137 research outputs found

    Optimization of HIV and tuberculosis co-treatment in Tanzania : drug-drug interactions and clinical outcomes

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    Background: Sub-Saharan Africa has been greatly affected by the HIV epidemic, with an estimated 23.5 million people living with HIV/AIDS (PLWHA) residing within this region by the end of 2011, being the leading course of morbidity and mortality. Tanzania is one of the countries in this region with an HIV prevalence of 5.7% i.e approximately 2.7 million PLWHA. The most common opportunistic infection in sub-Saharan Africa is tuberculosis (TB). Currently HIV and TB are the leading cause of morbidity and mortality in Tanzania. The management of these two infections in individuals with the dual infection is challenging due to drug-drug interactions that could potentially lead to toxicities or ineffective treatment outcomes for one or both diseases. This thesis aims to describe the socio-demographic and clinical characteristics as well as the clinical outcomes of treatment.Methods: We first performed a baseline study of a clinical HIV infected population enrolled at the HIV care and treatment centre (CTC) at Muhimbili National Hospital between June 2004 and September 2008. Based on this clinical experience, a cohort of HIV infected patients, with or without TB who were HAART naïve with CD4 cell counts Results: Most patients presenting to the CTC had advanced immune deficiency. Significantly higher proportions were female patients. With the free access to HAART in the later years, patients presented earlier to the CTC in the course of HIV disease. For the co-infection cohort study a total of 255 HIV only patients and 231 HIV-TB patients were recruited. The HIV-TB patients had significantly lower body mass index, Karnofsky scores and haemoglobin compared to those with HIV only, despite similar baseline CD4 cell counts. Mortality was similar in both the HIV only and those with HIV-TB, being 10.9% (16 deaths/100person years) and 11.3% (17 deaths/100py) respectively with the predictors for mortality being advanced disease such as low CD4 counts, low baseline WBC, oral candidiasis and Kaposis sarcoma. HIV only patients had significantly higher plasma efavirenz concentrations compared to the HIV-TB patients 4 weeks after HAART initiation indicating an interaction with rifampicin. Female gender and those with CYP2B6*6/*6 genotype also had significantly higher plasma efavirenz concentrations. Pharmacogenetic variants play a role in plasma efavirenz concentrations and long-term efavirenz autoinduction. The proportion of patients with efavirenz concentrations below the therapeutic range (Conclusion: Patients enrolled at the CTCs are predominantly females, and present with advanced immune deficiency that ultimately puts them at a higher risk of dying. Pharmacogenetic variants influence efavirenz concentrations where slow metabolizers are at a higher risk of presenting with higher efavirenz concentrations, DILI and neuropsychiatric manifestations. The DILI seen in our setting is mild, transient and does not require treatment interruption. Patients using efavirenz alone are at a higher risk of developing neuropsychiatric manifestations compared to those who concomitantly use rifampicin. The WHO recommended efavirenz dosage of 600mg daily can be used with rifampicin among Tanzanian patients without compromise to their treatment outcomes.List of scientific papersI. Mugusi SF, Mwita JC, Francis JM, Aboud S, Bakari M, Aris EA, Swai AB, Mugusi FM, Pallangyo K, Sandstrom E. Effect of improved access to antiretroviral therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. BMC Public Health. 2010 May 28;10:291. https://doi.org/10.1186/1471-2458-10-291 II. Mugusi SF, Ngaimisi E, Janabi MY, Mugusi FM, Minzi OM, Sasi PG, Bakari M, Lindquist L, Aklillu E, Sandstrom EG. Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania. Antivir Ther. 2012;17(2):265-74. https://doi.org/10.3851/IMP1956 III. Ngaimisi E, Mugusi S, Minzi OM, Sasi P, Riedel KD, Suda A, Ueda N, Janabi M, Mugusi F, Haefeli WE, Burhenne J, Aklillu E. Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients. Clin Pharmacol Ther. 2010 Nov;88(5):676-84. https://doi.org/10.1038/clpt.2010.172 IV. Mugusi S, Ngaimisi E, Janabi M, Minzi O, Bakari M, Riedel KD, Burhenne J, Lindquist L, Mugusi F, Sandstrom E, Aklillu E. Liver enzyme abnormalities and associated risk factors in HIV patients on efavirenz-based HAART with or without tuberculosis co-infection in Tanzania. PLoS One. 2012;7(7):e40180. https://doi.org/10.1371/journal.pone.0040180 V. Mugusi S, Ngaimisi E, Janabi M, Mugusi F, Minzi O, Aris E, Bakari M, Bertilsson L, Burhene J, Sandstrom E, Aklillu E. Neuropsychiatric manifestations among HIV-1 infected African patients receiving Efavirenz based HAART with or without Tuberculosis treatment containing Rifampicin. [Manuscript]</p

