The possibility of incorporating generics into combination antiretroviral therapy and breaking apart once-daily single-tablet regimens (STRs), may result in less efficacious medications and/or more complex regimens with the expectation of marked monetary savings. A modeling approach that assesses the merits of such policies in terms of lifelong costs and health outcomes using adherence and effectiveness data from real-world U.S. settings.A comprehensive computer-based microsimulation model was developed to assess the lifetime health  and economic outcomes in HIV-1 infected patients initiating STRs compared with multiple-table regimens including generic medications where possible (gMTRs). The STRs considered included tenofovir disoproxil fumarate/emtricitabine and efavirenz or rilpivirine or elvitegravir/cobicistat. gMTRs substitutions included each counterpart to STRs, including generic lamivudine for emtricitabine and generic versus branded efavirenz.Life expectancy is estimated to be 1.301 years higher (discounted 0.619 QALY gain) in HIV-1 patients initiating a single-tablet regimen in comparison to a generic-based multiple-table regimen. STRs were associated with an average increment of $26,547.43 per patient in medication and $1,824.09 in other medical costs due to longer survival which were partially offset by higher inpatients costs  with gMTRs treatment. Overall, STRs presented incremental lifetime costs of $16,335.91 compared with gMTRs, resulting in an incremental cost-effectiveness ratio of $26,383.82 per QALY gained.STRs continue to represent good value for money under contemporary cost-effectiveness thresholds despite substantial price reductions of generic medications in the U. S. Innovations in antiretroviral therapy (ART) have dramatically altered the natural history of HIV infection, transforming it into a manageable chronic disease . ART hasIncreasing life expectancy contribute to increased total lifetime costs of HIV care, posing challenges for funders despite annual costs of treating someone with HIV having remained fairly constant over the years . Many diAt first glance, these strategies seem appealing because they appear to present significant economic savings. Caution is warranted in interpreting these results, however, because some of these economic analyses are focused mainly on ART costs, ignoring other important costs such as inpatient and outpatient costs, or even wider economic societal implications, that may account for up to 45% of the total lifetime costs of HIV care –10. MoreThere is evidence that antiretroviral pill burden and treatment adherence are key determinants of the risk of hospitalization and inpatients costs , 12. PatAlso of concern is the justification of monetary savings being considered at the expense of potential health losses without adequately addressing the fact that societal value for a health loss is regarded to be substantially higher than the societal value for a health gain, i.e. monetary saving required to move from optimal to sub-optimal therapy are higher than the maximum willingness to pay for a health gain obtained by moving from lower to a higher health status .The present study includes a computer-based microsimulation model of HIV disease progression based on adherence and effectiveness data from real-world settings in the US to comprehensively assess the long-term health and economic outcomes of HIV infected patients initiating single-tablet regimens (STRs) compared with multiple-tablet regimens including generic medications when possible (gMTRs).In a simulation study two treatment strategies were considered for HIV-1 infected adult patients initiating first-line ART : a brandThe expected long-term, comparative economic and clinical impact of the proposed treatment strategies were analyzed using a microsimulation cost-effectiveness model for HIV treatment. Given the chronic and progressive nature of the disease, the model considered a lifetime time horizon. The economic impact was measured in terms of the expected total per-person cost to the U.S. health system, whereas the clinical impact or effectiveness was measured in terms of corresponding expected quality-adjusted life-years (QALY). Following U.S. recommendations, an annual 3% discount rate was applied to both costs and effectiveness. Deterministic sensitivity analysis was used to assess parameter uncertainty, where possible.At the core of the microsimulation model lies a state-transition model , in whicPatients enter the model in the “non-suppressed” state (transition 0), where they initiate first-line therapy. Within this state, a monthly probability of virologic suppression (VS), applied during the first 6 months of therapy, determines if and when a patient moves to the “suppressed” state, and can be considered a responder to therapy (transition 1). Patients in the “non-suppressed” state that do not achieve VS within the first 6 months of therapy move to the “non-suppressed” state of the subsequent therapy line at the next scheduled medical visit (transition 2).Once transitioned to the “suppressed” state, from the 7th month of therapy onwards, patients are subject to a monthly probability of virologic failure after suppression has been achieved (VF). Upon VF, patients move to the “rebound” state (transition 3), where they stay until the next scheduled medical visit, upon which they move to the “non-suppressed” state of the subsequent therapy line (transition 4).Irrespective of their state of virologic suppression, patients are continuously subject to a monthly probability of discontinuation due to reasons other than VF (transitions 5). Upon discontinuation while in the “suppressed” state, patients immediately transition to the “suppressed” state of the subsequent therapy line. For the remaining non-virologically suppressed states, patients transition to the “non-suppressed” state of the subsequent therapy line. Finally, patients are also continuously subject to a monthly probability of death  and first-line treatment strategy (STR vs. gMTR) dependent adherence levels. Every patient is simulated under both an STR and a gMTR first-line strategy . Differential adherence between STRs and gMTRs is assumed to influence virologic response for first-line therapy only. Subsequent therapy lines are the same for all patients, irrespective of first-line STR or gMTR strategy. At each monthly cycle, the characteristics associated with each patient, including age, HIV-1 RNA viral load, CD4+ T cell count, quality of life (QoL), and health care and drug costs, are tracked and updated. An influence diagram relating the different model components can be found in 3  , present3 . Mean ag3  7]..3  phase II or III randomized clinical trials, with preference to phase III studies; 2) patient characteristics in terms of the number of previous therapy lines that best fitted the therapy line in question; 3) follow-up data in at least two points in time, with preference for the most recent studies with more available time-points and longer follow-up .First-line gMTR, EFV+TDF+3TC has been studied in clinical trial setting in Study 903 , 24 and The first-line therapy virologic suppression and failure probabilities presented in Monthly probabilities for discontinuation due to other reasons were determined from the clinical trials used for the calibration of virologic response probabilities, considering discontinuations for all reasons (including adverse events) except virologic failure (lack of efficacy) and death .Monthly probabilities of death were determined by multiplying CD4+ T cell count dependent standardized mortality ratios (SMR) to gender and age specific base mortality rates reported by the Center for Disease Control and Prevention (CDC) national vital statistics  38]..38].While in the “suppressed” state , patient3 and by an annual rate of 0.17 otherwise [For patients in the “rebound” state, viral load is reset to the highest level ever observed since treatment initiation (≥ 50 RNA cps/mL), after which it keeps increasing on a log10 scale, by an annual rate of 0.11 while CD4+ T cell counts are greater than or equal to 200 cells/mmtherwise . CD4+ T therwise .For patients in the “non-suppressed” state that will never suppress, viral load and CD4+ T cell count evolution is equivalent to that of patients in the “rebound” state. For the remaining patients, viral load and CD4+ T cell count are equivalent to the evolution discussed for patients in the “suppressed” state.Costs accounted for in the model include ART costs, hospitalizations (inpatient) costs, and other medical expenses . All cost, 2015; Unit ART costs were based on data from First Databank,   and are The model simulated 200,000 hypothetical individuals initiating ART  using real-world evidence. All results represent the averages of each group of hypothetical individuals (STR vs. gMTR) and are discounted at 3.0% per annum.After incorporating real-world evidence, over the lifetime of a patient an additional discounted 0.619 QALYs (14.466 vs. 13.847) were estimated to be gained with STRs compared with gMTRs . Single-Undiscounted life expectancy after ART initiation was estimated to be 22.4 years for STR and 21.1 years, with a benefit of 1.3 years in favor of the STR treatment. The undiscounted QALY gain for STR over gMTR was 1.3 QALY for a marginal lifetime cost of $41,188.85 resulting in an undiscounted ICER of $31,910.87 per QALY gained.A deterministic sensitivity analysis was conducted to determine the factors that had the greatest influence on the ICER. The range of variation to each parameter is described in the As shown in the Tornado diagram, the ICER increased when baseline CD4 cell count, gEFV price discount, percentage of patients suppressed at 48 weeks for EFV-based gMTR and odds ratio of ≥95% adherence are assumed higher than in the base case. The opposite is true for a higher percentage decrease in hospitalizations on STR vs. MTR, higher standardized mortality ratios and higher quality of life utilities.th-line therapy, a successive sequence of further therapy lines with efficacy, safety and cost parameterization equal to that of the 6th-line, results in a dominant