High Prevalence of Cryptococcal Antigenemia among HIV-infected Patients Receiving Antiretroviral Therapy in Ethiopia

Background

Cryptococcal disease is estimated to be responsible for significant mortality in Sub-Saharan Africa; however, only scarce epidemiology data exists. We sought to evaluate the prevalence of and risk factors for cryptococcal antigenemia in Ethiopia.

Methods

Consecutive adult HIV-infected patients from two public HIV clinics in Addis Ababa, Ethiopia were enrolled into the study. A CD4 count ≤200 cells/μl was required for study participation. Patients receiving anti-retroviral therapy (ART) were not excluded. A cryptococcal antigen test was performed for all patients along with an interview, physical exam, and medical chart abstraction. Logistic regression analysis was used to assess risk factors for cryptococcal antigenemia.

Results

369 HIV-infected patients were enrolled; mean CD4 123 cells/μl and 74% receiving ART. The overall prevalence of cryptococcal antigenemia was 8.4%; 11% in patients with a CD4 count <100 cells/μl, 8.9% with CD4 100 to 150 cells/μl and 5.7% with CD4150-200 cell/μl. 84% of patients with cryptococcal antigenemia were receiving ART. In multivariable analysis, increasing age, self reported fever, CD4 count <100 cells/μl, and site of screening were associated with an increased risk of cryptococcal antigenemia. No individual or combination of clinical symptoms had optimal sensitivity or specificity for cryptococcal antigenemia.

Conclusion

Cryptococcal antigenemia is high in Ethiopia and rapid scale up of screening programs is needed. Screening should be implemented for HIV-infected patients with low CD4 counts regardless of symptoms or receipt of ART. Further study into the effect of location and environment on cryptococcal disease is warranted.     

Stigma against Tuberculosis Patients in Addis Ababa,Ethiopia

BackgroundStigma attached to tuberculosis contributes to the limited effectiveness of current TB control approaches. However, there is a dearth of studies that explore the causes of stigma attached to tuberculosis and its effects on patients and tuberculosiscontrol programs in Ethiopia.MethodsAn institution-based qualitative study was conducted at St. Peter Tuberculosis Specialized Hospital in Addis Ababa, Ethiopia from July to August, 2015. Ten in-depth interviews and 6 key-informant interviews were carried out among tuberculosis patients and healthcare workers, respectively.The Open Code computer software package was used to analyze the data thematically.ResultsThe study revealed that fear of infection and inappropriate health education messages by media were the main causes of tuberculosis stigma. The patients experienced isolation within their family and community, separation, and financial crisis. The stigma attached to tuberculosis may contribute to delayed healthcare seeking, poor treatment adherence, and poor prognosis.ConclusionInterventions thatreduce the stigma attached to tuberculosis should target on areas, such as creating community awareness, patient counseling on problem-solving and emotional skills, preparing culturally sensitive and scientifically sound media messages, providing financial support for the patients, and enhancing the qualities of the healthcare workers, such as empathy, concern, respect for the patient and cultural sensitivity.     

Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children

Background

In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6–36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth.

Methods

HIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions).

Results

In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures).

Conclusions

In this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.     

A Description of Mortality Associated with IPT plus ART Compared to ART Alone among HIV-Infected Individuals in Addis Ababa,Ethiopia: A Cohort Study

Background

Tuberculosis (TB) is the most common human immunodeficiency virus (HIV) associated opportunistic infection. It is the leading cause of death in HIV-infected individuals in sub-Saharan Africa. Anti-retroviral therapy (ART) and isoniazid preventive therapy (IPT) are the two useful TB preventative strategies available to reduce TB among people living with HIV (PLHIV). Therefore, the aim of this study is to compare mortality associated with IPT taken together with ART, as well as ART alone, among PLHIV.

Methods

A retrospective cohort study was undertaken at Tikur Anbessa Specialized Hospital (TASH) and Zewditu Memorial Hospital (ZMH) on 185 patients receiving IPT (6 months) plus ART and 557 patients receiving ART alone. Mortality rates (MR) per 100 person-years (PYs) were used to compare mortality rates amongst the groups. Time-to-death and survival probabilities of the patients were determined using the Kaplan Meier Method. The Cox Proportional Hazard Model was employed to estimate the effect of IPT plus ART on survival of PLHIV.

