The Impact of Treatment as Prevention on the HIV Epidemic in British Columbia, Canada.

PURPOSE OF REVIEW: This study proposes to describe the impact of a publicly funded Treatment as Prevention (TasP) strategy in British Columbia (BC), Canada, in decreasing the individual and public health impact of the HIV/AIDS Epidemic. RECENT FINDINGS: In BC, TasP has been associated with a steady decline in HIV-related morbidity and mortality. At the same time, a demographic transition was observed among people living with HIV (PLWH), with the majority of those on antiretroviral treatment (ART) now ≥ 50 years of age, living with at least one comorbidity, and dying from age-associated comorbidities. We also documented a progressive increase in the proportion of viral load suppression as a result of ART expansion. While the pre-ART CD4 T cell count has increased steadily in recent years, there is still a large proportion of PLWH being diagnosed in later stages of HIV infection. New HIV diagnoses have been rapidly declining, however to a lesser extent among men who have sex with men (MSM), and BC is currently experiencing an increase in infectious syphilis cases in this population. These facts reinforce the effectiveness of TasP in decreasing HIV transmission, but at the same time, it highlights the need for further innovation to enhance the control of HIV and syphilis among MSM. This study supports the development of new approaches that address existing gaps in the TasP strategy in BC, and the future health needs of PLWH.

The potential impact of initiating antiretroviral therapy with integrase inhibitors on HIV transmission risk in British Columbia, Canada.

BACKGROUND: Available agents within the integrase strand-transfer inhibitor (INSTI) class have been shown to lead to a faster decay in viral load than other regimens. Therefore, we estimated the potential reduction in HIV transmission risk among antiretroviral-naïve individuals initiating on INSTI-based antiretroviral therapy (ART), focusing on the gay, bisexual and other men who have sex with men (gbMSM) population and various degrees of sexual activity. METHODS: Using two mathematical models that estimate the HIV transmission risk corresponding to different viral loads, we estimated the average probability of HIV transmission per risky contact for gbMSM during the six months post-ART initiation, stratified by stage of HIV infection, viral load at ART initiation and type of first-line ART (i.e., INSTI or non-INSTI-based ART). This study focused individuals who initiated ART between 2011 and 2016 with at least one year of follow-up in British Columbia, Canada. FINDINGS: Time to first virologic suppression for INSTI-based regimens was 21.4 days (95% credible interval (CI) 19.9-23.2), compared to 58.6 days (95% CI 54.1-62.2) for non-INSTI regimens. We showed that INSTI-based regimens could reduce the HIV transmission risk by at least 25% among those with viral load ≥ 5 log10 copies/mL at ART initiation. INTERPRETATION: Initiating ART on INSTI-based regimens has the potential to reduce HIV transmission risk among individuals with high baseline viral load levels, especially among those with high levels of sexual activity. FUNDING: The British Columbia Ministry of Health, the Canadian Institutes of Health Research, and the Michael Smith Foundation for Health Research.

Missed opportunities for earlier diagnosis of HIV in British Columbia, Canada: A retrospective cohort study.

BACKGROUND: Late HIV diagnosis is associated with increased AIDS-related morbidity and mortality as well as an increased risk of HIV transmission. In this study, we quantified and characterized missed opportunities for earlier HIV diagnosis in British Columbia (BC), Canada. DESIGN: Retrospective cohort. METHODS: A missed opportunity was defined as a healthcare encounter due to a clinical manifestation which may be caused by HIV infection, or is frequently present among those with HIV infection, but no HIV diagnosis followed within 30 days. We developed an algorithm to identify missed opportunities within one, three, and five years prior to diagnosis. The algorithm was applied to the BC STOP HIV/AIDS population-based cohort. Eligible individuals were ≥18 years old, and diagnosed from 2001-2014. Multivariable logistic regression identified factors associated with missed opportunities. RESULTS: Of 2119 individuals, 7%, 12% and 14% had ≥1 missed opportunity during one, three and five years prior to HIV diagnosis, respectively. In all analyses, individuals aged ≥40 years, heterosexuals or people who ever injected drugs, and those residing in Northern health authority had increased odds of experiencing ≥1 missed opportunity. In the three and five-year analysis, individuals with a CD4 count <350 cells/mm3 were at higher odds of experiencing ≥1 missed opportunity. Prominent missed opportunities were related to recurrent pneumonia, herpes zoster/shingles among younger individuals, and anemia related to nutritional deficiencies or unspecified cause. CONCLUSIONS: Based on our newly-developed algorithm, this study demonstrated that HIV-diagnosed individuals in BC have experienced several missed opportunities for earlier diagnosis. Specific clinical indicator conditions and population sub-groups at increased risk of experiencing these missed opportunities were identified. Further work is required in order to validate the utility of this proposed algorithm by establishing the sensitivity, specificity, positive and negative predictive values corresponding to the incidence of the clinical indicator conditions among both HIV-diagnosed and HIV-negative populations.

Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50.

OBJECTIVE: We sought to determine the incidence and factors associated with development of diabetes mellitus (DM) in older HIV-infected individuals. RESEARCH DESIGN AND METHODS: We analyzed data from people living with HIV (PLWH) ≥50 years of age enrolled in a large urban HIV outpatient clinic in Vancouver, British Columbia. Patients were categorized as having DM if they had random blood sugar ≥11.1 mmol/L, fasting blood sugar ≥7 mmol/L, HbA1C ≥6.5%, antidiabetic medication use during the follow-up period, or medical chart review confirming diagnosis of DM. We estimated the probability of developing DM, adjusting for demographic and clinical factors, using a logistic regression model. RESULTS: Among 1065 PLWH followed for a median of 13 years (25th and 75th percentile (Q1-Q3): 9-18), the incidence of DM was 1.61/100 person-years follow-up. In the analysis of factors associated with new-onset DM (n=703), 88% were male, 38% had a history of injection drug use, 43% were hepatitis C coinfected, and median body mass index was 24 kg/m2 (Q1-Q3: 21-27). Median age at antiretroviral therapy (ART) initiation was 48 years (Q1-Q3: 43-53) and at DM diagnosis was 55 years (Q1-Q3: 50-61). Patients who started ART in 1997-1999 and had a longer exposure to older ART were at the highest risk of developing DM. CONCLUSIONS: Among PLWH aged ≥50 years, the incidence of DM was 1.39 times higher than men in the general Canadian population of similar age. ART initiated in the early years of the epidemic and exposure to older ART appeared to be the main drivers of the development of DM.

Efficacy and safety of "unboosting" atazanavir in a randomized controlled trial among HIV-infected patients receiving tenofovir DF.

OBJECTIVES: To assess safety and efficacy of a switch to unboosted atazanavir (ATV) among HIV-infected adults receiving ATV/ritonavir (r) and tenofovir disoproxil fumarate (TDF). METHODS: HIV-infected adults with viral load (VL) <40 copies/mL at screening and <150 copies/mL consistently for ≥3 months while receiving a regimen including ATV/r and TDF were randomized to continue ATV/r 300/100 mg daily (control) or change to ATV 400 mg daily (switch), while maintaining their TDF backbone. The primary outcome was proportion of subjects without treatment failure (regimen switch or VL > 200 copies/mL twice consecutively) at 48 weeks. RESULTS: Fifty participants (46 male, median age 47 years) were randomized, 25 to each arm. At week 48, treatment success occurred in 76% in the control arm and 92% in the switch arm (ITT, p = 0.25). ATV trough levels at week 9 were higher in controls (median 438 ng/mL) than in the switch arm (median 124 ng/mL) (p = 0.003), as was total bilirubin at week 48 (median 38 µmol/L and 28 µmol/L, respectively; p = 0.02). Estimated glomerular filtration rate (eGFR) decreased in the control arm (p = 0.007), but did not change in the switch arm. At week 48, eGFR was higher in the switch arm (median 96 mL/min) than in the control arm (median 85 mL/min) (p = 0.035), but the arms were similar with respect to fasting glucose, C-reactive protein, and lipid parameters. CONCLUSIONS: Switching from ATV/r to unboosted ATV appears to be safe and effective in selected virologically suppressed patients receiving TDF-containing regimens, and may have favorable effects on bilirubin and renal function.

No association between HIV status and risk of non-fatal overdose among people who inject drugs in Vancouver, Canada.

