ResearchPad - antiretrovirals https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Adherence to antiretroviral therapy and associated factors among Human immunodeficiency virus positive patients accessing treatment at Nekemte referral hospital, west Ethiopia, 2019]]> https://www.researchpad.co/article/elastic_article_7637 Antiretroviral therapy has a remarkable clinical effect in reducing the progress of Acquired Immune Deficiency Syndrome. The clinical outcome of Anti-Retroviral therapy depends on strict adherence. Poor adherence reduces the effectiveness of antiretroviral therapy and increases viral replication. With changes in service delivery over time and differences in socio-demographic status from region to region, it is essential to measure adherence. Therefore, this study aimed to assess adherence to antiretroviral therapy and its associated factors among HIV/AIDS patients accessing treatment at Nekemte referral hospital, West Ethiopia.MethodsInstitutional based cross-sectional study was conducted on 311 HIV/AIDS patients from March 01 to March 30, 2019. The study participants were selected by a simple random sampling method and interviewed using structured questionnaires. Bivariable logistic regression was conducted to find an association between each independent variable and adherence to antiretroviral medication. Multivariable logistic regression was used to find the independent variables which best predict adherence. The statistical significance was measured using odds ratio at a 95% confidence interval with a p-value of less than 0.05.ResultsOut of a total of 311 patients sampled, 305 were participated in the study, making a response rate of 98.07%. From these 305 study participants,73.1% (95% CI = 68.2, 78.0) were adherent to their medication. Having knowledge about HIV and its treatment (AOR = 8.24, 95% CI: 3.10, 21.92), having strong family/social support (AOR = 6.21, 95% CI: 1.39, 27.62), absence of adverse drug reaction (AOR = 5.33, 95% CI: 1.95, 14.57), absence of comorbidity of other chronic diseases (AOR = 5.72, 95% CI: 1.91, 17.16) and disclosing HIV status to the family (AOR = 5.08, 95% CI: 2.09, 12.34) were significantly associated with an increased likelihood of adherence to antiretroviral medication.ConclusionThe level of adherence to antiretroviral therapy was found low compared to WHO recommendation. The clinician should emphasize reducing adverse drug reaction, detecting and treating co-morbidities early, improving knowledge through health education, and encouraging the patients to disclose their HIV status to their families. ]]> <![CDATA[Feasibility and acceptability of novel methods to estimate antiretroviral adherence: A longitudinal study]]> https://www.researchpad.co/article/5c478c5dd5eed0c484bd1de9

Due to marked reductions in morbidity and mortality, antiretroviral (ARV) adherence monitoring is of high interest. Researchers and clinicians often resort to the most feasible and cost-effective adherence methods possible, which may result in biased or inaccurate estimates and require the physical presence of a participant at a research or clinic site. The objective of our study was to evaluate the feasibility and acceptability of three objective, innovative, and remote methods to estimate ARV adherence which may be conducted with less time and financial resources in a wide range of clinic and research settings. These three methods included: (a) text-messaged photographs of pharmacy refill dates to measure refill-based adherence, (b) text-messaged photographs of ARV medications to estimate pill-count-based adherence, and (c) home-collected hair samples for the measurement of ARV concentration to determine pharmacologic-based adherence. We conducted a pilot study from March through October 2017 to examine the feasibility and acceptability of these three adherence measures and the remotely conducted study procedures in 93 adults living with HIV nationwide. From our diverse national sample of participants, 95.7% were retained until the end of the study, 89.9% sent all text messages, and 84.3% sent all hair samples. Approximately 74.2% of participants reported excellent overall experience with the study, 60.2% were very or extremely satisfied with participating in a hair collection study, and 76.3% noted extremely high likelihood of participating in a similar study including text messaging pictures of medications or refill dates. We noted high levels of feasibility and acceptability with the remote study methodology, collection of photographed and text messaged pharmacy refill dates and pill counts, and home-collected hair samples. Here we describe the feasibility and acceptability metrics, results from the exit qualitative interviews with the participants, and lessons learned. These adherence measures represent innovative approaches to expand monitoring tools for HIV treatment and prevention adherence in future research.

