Genotypic susceptibility score (GSS) and CD4+ T cell recovery in HIV-1 patients with suppressed viral load.

OBJECTIVES: HIV drug resistance, measured by the genotypic susceptibility score (GSS), has a deleterious effect on the virological outcome of HIV-1-infected patients. However, it is not known if GSS retains any predictive value for CD4 recovery in patients with suppressed viral load. METHODS: Four hundred and six patients on virological failure (>500 copies/mL) with GSS : <6 months prior to switch therapy who achieved undetectable plasma viral load (<50 copies/mL) within 1 year, remained undetectable >1 year on an unchanged regimen and had CD4 data available during entire follow-up were included. Adjusted and unadjusted analyses of all characteristics at switch related to CD4 recovery were made for three time frames: (i) 'switch-suppression'; (ii) 'suppression-1 year'; and (iii) 'switch-1 year'. RESULTS: Higher GSS was associated with a greater CD4 recovery between 'switch' and '1 year' in the unadjusted analysis (P = 0.010); however, the effect of GSS was no longer statistically significant after adjusting for pre-switch clinical (CD4 count and plasma viral load) and demographic variables. Furthermore, only a lower pre-switch CD4 count was associated with increased CD4 recovery in the 'suppression-1 year' period in both unadjusted and adjusted models. The main CD4 recovery occurred in 'switch-suppression' and the variables associated, both unadjusted and adjusted, were CD4 and plasma viral load at switch, maintaining a trend for GSS (P = 0.06). CONCLUSIONS: In individuals who re-suppressed HIV viraemia after switching therapy, regimens having a higher GSS were associated with improved CD4 recovery only during the period from switch to virological suppression, but, once viral load is re-suppressed, the GSS of the new regimen has no further effect on subsequent CD4 recovery.

A two-day workshop reviewing Canadian provincial and national HIV care cascade indicators, reporting, challenges, and recommendations.

BACKGROUND: The HIV care cascade is an indicators-framework used to assess achievement of HIV clinical targets including HIV diagnosis, HIV care initiation and retention, initiation of antiretroviral therapy, and attainment of viral suppression for people living with HIV. METHODS: The HIV Care Cascade Research Development Team at the CIHR Canadian HIV Trials Network Clinical Care and Management Core hosted a two-day virtual workshop to present HIV care cascade data collected nationally from local and provincial clinical settings and national cohort studies. The article summarizes the workshop presentations including the indicators used and available findings and presents the discussed challenges and recommendations. RESULTS: Identified challenges included (1) inconsistent HIV care cascade indicator definitions, (2) variability between the use of nested UNAIDS's targets and HIV care cascade indicators, (3) variable analytic approaches based on differing data sources, (4) reporting difficulties in some regions due to a lack of integration across data platforms, (5) lack of robust data on the first stage of the care cascade at the sub-national level, and (6) inability to integrate key socio-demographic data to estimate population-specific care cascade shortfalls. CONCLUSION: There were four recommendations: standardization of HIV care cascade indicators and analyses, additional funding for HIV care cascade data collection, database maintenance and analyses at all levels, qualitative interviews and case studies characterizing the stories behind the care cascade findings, and employing targeted positive-action programs to increase engagement of key populations in each HIV care cascade stage.

HISTORIQUE: La cascade des soins du VIH est un cadre d'indicateurs utilisé pour évaluer l'atteinte des cibles cliniques du VIH, y compris le diagnostic, le début et le maintien des soins, le début du traitement antirétroviral et l'obtention de la suppression virale chez les personnes qui vivent avec le VIH. MÉTHODOLOGIE: L'équipe de développement de la recherche sur la cascade des soins du VIH située au noyau de perfectionnement de la gestion clinique du Réseau canadien pour les essais VIH des IRSC a organisé un atelier virtuel de deux jours pour présenter les données sur la cascade des soins du VIH amassées dans les milieux cliniques locaux et provinciaux et les études de cohorte de tout le pays. L'article résume les présentations d'ateliers, y compris les indicateurs utilisés et les observations disponibles, et présente les défis et recommandations abordés. RÉSULTATS: Les défis mis en évidence incluaient 1) les définitions hétérogènes des indicateurs de la cascade des soins sur le VIH, 2) la variabilité entre l'utilisation des cibles d'ONUSIDA imbriquées et les indicateurs de cascade des soins du VIH, 3) des approches analytiques variables d'après diverses sources de données, 4) la déclaration des difficultés dans certaines régions à cause de l'absence d'intégration entre les plateformes de données, 5) l'absence de données vigoureuses sur la première étape de la cascade des soins infranationaux et 6) l'incapacité d'intégrer les principales données sociodémographiques pour évaluer les écueils de la cascade des soins populationnels. CONCLUSION: Quatre recommandations ont été formulées : la standardisation des indicateurs et des analyses de la cascade des soins du VIH, le financement supplémentaire de la collecte de la cascade des soins du VIH, l'entretien des bases de données et les analyses à tous les échelons, les entrevues qualitatives et les études de cas qui caractérisent les histoires qui se cachent derrière les observations tirées de la cascade des soins et le recours à des programmes d'action positive ciblés pour accroître la participation de populations clés à chaque étape de la cascade des soins du VIH.

Determinants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1-Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapy.

BACKGROUND: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. METHODS: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. RESULTS: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm. DISCUSSION: Starting ART with a CD4 cell count of ≥500 cells/mm makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.

The impact of methadone maintenance therapy on hepatitis C incidence among illicit drug users.

AIMS: To determine the relationship between methadone maintenance therapy (MMT) and hepatitis C (HCV) seroconversion among illicit drug users. DESIGN: A generalized estimating equation model assuming a binomial distribution and a logit-link function was used to examine for a possible protective effect of MMT use on HCV incidence. SETTING: Data from three prospective cohort studies of illicit drug users in Vancouver, Canada between 1996 and 2012. PARTICIPANTS: A total of 1004 HCV antibody-negative illicit drug users stratified by exposure to MMT. MEASUREMENTS: Baseline and semi-annual HCV antibody testing and standardized interviewer-administered questionnaire soliciting self-reported data relating to drug use patterns, risk behaviors, detailed socio-demographic data and status of active participation in an MMT program. FINDINGS: One hundred and eighty-four HCV seroconversions were observed for an HCV incidence density of 6.32 [95% confidence interval (CI) = 5.44-7.31] per 100 person-years. After adjusting for potential confounders, MMT exposure was protective against HCV seroconversion [adjusted odds ratio (AOR) = 0.47; 95% CI = 0.29-0.76]. In subanalyses, a dose-response protective effect of increasing MMT exposure on HCV incidence (AOR = 0.87; 95% CI = 0.78-0.97) per increasing 6-month period exposed to MMT was observed. CONCLUSION: Participation in methadone maintenance treatment appears to be highly protective against hepatitis C incidence among illicit drug users. There appears to be a dose-response protective effect of increasing methadone exposure on hepatitis C incidence.

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era.

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 10(9)/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 10(9)/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.