Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières

OBJECTIVES: To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. DESIGN/METHODS: We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. RESULTS: Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. CONCLUSION: The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment

First isolation of Leishmania from Northern Thailand:case report, identification as Leishmania martiniquensis and phylogenetic position within the Leishmania enriettii complex

Since 1996, there have been several case reports of autochthonous visceral leishmaniasis in Thailand. Here we report a case in a 52-year-old Thai male from northern Thailand, who presented with subacute fever, huge splenomegaly and pancytopenia. Bone marrow aspiration revealed numerous amastigotes within macrophages. Isolation of Leishmania LSCM1 into culture and DNA sequence analysis (ribosomal RNA ITS-1 and large subunit of RNA polymerase II) revealed the parasites to be members of the Leishmania enriettii complex, and apparently identical to L. martiniquensis previously reported from the Caribbean island of Martinique. This is the first report of visceral leishmaniasis caused by L. martiniquensis from the region. Moreover, the majority of parasites previously identified as "L. siamensis" also appear to be L. martiniquensis

Incidence and risk factors of antiretroviral treatment failure in treatment-naïve HIV-infected patients at Chiang Mai University Hospital, Thailand

<p>Abstract</p> <p>Background</p> <p>The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients.</p> <p>Methods</p> <p>A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand.</p> <p>Results</p> <p>From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm³(IQR 22, 127). GPO-VIR^®(a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm³) and the increment of CD4 cell count of < 50 cell/mm³after 6 months of cART were the predictors for immunological failure (p < 0.001).</p> <p>Conclusions</p> <p>This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART.</p

Hepatitis B Vaccination Induced TNF- α

We investigated cytokine production and expression of degranulation marker CD107a after different strategies of hepatitis B virus (HBV) vaccination in human immunodeficiency virus-infected individuals, which were three doses of 20 μg (standard dose group), four doses of 20 μg (four doses group), or four doses of 40 μg (four double doses group), compared to standard dose vaccination in healthy controls. PBMCs collected at different time points were stimulated in vitro with recombinant hepatitis B surface antigen and analyzed by flow cytometry. There was an increase in TNF-α production of total and memory CD4+ T cells at 7 months after vaccination in healthy controls compared to the HIV+ group, which received the same standard vaccination regimen. An increase in the IL-2-producing memory CD4+ T cells in the healthy control group was also observed at 7 months after vaccination. No differences were observed between the healthy controls and both groups of four doses at any time point of study. These results suggest that the standard HBV vaccination schedule might induce better production of TNF-α and IL-2 from CD4+ T cells in healthy individuals. Modification of HBV vaccination schedule by increasing the frequency and/or dosage may improve the CMI response in HIV-infected individuals. This trial is registered with NCT1289106

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

Breaches in Infection Prevention and Controls Discovered During an Outbreak Investigation of Two Unlinked Cases of Pseudomonas aeruginosa Bloodstream Infections in a Cardiovascular Thoracic Surgery Unit

Two patients with Pseudomonas aeruginosa bloodstream infections were diagnosed a week apart in a cardiovascular thoracic (CVT) surgery unit where there had been no cases of P. aeruginosa infections in the preceding 6 months. An outbreak investigation was conducted. Medical records were reviewed to identify potential common exposure in both patients. Outbreak investigation procedures included cultures of intravenous infusions and various solutions in the operating theatre and the general CVT surgery unit, the intensive care unit and the intermediate care unit, and monitoring compliance with the central line associated bloodstream infection prevention bundle. Both the blood cultures of the two patients as well as the liquid soap used for hand washing in the unit grew P. aeruginosa. However, there were three clonalities of isolates, the first from patient A, the second from patient B, and the third from the liquid soap. Other intravenous infusions and various solutions, i.e., normal saline solution, lactate ringer solutions, solutions for cardiopulmonary bypass circuits, and skin antisepsis, did not grow potential pathogens. In conclusion, although these were unlinked cases, investigation of the cases uncovered breaches in infection control practices and provided an opportunity to improve the infection control strategies in our institution.. KEYWORDS P. aeruginosa, bloodstream infection, outbreak, outbreak investigation, infection contro

Adherence to antiretroviral therapy for HIV in sub-Saharan Africa and Asia: a comparative analysis of two regional cohorts