]]>
<![CDATA[Long-term tolerability and effectiveness of raltegravir in Japanese patients: Results from post-marketing surveillance]]> https://www.researchpad.co/article/5c3fa596d5eed0c484ca6253

Antiretroviral agents are approved in Japan based on non-clinical and clinical data reported from overseas. Neither the long-term tolerability nor the effectiveness of raltegravir or other integrase strand transfer inhibitors in Japan is known. This study reports on the long-term tolerability and effectiveness of raltegravir in Japanese clinical practice using data collected through approximately 9 years of post-marketing surveillance. This observational survey used data on human immunodeficiency virus (HIV) infected patients initiated treatment with raltegravir between 2008 and 2017 in the HIV-related drug (HRD) cooperative survey to assess the safety and effectiveness of raltegravir in real world clinical practice. There were totally 1,303 patients prescribed raltegravir across 30 institutions; 1,293 patients and 1,178 patients were included for the safety and effectiveness analyses, respectively. The overall risk of adverse drug reaction was 17.25%, with abnormal hepatic function and hyperlipidaemia (<1.5%) having the highest proportion. Median HIV-1 RNA viral loads rapidly decreased below 40 copies/mL after 3 months of raltegravir use in treatment-naïve patients, and consistently sustained below 40 copies/mL after the start of raltegravir use in treatment-experienced patients. Among the patients who were treated for 7 years, 92.00% (95% CI: 73.97–99.02) maintained HIV-1 RNA viral load below 50 copies/mL. Additionally, CD4+ cell counts exceeded >500 cells/μL in treatment-naïve and treatment-experienced patients after 3 years and 4 years of treatment, respectively. In Japanese HIV patients, long-term treatment with raltegravir is well-tolerated and effective at viral suppression as measured by HIV-1 RNA levels and subsequent change in CD4+ cell counts. Such benefits can be expected for not only treatment-naïve but also treatment-experienced patients.

]]>
<![CDATA[HIV-1 Variants and Drug Resistance in Pregnant Women from Bata (Equatorial Guinea): 2012-2013]]> https://www.researchpad.co/article/5989da39ab0ee8fa60b87333

Objectives

This is the first study describing drug resistance mutations (DRM) and HIV-1 variants among infected pregnant women in Equatorial Guinea (GQ), a country with high (6.2%) and increasing HIV prevalence.

Methods

Dried blood spots (DBS) were collected from November 2012 to December 2013 from 69 HIV-1 infected women participating in a prevention of mother-to-child transmission program in the Hospital Regional of Bata and Primary Health Care Centre María Rafols, Bata, GQ. The transmitted (TDR) or acquired (ADR) antiretroviral drug resistance mutations at partial pol sequence among naive or antiretroviral therapy (ART)-exposed women were defined following WHO or IAS USA 2015 lists, respectively. HIV-1 variants were identified by phylogenetic analyses.

Results

A total of 38 of 69 HIV-1 specimens were successfully amplified and sequenced. Thirty (79%) belonged to ART-experienced women: 15 exposed to nucleoside reverse transcriptase inhibitors (NRTI) monotherapy, and 15 to combined ART (cART) as first regimen including two NRTI and one non-NRTI (NNRTI) or one protease inhibitor (PI). The TDR rate was only found for PI (3.4%). The ADR rate was 37.5% for NNRTI, 8.7% for NRTI and absent for PI or NRTI+NNRTI. HIV-1 group M non-B variants caused most (97.4%) infections, mainly (78.9%) recombinants: CRF02_AG (55.2%), CRF22_A101 (10.5%), subtype C (10.5%), unique recombinants (5.3%), and A3, D, F2, G, CRF06_cpx and CRF11_cpx (2.6% each).

Conclusions

The high rate of ADR to retrotranscriptase inhibitors (mainly to NNRTIs) observed among pretreated pregnant women reinforces the importance of systematic DRM monitoring in GQ to reduce HIV-1 resistance transmission and to optimize first and second-line ART regimens when DRM are present.

]]>
<![CDATA[Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf613

Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350–550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

]]>
<![CDATA[Effectiveness and tolerance of single tablet versus once daily multiple tablet regimens as first-line antiretroviral therapy - Results from a large french multicenter cohort study]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc34d

Objectives

Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART.

Methods

Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat’AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM).

Results

Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, p<0.0001) and the PSM cohort (HR = 0.55, p<0.0001). This difference disappeared when censoring ART modification for simplification, both in the IPWT (HR = 0.97, p = 0.65) and the PSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, p<0.0001), but not in the PSM cohort (HR = 1.22, p = 0.11).

Conclusion

First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar.

]]>
<![CDATA[Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database]]> https://www.researchpad.co/article/5989da9dab0ee8fa60ba441c

Background

Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.

Methods

Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed.

Results

Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based).

Conclusions

The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.

]]>
<![CDATA[A Public Health Paradox: The Women Most Vulnerable to Malaria Are the Least Protected]]> https://www.researchpad.co/article/5989da7aab0ee8fa60b984f9

Raquel Gonzalez and colleagues highlight an urgent need to evaluate antimalarials that can be safely administered to HIV-infected pregnant women on antiretroviral treatment and cotrimoxazole prophylaxis.

]]>
<![CDATA[Single Nucleotide Polymorphisms in Cellular Drug Transporters Are Associated with Intolerance to Antiretroviral Therapy in Brazilian HIV-1 Positive Individuals]]> https://www.researchpad.co/article/5989daeeab0ee8fa60bc04b1

Adverse reactions are the main cause of treatment discontinuation among HIV+ individuals. Genes related to drug absorption, distribution, metabolism and excretion (ADME) influence drug bioavailability and treatment response. We have investigated the association between single nucleotide polymorphisms (SNPs) in 29 ADME genes and intolerance to therapy in a case-control study including 764 individuals. Results showed that 15 SNPs were associated with intolerance to nucleoside and 11 to non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs), and 8 to protease inhibitors (PIs) containing regimens under alpha = 0.05. After Bonferroni adjustment, two associations remained statistically significant. SNP rs2712816, at SLCO2B1 was associated to intolerance to NRTIs (ORGA/AA = 2.37; p = 0.0001), while rs4148396, at ABCC2, conferred risk of intolerance to PIs containing regimens (ORCT/TT = 2.64; p = 0.00009). Accordingly, haplotypes carrying rs2712816A and rs4148396T alleles were also associated to risk of intolerance to NRTIs and PIs, respectively. Our data reinforce the role of drug transporters in response to HIV therapy and may contribute to a future development of personalized therapies.

]]>
<![CDATA[Access and response to direct antiviral agents (DAA) in HIV-HCV co-infected patients in Italy: Data from the Icona cohort]]> https://www.researchpad.co/article/5989db5cab0ee8fa60bdfe11

Background

Real-life data on access and response to direct antiviral agents (DAA) in HIV-HCV coinfected individuals are lacking.

Methods

HCV viremic, HIV-positive patients from Icona and Hepaicona cohorts naïve to DAA by January 2013 were included. Access and predictors of starting DAA were evaluated. Switches of antiretroviral drugs at starting DAA were described. We calculated sustained virological response (SVR12) in those reaching 12 weeks after end-of-treatment (EOT), and defined treatment failure (TF) as discontinuation of DAA before EOT or non-SVR12. Statistical analyses included Kaplan-Meier curves, univariable and multivariable analyses evaluating predictors of access to DAA and of treatment outcome (non-SVR and TF).

Results

2,607 patients included. During a median follow-up of 38 (IQR:30–41) months, 920 (35.3%) patients started DAA. Eligibility for reimbursement was the strongest predictor to access to treatment: 761/1,090 (69.8%) eligible and 159/1,517 (10.5%) non-eligible to DAA reimbursement. Older age, HIV-RNA≤50 copies/mL were associated to faster DAA initiation, higher CD4 count and HCV-genotype 3 with delayed DAA initiation in those eligible to DAA reimbursement. Up to 28% of patients (36% of those on ritonavir-boosted protease inhibitors, PI/r) underwent antiretroviral (ART) modification at DAA initiation. 545/595 (91.6%) patients reaching EOT achieved SVR12. Overall, TF occurred in 61/606 patients (10.1%), with 11 discontinuing DAA before EOT. Suboptimal DAA was the only independent predictor of both non-SVR12 (AHR 2.52, 95%CI:1.24–5.12) and TF (AHR: 2.19; 95%CI:1.13–4.22).

