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This study aimed to assess the prevalence and reasons for nonadherence to cotrimoxazole prophylaxis therapy. A cross-sectional study was conducted among people living with HIV attending Ayder Comprehensive Specialized Hospital. Data were collected through interviews and reviews of medical records. Binary logistic regression was employed to analyze factors associated with CPT nonadherence. Approximately two-thirds (65.5%) of the participants were non-adherent to co-trimoxazole prophylaxis therapy. The main reasons for non-adherence were side effects, pill fatigue and forgetfulness. Strategies to improve adherence to co-trimoxazole prophylaxis therapy should focus on the combined patient, clinical and medication related issues of people living with HIV. [ABSTRACT FROM AUTHOR]

This bioequivalence study was conducted to evaluate two oral formulations of cotrimoxazole tablets in healthy Chinese subjects. All 26 subjects recruited to this study were randomly and evenly classified into two groups and received a single dose (sulfamethoxazole: 400 mg and trimethoprim: 80 mg) of test cotrimoxazole tablets (generic drug) or reference cotrimoxazole tablets (branded drug). After a 7-day washout period, these subjects received one dose of reference drug or test drug. Blood samples were collected from participants before and up to 48 h after dosing to assess the concentration of sulfamethoxazole (SMX) and trimethoprim (TMP) in plasma and a plasma concentration-time curve was drawn. Then, the pharmacokinetics parameters were calculated accordingly. Our data revealed that there were no significant differences observed in the maximum plasma concentration (Cmax), area under the curve from time 0 to the last measurable concentration (AUC0-t), and area under the curve from time 0 to infinity (AUC0-∞) between the two formulations. For SMX, the 90% confidence intervals (CI) of the geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were 104.03-113.92%, 100.46-103.70%, and 100.41-103.81%, respectively. Similarly, for Trimethoprim (TMP), the 90% CI ranged from 98.54 to 106.95% for Cmax, from 99.31 to 107.68% for AUC0-t, and from 99.49 to 107.55% for AUC0-∞. Importantly, all these 90% CI values fell within the range of 80.00–125.00%, indicating that the test drug is bioequivalent to the reference drug. Furthermore, throughout the entire trial, no suspected serious adverse events were reported, indicating the safety profile of the newly developed generic cotrimoxazole. In summary, our study demonstrates that the newly developed generic formulation of cotrimoxazole is bioequivalent to the branded formulation under fasting conditions. [ABSTRACT FROM AUTHOR]

Background: Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. Methods: A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0–14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. Results: Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). Conclusions: Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed. [ABSTRACT FROM AUTHOR]

Background: Coinfection with malaria and HIV is common in Sub-Saharan Africa. In the advent of a decline in the global incidence of malaria, it is important to generate updated data on the burden of malaria in people living with HIV (PLWHIV). This study was designed to determine the prevalence of malaria in PLWHIV in Yaounde, Cameroon, as well determine the association between CD4 (+) T cell count and malaria in the study population.Methods: In a cross sectional study performed between April 2015 and June 2016, 355 PLWHIV were enrolled and blood samples were collected for analysis. Complete blood count was performed using an automated haematology analyser (Mindray®, BC-2800) and CD4 (+) T cell count was performed using a flow cytometer (BD FASCount™). Giemsa-stained blood films were examined to detect malaria parasite. The Pearson's chi-square, student's T-test, ANOVA, and correlation analysis were all performed as part of the statistical analyses.Results: The prevalence of malaria observed in the study was 7.3 % (95 % CI: 4.8-10.6). No significant association was observed between the prevalence of malaria and age or gender. The prevalence of malaria was higher in participants who were not sleeping in insecticide treated bed nets, ITNs (p < 0.001); and in participants who were not on cotrimoxazole prophylaxis (p = 0.002). The prevalence of malaria (p < 0.001) and malaria parasite density (p = 0.005) were observed to be progressively higher in participants with CD4 (+) T cell count below 200cells/μl. Furthermore, the mean CD4 (+) T cell count was observed to be lower in participants coinfected with malaria compared to non-coinfected participants (323.5 vs 517.7) (p < 0.001). In this study, a negative correlation was observed between malaria parasite density and CD4 (+) T cell count (p = 0.019).Conclusions: A low prevalence of malaria was observed in the study population. Some of the factors accounting for the low prevalence of malaria in this study population may include the health seeking habit of PLWHIV, the use of cotrimoxazole based chemoprophylaxis, and their cautious use of ITNs. [ABSTRACT FROM AUTHOR]