Introduction Our understanding of how to achieve optimal long-term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV-positive persons receiving ART who were enrolled in a bi-regional cohort in sub-Saharan Africa and Asia. Methods This multicentre prospective study of adults starting first-line ART assessed patient-reported adherence at followup clinic visits using a 30-day visual analogue scale. Determinants of suboptimal adherence (<95%) were assessed for six-month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier. Results Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p < 0.001). In the African cohort, determinants of suboptimal adherence were male sex (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06–1.53; p = 0.009), younger age (OR 0.8 per 10 year increase; 0.8–0.9; p = 0.003), use of concomitant medication (OR 1.8, 1.0–3.2; p = 0.044) and attending a public facility (OR 1.3, 95% CI 1.1–1.7; p = 0.004). In the Asian cohort, adherence was higher in men who have sex with men (OR for suboptimal adherence 0.6, 95% CI 0.4–0.9; p = 0.029) and lower in injecting drug users (OR for suboptimal adherence 1.6, 95% CI 0.9–2.6; p = 0.075), compared to heterosexuals. Risk of suboptimal adherence decreased with longer ART duration in both regions. Participants in low- and lower-middle-income countries had a higher risk of suboptimal adherence (OR 1.6, 1.3–2.0; p < 0.001), compared to those in upper-middle or high-income countries. Suboptimal adherence was strongly associated with virological failure, in Africa (OR 5.8, 95% CI 4.3–7.7; p < 0.001) and Asia (OR 9.0, 95% CI 5.0–16.2; p < 0.001). Patient-reported adherence barriers among African participants included scheduling demands, drug stockouts, forgetfulness, sickness or adverse events, stigma or depression, regimen complexity and pill burden. Conclusions Psychosocial factors and health system resources may explain regional differences. Adherence-enhancing interventions should address patient-reported barriers tailored to local settings, prioritizing the first years of ART

Cardiovascular risks in Asian HIV-infected patients receiving boosted-protease inhibitor-based antiretroviral treatment

Introduction: Increased risk of cardiovascular disease in HIV-infected patients was tought to be the cause of multiple mechanistic factors, which changing the HIV care landscape. Antiretroviral therapy (ART), especially protease inhibitors (PI), is one of common HIV treatments that may have some association with this. The mechanism of PI in comparison to other regimens, however, are not clearly understood. Methodology: Age-and gender-match HIV-infected patients treated with either boosted-PI-based regimen (boosted-PI group, N=30) or NNRTI-based ART (non-PI group, N = 30) were recruited for this cross-sectional study. Parameters determined cardiovascular risks, inflammation, endothelial function, and bone metabolic function were evaluated. Results: Compared with non-PI, patients in the boosted-PI group had more evidence of dyslipidemia. No statistical difference in the prevalence of subclinical atherosclerosis was found between the two groups. Circulating levels of inflammatory markers, C-reactive protein (CRP) (5.4±9.1 vs. 14.9 ± 19.4 mg/L, p = 0.019) and lectin-liked oxidized lipoprotein receptor-1 (LOX-1) (387 ± 299 vs. 554 ± 324 pg/mL, p = 0.042) were lower in boosted-PI group. Contrastingly, Vascular adhesion molecules-1 (VCAM-1) (160.2 ± 80.0 vs. 147.8 ± 66.3 ng/mL, p = 0.010), and osteoprotegerin (OPG) (153.7 ± 57.1 vs. 126.4 ± 35.8, p = 0.031) were higher. After adjustment in the multivariate analysis, PI treatment is the only independent parameter associated with the changes of CRP, LOX-1, VCAM-1, and OPG. Subgroup analysis showed that ARV treatment effects differed among participant having dyslipidemia. Conclusions: The major mechanism in which PI-mediated was triggering atherogenesis could be through alteration of lipid metabolism and endothelial function, but no evidence of accelerated pro-inflammatory response was attested

Diverse Contexts of Zoonotic Transmission of Simian Foamy Viruses in Asia

In Asia, contact between persons and nonhuman primates is widespread in multiple occupational and nonoccupational contexts. Simian foamy viruses (SFVs) are retroviruses that are prevalent in all species of nonhuman primates. To determine SFV prevalence in humans, we tested 305 persons who lived or worked around nonhuman primates in several South and Southeast Asian countries; 8 (2.6%) were confirmed SFV positive by Western blot and, for some, by PCR. The interspecies interactions that likely resulted in virus transmission were diverse; 5 macaque taxa were implicated as the source of infection. Phylogenetic analysis showed that SFV from 3 infected persons was similar to that from the nonhuman primate populations with which the infected persons reported contact. Thus, SFV infections are likely to be prevalent among persons who live or work near nonhuman primates in Asia

Loss to Followup in HIV-Infected Patients from Asia-Pacific Region: Results from TAHOD

This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger (P = 0.002), had HIV viral load ≥500 copies/mL or missing (P = 0.021), had shorter history of HIV infection (P = 0.048), and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P < 0.001). 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin (P < 0.001), missing recent HIV viral load (P < 0.001), negative hepatitis C test (P = 0.025), and previous temporary LTFU episodes (P < 0.001). Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced