[Show abstract][Hide abstract] ABSTRACT: Background. More than 11.7 million people are currently receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs), and focused efforts are needed to ensure high levels of adherence and to min- imize treatment failure. Recently, international targets have emphasized the importance of long-term virological suppression as a key measure of program performance. Methods. We systematically reviewed publications and conference abstracts published between January 2006
and May 2013 that reported virological outcomes among human immunodeficiency virus type 1 (HIV-1)–infected adults receiving first-line ART for up to 5 years in LMICs. Summary estimates of virological suppression after 6, 12, 24, 36, 48, and 60 months of ART were analyzed using random-effects meta-analysis. Intention-to-treat (ITT) anal- ysis assumed all participants who were lost to follow-up, died, or stopped ART as having virological failure. Results. Summary estimates of virological suppression remained >80% for up to 60 months of ART for all 184 in-
cluded cohorts. ITT analysis yielded 74.7% (95% confidence interval [CI], 72.2–77.2) suppression after 6 months and 61.8% (95% CI, 44.0–79.7) suppression after 48 months on ART. Switches to second-line ART were reported scarcely. Conclusions. Among individuals retained on ART, virological suppression rates during the first 5 years ofARTwere
high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years.
[Show abstract][Hide abstract] ABSTRACT: Background. More than 11.7 million people are currently receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs), and focused efforts are needed to ensure high levels of adherence and to minimize treatment failure. Recently, international targets have emphasized the importance of long-term virological suppression as a key measure of program performance.
Methods. We systematically reviewed publications and conference abstracts published between January 2006 and May 2013 that reported virological outcomes among human immunodeficiency virus type 1 (HIV-1)–infected adults receiving first-line ART for up to 5 years in LMICs. Summary estimates of virological suppression after 6, 12, 24, 36, 48, and 60 months of ART were analyzed using random-effects meta-analysis. Intention-to-treat (ITT) analysis assumed all participants who were lost to follow-up, died, or stopped ART as having virological failure.
Results. Summary estimates of virological suppression remained >80% for up to 60 months of ART for all 184 included cohorts. ITT analysis yielded 74.7% (95% confidence interval [CI], 72.2–77.2) suppression after 6 months and 61.8% (95% CI, 44.0–79.7) suppression after 48 months on ART. Switches to second-line ART were reported scarcely. Conclusions. Among individuals retained on ART, virological suppression rates during the first 5 years of ART were high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years.
[Show abstract][Hide abstract] ABSTRACT: Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.
[Show abstract][Hide abstract] ABSTRACT: Operational research to identify factors predicting poor clinical outcomes is critical to maximize patient care and prolong first-line regimens for those receiving free antiretroviral therapy (ART) in India. We sought to identify social or clinical factors amenable to intervention that predict virological outcomes after 12 months of ART. We examined a retrospective cohort of consecutive adults initiating free nonnucleoside reverse transcriptase inhibitor-based regimens. Individuals remaining in care 12 months post-ART initiation were tested for HIV viral load and surveyed to identify barriers and facilitators to adherence, and to determine clinic travel times and associated costs. Uni- and multivariate logistic regression identified factors predicting HIV viral load >200 copies/mL after 12 months of ART. Of 230 adults initiating ART, 10% of patients died, 8% transferred out, 5% were lost to follow-up, and 174/230 (76%) completed 12 months of ART, the questionnaire, and viral load testing. HIV viral load was <200 copies/mL in 140/174 (80%) patients. In multivariate models, being busy with work or caring for others (OR 2.9, p < 0.01), having clinic transport times ≥ 3 hours (OR 3.0, p = 0.02), and alcohol use (OR 4.8, p = 0.03) predicted viral load >200 copies/mL after 12 months of ART. Clinical outcomes following ART are related to programmatic factors such as prolonged travel time and individual factors such as being busy with family or using alcohol. Simple interventions that alter these factors should be evaluated to improve clinical outcomes for populations receiving free ART in similar settings.
AIDS Care 10/2013; 26(5). DOI:10.1080/09540121.2013.845282 · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish estimates of viral suppression in low- and middle-income countries (LMICs) in patients who received antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection.
Data on viral suppression after 12 months of ART in LMICs were collected from articles published in 2003 to 2011 and from abstracts of conferences held between 2009 and 2011. Pooled proportions for on-treatment and intention-to-treat populations were used as summary estimates. Random-effects models were used for heterogeneous groups of studies (I (2) > 75%).
Overall, 49 studies covering 48 cohorts and 30 016 individuals met the inclusion criteria. With thresholds for suppression between 300 and 500 copies of viral ribonucleic acid (RNA) per ml of plasma, 84.3% (95% confidence interval, CI: 80.4-87.9) of the pooled on-treatment population and 70.5% (95% CI: 65.2-75.6) of the intention-to-treat population showed suppression. Use of different viral RNA thresholds changed the proportions showing suppression: to 84% and 76% of the on-treatment population with thresholds set above 300 and at or below 200 RNA copies per ml, respectively, and to 78%, 71% and 63% of the intention-to-treat population at thresholds set at 1000, 300 to 500, and 200 or fewer copies per ml, respectively.
