TasP Strategy Research Articles

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

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. 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 ≥ 50years 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.

Modeling Combination Hepatitis C Virus Treatment and Prevention Strategies in a Network of People Who Inject Drugs in the United States.

Hepatitis C virus (HCV) treatment as prevention (TasP) strategies can contribute to HCV microelimination, yet complimentary interventions such as opioid agonist therapies (OAT) with methadone or buprenorphine and syringe services programs (SSPs) may improve the prevention impact. This modeling study estimates the impact of scaling up the combination of OAT and SSPs with HCV TasP in a network of people who inject drugs (PWID) in the United States. Using empirical data from Hartford, Connecticut, we deployed a stochastic block model to simulate an injection network of 1574 PWID. We used a susceptible-infected model for HCV and human immunodeficiency virus to evaluate the effectiveness of several HCV TasP strategies, including in combination with OAT and SSP scale-up, over 20 years. At the highest HCV prevalence (75%), when OAT coverage is increased from 10% to 40%, combined with HCV treatment of 10% per year and SSP scale up to 40%, the time to achieve microelimination is reduced from 18.4 to 11.6 years. At the current HCV prevalence (60%), HCV TasP strategies as low as 10% coverage per year may achieve HCV microelimination within 10 years, with minimal impact from additional OAT scale-up. Strategies based on mass initial HCV treatment (50 per 100 PWID the first year followed by 5 per 100 PWID thereafter) were most effective in settings with HCV prevalence of 60% or lower. Scale-up of HCV TasP is the most effective strategy for microelimination of HCV. OAT scale-up, however, scale-up may be synergistic toward achieving microelimination goals when HCV prevalence exceeds 60% and when HCV treatment coverage is 10 per 100 PWID per year or lower.

A22 Phylogenetic clustering of hepatitis C virus infection among people who inject drugs in Baltimore

The availability of effective, oral direct acting antivirals for hepatitis C virus (HCV) treatment has fueled optimism for HCV elimination through treatment as prevention (TasP) among people who inject drugs (PWID). Identifying characteristics of individuals in transmission networks would provide critical information for the development and implementation of effective, targeted HCV TasP strategies. The AIDS linked to the IntraVenous Experience (ALIVE) cohort has followed PWID in Baltimore since 1988. Sequencing of the HCV core/E1 region (342 nucleotides) was performed on HCV viremic samples from the most recent study visit attended by ALIVE participants between August, 2005 and December, 2016. Outgroup sequences were retrieved from GenBank through a BLAST search for HCV sequences similar to study sequences to support identification of ‘local clusters’ and were aligned to study sequences using Clustal O. Phylogenetic trees were inferred for each of HCV subtype 1a and 1b separately through maximum likelihood analysis implemented in the MEGA X software using the Tamura-Nei model with gamma distribution and invariant sites. Nucleotide substitution model selection was based on the corrected Akaike information criterion scores of various models in MEGA. Robustness of the resulting tree was assessed by bootstrapping with 1,000 replicates. Clusters were identified using ClusterPicker software (70% bootstrap threshold and 0.05 maximum genetic distance threshold). Sensitivity analyses were performed by varying the genetic distance threshold between 0.025 and 0.05 to determine the effect on identification of factors associated with clustering. HCV infection clustering was defined as > 2 participants with HCV genome sequences satisfying 70 per cent bootstrap and 0.05 genetic threshold distance requirement for sequence similarity. Logistic regression was used to assess sociodemographic factors associated with being in an HCV cluster. Among 512 HCV genotype 1 viremic PWID, HCV subtype prevalence was 83 per cent genotype 1a and 17 per cent genotype 1b. The median age of participants was 54 years, 68 per cent male, 87 per cent Black, and 38 per cent HIV infected. Overall, 9 per cent (n = 44) were grouped into 21 clusters, consisting of 20 pairs and 1 triad. Of the 425 genotype 1a and 87 genotype 1b samples evaluated, 8 per cent (n = 33) and 13 per cent (n = 11) respectively, were in clusters. In unadjusted analyses, membership in a cluster, was associated with younger age (odds ratio (OR) 1.5 [95% confidence interval (CI) 1.1–2.1] per 10 year age decrease); female sex (OR 2.8 [95% CI 1.5–5.3]), HIV infection (OR 4.9 [95% CI 2.5–9.9]), and living in East Baltimore (versus outside East Baltimore, OR 2.0 [95% CI 1.0–3.9]). In adjusted analyses, female sex (OR 2.0 [95% CI 1.0–3.9] and HIV infection (OR 5.4 [95% CI 2.6–11.1] remained independently associated with being in an HCV infection cluster. HIV-infected PWID and their networks should be prioritized for HCV treatment and prevention interventions given an increased likelihood of transmission in these groups.