scenario for STR as compared to gMTR: an increase of 0.49 discounted QALY, accompanied by $14,348 in discounted total cost savings.Considering second-line therapy effectiveness equal to that considered in Walensky et al. (2013)  decreaseThe cost-effectiveness results were most sensitive to baseline CD4+ T cell count, generic EFV price (% discount from branded EFV price) and 48 weeks virologic suppression rates for EFV-based gMTR. Sensitivity analysis to the values of other variables like the odds ratio of ≥95% adherence between STR and MTR, hospitalizations rates, second line-treatment effectiveness, standardized mortality ratios, quality of life utilities and costs revealed minor uncertainty in the range of 2% to 12% relative to baseline ICER.3 to 500–1000 cells/mm3, respectively.The assumption about the value of baseline CD4 count had the most impact in the variability of the ICER of STR over gMTR . It rangThe base case analysis already incorporated a substantial discount of 75% on the price of generic relative to branded efavirenz. Varying the price generic efavirenz up to a 95% discount was associated with a maximum ICER of $31,421/QALY . This vaIn this study we introduce a comprehensive model to assess the lifetime health and economic outcomes of HIV infected patients initiating STRs compared with MTRs including generic medications where possible. STRs considered are those composed of TDF/FTC and efavirenz or rilpivirine or elvitegravir/cobicistat. MTRs considered included the counterparts to STRs substituting emtricitabine by generic lamivudine (g3TC) and branded efavirenz by the generic. The underlying motivation was to understand the value for money of branded STRs in comparison to MTRs composed of generic medications available in the U.S. market.It is estimated that initial treatment for HIV infection with STRs would result in an enhanced life expectancy of 1.3 years (undiscounted) in comparison to use gMTRs. Lifetime health care costs are estimated to be higher with STR and partially offset by higher inpatients costs expected with gMTR treatment. We estimate a mean increment of $16,336 in lifetime health care costs with STR treatment over gMTR corresponding into an incremental cost of $26,384 per QALY. A sensitivity analysis to the key parameters of the model showed low level of uncertainty with ICER ranging from $13,790 to $33,211 per QALY.Our estimates of discounted lifetime medical costs of $547,540 in HIV-infected individuals starting up-to-date STRs are comparable with other recently published model based estimates  using a similar set of assumptions in patients initiating standard of care . Also, mOur study is subject to some limitations. The gMTR comparator in our study includes generic efavirenz and lamivudine in substitution of branded efavirenz and emtricitabine of EFV/TDF/FTC, RPV/TDF/FTC and EVG/COBI/TDF/FTC single-tablet regimens. In the literature, no direct evidence was found comparing these STRs and an MTR of RPV or EVG/COBI. In this case a simplifying assumption was made assuming the same relative measure of efficacy and safety between gEFV+TDF+g3TC and EFV/TDF/FTC (Study GS-236-102 and Study 903) , 23, 24,Although the gMTR comparators are not recommended options by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents , as the Reported efficacy was assumed valid irrespective of the high levels of adherence observed and different measurement techniques used in studies GS-236-102 and 903. In first- and subsequent-line therapies no pooling of efficacy and safety data was performed if different studies were identified reporting on the same ART regimen. Virologic failure probabilities calibrated on our study are relatively low as compared to virologic failure probabilities of other first- and subsequent-line regimens. This can be expected to influence the average time spent in first-line therapy and in consequence, lifetime results.Because little is known about the adherence-effectiveness relationship in integrase inhibitor (INI) based regimens for modeling purpose this relationship was based on results of populations mainly treated with EFV-based therapy (>60%) and variable NRTI-backbones , 49. DifThe STR associated benefit on adherence over MTR is based on Sweet et al. 2014)  and Sax   and SaxPatients discontinuing sixth-line therapy due to virologic failure or other reasons move to a seventh-line, where they are modelled as being in an ART-free non-suppressive state, with HIV-1 RNA viral load levels increasing from their highest value ever observed, and CD4+ T cell counts decreasing from their lowest value ever observed, until death. One might question the assumption used to model this seventh-line, in that it is not clear if patients failing multiple therapy-lines in reality move to an ART-free state. Furthermore, depending on the average time spent in previous therapy-lines and age reached when entering this seventh-line, its influence on overall results might be larger than intended. This was dealt with in a sensitivity analysis, assuming a successive sequence of further therapy lines with efficacy, safety and cost parameterization equal to that of the sixth-line therapy.Due to the computational expensiveness of the model, traditional probabilistic sensitivity analysis through a large number of model runs at different random input values was deemed unfeasible. Solutions to this problem have been suggested in the literature, a common one of which is through regression meta-modelling . The appConsistent with other model estimates , 53 and Most notably, real-word evidence suggests cost-savings in HIV-infected patients starting ART with STR in addition to health gains , 54, 56.In contrast to this evidence and to our results is the study by Walensky et al. (2013) estimating that the incremental cost-effectiveness for first-line branded STR in United States is over $100,000/QALY relative to gMTR. The authors suggest that starting or switching to generic based regimens would initially yield annual savings approaching $1 billion for programs that fund HIV treatment in the United States, at the expense of a slightly less effective generic alternative (1 QALY loss per patient). But because non-medication costs and the costs for other medications were not included, and adherence to ART was not explicitly modeled, we anticipate that these results may be subject to a high degree of uncertainty and potentially underestimate the total costs associated with gMTR. In fact, breaking down once-daily fixed-dose ART into their single components and switching emtricitabine by less efficacious lamivudine  may leadUnder these circumstances, until a once-a-day STR generic version is available it is likely that current gMTR possibilities may still be unattractive under contemporary cost-effectiveness thresholds  , and mayIt should be noted that at the time of analysis in the U.S. no generic fixed dosed combinations (FDCs) were marketed yet. The current analysis is only applicable to scenarios where switching from an STR to generics means a therapy complication. In countries where generic FDCs are available, differences between generic and non-generic STRs will mainly be due to costs differences between both.In conclusion, our modeled analysis demonstrates that STRs provided to HIV-1-infected treatment-naive individuals is cost-effective compared with gMTRs. We hope the findings from this study will provide further insight and help guide decisions.S1 Table(DOCX)Click here for additional data file.


Tenofovir (TDF) has replaced stavudine (d4T) as the preferred nucleoside reverse transcriptase inhibitor (NRTI) in first-line regimens in South Africa, but limited information is available on the resistance patterns that develop after the introduction of TDF. This study investigated the antiretroviral drug resistance patterns in South African HIV-1 subtype C-infected patients failing stavudine- (d4T) and tenofovir- (TDF) based first-line regimens and assess the suitability of TDF as the preferred first-line nucleotide reverse transcriptase inhibitor (NRTI).pol gene was sequenced using an in-house protocol and mutations were analysed using the IAS-USA 2014 Drug Resistance Mutation list.Resistance patterns of HIV-1 from 160 adult patients virologically failing TDF- (n = 80) and d4T- (n = 80) based first-line regimens were retrospectively analyzed. The Compared to d4T-exposed patients (n = 7), patients failing on a TDF-containing regimen (n = 43) were almost 5 times more likely to present with a K65R mutation (aRR 4.86 95% CI 2.29 – 10.34). Y115F was absent in the d4T group, and detected in 13.8% (n = 11) of TDF-exposed patients, p = 0.0007. Virus from 9 of the 11 patients (82.0%) who developed the Y115F mutation also developed K65R. Intermediate or high-level resistance to most NRTIs was common in the TDF-treatment group, but these patients twice more likely to remain susceptible to AZT as compared to those exposed to d4T (aRR 2.09 95% CI 1.13 – 3.90).The frequency of the TDF induced K65R mutation was higher in our setting compared to non-subtype C dominated countries. However, despite the higher frequency of cross-resistance to NRTIs, most patients remained susceptible to AZT, which is reflected in the South African treatment guidelines that recommend AZT as an essential component of second-line regimens. At the end of 2012 there were approximately 2.1 million people in South Africa on antiretroviral treatment (ART) , resultiBefore 2010, the widely used first-line regimen in South Africa consisted of stavudine (d4T) and lamivudine (3TC) in combination with efavirenz (EFV) or nevirapine (NVP) . Due to nd line regimens.This retrospective study compares HIV-1 antiretroviral drug resistance patterns in patients failing d4T- and TDF-based first-line regimens, assesses the suitability of TDF as the preferred first-line NRTI, and evaluates the impact of these resistance patterns on subsequent 2HIV drug resistance results obtained between January 2010 and August 2012 from adult patients failing ART were retrieved from the database at the HIV Genotyping Laboratory at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), South Africa. Only patients