The pooled estimates of viral suppression recorded after 12 months of ART in LMICs provide benchmarks that other ART programmes can use to set realistic goals and perform predictive modelling. Evidence from this review suggests that the current international target - i.e. viral suppression in > 70% of the intention-to-treat population, with a threshold of 1000 copies per ml - should be revised upwards.
Bulletin of the World Health Organisation 05/2013; 91(5):377-385E. DOI:10.2471/BLT.12.112946 · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Over 480,000 individuals receive free antiretroviral therapy (ART) in India yet data associating ART adherence with HIV viral load for populations exclusively receiving free ART are not available. Additionally estimates of adherence using pharmacy data on ART pick-up are not available for any population in India. After 12-months ART we found self-reported estimates of adherence were not associated with HIV viral load. Individuals with <100 % adherence using pharmacy data predicted HIV viral load, and estimates combining pharmacy data and self-report were also predictive. Pharmacy adherence measures proved a feasible method to estimate adherence in India and appear more predictive of virological outcomes than self-report. Predictive adherence measures identified in this study warrant further investigation in populations receiving free ART in India to allow for identification of individuals at risk of virological failure and in need of adherence support.
AIDS and Behavior 02/2013; 17(6). DOI:10.1007/s10461-013-0436-x · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A large proportion of patients receiving antiretroviral therapy (ART) in low and middle income countries (LMICs) have unknown treatment outcomes and are classified as lost to follow-up (LTFU). Physical tracing of patients classified as LTFU is common; however, effects of tracing on outcomes remains unclear. The objective of this systematic review is to compare estimates of LTFU, mortality and retention in LMIC in cohorts of patients with and without physical tracing.
We systematically identified studies in LMIC programmatic settings using MEDLINE (2003-2011) and HIV conference abstracts (2009-2011). Studies reporting the proportion LTFU 12-months after ART initiation were included. Tracing activities were determined from manuscripts or by contacting study authors. Studies were classified as "tracing studies" if physical tracing was available for the majority of patients. Summary estimates from the 2 groups of studies (tracing and non-tracing) for LTFU, mortality, stop of ART, transfers out, and retention on ART were determined. 261 papers and 616 abstracts were identified of which 39 studies comprising 54 separate cohorts (n = 187,666) met inclusion criteria. Of those, physical tracing was available for 46% of cohorts. Treatment programs with physical tracing activities had lower estimated LTFU (7.6% vs. 15.1%; p<.001), higher estimated mortality (10.5% vs. 6.6%; p = .006), higher retention on ART (80.0 vs. 75.8%; p = .04) and higher retention at the original site (80.0% vs. 72.9%; p = .02).
Knowledge of patient tracing is critical when interpreting program outcomes of LTFU, mortality and retention. The reduction of the proportion LTFU in tracing studies was only partially explained by re-classification of unknown outcomes. These data suggest that tracing may lead to increased re-engagement of patients in care, rather than just improved classification of unknown outcomes.
PLoS ONE 02/2013; 8(2):e56047. DOI:10.1371/journal.pone.0056047 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes.
[Show abstract][Hide abstract] ABSTRACT: The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.0 initiative, it is essential to strengthen HIVDR surveillance efforts in the face of increasing concern about HIVDR emergence and transmission.
[Show abstract][Hide abstract] ABSTRACT: Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.
AIDS and Behavior 10/2011; 15(7):1503-11. DOI:10.1007/s10461-010-9759-z · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Food insecurity is highly prevalent in HIV-infected populations, and analyses utilizing multiple assessments of food security to predict CD4 change are lacking. Five hundred Ninety-two patients with ≥ 4 food security assessments were followed prospectively. In the final model, for patients using antiretroviral therapy, increases in CD4 counts were on average 99.5 cells less for individuals with at least 1 episode of food insecurity compared with those consistently food secure (P < 0.001). Other sociodemographic factors were not predictive. Repeated assessments of food security are potent predictors of treatment response notwithstanding antiretroviral therapy use. Potential mechanisms for this association are proposed.
[Show abstract][Hide abstract] ABSTRACT: Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤ 6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.
[Show abstract][Hide abstract] ABSTRACT: Tularemia is a rare zoonotic disease caused by Francisella tularensis, a Gram-negative bacteria. The clinical manifestations of pulmonary tularemia resemble those of other airways infections. Recently, a case of pulmonary tularemia was diagnosed at Tufts Medical Center. The purpose of the current report is to document the utility of applying several diagnostic tools, including immunohistochemistry, electron microscopy, microbiology and molecular biology in confirming the diagnosis of pulmonary tularemia, particularly in convalescing cases (up to 3 weeks postpresentation) and after antibiotic therapy. Our study demonstrates the usefulness of microbiological studies followed by morphological evaluation and the limitation of the molecular biology analysis of posttherapy samples.
Pathology - Research and Practice 01/2011; 207(1):63-6. DOI:10.1016/j.prp.2010.07.002 · 1.56 Impact Factor