Conclusions

Only 35.3% had access to HCV treatment. Despite excellent rates of SVR12 rates (91.6%), only 21% (545/2,607) of our HIV-HCV co-infected patients are cured.

]]>
<![CDATA[The Scale of Self-Efficacy Expectations of Adherence to Antiretroviral Treatment: A Tool for Identifying Risk for Non-Adherence to Treatment for HIV]]> https://www.researchpad.co/article/5989dac1ab0ee8fa60bb0f37

Background

Identification of risk for non-adherence to treatment is a challenge for personalized care for people living with HIV. Standardized questionnaires of patients’ expectations of their capability to overcome obstacles for treatment adherence may be used as a pre-screening for risk identification. A scale of self-efficacy expectations of adherence to antiretroviral treatment (SEA-ART scale) was previously developed. This study assesses the scale validity in predicting non-adherence to ART in adults living with HIV.

Methods and Findings

A prospective cohort study applied a 21-item SEA-ART scale to 275 adults in ART treatment at an outpatient public service for HIV in Southern Brazil. ART medications taken were assessed at one-month follow-up; ART adherence was devised as an intake of 95% and more of the prescribed medication. A SEA-ART score was calculated by adding up the scores of all items. Multivariable logistic regression and the Area Under the Receiver-Operating-Characteristic Curve (AUROC) were applied to examine the ability of the SEA-ART score to predict non-adherence at follow-up. The SEA-ART score varied from 21 to 105; mean 93.9; median 103.0. Non-adherence was 30.3% (n = 81/267). The odds of non-adherence was 8% lower for each unit increase of the SEA-ART score; after adjustment for age, sex, formal education and time in treatment (OR = 0.92; 95%CI 0.90–0.95; LRT for linear trend, p = 0.002). The AUROC was 0.80 (95%CI 0.73–0.87; p<0.001). The SEA-ART optimal cut-off value was 101, providing a sensitivity of 76.5%, a specificity of 73.1%, a positive predictive value of 55.4% and a negative predictive value of 87.7%. There was no evidence of difference in sensitivity, and specificity among groups organized by age, gender, formal education and time in treatment.

Conclusions

The SEA-ART scale appears to have a good capacity to discriminate between adherents and non-adherents at one-month follow-up. Further studies should confirm these results in other populations.

]]>
<![CDATA[An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy]]> https://www.researchpad.co/article/5989da94ab0ee8fa60ba1319

Objectives

The objective of this analysis is to perform an indirect comparison of elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF).

Methods

An indirect comparison was performed by using a generalization of Bucher's methodology to calculate risk differences. Two phase III clinical trials (GS-US-236-0102 and SINGLE—described above) were used.

Results

Results of the indirect comparison showed no statistically significant risk difference of the efficacy endpoint of achieving HIV RNA < 50 copies/mL between E/C/F/TDF and ABC/3TC + DTG for the ITT population at weeks 48, 96 and 144: respectively -3.7% (CI95% = [-10.8%; 3.4%]), -5.2% (CI95% = [-13.2%; 2.8%]) and -3.1% (CI95% = [-12.0%; 5.7%]). There was no statistically significant differences in the risk difference for serious adverse events (5.7% (CI95% = [-2.2%; 12.3%])), drug related adverse event (2.7% (CI95% = [-7.0%;12.4%])), drug related serious adverse event (0.8% (CI95% = [-1.6%;3.2%])) and death (0.5% (CI95% = [-0.8%;1.8%])), respectively, between E/C/F/TDF and ABC/3TC + DTG. A significant difference was found for discontinuation due to adverse events with a higher rate for E/C/F/TDF (difference = 8.6% (CI95% = [3.3%; 13.9%])). There was also no statistically significant risk difference of the viral resistance of 1.2% (CI95% = [-1.2; 3.7]) between E/C/F/TDF and ABC/3TC + DTG at week 48, 1.7% at week 96 (CI95% = [-1.1; 4.5]) and 2.2% (CI95% = [-1.0; 5.4]) at week 144.