on d4T- (n = 80) or TDF-based (n = 80) first-line regimens with at least one resistance mutation were randomly selected and included in this study. Demographic and clinical data collected from laboratory request forms or the laboratory information system (LIS) included age, gender, viral load, CD4 cell count, antiretroviral drug treatment regimen and duration on failing treatment.reverse transcriptase and protease regions of the virus were amplified using an in-house resistance testing assay as previously described [Viral RNA was extracted from 500μl of plasma using the automated EasyMag system  according to manufacturer’s instructions. The escribed ,12. Sampescribed . The resescribed . Mega veescribed  was usedpol nucleotide sequences were submitted to GenBank using Sequin v9.50 (www.ncbi.nlm.nih.gov/Sequin) and are available under accession numbers KM115717 to KM115876.The GraphPad software  was used to perform Fischer’s exact test. A p-value of <0.05 was considered statistically significant. Log-binomial regression analysis was used to test the association between different mutations and NRTI (TDF vs. d4T) or NNRT (EFV vs. NVP) pressure. The relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated. Mutations identified as being significantly associated with drug pressure in the univariate analysis (p<0.2) and priori variables of importance were included in multivariate models. Models were adjusted (aRR) for CD4 count, viral load and time on ART where possible, which is limited by the number of observations in each cell after stratification.This study was conducted with Ethical clearance by the Research on Human Subjects  Committee at the University of the Witwatersrand (Clearance Number M120730). Due to the retrospective nature of this study, no informed consent was obtained from the patients. This is in line with the Research on Human Subjects  Committee policy which states informed consent is not required for this type of study and a waiver was hence granted.One hundred and sixty (n = 160) sequences were included for analysis. These sequences were obtained from patients failing d4T+3TC+EFV/NVP (n = 80) and patients failing TDF+3TC+EFV/NVP (n = 80). HIV-1 subtype C was the dominant subtype , with only one patient being infected with an unassigned subtype (0.6%) The median age of patients was 36 years, (range: 16–62) and most patients were female . The median time on the failing treatment was 38 months (range: 0.5–95 months) for the patients exposed to d4T and 12 months (range: 0.5–50 months) for the TDF-exposed patients (p<0.0001). The patient demographics and clinical characteristics are summarized in The most common NRTI mutation in both the d4T- and TDF-exposed patients was M184V/I , with M184V as the predominant mutation . The K70At least one Thymidine Analogue Mutation (TAM) was detected in 27.5% (n = 22) of the patients exposed to TDF and 31.3% (n = 25) of the d4T-exposed patients . The accThe K103N mutation was the most common non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation. This mutation was more common in the EFV group  compared to the NVP group , (aRR 1.43 95% CI 1.02–2.01) , Table 2The antiretroviral drug resistance profiles observed in both groups are depicted in High-level resistance to etravirine (ETR) was observed in low numbers in both the TDF and d4T treatment groups. Only 8.8% (n = 7) of the d4T-exposed patients and 12.5% (n = 10) of the TDF patients presented with high-level resistance to ETR. Almost one in four from the d4T-exposed group  and 1 in three patients in the TDF-exposed group  presented with high-level resistance to RPV. Intermediate resistance to ETR and RPV was observed in 60.0% (n = 48) and 47.5% (n = 38) of the TDF-treated patients and 42.5% (n = 34) and 43.8% (n = 35) of the d4T-exposed patients.In recent years, South Africa has shown significant progress in initiating HIV-infected patients on ART. However, like other African countries, South Africa has a limited number of antiretroviral drug options available; therefore it is necessary to monitor the HIV-1 drug resistance patterns that develop under the current treatment regimens, and to assess the suitability of available second line regimens. In this respect the antiretroviral drug resistance profiles among d4T-treated patients were compared with the resistance patterns developed under TDF pressure.Since TDF is a recent addition to South African ART guidelines, the finding that duration of treatment was significantly longer in the d4T group, when compared to the TDF group, was an expected one. Although the development of TAMs has been associated with prolonged treatment failure , no assoIn vitro experiments with TDF-3TC exposure showed that Y115F is commonly selected after the development of K65R [nd-line regimen.Y115F was absent in the d4T-exposed patients and detected in 13.8% of the TDF-exposed patients, which confirms the findings of a recent South African study , however of K65R , which i of K65R  whereas  of K65R , highlig of K65R . HoweverOur data shows that fewer TDF-exposed patients remained fully susceptible to the second generation NNRTIs ETR and RPV as compared to those patients exposed to d4T-regimens. Nonetheless, in less than 13.0% of the TDF-exposed patients, high-level resistance to these second-generation NNTRIs was detected.This study had certain limitations, namely the fact that it was a retrospective analysis of routine laboratory data with limited clinical data and, occasionally, incomplete antiretroviral treatment history. In some cases this may have led to incorrect categorization of the patients with regards to their ART exposure. In the absence of national HIV-1 drug resistance testing guidelines, the dataset may be biased towards sampling patients under the care of clinicians reliant on HIV-1 drug resistance testing for clinical management and may not provide a proportional representation of patients failing ART in South Africa.st- and 2nd- line treatment in South Africa, was more frequently observed after TDF-exposure compared to d4T-exposure. Despite the NRTI cross-resistance caused by K65R, most patients remained susceptible to AZT regardless of d4T or TDF-exposure. This is reflected in the South African treatment guidelines, which recommend AZT as an essential component of 2nd line regimens [Overall, these results demonstrate that the frequency of the K65R mutation is higher in South African HIV-1 subtype C infected patients when compared to other countries where non-subtype C viruses dominate the epidemic. High-level resistance to NRTIs, which are the backbone of 1regimens . Based o


We designed a randomized, controlled prospective study aimed at comparing efficacy and tolerability of ezetimibe+fenofibrate treatment versus pravastatin monotherapy in dyslipidemic HIV-positive (HIV+) patients treated with protease inhibitors (PIs).We consecutively enrolled 42 HIV+ dyslipidemic patients on stable PIs therapy (LDL cholesterol >130 mg/dl or triglycerides 200–500 mg/dl with non-HDL cholesterol >160 mg/dl). After basal evaluation, patients were randomized to a six-month treatment with ezetimibe 10 mg/day+fenofibrate 200 mg/day or with pravastatin 40 mg/day. Both at the basal evaluation and after the six-month treatment, the patients underwent blood tests for lipid parameters, and muscle and liver enzymes.p<0.01) in both groups. high-density lipoprotein (HDL) cholesterol increased  and triglycerides decreased  in the ezetimibe+fenofibrate group, whereas both parameters remained unchanged in the pravastatin group. Mean values of creatine kinase (CK), alanine aminotransferase and aspartate aminotransferase were unchanged in both groups; only one patient in the pravastatin group stopped the treatment after two months, due to increased CK.At baseline, the two groups (21 patients each) were similar with regards to gender, age, BMI, blood pressure and virologic and metabolic parameters. After the six-month therapy, total cholesterol, LDL cholesterol and non-HDL cholesterol decreased significantly (In dyslipidemic HIV+ patients on PI therapy, the association of ezetimibe+fenofibrate is more effective than pravastatin monotherapy in improving lipid profile and is also well tolerated. The introduction of highly active antiretroviral therapy (HAART) has fundamentally changed the natural history of HIV disease, leading to a significant increase in life expectancy. However, a wide range of metabolic alterations has been found with increased frequency in HIV-positive (HIV+) patients treated with HAART, especially during therapy with protease inhibitors (PIs). These abnormalities mainly involve lipids  cholesterol, low levels of high-density lipoprotein (HDL) cholesterol) and glucose metabolism  –6 and plThe following approach has been outlined for the treatment of dyslipidemia in HIV+ patients : statin Ezetimibe is a lipid-lowering agent that inhibits the intestinal absorption of cholesterol  and is cStarting from these data, we decided to evaluate whether ezetimibe+fibrate can be a useful and safe alternative to statin monotherapy in dyslipidemic HIV+ patients treated with PIs. To this aim, we designed a randomized, controlled, prospective, open pilot study, comparing the lipid-lowering efficacy and the tolerability of a six-month treatment with ezetimibe+fenofibrate versus pravastatin monotherapy.Among the HIV+ patients referred to our outpatients’ clinic of Infectious Diseases, we consecutively enrolled HIV+ adults (age>18 years) with the following characteristics: stable therapy with PIs for at least 12 months, LDL cholesterol >130 mg/dl or triglycerides 200–500 mg/dl with non-HDL cholesterol >160 mg/dl, unresponsive to diet and regular physical exercise for at least three months.Exclusion criteria were as follows: history of dyslipidemia before antiretroviral therapy, history of cardiovascular and/or cerebrovascular diseases, Cushing's syndrome, hypothyroidism, type 1 or type 2 diabetes mellitus, renal failure, previous or current therapy with lipid-lowering agents, antihypertensive drugs or oestrogens, current abuse of drugs and/or alcohol.2).Following these criteria, we enrolled 42 patients  and blood tests for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CK), serum creatinine, fasting glucose, fasting insulin, high-sensitivity C-reactive protein (hsCRP), CD4+ count and viral load.The patients were then randomized to a six-month treatment with ezetimibe 10 mg/day+fenofibrate 200 mg/day or with pravastatin 40 mg/day.Throughout the treatment, patients underwent monthly visits, with clinical evaluation and blood tests for plasma creatinine, CK, ALT and AST.After six months, the patients underwent the last evaluation with blood tests for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, CK, ALT, AST, serum creatinine, fasting glucose, fasting insulin, hsCRP, CD4+ count and viral load .LDL cholesterol was measured directly on serum. HOMA index, a parameter of insulin resistance, was calculated as fasting plasma insulin (pmol/l)×fasting plasma glucose (mmol/l)/22.5 . Insulinif ALT and/or AST were ≥3 times the upper normal limit (confirmed by a second test within seven days), the patient was excluded from the study;if CK was ≥5 times the upper normal limit (confirmed by a second test within seven days) with or without myalgia, muscle weakness and/or cramps, the patient was excluded from the study.At each visit:compare mean basal and six-month values between the two groupsevaluate the effects of the two treatments (ezetimibe+fenofibrate vs. pravastatin) on metabolic parameters.The statistical evaluation of the results was carried out using 2 (between two treatment groups) by 2  analysis of variance (ANOVA), followed by the test of Scheffé, in order to:2 test.The distribution of PIs and NRTIs in the two groups was compared by means of χThe data are expressed as mean±SD; a probability value <0.05 was considered statistically significant.3) in 39 patients (95%), only two patients in the pravastatin group had detectable viral load (one patient 130 copies/mm3 and the other 100 copies/mm3).At the basal evaluation, the two groups were not significantly different with regard to gender , age , body mass index , clinic Mean values of all the metabolic parameters were not significantly different between the two groups .At the two-month visit, one patient treated with pravastatin stopped the treatment because of increased CK level (two blood tests one week apart); CK level returned within the normal limit after three weeks.. Body weight and diet also did not change.All the other 41 patients completed the six-month treatment; HAART therapy remained unchanged in all patients during the studyAfter the therapy, mean values of body mass index, serum creatinine, fasting glucose, HOMA index, ALT, AST, CK, CD4+ count  and virap<0.05) and non-HDL cholesterol  were significantly greater in the ezetimibe+fenofibrate group, whereas the extent of mean percentage LDL reduction  was similar between the two groups.Total cholesterol, LDL cholesterol and non-HDL cholesterol decreased significantly in both groups ; mean peHDL cholesterol increased and triglycerides decreased significantly in the ezetimibe+fenofibrate group, whereas both parameters remained unchanged in the pravastatin group .ANOVA (2×2 factors) showed a significant treatment effect of ezetimibe+fenofibrate on lipid parameters .To our knowledge, this is the first study testing efficacy and feasibility of a new therapeutic strategy for dyslipidemia in HIV+ patients on HAART therapy. Our results show that a six-month treatment with ezetimibe+fenofibrate is well tolerated and is as effective as pravastatin in reducing LDL cholesterol, while being also able to reduce triglycerides and to increase HDL cholesterol, both instead unchanged with pravastatin monotherapy.Since we wanted to compare the effects of the two treatments on lipid profile and on liver and muscle enzymes, we tried to avoid possible confounding factors by selecting patients with normal lipid profile before HAART treatment, on stable therapy with boosted PIs for at least 12 months and with at least three months of diet and physical exercise ineffective on dyslipidemia. In order to avoid any influence on lipid profile, we excluded patients with previous or on-going treatment with antihypertensive drugs, statins or oestrogens; we also excluded subjects with current alcohol and/or drug abuse, both able to modify liver and muscle enzymes. We decided that blinded treatment was not necessary since the placebo effect was in our opinion negligible with regards to the parameters evaluated in the study. Finally, we did not rely on the Friedewald equation to calculate LDL level, but we chose to measure directly LDL cholesterol on serum.Patients were selected based on the 2003 guidelines which suggest pharmacological treatment of dyslipidemia in HIV+ patients when LDL cholesterol is >130 mg/dl or triglycerides level is between 200 and 500 mg/dl with non-HDL cholesterol >160 mg/dl. For these lipid levels, the guidelines suggest statin monotherapy. We opted for pravastatin because, while its antidyslipidemic efficacy is lower than other statins, it is well tolerated in HIV+ subjects and it does not significantly interact with anti-retroviral drugs since it is not metabolized by cytochrome P450 CYP3A4 .Due to the difficulties in reaching lipid goals in HIV+ patients, therapeutics options other than statin monotherapy have to be taken into consideration. In clinical practice, fibrates are added to statin therapy when triglycerides are very high or, more often, when statin monotherapy fails to achieve target lipid goals. The fibrate+statin combination is included in the guidelines for the general population and also for HIV+ patients, but this treatment needs to be closely monitored because of the increased risk of side effects. The risk is even more relevant in HIV+ patients on HAART due to the known greater incidence of liver and muscle damages in such patients . TherefoIn our prospective, randomized, controlled study, ezetimibe+fibrate treatment induced a decrease of LDL cholesterol similar to that observed in pravastatin monotherapy; this is in agreement with a limited sample of data in HIV+ patients showing that ezetimibe monotherapy is as effective as pravastatin in decreasing LDL cholesterol ,25. The With regards to the evaluation of our results, we want to underline that HAART, body weight and diet, which are all possible confounding factors, remained unchanged in all the patients.Both treatments did not significantly influence insulin sensitivity as HOMA index was unchanged after the six-month therapy. It is interesting to note that basal mean value of HOMA index was above the upper normal limit (>2.5)  in both With regards to systemic inflammation, basal mean values of hsCRP were similar between the two groups and showed a non-statistically significant decrease in both groups as well. It should however be noted that the extent of CRP reduction was greater in the pravastatin arm than in the ezetimibe+fenofibrate arm. The anti-inflammatory effect of statin is well known; hence, it cannot be excluded that a similar study on a larger number of patients would show a significantly different trend of CRP in the two treatment groups.With regards to the possible side effects of the two lipid-lowering treatments, mean levels of liver enzymes and CK remained unchanged in both groups; only one patient treated with pravastatin had to stop therapy after two months because of very high levels of CK that returned within the normal limits after three weeks from the discontinuation of the treatment.The main limitation of our study is the small number of patients enrolled, which is due to the restrictive selection criteria employed. However, we believe that the finding of statistically significant differences between the two treatments in a small number of subjects makes the results of our study even more interesting. After the beginning of our study, other statins that are more potent than pravastatin and without clinically significant interactions became available (e.g. rosuvastatin); it is possible that our results would be different if the comparison were to be made with one of the new statins. Finally, this study was designed to compare the two treatments’ effects on biochemical endpoints; hence, our analysis cannot give insights about the effectiveness of the treatments in reducing cardiovascular diseases; this endpoint would require a different, multi-year study on a much larger number of patients.In HIV+ patients on HAART, it is essential to implement therapies, such as treatment of dyslipidemia, aimed at reducing cardiovascular risk. Our pilot study shows that in these patients the association of ezetimibe+fenofibrate is more effective than pravastatin monotherapy in improving lipid profile and is also well tolerated.


Targeted viral load (VL) strategy is followed in the ART programme of India. Patients failing antiretroviral therapy, undergo VL testing and switched to 2ndline ART if VL is >5000 copies/ml.Data of patients referred to School of Tropical Medicine, Kolkata for suspected treatment failure (TF) was analyzed for the period of December2008 to November2013 to ascertain the positive predictive value (PPV) of immunologic and/or clinical parameter for confirming virologic failure (VF) and to observe the short term outcome of secondline treatment. Paired t- test was used for data analysis.3 at suspected TF. Number of patients failing by immunologic, clinical and clinicoimmunologic criteria was 414(74%), 11(2%) & 135(24%) respectively with corresponding PPV of 48%, 46% & 63% respectively. PPV of CD4 falling below baseline, >50% drop from on-treatment peak value and failure to reach 100 cells/mm3 after 12 months of ART was 37%, 55% and 25% respectively. Among 216 patients with minimum 6 months follow-up, the median CD4 & VL changed significantly following 6 months of secondline ART . Undetectable VL was achieved in 164(76%). Out of 284 patients starting secondline ART, 25 (8.8%) died within 6 months.VF was noted in 287(51.3%) of 560 patients ; median CD4 109 cells/mmImmunoclinical criteria have low PPV in diagnosing VF. Despite late switch, majority (76%) could achieve undetectable VL at 6 months but the high early mortality (8.8%) is a concern.


Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.Among 76 participants, higher baseline IDO activity was associated with lower CD4IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO. Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that catalyzes the initial rate-limiting step in Trp catabolism, leading to the production of immunoregulatory catabolites (collectively known as kynurenines [Kyn]) However, IDO has now been deemed as an immune mediator in HIV pathogenesis. The IDO gene promoter contains multiple sequence elements that are responsive to proinflammatory mediators In the pre-antiretroviral therapy era, high IDO activity had been documented in untreated HIV infection and associated with disease progression HIV-infected patients naïve to therapy (n = 76) and healthy controls (n = 16) were enrolled at Shanghai Public Health Clinical Center. HIV-infected patients with opportunistic infections were excluded in order to avoid the influence of other pathogens. Ethical approval was granted by the Ethics Committee of Shanghai Public Health Clinical Center. Written informed consent was obtained from each subject. Clinical data and blood samples from patients were collected. Whole blood samples (5 mL) were obtained from all subjects and plasma samples were collected for the quantification of Trp and Kyn concentrations, as well as soluble CD14 (sCD14) levels. An additional 5 mL whole blood sample was obtained from a random subset of patients naïve to therapy (n = 21) and from all healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and stained for myeloid DC (mDC) and plasmacytoid DC (pDC) markers using the following methods.Plasma samples were heat-inactivated and stored at −80°C before they were analyzed. Plasma concentrations of Trp and Kyn were simultaneously determined using high-performance liquid chromatography, as previously described Plasma samples were diluted and sCD14 was measured in duplicate using a commercially available ELISA assay , and analyzed according to the manufacturer's recommended procedure.−HLA-DR+CD11c+, while pDC were characterized as Linage−HLA-DR+CD123+. Data was exported and analyzed using FlowJo software v7.6.1.Cell surface markers were measured using a flow cytometer . The following antibodies were used: Linage-FITC, HLA-DR-APC, CD123-PE, and CD11c-PerCP-Cy5.5 . The Fixable Viability Dye eFluor 780  was used to exclude dead cells from the analysis. Magnetic beads coated with anti-rat and -mouse antibodies were used as positive and/or negative controls for calculating compensation . We characterized mDC as Linaget-test was performed to assess differences between two groups. Wilcoxon rank-sum tests were used for non-normally distributed data. Matched samples were analyzed using paired Student's t-test. For correlation calculations, Spearman's rank correlation coefficient “rho” was used. Analyses were two-sided and the confidence intervals (CI) were set to 95%. Results were considered to be significant when the p-value was less than 0.05. All statistical analyses were done using STATA 12.0  and GraphPad Prism 6.0 software .The normality of the data was assessed using the Shapiro–Wilk test. Normally distributed data were shown as the mean ± standard deviation, whereas non-normally distributed data were shown as the median (with the interquartile range). Student's + T cell count of enrolled HIV-infected patients was 248 cells/mm3 (121–297 cells/mm3). The majority of patients  received two nucleoside reverse-transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse-transcriptase inhibitor (NNRTIs), while the other 3.9% (3/76) of patients received two NNRITs plus one protease inhibitor (PI) regimens. The viral load of most patients  was undetectable (<40 copies/mL) after 1 year of therapy.Among the 76 enrolled HAART-naïve patients, 76.3% (58/76) were male with a median age of 32 (28–39.5) years old. These characters were comparable to the healthy control cohort . The basP = 0.0015; and 3022 nM [2531–3513 nM] vs. 2304 nM [1775–2795 nM] for Trp and Kyn, respectively; P = 0.0005; P<0.0001; P = 0.0025), but still could not normalize it , which is not inducible and is mainly expressed in the liver Collectively, our results show that IDO activity is elevated in HIV-infected patients, which was partially associated with microbial translocation. HAART could decrease IDO activity, but not fully corrected it after one year treatment.Figure S1The relationship between CD4 to CD8 ratio and plasma concentrations of tryptophan (A) and kynurenine (B), and the activity of IDO (C) in HIV-infected patients.(TIF)Click here for additional data file.Figure S2+ T cell changes from baseline to IDO activity (A) and plasma sCD14 level (B) in HIV-infected patients.The relationship between delta CD4(TIF)Click here for additional data file.Raw Data S1(ZIP)Click here for additional data file.


Several studies from resource-limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers.3; CD4 < baseline; >30% drop in CD4), by calculating the proportion with the outcome and the observed sensitivity, specificity, positive and negative predictive value of the predictor score compared to the gold standard of virologic failure.We analyzed data from HIV-positive adults initiated on antiretroviral therapy (ART) in Johannesburg, South Africa, between April 2004 and February 2010. Viral failure was defined as ≥2 consecutive HIV-RNA viral loads >400 copies/ml following suppression ≤400 copies/ml. We used Cox-proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Weights for each predictor associated with virologic failure were created as the sum of the natural logarithm of the adjusted HR and dichotomized with the optimal cut-off at the point with the highest sensitivity and specificity (i.e. ≤4 vs. >4). We assessed the diagnostic accuracy of predictor scores cut-offs, with and without CD4 criteria  and laboratory and clinical follow-up data  <100 fl, CD4 count <200 cells/mm3, new or recurrent WHO stage III/IV condition, diagnosis of new condition or symptom and regimen change). Overall, 51.4% had a score 51.4% had a score ≥4 and 48.6% had a score <4. A predictor score including CD4 criteria performed better than a score without CD4 criteria and better than WHO clinico-immunological criteria or WHO clinical staging to predict virologic failure .We matched 919 patients with virologic failure (1:3) to 2756 patients without. Our predictor score included variables at ART initiation (i.e. gender, age, CD4 count <100 cells/mmPredictor scores or risk categories, with CD4 criteria, could be used to identify patients at risk of virologic failure in resource-limited settings so that these patients may be targeted for focused interventions to improve HIV treatment outcomes. In 2012, 9.7 million people in low- and middle-income countries received antiretroviral therapy (ART), representing 61% of all who were eligible under the 2010 WHO HIV treatment guidelines .Measurement of HIV viral RNA  has been shown to be one of the best predictors of clinical disease progression, as well as being the main parameter to assess treatment response in HIV-positive patients . The diaWith the expansion of ART, there is an urgent need for alternative low-cost predictors of virologic failure in resource-limited settings. Monitoring the efficacy of ART in resource-constrained settings remains a critical challenge and current research priorities include optimizing monitoring strategies and developing simpler, cheaper assays that can be administered by minimally trained clinic personnel . TargeteThe study was a retrospective analysis of data collected from a cohort of HIV-positive adults initiated on ART at the Themba Lethu Clinic (TLC), Johannesburg. This cohort has been described elsewhere . By the 3, those with baseline viral load ≤400 copies/ml and those receiving second-line ART (regimen containing either didanosine or a protease inhibitor such as lopinavir-ritonavir) at ART initiation. We also excluded pregnant women as they are initiated using different criteria and are typically placed on lopinavir and ritonavir rather than EFV.Eligible subjects included HIV-positive ART naïve adults (≥18 years of age) who were initiated according to South African National Department of Health ART treatment guidelines onto a standard first-line regimen of stavudine (d4T) or zidovudine (AZT) with lamivudine (3TC) and either efavirenz (EFV) or nevirapine (NVP) between April 2004 and February 2010. The analysis was limited to patients who had two or more viral load results recorded and more than six months on ART. We excluded those who were not ART naïve, those who transferred in from another antiretroviral (ARV) treatment site, those with a baseline CD4 count >350 cells/mmSince 2004, patient data have been captured electronically. Between 2004 and 2010, monitoring tests were done every six months but after 2010 this changed to 6 and 12 months during the first year of treatment and yearly thereafter . After AOur primary outcome was virologic failure defined as sustained or two consecutive HIV-RNA (≥400 copies/ml) following suppression below this level . Viral f2), haemoglobin (Hb), haematocrit (%), to mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), mean cell volume (MCV), platelet count, total lymphocyte count, white blood cell (WBC) count, systolic and diastolic blood pressure, oral candidiasis, WHO stage III or IV condition and serum albumin. Of the 27, 12 were included in the final predictor score.Candidate predictors for the monitoring algorithm were divided into baseline and follow-up variables. Over 27 inexpensive, routinely collected variables were included in a preliminary analysis ,26. Thes3, current weight below baseline or new/recurrent WHO stage III/IV condition) and 2) the difference in value between the two visits prior to the outcome (i.e. drop in MCV or haematocrit by more than 20% or drop in weight by more than 5 kg). The cut-offs used for these variables were obtained from literature and a dichotomous outcome was obtained for each variable (0 for No and 1 for Yes) . Second, the sensitivity of the predictor score with CD4 criteria performed better than the predictor score without CD4 criteria (57.1% vs. 40.9%). Although the usefulness of the predictor score would be limited by access to CD4 count measurements, Marinucci and colleagues reported that by 2010 over 60% of rural ART clinic had access to CD4 count measurements on site . Therefolleagues .WHO recognizes the importance of regular monitoring, including viral load, for reinforcing adherence to ART ,43. ThisWe identified a predictor score that had an acceptable diagnostic performance – comparable to other studies – and performs better than WHO clinic-immunological criteria or WHO staging. This algorithm has a number of strengths, including virologic failure based on two consecutive viral loads, the score uses clinical and laboratory values at the visit preceding virologic failure and that the score can be applied at any point six months after the start of the treatment.The advantage of scoring systems is that they are more flexible than WHO criteria in allowing ART providers to choose the proportion of the population that undergo targeted viral load testing  . For exa


PREVALEAT II  is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular (CV) risk in advanced HIV-infected antiretroviral (ARV) naïve patients starting their first antiretroviral therapy (ART).2 nonparametric method.All consecutive naïve patients with CD4 cell count<200/mL starting any PI/r-based or NNRTI-based + 2 NRTIs regimen from January 2010 to January 2013 in the participant centres were enrolled. At baseline and after 3 (T1), 6 (T2) and 12 (T3) months patients were subjected to epi-aortic vessels ultrasonography and brachial artery flow mediated dilation (FMD). Viral load, CD4+ cell count, serum lipid values, serum glucose, endothelial activation (ICAM-1 and VCAM-1) and inflammatory markers (IL-6 and hsCRP) values were recorded at the same time. Data about independent risk factors for HIV infection and CV disease are taken at time 0. We enrolled 94 patients: 81% males, 87% caucasians, 40% smokers, 8.2% HCV co-infected and 3.5% with lipodystrophy; 33% of them were homosexuals, 12% drug addicts; 23% were AIDS at presentation. Statistical data analysis has been conducted by the χIn Our data evidence at baseline has a relevant deterioration of CV conditions in terms of ultrasonographic data, FMD, inflammation and cytokine markers among advanced naïves. During follow-up epi-aortic lesions tend to worsen but not significantly, percentage of pathologic FMD remains stable. Regarding markers of endothelial activation ICAM-1 significantly worsens during the period of observation; also VCAM-1 has a trend towards the worsening while not significantly. Conversely, a significant improvement was observed for the markers of inflammation D-dimers and high sensitivity C-reactive protein (hsCRP). IL-6 improved but not significantly. Serum lipid profile shows an increase of HDLc and total cholesterol, but not of LDLc. In conclusion, after a twelve-month follow-up period, CV risk of the patients remains high. ARV therapy seems in fact to improve only non-specific and poor sensitive inflammation biomarkers and HDLc; markers of endothelial activations tend to worsen, intima-media ultrasonography and FMD do not show relevant modifications. Further data are warranted to better understand the role of the different ARV regimens.


Mycobacterium avium complex (MAC) commonly infects those with CD4 counts less than 50 cells/mm3. Three patients, with low baseline CD4 counts, presenting with NTM following the initiation of antiretroviral treatment are described in this case series. The first patient presented with disseminated NTM two weeks after commencing antiretroviral treatment. Acid fast bacilli were found in the liver, duodenum, and bone marrow and were suggestive of MAC microscopically. The second developed cervical lymphadenitis following the initiation of ART. Lymph node aspirate culture grew NTM. The last patient developed pancytopenia after 3 months of ART. AFB was seen on bone marrow biopsy. Culture of the bone marrow aspirate was suggestive of NTM. All three patients improved on ethambutol, clarithromycin, and rifampicin. NTM may be underdiagnosed in areas with a high TB prevalence and should be actively excluded by culture.The prevalence of nontuberculous mycobacteria infection (NTM) in Sub-Saharan Africa is estimated to be less than 1%. NTM is often underdiagnosed or misdiagnosed as tuberculosis in patients who present with immune reconstitution syndrome (IRS) following initiation of antiretroviral treatment (ART). Immune reconstitution syndrome is common in patients who start ART with low CD4 counts and high HIV viral load. Furthermore, Mycobacterium avium complex (MAC) [3. While lung disease is common in the immunocompetent, MAC often presents with disseminated disease in the HIV infected individual [Nontuberculous mycobacterium (NTM) is a ubiquitous environmental organism and the majority of organisms within this family are not pathological in humans , 2. The  Mycobacterium avium complex of 10% in 100 HIV infected patients with symptoms suggestive of tuberculosis [South Africa has a high prevalence of HIV infected patients, many of whom have very low CD4 counts. A South African study by Pettipher et al. showed a prevalence ofrculosis –9. As ouMycobacterium avium complex is the commonest cause of IRS in North America and Europe but there is little evidence to suggest that this disease entity is a problem in Africa [n Africa . Three c3 was referred with cholestatic jaundice. He had recently commenced a fixed dose combination of emtricitabine, tenofovir DF, and efavirenz and was well prior to initiating ART. He developed jaundice two weeks after initiating these drugs. The ART drugs were discontinued by the referring physician as drug induced liver injury was suspected. He was asymptomatic prior to initiating ART. On examination he was emaciated, had yellow sclera and pale conjunctiva, and had a liver span of 18 cm and splenomegaly measuring 5 cm below the costal margin.A 20-year-old HIV infected male with a baseline CD4 count of 17 cells/mmHis baseline and follow-up blood investigations are shown in The liver ultrasound failed to detect biliary obstruction and a liver biopsy was undertaken to rule out an infiltrative cause of the cholestatic jaundice such as mycobacterial, fungal, or nonbenign infiltration. A gastroscope was performed to investigate the normocytic, normochromic anaemia, and the suspicious lesions noted at gastroscopy were biopsied. In view of the bicytopenia and the absence of a plausible cause, a bone marrow aspiration and biopsy were also performed. The liver biopsy showed multiple acid fast bacilli; however the SD Bioline MPT64 TB Antigen Rapid was negative. Mycobacteria avium complex; however polymerase chain reaction was unable to identify the species. The duodenal biopsy and bone marrow trephine biopsy also showed AFBs. The TB culture was negative for mycobacteria tuberculosis, and microscopy was suggestive ofHe was commenced on rifampicin, isoniazid, ethambutol, pyrazinamide, and clarithromycin because a definitive microbiological diagnosis of TB or NTM was difficult to attain. After a two-month period of treatment, the patient showed significant clinical improvement.The baseline HIV viral load was not done; however his viral load at 2 weeks of ART and following discontinuation of the drug for suspected drug induced hepatitis was 227 226 copies/mL. A HIV viral load, after 5 months of antiretrovirals, in June 2014 was 756 copies/mL.3. She had a productive cough and constitutional symptoms, in February 2013, and Ziehl Neelsen stain showed AFB on a sputum sample. Sensitive mycobacteria tuberculosis was detected on GeneXpert MTB/Rif of expectorated sputum. She was commenced on TB treatment and completed a six-month regimen of rifampicin, isoniazid, ethambutol, and pyrazinamide. After completing TB treatment she developed right sided anterior cervical lymphadenopathy, right upper quadrant abdominal pain, vomiting, and nausea. Fine needle aspiration of the lymph node revealed pus that contained AFBs. Drug resistant TB was the initial consideration and the pus was sent for TB culture.A 26-year-old female commenced combination ART in February 2013 with a baseline CD4 count of 63 cells/mm Mycobacteria tuberculosis; however NTM was detected. The patient was commenced on rifampicin, ethambutol, and clarithromycin, and the lymphadenopathy resolved without further surgical intervention.TB culture failed to grow3. The diagnosis of mycobacteria tuberculosis, made after the initiation of antiretroviral treatment, was probably due to nontuberculous mycobacteria immune reconstitution syndrome or TB/NTM coinfection. The NTM infection was not associated with an increase in viral load or a decline in CD4 count; therefore it is likely that this patient had dual TB/NTM associated IRS, rather than a new opportunistic infection. Serial ART monitoring blood results and TB investigations are presented in She did not have a baseline HIV viral load but she responded very rapidly to ART and had an undetectable viral load within 5 months of treatment. At one-year follow-up her HIV viral load was undetectable, and her CD4 count was 231 cells/mm3 in August 2013. A viral load and CD4 count at 3 months of ART were 580 copies/mm3 and 278 cells/mm3, respectively. He was referred for investigation of pancytopenia. A 31-year-old male was admitted with biopsy confirmed cutaneous histoplasmosis. He had developed plaques a few months prior to commencing ART. His baseline CD4 count was 29 cells/mmAt his 6-month follow-up visit he had a normal full blood count. Follow-up blood results are captured in Immune reconstitution syndrome (IRS) is an inflammatory phenomenon that occurs following the initiation of ART in patients with very low CD4 counts . Patient Mycobacteria avium complex, may be underdiagnosed or misdiagnosed as TB [Tuberculosis is a common manifestation of IRS in South Africa but NTM, especiallyed as TB . The symed as TB .Common Acid Fast Pathogens Found in HIV Infected Hosts. Consider the following: M. tuberculosis, M. leprae, and M. avium-intracellulare,all mycobacteria includingActinomyces nocardia,Cryptosporidium parvum,Isospora belli.NTM IRIS may manifest as lymphadenitis, pulmonary infiltrates, intra-abdominal lymphadenopathy, or hepatosplenomegaly. Other uncommon foci of infection are bone, skin, and urogenital tract , 2. The Treatment includes ethambutol and clarithromycin . Rifabut3. This is currently not recommended in South Africa because of the high prevalence of tuberculosis and the increasing incidence of drug resistant TB. Azithromycin has been compared to rifabutin in randomized control trials and has been shown to be more efficacious with a slightly higher rate of adverse events [ Mycobacteria avium complex exposed to azithromycin in prophylactic doses may develop resistance to both azithromycin and clarithromycin and should be therefore used with caution [Prophylaxis with rifabutin is indicated in patients with CD4 counts less than 50 cells/mme events . Mycobac caution .Due to the recent implementation of GeneXpert MTB/Rif for the diagnosis of TB in South Africa the prevalence of NTM may increase. Prevalence studies are needed as GeneXpert MTB/Rif and SD Bioline MPT64 TB Antigen Rapid have shown that all acid fast bacilli need not be identified as mycobacteria tuberculosis . Culture Mycobacterium avium complex be commenced without delay in HIV infected patients with CD4 counts less than 100 cells/mm3, where AFB is seen on microscopy of a sterile sample and MTB is not detected on GeneXpert.Speciation is often unavailable in resource limited countries. We recommend that treatment forNTM is an increasingly common opportunistic infection affecting HIV infected patients in Southern Africa.It should be considered in patients who present with a paradoxical worsening or new onset of symptoms after commencing ART, despite being on TB treatment and a low baseline CD4 count.Diagnosis is often difficult as the presentation is similar to tuberculosis and can only be made by TB culture.SD Bioline MPT64 TB Antigen Rapid is a useful diagnostic tool and helps to differentiate between MTB and NTM.