Background: The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX). Methods: This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use. Results: 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30. Conclusions: The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643 [ABSTRACT FROM AUTHOR]

Background: Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4+ T cells-mediated immunity in HEU children is still not fully understood. Methods: Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4+ T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4+ T cells responses were measured by intracellular cytokine staining assay. Results: There were no differences in the proportions of naïve, effector and memory CD4+ T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNFproducing CD4+ T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparumspecific IFN-γ-producing CD4+ T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis. Conclusion: The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4+ T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4+ T cells leads to higher risk to malaria disease remains unknown and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Cotrimoxazole prophylaxis has an antimalarial effect which could have an additional protective effect against malaria in HIV-infected children on antiretroviral therapy (ART). We measured the incidence and associated factors of malaria in HIV-infected children on ART and/or cotrimoxazole in Abidjan, Côte d’Ivoire. Methods: All HIV-infected children <16 years, followed-up in the IeDEA West-African paediatric cohort (pWADA) in Abidjan, were prospectively included from May to August 2012, the rainy season. Children presenting signs suggesting malaria had a thick blood smear and were classified as confirmed or probable malaria. We calculated incidence density rates (IR) per 100 child-years (CY). Risk factors were assessed using a Poisson regression model. Results: Overall, 1117 children were included, of whom 89 % were ART-treated and 67 % received cotrimoxazole. Overall, there were 51 malaria events occurring in 48 children: 28 confirmed and 23 probable; 94 % were uncomplicated malaria. The overall IR of malaria (confirmed and probable) was 18.3/100 CY (95 % CI: 13.3-23.4), varying from 4.2/100 CY (95 % CI: 1.1-7.3) in children on ART and cotrimoxazole to 57.3/100 CY (95 % CI: 7.1-107.6) for those receiving no treatment at all. In univariate analysis, age <5 years was significantly associated with a 2-fold IR of malaria compared to age >10 years (incidence rate ratio [IRR] = 2.18, 95 % CI: 1.04-4.58). Adjusted for severe immunodeficiency, cotrimoxazole reduced significantly the IR of first malarial episode (adjusted IRR [aIRR] = 0.13, 95 % CI: 0.02-0.69 and aIRR = 0.05, 95 % CI:0.02-0.18 in those off and on ART respectively). Severe immunodeficiency increased significantly the malaria IR (aIRR = 4.03, 95 % CI: 1.55-10.47). When considering the IR of confirmed malaria only, this varied from 2.4/100 CY (95 % CI: 0.0-4.8) in children on ART and cotrimoxazole to 34.4/100 CY (95 % CI: 0.0-73.3) for those receiving no treatment at all. In adjusted analyses, the IR of malaria in children on both cotrimoxazole and ART was significantly reduced (aIRR = 0.05, 95 % CI: 0.01-0.24) compared to those receiving no treatment at all. Conclusions: Cotrimoxazole prophylaxis was strongly protective against the incidence of malaria when associated with ART in HIV-infected children. Thus, these drugs should be provided as widely and durably as possible in all HIV-infected children <5 years of age. [ABSTRACT FROM AUTHOR]

Background: Nitroxoline, a hydroxychinoline derivate, has been used for many years to treat urinary tract infections (UTI). Many uncontrolled, but only few controlled clinical studies have been published. Four so far unpublished, controlled clinical studies were meta-analysed. Methods: A narrative literature review was performed. In addition the individual patient data (IPD) of 466 females with uncomplicated UTI of four prospective, single blind, randomized, clinical studies with similar protocols using nitroxoline (250 mg tid) versus cotrimoxazole (960 mg bid) or norfloxacin (400 mg bid) as controls for 5 days (sporadic UTI) or 10 days (recurrent UTI) were meta-analysed. The primary aim was eradication of bacteriuria 7–13 days after end of therapy (test of cure). Clinical efficacy was determined by elimination of symptoms and safety by adverse events and laboratory tests. Results: Reviewing a total of 26 uncontrolled, 2 controlled and one postmarketing studies including more than 11,000 patients, good efficacy and safety of nitroxoline could be confirmed. In the four unpublished controlled studies a total of 234 patients were treated orally with nitroxoline and 232 with controls. The safety of nitroxoline was very good and comparable to the controls (adverse events 9.4% vs 7.8%; p = 0.360). In the mMITT set (at least one outcome result), in the PP set (test of cure outcome) and in the modified PP set (missing test of cure rated failure) more than 90% of the patients showed eradication of bacteriuria with nitroxoline, which also met statistical non-inferiority compared to the controls (10% non-inferiority margin) in all three evaluation sets. The clinical efficacy was similar between the two treatment groups. Conclusion: The IPD meta-analysis using objective parameters (elimination of bacteriuria) demonstrated equivalent efficacy (non-inferiority) of nitroxoline with the controls tested (cotrimoxazole, norfloxacin) in the treatment of uncomplicated UTI. Considering the good safety and efficacy of nitroxoline as also shown in many uncontrolled and observational studies and the world wide increase of resistance of uropathogens against cotrimoxazole and fluoroquinolones, but not against nitroxoline within the last 20 years, nitroxoline should be reconsidered as one of the first line antibiotics for the treatment of uncomplicated UTI. [ABSTRACT FROM AUTHOR]