]]>
<![CDATA[Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial]]> https://www.researchpad.co/article/5989db5eab0ee8fa60be0a8f

Introduction

Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a “bridging strategy” to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance.

Materials & methods

Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis.

Results

Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14–20), 472 cells/mm3 (IQR 384–651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2–4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms.

Conclusions

Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed.

Trial registration

Clinical Trials.gov NCT01338025

]]>
<![CDATA[Time from HIV diagnosis to commencement of antiretroviral therapy as an indicator to supplement the HIV cascade: Dramatic fall from 2011 to 2015]]> https://www.researchpad.co/article/5989db5bab0ee8fa60bdfda8

Introduction

The HIV care cascade is increasingly used to evaluate HIV treatment programs at the population level. However, the cascade indicators lack the ability to show changes over time, which reduces their utility to guide health policy. Alternatives have been proposed but are complex or result in a delay in results. We propose a new indicator of ART uptake, the time from HIV diagnosis to commencement of ART, and compare it to the existing cascade indicator of proportion of patients on treatment and the WHO proposed cohort cascade indicator of proportion of patients on treatment within one year of diagnosis.

Methods and materials

Records from patients from the two largest HIV treatment centres in the state of Victoria, Australia (Melbourne Sexual Health Centre and The Alfred Hospital Department of Infectious Diseases) from 2011 to 2015 were extracted. The intervals between date of diagnosis, entry into care and initiation of ART were compared.

Results and discussion

From 2011 to 2015 the proportion of in-care patients who were on ART rose from 87% to 93% (p<0.0001). From 2011 to 2014, the proportion of patients in care and on ART within one year of diagnosis increased from 43.4% to 78.9% (p = 0.001). The median time from diagnosis to ART fell from 418 days (IQR: 91–1176) to 77 days (IQR: 39–290)(p<0.001) by calendar year in which ART was commenced.

Conclusions

From 2011 to 2015 there were substantial and clinically important falls in the median time from diagnosis to commencing ART in those that commenced ART. The size of this dramatic change was not apparent when only reporting the proportion of patients on ART. Time to ART is a useful indicator and can be used to supplement existing cascade indicators in measuring progress toward universal ART coverage.

]]>
<![CDATA[Current use of statins reduces risk of HIV rebound on suppressive HAART]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbdbf

Background

Despite compelling evidence for activity against HIV-1 in vitro, a virologic effect of statins has not been shown in clinical studies. Given their short plasma half-lives, such an effect may be transient and only apparent during ongoing exposure.

Methods

We studied all HIV infected US-Veterans who started HAART 1995–2011, had a documented HIV viral load (VL) >1000 copies/mL, reached an undetectable VL on HAART, and had ≥1 follow-up VL within 13 months. We defined virologic failure (VF) as the first VL >1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. We built a time-updated drug exposure model for antiretrovirals (ARVs), statins, and other cardiovascular drugs (CVMs), investigating current use (yes/no), recent use (proportion of days used), and categorical use (ever/never). We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin and CVM use and VF.

Results

19,324 veterans met inclusion criteria. Median follow-up was 13 months (IQR: 5–32 months); 63% experienced VF after a median time of 9 months (IQR 4–21 months). Almost 1/3 patients ever used statins but exposure comprised only 41% of follow-up time covered after initial prescription. Unadjusted, current statin use was associated with a hazard ratio (HR) for VF of 0.60 (CI: 0.56–0.65). This remained statistically significant after multivariate adjustment (MVA) for demographics, HIV and HAART parameters [HR 0.81 (CI: 0.75–0.88), p<0.001] and IPW (truncation <1%/>99%) HR: 0.83 (CI: 0.75–0.92), p<0.001]. No independent association was observed for other CVMs. The association between categorical-statin use and VF after MVA was much weaker: HR 0.94 (CI: 0.88–1.00, p = 0.04).

