Using observational cohort data from Key populations to plan HIV intervention studies

Background: Globally, new HIV-infections continue to occur mostly in Sub-Saharan Africa despite the known-to-work HIV-prevention interventions. Suboptimal adherence to the available HIV prevention interventions is cited. Vaccination could help minimise non-adherence to an HIV preventive intervention but does require the completion of the full vaccination schedule. An HIV vaccine would be a useful addition to HIV prevention packages, but vaccines need assessment in efficacy trials and investigators need suitable populations for trials. Key populations including Fisher-folks (FF) and Female Sex Workers (FSW) in Uganda could be useful. However, available data for planning trials in these populations come from observational cohorts and evidence suggests that trial environment and/or participants selection could differ from observational cohorts, which could alter trial targeted outcomes. This difference was investigated using Simulated HIV-vaccine efficacy trials (SiVETs); a trial that mimicked an HIV vaccine efficacy trial using a proxy vaccine. Methods: Two SiVETs were nested within observational cohorts of FF (2012 – 2014) and FSW (2014-2017). The SiVETs screened and enrolled participants from observational cohorts, and administered a licensed Hepatitis B vaccine at 0, 1 and 6 months as a proxy for an HIV-vaccine. Over the 12 month follow-up, SiVETs conducted HIV testing, risk behaviour assessment, and promoted and provided reliable contraceptives to women. Results: In total, there were 3989 [1575 FF & 2414 FSW] participants in the observational cohorts and 572 [282 FF & 290 FSW] of these were enrolled into SiVETs. There were significant differences between characteristics of participants in SiVETs and those in the observational cohorts. At 12-months, HIV incidence and risk behaviours were higher in the observational cohorts than SiVETs while retention was lower. Promotion and provision of reliable contraceptives in SiVETs increased the proportion of women using them from 55% at baseline to >90% at the end of vaccination. Conclusion: Researchers designing HIV efficacy trials using observational data in these and similar populations need to consider potential for changes in the targeted trial outcomes following recruitment into trials and its effect on trial statistical power

Timeliness of Clinic Attendance is a good predictor of Virological Response and Resistance to Antiretroviral drugs in HIV-infected patients

Ensuring long-term adherence to therapy is essential for the success of HIV treatment. As access to viral load monitoring and genotyping is poor in resource-limited settings, a simple tool to monitor adherence is needed. We assessed the relationship between an indicator based on timeliness of clinic attendance and virological response and HIV drug resistance

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health system, Tanzania introduced patient centred treatment (PCT). PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice. The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken. The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes</p> <p>Methods</p> <p>Cohort analysis comparing patients treated under the PCT strategy (registered April-September 2006) with patients treated under health-facility-based DOT (registered April-September 2005). The primary outcome was the cure rate. Differences were assessed by calculating the risk ratios. Associations between characteristics of the supporters and treatment outcomes in the group of patients opting for home-based DOT were assessed through logistic regression.</p> <p>Results</p> <p>In the PCT cohort there were 1208 patients and 1417 were included in the historic cohort. There was no significant difference in cure rates between the cohorts (risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.96-1.16). In the PCT cohort, significantly more patients had successful treatment (cure or treatment completed; RR: 1.10; 95%CI: 1.01-1.15). There were no characteristics of supporters that were associated with treatment outcome.</p> <p>Conclusion</p> <p>The PCT approach showed similar cure rates and better treatment success rates compared to daily health-facility DOT. The results indicate that there are no specific prerequisites for the supporter chosen by the patient. The programmatic setting of the study lends strong support for scaling-up of TB treatment observation outside the health facility.</p

Women experience a better long-term immune recovery and a better survival on HAART in Lao People's Democratic Republic.

<p>Abstract</p> <p>Background</p> <p>In April 2003, Médecins Sans Frontières launched an HIV/AIDS programme to provide free HAART to HIV-infected patients in Laos. Although HIV prevalence is estimated as low in this country, it has been increasing in the last years. This work reports the first results of an observational cohort study and it aims to identify the principal determinants of the CD4 cells evolution and to assess mortality among patients on HAART.</p> <p>Methods</p> <p>We performed a retrospective database analysis on patients initiated on HAART between 2003 and 2009 (CD4<200cells/μL or WHO stage 4). We excluded from the analysis patients who were less than 16 years old and pregnant women. To explore the determinants of the CD4 reconstitution, a linear mixed model was adjusted. To identify typical trajectories of the CD4 cells, a latent trajectory analysis was carried out. Finally, a Cox proportional-hazards model was used to reveal predictors of mortality on HAART including appointment delay greater than 1 day.</p> <p>Results</p> <p>A total of 1365 patients entered the programme and 913 (66.9%) received an HAART with a median CD4 of 49 cells/μL [IQR 15–148]. High baseline CD4 cell count and female gender were associated with a higher CD4 level over time. In addition, this gender difference increased over time. Two typical latent CD4 trajectories were revealed showing that 31% of women against 22% of men followed a high CD4 trajectory. In the long-term, women were more likely to attend appointments without delay. Mortality reached 6.2% (95% CI 4.8-8.0%) at 4 months and 9.1% (95% CI 7.3-11.3%) at 1 year. Female gender (HR=0.17, 95% CI 0.07-0.44) and high CD4 trajectory (HR=0.19, 95% CI 0.08-0.47) were independently associated with a lower death rate.</p> <p>Conclusions</p> <p>Patients who initiated HAART were severely immunocompromised yielding to a high early mortality. In the long-term on HAART, women achieved a better CD4 cells reconstitution than men and were less likely to die. This study highlights important differences between men and women regarding response to HAART and medical care, and questions men’s compliance to treatment.</p