    Risk Factors for Anaemia Among HIV Infected Children Attending Care and Treatment Clinic at Muhimbili National Hospital in Dar es Salaam, Tanzania

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    There is paucity of data describing the risk factors for anaemia among HIV infected children in Tanzania. This cross sectional study was carried out to determine the contributing factors for anaemia among HIV-infected children attending Muhimbili National Hospital in Dar es Salaam. Both univariate and multivariate logistic regression analyses were performed to identify possible factors associated with anaemia in HIV-infected children. A total of 75 (44%) patients among 167 recruited HIV-infected children aged 6 months to 59 months of were found to be anaemic (Hg<11g/dl). Multivariate logistic regression demonstrated that not being on HAART (OR 3.40, 95%CI (1.20-9.60), having CD4% <25% (OR 2.30, 95%CI (1.20-34.60), having a history of tuberculosis (TB) (OR 3.23, 95%CI (1.10-9.70) and having hookworm infestation (OR 5.97, 95%CI (1.92-18.4) were independent risk factors for anaemia among HIV infected children. The analyses also showed that being HIV positive for ≥ 2.5 years resulted into a low risk of severe anaemia compared to being HIV positive for < 2.5 years. Taking multivitamins (OR 0.07, 95%, CI (0.020-0.30) and antihelminthics (OR 0.27, 95%CI (0.10-0.74) were also protective against anaemia in children. Similar factors (with exception of using antihelmintics) were associated with severe anaemia. In conclusion the factors associated with anaemia in HIV infected children were multifactorial in nature. Efforts to correct anaemia in HIV infected children should include use of HAART and treatment of infections such as TB and hookworms

    Primary Antimicrobial Resistance Among Mycobacterium Tuberculosis Isolates from HIV Seropositive and HIV Seronegative Patients in Dar es Salaam Tanzania.

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    The United Republic of Tanzania is one of the 22 high M. tuberculosis burden countries. Data collected between 2002 and 2007 indicate that the global prevalence of drug-resistant M. tuberculosis including MDR vary greatly. The varied drug-resistance patterns make continuous surveillance of drug resistance an essential component of tuberculosis control program. M. tuberculosis isolates were obtained from consenting adult tuberculosis patients involved in a placebo-controlled study to evaluate the efficacy of multivitamin supplements on response to anti-Tb treatment in Dar es Salaam, Tanzania. Antimicrobial susceptibility testing was done on four antimicrobial agents namely streptomycin, isoniazid, ethambutol and rifampicin. HIV testing and CD4+ T lymphocytes enumeration were also done. A total of 280 M. tuberculosis isolates from 191 (68%) males and 89 (32%) female patients with no previous history of anti-tuberculosis treatment exceeding 4 weeks in the previous 12 months were tested. Among these, 133 (47%) patients were HIV seropositive. Fourteen (5.0%) isolates were resistant to any of the anti-tuberculosis drugs. The prevalence of primary resistance was 5.0%, 0.7%, 0.4% and 0% for isoniazid, streptomycin, rifampicin and ethambutol respectively. One isolate (0.4%) was MDR, with resistance to isoniazid, streptomycin and rifampicin. M. Tb primary resistance rate in a selected population in Dar es Salaam Tanzania is low and efforts should be undertaken to support the Tuberculosis program

    A Case-Control Study of Factors Associated with Non-Adherent to Antiretroviral Therapy Among HIV Infected People in Pwani Region, Eastern Tanzania