Results

The mortality cases noted in patients treated by IPT plus ART versus ART alone were 18 (4.5 cases/100 PYs) and 116 (10 cases/100 PYs), respectively. In reference to the ART alone, the IPT plus ART reduced the likelihood of death significantly (aHR 0.48; 95% CI 0.38–0.69) and median time to death was about 26 months (IQR 19–34). Moreover, WHO stage IV (aHR 2.42: 95% CI 1.42–4.11), CD4 values ≥350cells/mm3 (aHR 0.52; 95% CI 0.28–0.94), adherence to ART (aHR 0.12; 95% CI 0.08–0.20), primary levels of education (aHR 2.20; 95% CI 1.07–4.52); and alcohol consumption (aHR 1.71; 95% CI 1.04–2.81) were factors strongly associated with mortality.

Conclusion

We found that PLHIV treated by the IPT plus ART had a lower likelihood of mortality and delayed time-to-death when compared to patients treated by ART alone.     

Heavy Metal Concentration in the Urban Environment of Addis Ababa,Ethiopia

This work assesses the issue of whether the measured concentrations of heavy metals in soil, rocks, surface and ground waters in Addis Ababa can be related to anthropogenic contamination or natural weathering of rocks. Heavy metal analyses of rocks, soils, streams, springs and boreholes have been carried out to identify the presence of potentially harmful solutes. The maximum concentration of total chromium measured is 269 ppm in the northern, industry-free zone of Addis Ababa in the B ₂-horizon of soil profile (cambisol). The Ni/Cr ratio in the rocks is higher than soils, which could indicate the presence of high concentrations of Cr in soils is from weathering processes. A comparative study of different samples collected from various parts of the city indicates that the chemical composition of the hydrothermally affected volcanic rocks plays an important role in increasing heavy metal concentration in the study area. The fresh country rocks contain relatively low concentrations of heavy metals, as shown by background values. The statistical evaluation indicates that the hydrothermally altered rocks contain far higher mean heavy metal concentrations than the fresh acidic rocks (background values). Consequently, soils derived from altered rocks are enriched with respect to heavy metals. From this study it was possible to observe that the rock and soil outcrops of Addis Ababa are anomalously rich in heavy metals derived from hydrothermal activity. Therefore, heavy metal concentrations in the surrounding rocks and soils are related to geogenic sources whereas anthropogenic contribution as a cause of these concentrations is minor.     

Macroinvertebrate‐based bioassessment of rivers in Addis Ababa,Ethiopia

Chemical‐based studies have shown pollution of rivers in Addis Ababa, Ethiopia. However, as bioassessment is not a component of the river assessment and monitoring programmes, information on the ecological status of the rivers is limited. The study assessed the ecological status of the Little and Greater Akaki Rivers using macroinvertebrates. Macroinvertebrates were collected from twelve sites twice in the dry and wet seasons. There was abundance of few tolerant, collector‐gatherer taxa with a loss of most sensitive taxa that used to be part of the river systems. Macroinvertebrate communities from upper and lower reaches showed complete differentiation on the nonmetric multidimensional scaling (NMS) ordination graph with upstream reaches composed of relatively sensitive taxa while the lower reaches dominated by tolerant taxa. Multiresponse permutation procedure (MRPP) showed significant difference between the two reaches. Macroinvertebrate communities from the dry and wet seasons did not show differentiation on the NMS ordination graph and MRPP did not show significant difference. Both rivers scored low in the South African Scoring System (SASS 5) and ETHbios, indicating ecological degradation. The results suggest that several decades of environmental degradation might have led to impoverished regional species pool, consisting mainly tolerant and generalist taxa constant throughout the year.     

Investigation outcomes of tuberculosis suspects in the health centers of Addis Ababa, Ethiopia

Background

Little is known about the prevalence of tuberculosis (TB) and HIV among TB suspects in primary health care units in Ethiopia.

Methods

In the period of February to March, 2009, a cross sectional survey was done in 27 health centers of Addis Ababa to assess the prevalence of TB and HIV among TB suspects who have > = 2 weeks symptoms of TB such as cough, fever and weight loss. Diagnosis of TB and HIV was based on the national guidelines. Information concerning socio-demographic variables and knowledge of the respondents about TB was collected using pretested questionnaire.

