± 2.3 years) in 1993–1995 to 23.6 years (± 4.4 years) in 2002–2004. Subjects in 1993–1995 were more likely to die than those who started therapy in 2002–2004 (hazard ratio 2.78; 95% CI 1.92–3.85). Patients who initiated dual therapy or therapies containing three or more antiretroviral drugs were, respectively, 1.49 (95% CI 1.23–1.82) and 2.56 (95% CI 2.13–3.13) times less likely to die than those who started on monotherapy. Conclusion: A significant and progressive decrease in mortality and increase in life expectancy were observed over the 12-year study period. The increase in life expectancy and decrease in mortality were directly associated with the use of modern forms of HAART.

Expanded Access to Highly Active Antiretroviral Therapy: A Potentially Powerful Strategy to Curb the Growth of the HIV Epidemic

Antiretroviral-therapy rollout in resource-poor countries is often associated with limited, if any, HIV-RNA monitoring. The effect of variable monitoring on the emergence of resistance after therapy with commonly used drug combinations was assessed by systematic review of studies reporting resistance in patients infected with HIV with a CD4 count of fewer than 200 cells per muL treated with two nucleoside analogues (including a thymidine analogue) and a non-nucleoside reverse transcriptase inhibitor. 8376 patients from eight cohorts and two prospective studies were analysed. Resistance at virological failure to non-nucleoside reverse transcriptase inhibitors at 48 weeks was 88.3% (95% CI 82.2-92.9) in infrequently monitored patients, compared with 61.0% (48.9-72.2) in frequently monitored patients (p<0.001). Lamivudine resistance was 80.5% (72.9-86.8) and 40.3% (29.1-52.2) in infrequently and frequently monitored patients, respectively (p<0.001); the prevalence of at least one thymidine analogue mutation was 27.8% (21.2-35.2) and 12.1% (5.9-21.4), respectively (p<0.001). Genotypic resistance at 48 weeks to lamivudine, nucleoside reverse transcriptase inhibitors (thymidine analogue mutations), and non-nucleoside reverse transcriptase inhibitors appears substantially higher in less frequently monitored patients. This Review highlights the need for cheap point-of-care viral-load tests to identify early viral failures and limit the emergence of resistance.

Highly Active Antiretroviral Therapy and Survival in HIV-Infected Injection Drug Users

Objective:To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens. Methods:Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N = 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective. Results:The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value <0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and boosted protease inhibitor-based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality. Conclusions:Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.