BACKGROUND: The evidence to date on whether HIV infection increases the risk of accidental drug overdose among people who inject drugs (PWID) is equivocal. Thus, we sought to estimate the effect of HIV infection on risk of non-fatal overdose among two parallel cohorts of HIV-positive and -negative PWID. METHODS: Data were collected from a prospective cohort of PWID in Vancouver, Canada between 2006 and 2013. During biannual follow-up assessments, non-fatal overdose within the previous 6months was assessed. Bivariable and multivariable generalized mixed-effects regression models were used to determine the unadjusted and adjusted associations between HIV status, plasma HIV-1 RNA viral load, and likelihood of non-fatal overdose. RESULTS: A total of 1760 eligible participants (67% male, median age=42, and 42% HIV-positive at baseline) were included. Among 15,070 unique observations, 649 (4.3%) included a report of a non-fatal overdose within the previous 6months (4.4% among seropositive and 4.3% among seronegative individuals). We did not observe a difference in the likelihood of overdose by HIV serostatus in crude (odds ratio [OR]: 1.05, p=0.853) analyses or analyses adjusted for known overdose risk factors (adjusted OR [AOR]: 1.19, p=0.474). In a secondary analysis, among HIV-positive PWID, we did not observe an association between having a detectable viral load and overdose (AOR: 1.03, p=0.862). CONCLUSIONS: Despite the evidence that HIV infection is a risk factor for fatal overdose, we found no evidence for a relationship between HIV disease and non-fatal overdose. However, overdose remains high among PWID, indicating the need for ongoing policy addressing this problem, and research into understanding modifiable risk factors that predict non-fatal overdose.

Effects of a switch from tenofovir- to abacavir-based antiretroviral therapy, with or without atazanavir, on renal function.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF)-associated renal dysfunction may abate when TDF is replaced with abacavir (ABC). The extent to which the third drug atazanavir contributes to renal dysfunction is unclear. METHODS: A retrospective analysis was conducted on adults who had plasma viral load (pVL)<200 copies/mL for≥six months while receiving TDF/lamivudine (3TC) - or TDF/emtricitabine (FTC)-based antiretroviral therapy (ART), then switched to ABC/3TC while retaining the third drug in the ART regimen. CD4, pVL, creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine albumin to creatinine ratio and serum lipids were compared between pre-switch baseline and 3, 6 and 12 months after the switch to ABC. RESULTS: A total of 286 patients switched from TDF to ABC between 2004 and 2014: 232 (81%) male, median age 48 years (interquartile range (IQR) 42, 56). The third drug was atazanavir (± ritonavir) in 141 (49%) cases. The pVL was<50 copies/mL in 93 to 96% at all time points. Median serum creatinine was 93 µmol/L (IQR 80-111) at baseline and decreased to 88 µmol/L (IQR 78-98) at 12 months after the switch to ABC. Median eGFR increased from 74 (IQR 60-88) mL/min at baseline to 80 mL/min (IQR 69-89) at 12 months. Results were not significantly different between patients on atazanavir versus those on another third drug. CONCLUSIONS: Viral suppression was maintained among patients who switched from TDF/3TC or TDF/FTC to ABC/3TC. Serum creatinine and eGFR improved up to 12 months after switching to ABC/3TC, irrespective of whether or not patients were also receiving atazanavir±ritonavir.

Socioeconomic marginalization and plasma HIV-1 RNA nondetectability among individuals who use illicit drugs in a Canadian setting.

OBJECTIVE: Given that people who use illicit drugs (PWUD) often engage in prohibited income generation to support their basic needs, we sought to examine the role of these activities in shaping antiretroviral therapy (ART) adherence and plasma HIV RNA-1 viral load suppression among HIV-infected PWUD. DESIGN: Longitudinal analyses among HIV-positive, ART-exposed PWUD in the AIDS Care Cohort to evaluate Exposure to Survival Services prospective cohort study (2005-2013). METHODS: Generalized linear mixed-effects and mediation analyses examined the relationship between prohibited income generation (e.g., sex work, drug dealing, theft, street-based income) and virologic suppression (plasma viral load ≤50 copies/ml plasma) adjusting for adherence and potential confounders. RESULTS: Among 687 HIV-infected PWUD, 391 (56.9%) individuals reported prohibited income generation activity during the study period. In multivariate analyses, prohibited income generation remained independently and negatively associated with virologic suppression (adjusted odds ratio: 0.68, 95% confidence interval: 0.52-0.88) following adjustment for hypothesized confounders, including high-intensity drug use, ART adherence and homelessness. Although partially mediated by ART adherence, the relationship between prohibited income generation and virologic suppression was maintained in mediation analyses (Sobel statistic = -1.95, P = 0.05). CONCLUSION: Involvement in prohibited income generation decreases the likelihood of virologic suppression directly and indirectly through its negative association with ART adherence. These findings suggest that linkages between socioeconomic marginalization, the criminalization of illicit drug use, and insufficient employment opportunities may produce barriers to access and retention in care. Programmatic and policy interventions that decrease socioeconomic vulnerability may therefore reduce HIV-related morbidity, mortality, and onward transmission.