Discordance of Self-report and Laboratory Measures of HIV Viral Load Among Young Men Who Have Sex with Men and Transgender Women in Chicago: Implications for Epidemiology, Care, and Prevention.

Suppressing HIV viral load through daily antiretroviral therapy (ART) substantially reduces the risk of HIV transmission, however, the potential population impact of treatment as prevention (TasP) is mitigated due to challenges with sustained care engagement and ART adherence. For an undetectable viral load (VL) to inform decision making about transmission risk, individuals must be able to accurately classify their VL as detectable or undetectable. Participants were 205 HIV-infected young men who have sex with men (YMSM) and transgender women (TGW) from a large cohort study in the Chicago area. Analyses examined correspondence among self-reported undetectable VL, study-specific VL, and most recent medical record VL. Among HIV-positive YMSM/TGW, 54% had an undetectable VL (< 200 copies/mL) via study-specific laboratory testing. Concordance between self-report and medical record VL values was 80% and between self-report and study-specific laboratory testing was 73%; 34% of participants with a detectable study-specific VL self-reported an undetectable VL at last medical visit, and another 28% reported not knowing their VL status. Periods of lapsed viral suppression between medical visits may represent a particular risk for the TasP strategy among YMSM/TGW. Strategies for frequent viral load monitoring, that are not burdensome to patients, may be necessary to optimize TasP.

The need for treatment scale-up to impact HCV transmission in people who inject drugs in Montr\xe9al, Canada: a modelling study

BackgroundHCV transmission remains high in people who inject drugs (PWID) in Montréal. New direct-acting antivirals (DAAs), highly effective and more tolerable than previous regimens, make a “Treatment as Prevention” (TasP) strategy more feasible. This study assesses how improvements in the cascade of care could impact hepatitis C burden among PWID in Montréal.MethodsWe used a dynamic model to simulate HCV incidence and prevalence after 10 years, and cirrhosis complications after 10 and 40 years. Eight scenarios of improved cascade of care were examined.ResultsUsing a baseline incidence and prevalence of 22.1/100 person-years (PY) and 53.1%, implementing the current cascade of care using DAAs would lead to HCV incidence and prevalence estimates at 10 years of 9.4/100PY and 55.8%, respectively. Increasing the treatment initiation rate from 5%/year initially to 20%/year resulted in large decreases in incidence (6.4/100PY), prevalence (36.6%), and cirrhosis complications (−18%/-37% after 10/40 years). When restricting treatment to fibrosis level ≥ F2 instead of F0 (reference scenario), such decreases in HCV occurrence were unreachable. Improving the whole cascade of care led to the greatest effect by halving both the incidence and prevalence at 10 years, and the number of cirrhosis complications after 40 years.ConclusionsThe current level of treatment access in Montréal is limiting a massive decrease in hepatitis C burden among PWID. A substantial treatment scale-up, regardless of fibrosis level, is necessary. While improving the rest of the cascade of care is necessary to optimize a TasP strategy and control the HCV epidemic, a treatment scale-up is first needed.

Uptake of treatment as prevention for HIV and continuum of care among HIV-positive men who have sex with men in Nigeria.