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    Non-adherence is one of the major causes of treatment failure which leads to increased morbidity and mortality caused by opportunistic infections. Optimal anti-retroviral therapy (ART) adherence is essential for maximal suppression of viral replication and long term survival of patients. In order to develop effective public health interventions in the context of scaling ART services to peripheral areas, it is important to evaluate factors associated with non-adherence among HIV-infected individuals in Pwani Region. The purpose of this study was to identify factors related to non-adherence to ART among HIV infected people in Pwani Region eastern of Tanzania. A case-control study was carried out at Tumbi Hospital and Chalinze Health Centre in Pwani Region in eastern Tanzania. A structured questionnaire was used to assess non-adherence and adherence to doses instruction and time schedule. Patients with less than 95% adherence were defined as cases while those with more than 95% adherence became controls. A structured questionnaire containing factors known to be associated with non-adherence to ART in similar settings was administered. Univariate and multivariate conditional logistic regression was performed to identify factors associated with non-adherence. A total of 79 cases and 237 controls matched by age and sex were studied. A high proportion of cases and controls (77.2% and 84.8%) had good knowledge of ART benefits, adherence and eligibility. Majority of cases (73.3%) and controls (69.2%) used public transport to access ART services. More than half of cases (53.2%) missed clinic appointments due to lack of bus fare or other reasons and was associated with ART non adherence (mOR 4.2, 95%CI, 2.2-8.1 and 2.1,95%CI 1.2-4.2). Disclosure to confidants only and failure to disclose HIV-test positive status were associated with non adherence (mOR 3.3, 95%CI 1.3-8.5 and 2.3, 95%CI 1.2-7.1). Alcohol use was associated with non adherence to ART (mOR 1.9, 95%CI 1.4-3.7). Patients who were not satisfied with providers were more likely to be non adherence to ART (mOR 2.0, 95%CI 1.2-3.8). In conclusion, these findings show that adherence is a process which is depended on local specific adherence factors. Adherence improvement strategies need to consider site specific adherence determinants, patient experiences and concern

    A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis.

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    Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

    Risk Factors for Mortality among HIV-Positive Patients with and Without Active Tuberculosis in Dar es Salaam, Tanzania.

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    The aim of this study was to describe risk factors for mortality and clinical characteristics of HIV-infected patients with and without tuberculosis (TB) coinfection. A cohort of HIV-infected patients with CD4(+) T-cell counts of ≤200 cells/μl was recruited, consisting of 255 HIV-infected patients without active TB and 231 patients with active TB. All received a well-supervised treatment with an efavirenz-based HAART, and those coinfected with TB received appropriate anti-TB treatment. They were followed up for 48 weeks after HAART initiation. Common presenting symptoms in HIV-only patients were fever (36.5%), headache (34.5%), skin rash (34.5%) and weight loss (32%), while in HIV-TB patients the symptoms were weight loss (58%), cough (57.6%), night sweats (44.6%) and fever (34.2%). HIV-TB patients had significantly lower body mass index, Karnofsky scores and haemoglobin levels compared to those infected with HIV only, despite similar baseline CD4(+) T-cell counts. Overall, 12 (4.7%) HIV patients developed TB and 7 (3%) HIV-TB patients had worsening of their TB symptoms during the study period. Mortality was similar in the two groups, being 10.9% (16 deaths per 100 person years) and 11.3% (17 deaths per 100 person years) in HIV-only and HIV-TB patients, respectively. Overall, more males (13.1%) died compared to females (9.6%). Predictors of mortality were presence of oral candidiasis, Kaposi's sarcoma, low Karnofsky score, and low baseline white blood cell and CD4(+) T-cell counts. The outcomes following well-supervised treatment of HIV-TB patients are similar to those in patients with HIV alone. Predictors of mortality were those of advanced disease

    Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

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    We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

    Optimization of HIV and tuberculosis co-treatment in Tanzanian patients : emphasis on pharmacogenetics and drug interactions