Conclusion

Current statin exposure was associated with reduced risk of VF in univariate, multivariate, and inverse-probability-weighted models. Our results highlight the importance of time-updated medication exposure models for observational studies.

]]>
<![CDATA[Pharmaceutical Availability across Levels of Care: Evidence from Facility Surveys in Ghana, Kenya, and Uganda]]> https://www.researchpad.co/article/5989da78ab0ee8fa60b975d0

Objective

In this study we use facility-level data from nationally representative surveys conducted in Ghana, Kenya, and Uganda to understand pharmaceutical availability within the three countries.

Methods

In 2012, we conducted a survey to capture information on pharmaceuticals and other facility indicators from over 200 facilities in each country. We analyze data on the availability of pharmaceuticals and quantify its association with various facility-level indicators. We analyze both availability of essential medicines, as defined by the various essential medicine lists (EMLs) of each respective country, and availability of all surveyed pharmaceuticals deemed important for treatment of various high-burden diseases, including those on the EMLs.

Results

We find that there is heterogeneity with respect to availability across the three countries with Ghana generally having better availability than Uganda and Kenya. To analyze the relationship between facility-level factors and pharmaceutical stock-out we use a binomial regression model. We find that the factors associated with stock-out vary by country, but across all countries both presence of a laboratory at the facility and presence of a vehicle at the facility are significantly associated with reduced stock-out.

Conclusion

The results of this study highlight the poor availability of essential medicines across these three countries and suggest more needs to be done to strengthen the supply system so that stock remains uninterrupted.

]]>
<![CDATA[Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China]]> https://www.researchpad.co/article/5989da7fab0ee8fa60b99f9d

Background

China’s National Free Antiretroviral Treatment Program (NFATP) has substantially increased the survival rate since 2002. However, the emergence of HIV drug resistance (HIVDR) limits the durability and effectiveness of antiretroviral treatment (ART) in at risk patients.

Method

A cross-sectional survey was conducted among patients having received a median of 13.9 months of ART in eight provinces in China. Demographic and clinical information was collected, and venous blood was sampled for CD4 cell counts, measurement of the HIV viral load (VL), and HIV drug resistance (HIVDR) genotyping. Possible risk factors for HIVDR were analyzed by the logistic regression model.

Results

The study included 765 patients. Among them, 65 patients (8.5%) had virological failure (VLF) defined as ≥1,000 copies/ml. Among the individuals with VLF, 64 were successful genotyped, and of these, 33 had one or more HIVDR mutations. The prevalence of HIVDR mutations among patients receiving first-line ART was 4.3% (33/765). All of the patients with HIVDR mutations were resistant to non-nucleoside transcriptase inhibitors, 81.8% were resistant to nucleoside reverse transcriptase inhibitors, and only 3% had mutations that caused resistance to protease inhibitors. Having lower ratios of drug intake in the past month and dwelling in two southwestern provinces were factors independently associated with the emergence of HIVDR.

Conclusion

Most patients receiving first-line ART treatment achieved sound virological and immunological outcomes. However, poor adherence is still a key problem, which has led to the high rate of HIVDR. It was notable that the proportion of drug resistance widely varied among the provinces. More studies are needed to focus on adherence.

]]>
<![CDATA[Long-Term Durability of Tenofovir-Based Antiretroviral Therapy in Relation to the Co-Administration of Other Drug Classes in Routine Clinical Practice]]> https://www.researchpad.co/article/5989da2eab0ee8fa60b835a8

Background

In clinical trials, toxicity leading to tenofovir disoproxil fumarate (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it seems to be higher, particularly when TDF is co-administered with ritonavir-boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of TDF discontinuations in clinical practice and to identify factors associated with the risk of stopping TDF.

Methods

All antiretroviral treatment (ART)-naive patients initiating a TDF-based regimen were selected from the ICONA Foundation Study cohort. The primary outcome was TDF discontinuation regardless of the reason; secondary outcome measures were TDF discontinuation due to toxicity and selective TDF discontinuation (that is, TDF discontinuation or substitution, maintaining unchanged the remaining antiretroviral treatment).