Background: Drug use evaluation is a performance improvement method that focuses on evaluating and improving drug use process to achieve optimal patient outcomes. Drug use evaluation helps in identifying, preventing or resolving actual and potential drug related problems. The objective of the study was to evaluate the use of cotrimoxazole as preventive therapy in people living with HIV/AIDS in Boru Meda Hospital, Northeast Ethiopia. Methods: A retrospective drug use evaluation was conducted on patients' medical history records based on a validated drug use evaluation criteria according to the national guideline. Medical history records of 248 patients were selected using systematic sampling method. Results: The result showed that 49.6% of the patients were at WHO clinical stage III at the start of cotrimoxazole preventive therapy. In this study, the use of cotrimoxazole preventive therapy was consistent with the guideline in the rationale for indication (97.98%), dose (96.77%), and its use despite the presence of contraindications (91.93%). Problems regarding drug-drug interaction were identified in 49.59% of cases, and 20.97% of patients discontinued cotrimoxazole preventive therapy due to different reasons. Conclusions: In most patients cotrimoxazole preventive therapy was consistent with the national guideline regarding the rationale for indication, dose, discontinuation and its use in the presence of contraindications [ABSTRACT FROM AUTHOR]

Background: Mozambique presents a very high prevalence of both malaria and HIV infection, but the impact of co-cancel infection on morbidity in this population has been rarely investigated. The aim of this study was to describe the prevalence and clinical characteristics of malaria in hospitalized adult HIV-positive patients, treated and untreated with combination anti-retroviral therapy (ART) and cotrimoxazole (CTX)-based chemoprophylaxis, compared to HIV negatives. Methods: From November to December 2010, all adult patients consecutively admitted to the Department of Internal Medicine of Beira Central Hospital, Sofala Province, Mozambique, were submitted to HIV testing, malaria blood smear (MBS) and, in a subgroup of patients, also to the rapid malaria test (RDT). Socio-demographical and clinical data were collected for all patients. The association of both a positive MBS and/or RDT and diagnosis of clinical malaria with concomitant HIV infection (and use of CTX and/or ART) was assessed statistically. Frequency of symptoms and hematological alterations in HIV patients with clinical malaria compared to HIV negatives was also analysed. Sensitivity and specificity for RDT versus MBS were calculated for both HIV-positive and negative patients. Results: A total of 330 patients with available HIV test and MBS were included in the analysis, 220 of whom (66.7%) were HIV-positive. In 93 patients, malaria infection was documented by MBS and/or RDT. RDT sensitivity and specificity were 94% and 96%, respectively. According to laboratory results, the initial malaria suspicion was discarded in about 10% of cases, with no differences between HIV-positive and negative patients. A lower malaria risk was significantly associated with CTX prophylaxis (p=0.02), but not with ART based on non nucleoside reverse-transcriptase inhibitors (NNRTIs). Overall, severe malaria seemed to be more common in HIV-positive patients (61.7%) compared to HIV-negatives (47.2%), while a significantly lower haemoglobin level was observed in the group of HIV-positive patients (9.9±2.8mg/dl) compared to those HIV-negative (12.1±2.8mg/dl) (p=0.003). Conclusions: Malaria infection was rare in HIV-positive individuals treated with CTX for opportunistic infections, while no independent anti-malarial effect for NNRTIs was noted. When HIV and malaria co-infection occurred, a high risk of complications, particularly anaemia, should be expected. [ABSTRACT FROM AUTHOR]