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    Treatment of HIV and its comorbidities particularly tuberculosis is complicated by wide inter-individual variations in drug exposure due to drug-interactions and variable expressions of drug metabolizing enzymes and transporters. Efavirenz in particular, is an antiretroviral characterized by wide inter-individual variation in exposure. Unfortunately, it also has narrow therapeutic range resulting into considerable proportions of patients with sub-therapeutic or supra-therapeutic concentrations. This thesis describes sources of variation in EFV plasma levels and evaluates its enzyme induction and hepatotoxicity; so as to inform appropriate dose optimization.We recruited HIV infected patients with tuberculosis (arm2) and without (arm1) both in Tanzania and Ethiopia. Patients took EFV 600mg based antiretroviral therapy (HAART) and for arm2, rifampicin (RIF) based anti-TB was initiated 4 weeks before HAART. They were followed for 48 (arm1) and 52 (arm2) weeks to collect information on plasma efavirenz exposure (week 4 and 16), immunological and virological outcomes (weeks 0, 12, 24, 36 and 48), liver and renal functional tests and complete blood count (weeks 0, 2, 4, 6, 8, 12, and monthly thereafter) and genotyping for SNPs in EFV metabolizing enzymes CYP2B6*6 c.516G>T, CYP3A5 (*3, *6, *7), UGT2B7 -372G>A and drug transporters ABCB1 (c.3435C>T and c4036A>G) and SLCO1 (388A>G and 521T>C).Among arm1, patients with CYP2B6 homozygous wild type (fast metabolizers) had significant decrease in mean EFV plasma level between week 4 and 16. Consequently, a significantly large proportion these patients had sub-therapeutic plasma level at week 16 compared to week 4, indicating prolonged auto-induction in these individuals.Among arm2, only fast metabolizers had significantly lower efavirenz level, 4 weeks after HAART, compared to their counterpart in arm 1 implying that rifampicin induction occurred only in these individuals. Due to prolonged auto-induction in arm1 fast metabolizers, plasma levels between arm1 and arm2 were comparable at week 16 even when stratified by genotype implying that CYP2B6 genetic polymorphisms, but not rifampicin, influence efavirenz exposure after prolonged treatment.ABCB1 4036A>G SNP was associated with higher EFV levels at week 4 while CYP3A5 (*3, *6, *7) alleles combined, were partially associated with variability in efavirenz metabolic ratio changes between week 4 and 16 among patients with CYP2B6*6/*6 genotype (poor metabolizers).Ethiopians, even after controlling for genetic and other differences, had lower efavirenz exposure and lower immunological outcomes compared to Tanzanians.Efavirenz induction of CYP3A4/5 among arm1 was highest (about 5 times) in poor and lowest (about 2 times) in fast metabolizers. After completion of TB therapy, induction dropped to 60% of its maximum, suggesting continued but lower induction of CYP3A4/5 by efavirenz.EFV with or without rifampicin was associated with mild and transient elevation of liver enzymes. Only CYP2B6*6/*6 genotype and hepatitis C co-infection were associated with such elevations, suggesting that efavirenz is safe for both treatments but caution and monitoring of plasma levels among poor metabolizers and those co infected with hepatitis C should be exercised.Time on therapy (with and without rifampicin co treatment), CYP2B6c516G>T, ABCB1c4036A>G, ethnicity and CYP3A5 (*3, *6, *7) alleles combined, can be used as priori for Bayesian estimation of individual pharmacokinetic parameters during dose adjustments. The SNP, CYP2B6c516G>T, influences induction of CYP3A4/5 in gene dose dependent manner, therefore it should be considered during dose optimization of concomitant drugs taken with efavirenz.It may be necessary to lower doses for concomitant CYP3A4/5 substrate drugs, whose doses were elevated during HIV/TB co treatment, after completion of TB therapy if such drugs have narrow therapeutic range.List of scientific papersI. Ngaimisi E, Mugusi S, Minzi OM, Sasi P, Riedel KD, Suda A, Ueda N, Janabi M, Mugusi F, Haefeli WE, Burhenne J, Aklillu E. Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients. Clin Pharmacol Ther. 2010 Nov; 88(5):676-84. https://doi.org/10.1038/clpt.2010.172 II. Ngaimisi E, Mugusi S, Minzi O, Sasi P, Riedel KD, Suda A, Ueda N, Janabi M, Mugusi F, Haefeli WE, Bertilsson L, Burhenne J, Aklillu E. Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis. Clin Pharmacol Ther. 2011 Sep; 90(3):406-13. https://doi.org/10.1038/clpt.2011.129 III. Eliford Ngaimisi and Abiy Habtewold, Omary Minzi, Eyasu Makonnen, Sabina Mugusi, Wondwossen Amogne, Getnet Yimer, Klaus-Dieter Riedel, Philip Sasi, Mohammed Janabi, Getachew Aderaye, Ferdinand Mugusi, Leif Bertilsson, Eleni Aklillu, and Juergen Burhenne. Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes: A parallel-group prospective cohort study in two Sub-Saharan Africa populations. [Submitted]IV. E Ngaimisi, OM Minzi, S Mugusi, P Sasi, K-D Riedel, A Suda, N Ueda, M Janabi, F Mugusi, L Bertilsson, J Burhenne, E Aklillu and U Diczfalusy. Pharmacokinetic modeling of CYP3A activity biomarker during efavirenz alone and with rifampicin co-treatment in HIV patients: A prospective cohort study. [Manuscript]V. Mugusi S, Ngaimisi E, Janabi M, Minzi O, Bakari M, Riedel KD, Burhenne J, Lindquist L, Mugusi F, Sandstrom E, Aklillu E.Liver enzyme abnormalities and associated risk factors in HIV patients on efavirenz-based HAART with or without tuberculosis co-infection in Tanzania. PLoS One. 2012; 7(7):e40180. https://doi.org/10.1371/journal.pone.0040180 </p

    Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

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    To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

    Challenges of Continuum of HIV/AIDS Care and Treatment in Tanzania: The Effects of Parasites Co-Infections, HIV Clinical Manifestations, and Adherence to Antiretroviral Therapy

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    In Tanzania, the National AIDS Control Program with the support of Non-Government Organizations is scaling-up Antiretroviral Therapy (ART) services to peripheral (rural) health facilities. The aim of scaling-up is to improve availability, access and adherence to ART by all HIV-infected population. HIV-infected persons in peripheral (rural) areas are at increased risk for several medical co-morbidities including tuberculosis, bacterial and parasitic infections. As ART is successfully made universally available, non-AIDS co-morbidities caused by helminths and malaria will emerge as leading problems that will complicate care, adherence to ART and retention. These challenges can be improved by comprehensive and multidisciplinary management strategies. In addition a range of interventions such as counselling, use of treatment assistants and integrated health services delivery need to be enhanced to improve adherence and treatment of co-morbidities. However, concerns are raised regarding proper HIV/AIDS management in the peripheral (rural) settings which focuses on clinical monitoring and treatment of opportunistic infections. Clinical monitoring is based on WHO clinical stages and CD4+ T-lymphocyte counts. Clinicians in the peripheral (rural) settings faces challenges in accessing CD4+ T-lymphocyte counts, HIV and AIDS clinical features not corresponding with WHO clinical stages, co-infections and co-morbidity. The aim of the work reported in this thesis was to conduct research to investigate effects of concurrent parasites infections and challenges of HIV/AIDS case management on peripheral (rural) patients in order to contribute information towards better care for HIV/AIDS patients in Tanzania. The studies were conducted at Tumbi Hospital and Chalinze Health Centre in Tanzania between April 2008 and June 2009. The research consisted of three sub-studies carried out consecutively utilizing different study designs and populations. The first study examined the effects of parasite co-infection on CD4+ T-lymphocyte counts, WHO clinical staging and haemoglobin. In addition, the study attempted to develop a simplified clinical staging by utilizing local experiences HIV/AIDS clinical manifestation. Adult patients registering for the first time at HIV-clinic were clinically examined for malaria parasites and helminths. CD4 counts and haemoglobin were also analyzed. Patients were initiated on treatments according to their respective diagnosis and followed up for six months. At 6 months, clinical procedures were performed similar to first contact assessment. The second study utilized a case-control design to elucidate factors associated with non-adherence to ART. Adult patients attending care and treatment at the study clinics and being on ART for at least three months were studied. Patients with ART adherence of less than 95%; and those with more than 95% were defined as cases and controls respectively. The third study was an observation study which documented experiences and lessons generated in the process of implementing ART services at Chalinze health centre. Clinical procedures were evaluated and document review was carried out to solicit patients’ characteristics and enrolment rates
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