Results

Of the 545 TB suspects, 506 (92.7%) of them participated in the study. The prevalence of both pulmonary and extra pulmonary TB was 46.0% (233/506). The smear positivity rate among pulmonary TB suspect was 21.3%. Of the TB suspects, 298 (58.9%) of them were tested for HIV and 27.2% (81/298) were HIV seropositive. Fifty percent of the HIV positive TB suspects had TB. TB suspects who had a contact history with a TB patient in the family were 9 times more likely to have TB than those who did not have a contact history, [OR = 9.1, (95%CI:4.0, 20.5)]. Individuals who had poor [OR = 5.2, (95%CI: 2.3, 11.2)] and fair knowledge [OR = 3.7, (95%CI: 1.3, 10.4)] about TB were more likely to have TB than individuals who had good knowledge.

Conclusion

In conclusion, the prevalence of TB among TB suspects with duration of 2 or more weeks is high. Fifty percent of the HIV positive TB suspects had TB. Case finding among TB suspects with duration of 2 or more weeks should be intensified particularly among those who have a contact history with a TB patient.     

Fertility decline driven by poverty: the case of Addis Ababa, Ethiopia

Demographic transition theory states that fertility declines in response to development, thus wealth and fertility are negatively correlated. Evolutionary theory, however, suggests a positive relationship between wealth and fertility. Fertility transition as a result of industrialization and economic development started in the late 19th and early 20th centuries in Western Europe; and it extended to some of the Asian and Latin American countries later on. However, economic crises since the 1980s have been co-incident with fertility decline in sub-Sahara Africa and other developing countries like Thailand, Nepal and Bangladesh in the last decade of the 20th century. A very low level of fertility is observed in Addis Ababa (TFR=1.9) where contraceptive prevalence rate is modest and recurrent famine as well as drought have been major causes of economic crisis in the country for more than three consecutive decades, which is surprising given the high rural fertility. Detailed socioeconomic and demographic characteristics of 2976 women of reproductive age (i.e. 15-49 years) residing in Addis Ababa were collected during the first quarter of 2003 using an event history calendar and individual women questionnaire. Controlling for the confounding effects of maternal birth cohort, education, marital status and accessible income level, the poor (those who have access to less than a dollar per day or 250 birr a month) were observed to elongate the timing of having first and second births, while relatively better-off women were found to have shorter birth intervals. Results were also the same among the ever-married women only model. More than 50% of women currently in their 20s are also predicted to fail to reproduce as most of the unmarried men and women are 'retreating from marriage' due to economic stress. Qualitative information collected through focus group discussions and in-depth interviews also supports the statistical findings that poverty is at the root of this collapse in fertility. Whilst across countries wealth and fertility have been negatively correlated, this study shows that within one uniform population the relationship is clearly positive.     

Drug-Resistant Tuberculosis among HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

Objective

To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa.

Design

Cross-sectional cohort study.

Methods

Consecutive HIV-infected adults (≥18y/o) initiating HIV care were enrolled from May 2007–May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed.

Results

1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42–150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0–12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9–30.5) compared to 5.2% (95% CI 2.1–8.9) among those with no prior TB. 5.1% (95% CI 2.4–9.5) had rifampin or rifampin plus INH resistance.

Conclusions

The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.     

Current Efavirenz (EFV) or Ritonavir-Boosted Lopinavir (LPV/r) Use Correlates with Elevate Markers of Atherosclerosis in HIV-Infected Subjects in Addis Ababa,Ethiopia

Background

HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD). Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa.

Methods

Adult HIV-negative (n = 36), treatment naïve (n = 51), efavirenz (EFV)-treated (n = 91), nevirapine (NVP)-treated (n = 95), or ritonavir-boosted lopinavir (LPV/r)-treated (n=44) subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Aortic pressure, augmentation pressure, and pulse wave velocity (PWV) were measured via applanation tonometry and carotid intima-media thickness (cIMT) and carotid arterial stiffness, and brachial artery flow-mediated dilation (FMD) were measured via non-invasive ultrasound. Body mass index, waist-to-hip circumference ratio (WHR), skinfold thickness, and self-reported fat redistribution were used to quantify lipodystrophy. CD4+ cell count, plasma HIV RNA levels, fasting glucose, total-, HDL-, and LDL-cholesterol, triglycerides, hsCRP, sVCAM-1, sICAM-1, leptin and complete blood count were measured.