Results

3,618 ART-naïve patients were included: 54% started a PI/r-based and 46% a NNRTI-based based regimen. Two-hundred-seventy-seven patients discontinued TDF and reintroduced ART within 30 days without TDF. The probability of TDF discontinuation regardless of the reason was of 7.4% (95%CI:6.4–8.5) by 2 years and 14.1% (95%CI:12.2–16.1) by 5 years. The 5-year KM estimates in the PI/r vs. NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for discontinuation due to toxicity. PI/r use and lower eGFR were associated with an increased risk of discontinuing TDF.

Conclusion

In our cohort, the frequency of TDF discontinuations was higher than that observed in clinical trials. Co-administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. Further studies are needed to clarify the mechanisms that might have led to this outcome.

]]>
<![CDATA[Views of Medical Doctors Regarding the 2013 WHO Adult HIV Treatment Guidelines Indicate Variable Applicability for Routine Patient Monitoring, for Their Family Members and for Themselves, in South-Africa]]> https://www.researchpad.co/article/5989da8aab0ee8fa60b9db03

South African doctors (n = 211) experienced in antiretroviral therapy use were asked via an online questionnaire about the WHO 2013 adult antiretroviral integrated guidelines, as well as clinical and personal issues, in three hypothetical scenarios: directing the Minister of Health, advising a family member requiring therapy amidst unstable antiretroviral supplies, and where doctors themselves were HIV-positive. Doctors (54%) favoured the 500 cells/μl WHO initiation threshold if advising the Minister; a third recommended retaining the 350 cells/μl threshold used at the time of the survey. However, they favoured a higher initiation threshold for their family member. Doctors were 4.9 fold more likely to initiate modern treatment, irrespective of their CD4 cell count, for themselves than for public-sector patients (95%CI odds ratio = 3.33–7.33; P<0.001, although lower if limited to stavudine-containing regimens. Doctors were equally concerned about stavudine-induced lactic acidosis and lipoatrophy. The majority (84%) would use WHO-recommended first-line therapy, with concerns split between tenofovir-induced nephrotoxicity (55%), and efavirenz central nervous system effects (29%). A majority (61%), if HIV-positive, would pay for a pre-initiation resistance test, use influenza-prophylaxis (85%), but not INH-prophylaxis (61%), and treat their cholesterol and blood pressure concerns conventionally (63% and 60%). Over 60% wanted viral loads and creatinine measured six monthly. A third felt CD4 monitoring only necessary if clinically indicated or if virological failure occurred. They would use barrier prevention (83%), but not recommend pre-exposure prophylaxis, if their sexual partner was HIV-negative (68%). A minority would be completely open about their HIV status, but the majority would disclose to their sexual partners, close family and friends. Respondents were overwhelmingly in favour of continued antiretrovirals after breastfeeding. In conclusion, doctors largely supported adult WHO guidelines as public policy, although would initiate treatment at higher CD4 counts for their family and themselves. Resistance to INH-prophylaxis is unexpected and warrants investigation.

]]>
<![CDATA[Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study]]> https://www.researchpad.co/article/5989db2eab0ee8fa60bd1c6c

Objectives

Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients.

Methods

We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT), missing = failure and on-treatment (OT) analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations.

Results

Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients). The main reasons for switching were drug toxicity/poor tolerability (60.5%) and simplification (20%). At week 48, the primary objective was achieved by 187 out of 205 (91.2%) patients by ITT analysis, and 187 out of 192 (97.4%) patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/μL (−50 to 189) and 1.2% (−1.3% to 4.1%), respectively, P<0.001. Thirty-eight adverse events (AE) were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 [2.4%]), toxicity/poor tolerability (4 [2%]), clinical decision (3 [1.5%]), loss to follow-up (3 [1.5%]), death (1 [0.5%]), and no clinical data (2 [1%]).

Conclusions

The results of this study confirms that ABC/3TC+RPV is an effective, safe, and cost-effective option for the treatment of patients with virologically stable HIV-1 infection.

]]>