Lopinavir/ritonavir (LPV/r) is the first ritonavir-boosted protease-inhibitor used in second-line anti-retroviral treatment (ART) in resource-limited regions. To evaluate the efficacy and safety outcomes of LPV/r in treatment-naïve and -experienced HIV-infected adults and pregnant women, we performed a meta-analysis of randomized controlled trials. Ten cohorts from 8 articles involving 2,584 ART-naïve patients, 5 cohorts from 4 articles involving 1,124 ART-experienced patients, and 8 cohorts from 7 articles involving 2,191 pregnant women were selected for the meta-analyses. For ART-naïve patients, the virologic response rate (72.3%) of LPV/r combined with tenofovir (TDF) plus lamivudine/emtricitabine (3TC/FTC) arms was significantly greater than that of LPV/r plus non-TDF-FTC arms . For ART-experienced patients, the use of LPV/r revealed a 55.7% probability of virologic success. The incidence of abnormal total cholesterol (6.9%) for ART-experienced patients was significantly lower than that for ART-naïve patients . The use of LPV/r in pregnant women revealed a mother-to-child transmission (MTCT) rate of 1.1%, preterm birth rate of 13.2%, and low birth weight rate of 16.2%. Our meta-analysis indicated that LPV/r was an efficacious regimen for ART-naïve patients and was more tolerable for ART-experienced patients. LPV/r also displayed a significant effect in preventing MTCT. Antiretroviral therapy (ART) is a kind of treatment using anti-HIV drugs for people who infect with human immunodeficiency virus (HIV). Continuous improvements in ART have transformed HIV infection from a debilitating fatal disease into a chronic treatable disease13457891011121315161778Further, it was noticed that there are no adequate studies related to HIV-infected pregnant women. Clinical studies have shown that wherever ART is available widely, it has reduced the mother-to-child transmission (MTCT) rates to 0–3.6%192021222324The search strategy initially identified 1,128 articles in total, of which 768 articles from Google Scholar and 360 articles from PubMed/Medline. Out of the total retrieved articles, the studies excluded after reviewing the titles and abstracts were 924 and 161, respectively. Of the remaining 43 studies that assessed LPV combined with other ART drugs to treat HIV-infected patients, 23 studies were finally excluded from the present study after detailed review for various reasons. Therefore, 8 articles78910111213151617192021222324+ T lymphocyte count. Data related to changes in lipid levels were used to evaluate the safety. According to the information provided in the publications, meta-analyses were conducted on the virologic response of all the cohorts. The changes in CD4+ T lymphocyte count and the blood lipid levels were described without meta-analysis due to the lack of enough information. Additionally, although almost all 15 studies in 18Effectiveness of LPV/r was assessed in 13 studies on 15 cohorts of ART-naïve and -experienced patients. Efficacy was determined on the basis of the virologic response  rate after 48-weeks' treatment and the changes in VL and CD4p = 0.018) or pre-protocol (PP) analysis (p = 0.019). Furthermore, ART drugs for ART-naïve patients were LPV/r combined with TDF in 5 cohorts and with non-TDF in the other 5 cohorts, respectively. The combined virologic response rate  of LPV/r plus TDF arms was significantly greater than that of LPV/r plus non-TDF arms . The meta-analyses were illustrated in For the efficacy measure of virologic response rate, data from 8 articles with 10 cohorts for ART-naïve patients and from 4 articles with 5 cohorts for ART-experienced patients were used in the meta-analysis. The virologic response rates in these studies and the combined virologic response rates are listed in + cell counts and the changes in CD4+ cell counts after 48-weeks' treatment from baselines in each study are shown in The baseline CD4Seven studies assessed the anti-retroviral effects of LPV/r in 8 cohorts of pregnant women. The assessment included the MTCT rate of HIV and the rates of preterm birth (<37 weeks gestation) and low birth weight (<2500 g). In studies reporting MTCT, preterm delivery and low birth weight, rates ranged from 0.6 to 1.8%, 8.7 to 25% and 11.4 to 20.3%, respectively. Other information about these studies is shown in At present, boosted PIs are the most recommended first-line therapy for NRTI- or non-nucleoside reverse-transcriptase inhibitors (NNRTI)-resistant patients and also the suggested therapy during the planning of pregnancy345In the ITT analysis for ART-naïve patients, the proportion of individuals with respect to virologic response rate was slightly different between LPV/r plus TDF and LPV/r plus non-TDF arms . However, other studies one RCT27 compar+ counts increased to 141–239 cells/mm3 from baseline. In the CASTLE study+ counts increased to 219 cells/mm3 from baseline. Even for patients with severely impaired baseline immune function, in whom the initial median level of CD4+ count was only 54 cells/mm3, LPV/r showed significant immunological efficacy by boosting CD4+ counts to 239 cells/mm3 from baseline to week 48+ counts of 121–169 cells/mm31516+ counts with few virological failures.In addition, our results indicated that LPV/r can effectively improve the immunological outcome. After treatment for 48 weeks, CD4et al.et al.Grade 3 or 4 treatment-related hyperlipemia was reported in ART patients. In 2 studies carried out by Ortiz Different studies have provided different answers to the question of whether the use of LPV/r-based ART during pregnancy confers an increased risk of preterm delivery. The meta-analysis of eight cohorts of 2,191 pregnant women with LPV/r resulted in a relatively low MTCT rate of 1.1%, preterm birth rate of 13.2%, and a low birth weight rate of 16.2%, which were similar to those of HIV-negative women in a small prospective cohort of six US centers2930A limitation of this study is that it only included publications in English. Moreover, for the meta-analysis of the efficacy of LPV/r for HIV-infected pregnant women, observational studies are prone to bias because the groups compared may be dissimilar in characteristics. Factors including local medical environments, maternal race, age, and previous obstetric history other than treatment might also be responsible for premature birth. It is also possible that different ART classes of agents, or even agents within each class, inconsistent research durations, and different time points of therapy might have different effects on the risk of premature delivery.This study demonstrated sufficient evidence to show that LPV/r was an efficacious regimen for ART-naïve patients and was more tolerable for ART-experienced patients. In addition, LPV/r displayed a significant effect in preventing MTCT.A computer-based literature search was conducted using search engines including Google Scholar and PubMed/Medline with ‘lopinavir/ritonavir' and ‘HIV/AIDS' as the search terms in the titles. Subsequently, literature on ART using LPV/r combined with other drugs was collected.Studies that assessed the effectiveness of LPV/r-based ART in HIV-infected patients, recruited adult HIV-infected patients, and gave the efficacy and/or safety outcomes were included in the current meta-analysis. Whereas the reviews of LPV/r treatment in HIV, pharmacokinetic studies of LPV/r in HIV-infected patients, studies that recruited HIV-infected children, duplicate publications or studies with similar data collection, and studies with incomplete data were excluded.Study selection was performed by reviewing the titles and abstracts of all examined articles, followed by a detailed review of the eligible articles. This process was carried out independently by 2 researchers (Q. Y. Yang and T. Zhang) without prior consideration of the results. They came to a consensus through discussion after any disagreement.+ T cell count, total cholesterol, triglyceride and low-density lipoprotein), and relevant outcome data. For HIV-infected adults, the primary outcomes of efficacy and safety were the virologic response rate and fasting lipid levels , respectively. For pregnant women, the primary efficacy outcome was the mother-to-child transmission rate. Any disagreements were resolved by discussion and consensus.Two researcher (J. Q. Chen and Y. L. Xu) independently extracted and then cross-checked the following data: the name of the first author, study design, publication year, the number of patients, analytic method, patients' characteristics (whether received ART and ART drugs used), baseline information of each patient . Heterogeneity for each combined rate was assessed by chi-square-based Q-test and the X.H. and H.W. wrote the main manuscript text, Q.Y., J.C., T.Z. and Y.X. searched the library and reviewed all articles, J.C. and H.C. conducted all meta-analysis, Z.L. and C.G. prepared all figures, N.L. wrote part of the manuscript. All authors reviewed the manuscript.