Results

PWV and normalized cIMT were elevate and FMD impaired in EFV- and LPV/r-treated subjects compared to NVP-treated subjects; normalized cIMT was also elevated and FMD impaired in the EFV- and LPV/r-treated subjects compared to treatment-naïve subjects. cIMT was not statistically different across groups. Treated subjects exhibited elevated markers of dyslipidemia, inflammation, and lipodystrophy. PWV was associated with age, current EFV and LPV/r used, heart rate, blood pressure, triglycerides, LDL, and hsCRP, FMD with age, HIV duration, WHR, and glucose, and cIMT with age, current EFV use, skinfold thickness, and blood pressure.

Conclusions

Current EFV- or LPV/r-treatment, but not NVP-treatment, correlated with elevated markers of atherosclerosis, which may involve mechanisms distinct from traditional risk factors.     

CD4 Cell Count Trends after Commencement of Antiretroviral Therapy among HIV-Infected Patients in Tigray,Northern Ethiopia: A Retrospective Cross-Sectional Study

Background

The rate and extent of CD4 cell recovery varies widely among HIV-infected patients with different baseline CD4 cell count strata. The objective of the study was to assess trends in CD4 cell counts in HIV-infected patients after initiation of antiretroviral therapy in Tigray, Northern Ethiopia.

Methods

A retrospective cross-sectional study was conducted by reviewing medical records of HIV patients who received antiretroviral treatment at twenty health centers in Tigray region during 2008–2012. Multi-stage cluster sampling technique was employed to collect data, and the data were analyzed using SPSS version 20.0 software.

Results

The median change from baseline to the most recent CD4 cell count was +292 cells/μl. By 5 years, the overall median (inter-quartile range, IQR) CD4 cell count was 444(263-557) cells/μl while the median (IQR) CD4 cell count was 342(246-580) cells/μl among patients with baseline CD4 cell counts ≤200 cells/μl, 500(241-557) cells/μl among those with baseline CD4 cell counts of 201–350 cells/μl, and 652(537-767) cells/μl among those with baseline CD4 cell counts >350 cells/μl. Higher baseline CD4 cell counts and being male were independently associated with the risk of immunological non-response at 12 months. Furthermore, it was also investigated that these factors were significant predictors of subsequent CD4 cell recovery.

Conclusions

Patients with higher baseline CD4 cell stratum returned to normal CD4 Cell counts though they had an increased risk of immunological non-response at 12 months compared to those with the least baseline CD4 cell stratum. The findings suggest that consideration be given to initiation of HAART at a CD4 cell count >350 cells/μl to achieve better immune recovery, and to HIV-infected male patients to improve their health seeking behavior.     

Retention in HIV Care and Predictors of Attrition from Care among HIV-Infected Adults Receiving Combination Anti-Retroviral Therapy in Addis Ababa

Background

Patient retention in chronic HIV care is a major challenge following the rapid expansion of combination antiretroviral therapy (cART) in Ethiopia.

Objective

To describe the proportion of patients who are retained in HIV care and characterize predictors of attrition among HIV-infected adults receiving cART in Addis Ababa.

Method

A retrospective analysis was conducted among 836 treatment naïve patients, who started cART between May 2009 and April 2012. Patients were randomly selected from ten health-care facilities, and their current status in HIV care was determined based on routinely available data in the medical records. Patients lost to follow-up (LTFU) were traced by telephone. Kaplan-Meier technique was used to estimate survival probabilities of retention and Cox proportional hazards regression was performed to identify the predictors of attrition.

Results

Based on individual patient data from the medical records, nearly 80% (95%CI: 76.7, 82.1) of the patients were retained in care in the first 3 and half years of antiretroviral therapy. After successfully tracing more than half of the LTFU patients, the updated one year retention in care estimate became 86% (95% CI: 83.41%, 88.17%). In the multivariate Cox regression analyses, severe immune deficiency at enrolment in care/or at cART initiation and ‘bed-ridden’ or ‘ambulatory’ functional status at the start of cART predicted attrition.

Conclusion

Retention in HIV care in Addis Ababa is comparable with or even better than previous findings from other resource-limited as well as EU/USA settings. However, measures to detect and enroll patients in HIV care as early as possible are still necessary.     

Poor Clinical Outcomes among Pneumonia Patients with Depressive Disorder

Background

Some studies suggested that psychological stress may be associated with the severity and duration of infectious diseases. In this population-based study, we investigated associations between depressive disorder (DD) and pneumonia outcomes in Taiwan with a large-scale database from the National Health Insurance.