Experimental evidence has shown that treatment of HIV infection with antiretroviral therapy (ART) prevents heterosexual transmission of HIV to an uninfected partner. However, the "real-world" application of this strategy to key populations such as men who have sex with men (MSM) has been limited. We report findings on acceptability of a treatment as prevention (TasP) strategy among HIV-infected MSM at a Trusted Community Center providing comprehensive HIV prevention and treatment services to MSM in Abuja, Nigeria. Using respondent-driven sampling (RDS), MSM who were 16 years and older and have engaged in either receptive or insertive anal intercourse within the previous 12 months were recruited into a prospective combination HIV prevention and treatment study (TRUST). Two weeks after enrollment, HIV testing and counseling was conducted. At each 3-month follow-up visits, HIV-infected individuals underwent clinical and laboratory evaluation, including CD4 count, plasma HIV viral load, immediate 3 weekly sessions of ART preparation, and then ART initiation per TasP strategy irrespective of CD4 count. Reasons for not engaging in pre-TasP preparation and TasP were documented. Characteristics associated with TasP engagement and loss to follow-up (LTFU) were determined using logistic and Cox regression, respectively. Of 186 HIV-positive MSM enrolled, 58 (31.2%) were on ART at the time of recruitment, whereas 128 (68.8%) were ART-naive and provided opportunity for engaging TasP. Of these, 70 (54.7%) engaged in TasP. Compared with MSM who did not engage in TasP, those who engaged had significantly lower mean CD4 count (P = 0.001), were more likely to be Christian (P = 0.01), and had disclosed being MSM to family (P = 0.02) or health care providers (P = 0.02). In multivariate models, disclosure of being MSM to health care providers remained significantly associated with uptake of TasP. Among individuals engaged in TasP, 10% were LTFU in care at 18 months since enrollment. Being engaged in TasP (relative hazards = 0.08, P < 0.001) and on ART (relative hazards = 0.17, P < 0.001) were associated with decreased risk of LTFU. Although there was high acceptance of HIV testing and low LTFU among individuals who were already on ART or engaged in TasP, a higher than expected proportion did not engage in TasP, suggesting the need for customized treatment preparation and an increase in enabling environments to support HIV treatment access with this key population.

Programmatic and ethical challenges in the implementation of treatment-as-prevention in the context of HIV and drug-resistant tuberculosis co-infection in sub-Saharan Africa

There is limited literature on programmatic challenges in the implementation of a treatment-as-prevention (TasP) strategy among human immunodeficiency virus (HIV) and drug-resistant tuberculosis (DR-TB) co-infected individuals in sub-Saharan Africa (SSA). This paper highlights specific programmatic challenges surrounding the implementation of this strategy among HIV and DR-TB co-infected populations in SSA. In SSA, limitations in administrative, human and financial resources and poor health infrastructure, as well as increased duration and complexity of providing long-term treatment for HIV individuals co-infected with DR-TB, pose substantial challenges to the implementation of a TasP strategy and warrant further investigation. A comprehensive approach must be devised to implement TasP strategy, with special attention paid to the sizable HIV and DR-TB co-infected populations. We suggest that evidence-informed and human rights–based guidelines for participant protection and strategies for programme delivery must be developed and tailored to maximise the benefits to those most at risk of developing HIV and DR-TB co-infection. Assessing regional circumstances is crucial, and TasP programmes in the region should be complemented by combined prevention strategies to achieve the intended goals.

Treatment as prevention in resource-limited settings: is it feasible to maintain HIV viral load suppression over time?

Recently, there has been increasing interest in the role of "treatment as prevention" (TasP). Some of the questions regarding TasP strategies arise from the perceived difficulties in achieving and maintaining viral load (VL) suppression over time and the risk of emergence of viral resistance that could compromise future treatment options. This study was conducted to assess these questions in a resource-limited setting. We performed a retrospective observational study of HIV-infected patients diagnosed in the pre-HAART era on follow-up at a private center from Buenos Aires, Argentina. Socio-demographic, clinical, and laboratory data were extracted from clinical charts. Analyses were performed to test for potential associations of selected variables with current virologic failure or use of third-line drugs. Of 619 patients on follow-up, 82 (13.2%) were diagnosed in the pre-HAART era. At the time of our study, 79 (96.3%) patients were on HAART, with a median duration of 14 years (IQR 12-15) of therapy, and exposure to mono or dual nucleoside reverse transcriptase inhibitors regimens in 47.8% of cases.Sixty-nine patients (87.3%) had undetectable VL, 37 (46.8%) never presented virologic failure, and 19 (24.1%) experienced only one failure. Thirteen patients (16.5%) were receiving third-line ART regimens, with an average of 2.7-fold more virologic failures than those on first- or second-line regimens (p = 0.007). Maintaining viral load suppression over time in resource-limited-settings is feasible.

Is Total Community Viral Load a Robust Predictive Marker of the Efficacy of the TasP Strategy?

A mild but significant association between a decrease in the total community viral load (CVL) and a decrease in the number of new HIV diagnoses was observed between 2005 and 2010 in the population of northern and eastern France. This result suggests that CVL could be used as robust marker of the efficacy of the "Treatment as Prevention" strategy, and it may even be stronger if a large number of undiagnosed patients and early HIV infection cases indicated by extend screening are included in the CVL measurement.