Methods

Our study defined 112,198 patients who were hospitalized with a principal diagnosis of pneumonia. We defined their admission date for treatment of pneumonia as the index date. Subsequently, we selected 2,394 patients with DD within 3 years prior to their index date and 11,970 matched patients without DD. We carried out separate conditional logistic regressions to explore the association of clinical pneumonia treatment outcome (ICU admission, use of mechanical ventilation, acute respiratory failure and in-hospital death) with previously diagnosed DD.

Results

Patients with DD had a significantly higher probability of an intensive care unit admission (18.1% vs. 12.9%; p<0.001), need for mechanical ventilation (21.9% vs. 18.1%; p<0.001) and in-hospital death (10.4% vs. 9.0%; p = 0.025) than patients without DD. The study showed that pneumonia patients with DD were respectively 1.41- (95% CI: 1.25∼1.59, p<0.001), 1.28- (95% CI: 1.14∼1.43, p<0.001), and 1.17- times (95% CI: 1.01∼1.36, p = 0.039) greater odds of being admitted to the ICU, need for mechanical ventilation, and in-hospital death than patients without DD after adjusting for monthly income, urbanization level, geographic region and Charlson Comorbidity Index score.

Conclusions

In conclusion, we found that pneumonia patients with DD were associated with poor treatment outcomes compared to patients without DD.     

High Mortality from Blood Stream Infection in Addis Ababa,Ethiopia, Is Due to Antimicrobial Resistance

Background

Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa.

Methods

Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co-resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time.

Results

Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38–25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3–164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3^rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3–4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32–7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole.

Conclusion

Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae-infected patients with isolates resistant to third generation cephalosporins. Strong and significant resistance covariation between 3^rd. generation cephalosporins, chloramphenicol, gentamicin, and co-trimoxazole was identified. Pronounced pancytopenia was common and associated with increased mortality. HIV positive patients had no excess mortality.     

Epidemiology of anti-tuberculosis drug resistance patterns and trends in tuberculosis referral hospital in Addis Ababa, Ethiopia

ABSTRACT: BACKGROUND: Drug-resistant TB has emerged as a major challenge facing TB prevention and control efforts. In Ethiopia, the extent/trend of drug resistance TB is not well known. The aim of this study was to determine the pattern and trend of resistance to first line anti-TB drugs among culture positive retreatment cases at St.Peter's TB Specialized Hospital. FINDINGS: A hospital based retrospective study was used to assess the pattern of anti-TB drug resistance among previously treated TB patients referred to St.Peter's TB Specialized Hospital from January 2004-December 2008 Gregorian calendar(GC) for better diagnosis and treatment. Among 376 culture positive for M. tuberculosis one hundred and two (27.1%) were susceptible to all of the four first line anti-TB drugs -Isoniazid (INH), Rifampicin (RIF), Ethambutol (ETB) & Streptomycin (STM). While 274 (72.9%) were resistant to at least one drug. Resistance to STM (67.3%) was found to be the most common and the prevalence of MDR-TB was 174 (46.3%). Trend in resistance rate among re-treatment cases from 2004 to 2008 showed a significant increase for any drug as well as for INH, RIF, and MDR resistance (P <0.05 for trend). CONCLUSIONS: There has been an increasing trend in drug resistance in recent years, particularly in retreatment cases. Therefore, establishing advanced diagnostic facilities for early detection of MDR-TB and expanding second line treatment center to treat MDR-TB patients and to prevent its transmission is recommended.     

Pharmacokinetics of Rifabutin in Japanese HIV-Infected Patients with or without Antiretroviral Therapy

Objective

Based on drug-drug interaction, dose reduction of rifabutin is recommended when co-administered with HIV protease inhibitors for human immunodeficiency virus (HIV)-associated mycobacterial infection. The aim of this study was to compare the pharmacokinetics of rifabutin administered at 300 mg/day alone to that at 150 mg every other day combined with lopinavir-ritonavir in Japanese patients with HIV/mycobacterium co-infection.

Methods

Plasma concentrations of rifabutin and its biologically active metabolite, 25-O-desacetyl rifabutin were measured in 16 cases with HIV-mycobacterial coinfection. Nine were treated with 300 mg/day rifabutin and 7 with 150 mg rifabutin every other day combined with lopinavir-ritonavir antiretroviral therapy (ART). Samples were collected at a median of 15 days (range, 5–63) of rifabutin use.

Results

The mean C_max and AUC_0–24 of rifabutin in patients on rifabutin 150 mg every other day were 36% and 26% lower than on 300 mg/day rifabutin, while the mean C_max and AUC_0–24 of 25–O-desacetyl rifabutin were 186% and 152% higher, respectively. The plasma concentrations of rifabutin plus its metabolite were similar between the groups within the first 24 hours, but it remained low during subsequent 24 to 48 hours under rifabutin 150 mg alternate day dosing.

Conclusion

Rifabutin dose of 150 mg every other day combined with lopinavir-ritonavir seems to be associated with lower exposure to rifabutin and its metabolite compared with rifabutin 300 mg/day alone in Japanese patients. Further studies are needed to establish the optimal rifabutin dose during ART. The results highlight the importance of monitoring rifabutin plasma concentration during ART.

Trial registration

UMIN-CTR (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=search&action=input&language=E) UMIN000001102     

Magnitude and Predictors of Anti-Retroviral Treatment (ART) Failure in Private Health Facilities in Addis Ababa,Ethiopia

BackgroundThe public health approach to antiretroviral treatment management encourages the public private partnership in resource limited countries like Ethiopia. As a result, some private health facilities are accredited to provide antiretroviral treatment free services. Evidence on magnitude and predictors of treatment failure are crucial for timely actions. However, there are few studies in this regard.ObjectiveTo assess the magnitude and predictors of ART failure in private health facilities in Addis Ababa, Ethiopia.MethodsThe study followed retrospective cohort design, with 525 adult antiretroviral treatment clients who started the treatment since October 2009 and have at least six months follow up until December 31, 2013. Kaplan Meier survival analysis and Cox proportional hazard model were used for analysis.ResultsTreatment failure, using the three WHO antiretroviral treatment failure criteria, was 19.8%. The immunologic, clinical, and virologic failures were 15%, 6.3% and 1.3% respectively. The mean and median survival times in months were 41.17 with 95% Confidence Interval (CI) [39.69, 42.64] and 49.00, 95% CI [47.71, 50.29] respectively. The multivariate cox regression analysis showed years since HIV diagnosis (Adjusted Hazard Ratio (AHR)=13.87 with 95% CI [6.65, 28.92]), disclosure (AHR=0.59, 95% CI [0.36, 0.96]), WHO stage at start (AHR=1.84, 95% CI [1.16, 2.93]), weight at baseline (AHR=0.58, 95% CI [0.38, 0.89]), and functionality status at last visit (AHR=2.57, 95% CI [1.59, 4.15]) were independent predictors of treatment failure.ConclusionThe study showed that the treatment failure is high among the study subjects. The predictors for antiretroviral treatment failure were years since HIV diagnosis, weight at start, WHO stage at start, status at last visit and disclosure.RecommendationsFacilities need to monitor antiretroviral treatment clients to avoid disease progression and drug resistance.     

Characteristics of Graves Disease in HIV-Infected Patients on Antiretroviral Therapy

ObjectiveTo demonstrate clinical and laboratory characteristics of Graves disease in human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART).MethodsThis is a single-institution study. All HIV-infected Thai patients who were diagnosed with Graves disease following the initiation of ART between January, 2007, and June, 2018, were retrospectively enrolled.ResultsOf the 24 subjects, the mean age was 39.6 ± 10 years at the time of Graves disease diagnosis. The male to female ratio was 1:1.2. Palpitation and weight loss were the most common clinical manifestations. Of the 6 patients (25%) with evidence of Graves orbitopathy, 1 had sight-threatening orbitopathy. Two patients also had other autoimmune diseases (vitiligo and psoriatic arthritis). The median CD4 cell counts at HIV and Graves disease diagnosis were 73.5 (interquartile range &lsqb;IQR], 15.5 to 189.5) and 525 (IQR, 402.3 to 725) cells/μL, respectively. The median time from ART commencement of the last effective ART regimen to the development of Graves disease was 29.5 (IQR, 13.8 to 48) months with a mean CD4 cell count increment of 328.7 ± 174.9 cells/μL. The median duration of antithyroid therapy was 34.5 (IQR, 23.8 to 51.0) months. Thirteen patients (54.2%) received radioactive iodine ablation.ConclusionGraves disease should be suspected in HIV-infected patients who present with palpitations and weight loss despite good immunologic response to ART. Awareness of this condition can lead to diagnosis and appropriate management. Unlike immune reconstitution disease associated with infection, Graves disease may develop many years after ART initiation.