While doxycycline is recommended as an alternative treatment of syphilis in patients with penicillin allergy or intolerance, clinical studies to compare serological response to doxycycline versus benzathine penicillin in treatment of early syphilis among HIV-infected patients remain sparse.We retrospectively reviewed the medical records of HIV-infected patients with early syphilis who received doxycycline 100 mg twice daily for 14 days (doxycycline group) and those who received 1 dose of benzathine penicillin (2.4 million units) (penicillin group) between 2007 and 2013. Serological responses defined as a decline of rapid plasma reagin titer by 4-fold or greater at 6 and 12 months of treatment were compared between the two groups.P<0.0001) and a higher proportion of patients with early latent syphilis . No statistically significant differences were found in the serological response rates to doxycycline versus benzathine penicillin at 6 months  and 12 months of treatment . In multivariate analysis, secondary syphilis, but not treatment regimen, was consistently associated with serological response at 6 and 12 months of follow-up.During the study period, 123 and 271 patients in the doxycycline and penicillin group, respectively, completed 6 months or longer follow-up. Ninety-one and 271 patients in the doxycycline and penicillin group, respectively, completed 12 months or longer follow-up. Clinical characteristics were similar between the two groups, except that, compared with penicillin group, doxycycline group had a lower proportion of patients with secondary syphilis (65.4% versus 41.5%, The serological response rates to a 14-day course of doxycycline and a single dose of benzathine penicillin were similar in HIV-infected patients with early syphilis at 6 and 12 months of follow-up. Patients with secondary syphilis were more likely to achieve serological response than those with other stages. According to the WHO estimate, there were 36.4 million cases of syphilis globally in adults aged between 15 and 49 years in 2008 According to the treatment guidelines for sexually transmitted diseases (STDs) by the Centers for Disease Control and Prevention (CDC) This multicenter, retrospective study was conducted by infectious diseases specialists at 9 hospitals designated for HIV care around Taiwan, where inpatient or outpatient HIV care, including combination antiretroviral therapy (cART), treatments of HIV-related opportunistic illnesses, and monitoring of plasma HIV RNA load (PVL) and CD4 lymphocyte counts, are reimbursed by the government. According to the national guidelines for management of HIV-infected patients, non-treponemal tests for syphilis are recommended to be performed every 6 to 12 months for those who do not have syphilis and every 3 to 6 months over a period of 2 years for those with treated syphilis. The treatment regimens for syphilis were prescribed according to the STDs treatment guidelines of US CDC in 2006 and 2010 We reviewed the medical records of the HIV-infected patients aged 20 years or greater, who presented with early syphilis and received a 14-day treatment course of doxycycline or a single dose of benzathine penicillin (2.4 MU) at the participating hospitals from January 2007 to August 2013. Patients were excluded from analysis, if antibiotics were concurrently given that were treatment options for syphilis such as ceftriaxone or azithromycin when early syphilis was diagnosed; or if those antibiotics were used for treatment of diseases other than syphilis during the 6 months of follow-up after doxycycline or benzathine penicillin treatment. Patients with RPR titers of less than 4 was not included because of concerns about increased risk of biological false-positive syphilis serologies (RPR titer of 1∶1 or 1∶2) The outcomes of interest were serological response rates at 6 and 12 months of treatment. We also examined the reasons of failure to achieve serological response at 6 and 12 months of treatment in the two groups (non-responders).A standardized case record form was used to collect information on demographic characteristics, risk behavior for HIV transmission, PVL and CD4 counts at baseline and during follow-up, cART, stage of syphilis, RPR titer before treatment and during the first 6 and 12 months of follow-up, and the first episode of recurrent syphilis and its stage.Treponema pallidum hemagglutination test  in the participating hospitals. Plasma HIV RNA load and CD4 lymphocyte count were quantified by the Cobas Amplicor HIV-1 Monitor™ Test, version 1.5,  and FACSFlow (Becton Dickinson), respectively.Serological tests for syphilis were performed with the use of rapid RPR test  and Early syphilis that includes primary, secondary and early latent syphilis was defined according to STDs treatment guidelines of US CDC in 2010 2 or Fisher's exact test whereas non-categorical variables were compared using Student's t test or Mann-Whitney U test. All tests were two-tailed and a P value <0.05 was considered significant. Multiple logistic regression method was used to identify factors associated with serological response at 6 and 12 months of treatment. We included the variables with a P-value <0.2 in the univariate analysis such as age, CD4 count <350 cells/µl, a history of prior syphilis, stage of syphilis and variables that were of biological significance such as antibiotic administered (doxycycline versus penicillin) in the multivariate logistic regression models.All statistical analyses were performed using SPSS software version 17.0 . Categorical variables were compared using χDuring the study period, 123 patients who received a 14-day course of doxycycline (doxycycline group) and 271 patients who received 1-dose benzathine penicillin (penicillin group) were enrolled. All patients in the penicillin group had completed 12 months or longer follow-up, while in the doxycycline group all patients had completed 6 months and 91 had completed 12 months or longer follow-up. The demographic and clinical characteristics are shown in P = 0.075), while at 12 months the response rates were similar between the two groups: 65.9% in the doxycycline group and 68.3% in the penicillin group (P = 0.681)  .P = 0.001). At 6 and 12 months of follow-up, patients who presented with secondary syphilis had a higher serological response rate than those who did not present with secondary syphilis ; in contrast, patients who presented with early latent syphilis had a lower response rate than those who did not present with early latent syphilis at 6 and 12 months    . A histoctively) .P = 0.004), while the associations between secondary syphilis  and CD4 <350 cells/µl  and serological response were of borderline significance (P = 0.006), while those with early latent syphilis were less likely to achieve serological response . The treatment regimen was not associated with serological response either at 6 months  or 12 months  of follow-up  and 12 months  of treatment in the multivariate analysis (P = 0.066) and 12 months  of follow-up.In the doxycycline group, secondary syphilis was the only factor that was statistically significantly associated with serological response both at 6 months  in the penicillin group and 45 patients (36.6%) in the doxycycline group were categorized as non-responders at 6 months after completion of treatment. The reasons for failure to achieve serological response at 6 months for the two groups are shown in Of the patients who had completed 12 months of follow-up after treatment, 86 and 31 patients in the penicillin and doxycycline group were categorized as non-responders. The reasons for failure to achieve serological response at 12 months for the two groups are shown in In this multicenter, retrospective observational study among HIV-infected patients with early syphilis, the serological response rate to a 2-week course of doxycycline (65.9%) was similar to that to a single dose of benzathine penicillin (68.3%) at 12 months of follow-up, though the response rate to doxycycline appeared to be lower than that to benzathine penicillin at 6 months of follow-up. In multivariate analysis, we found that secondary syphilis, but not treatment regimen, was associated with serological response at 6 and 12 months of follow-up.While statistically significant difference in terms of serological response to benzathine penicillin versus doxycycline was not demonstrated in this study, the response rates to doxycycline at 6 and 12 months of follow-up are lower compared with those reported in the previous studies 2 increase, adjusted OR, 1.237; 95% CI, 1.084–1.414, P = 0.002) in multivariate analysis that included age, CD4 count, a history of prior syphilis, and treatment  were excluded to prevent difficulties in interpretation of the response or biologic false-positive reaction; the serological responses were determined at the recommended 6 and 12 months after treatment; and we had a large number of patients as a comparator group who received the recommended a single dose of benzathine penicillin for early syphilis and were assessed using the same definitions. There are several limitations in our study, however, and interpretation of our results should be cautious. First, this is a retrospective study and the follow-up blood testing was not performed in all patients at the recommended 3- to 6-month intervals after treatment was administered. Missing data that was treated with the last-observed-carried-forward principle may have caused underestimation of the serological responses to doxycycline. If we adopt the definition of serologic response used in Ghanem study  In conclusion, our multicenter, retrospective study demonstrated that the serological response rates to a 14-day course of doxycycline and a single dose of benzathine penicillin were similar in HIV-infected patients with early syphilis at 6 and 12 months of follow-up. Patients with secondary syphilis were more likely to achieve serological response than those with other stages. Our findings may provide support to the guidelines Table S1Non-responders at 12 months in the doxycycline and penicillin group who had completed 12 months or longer follow-up.(DOCX)Click here for additional data file.Table S2Multivariate analysis of the factors associated with serological responses.(DOCX)Click here for additional data file.


Intestinal parasites (IPs) are major concerns in most developing countries where HIV/AIDS cases are concentrated and almost 80% of AIDS patients die of AIDS-related infections. In the absence of highly active antiretroviral therapy (HAART), HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic and other intestinal parasites. The aim of the study was to determine the prevalence of intestinal parasites in relation to CD4+ T cells levels and anemia among HAART initiated and HAART naïve pediatric HIV patients in a Model ART center in Addis Ababa, Ethiopia.A prospective comparative cross-sectional study was conducted among HAART initiated and HAART naive pediatric HIV/AIDS patients attending a model ART center at Zewditu Memorial Hospital between August 05, 2013 and November 25, 2013. A total of 180 (79 HAART initiated and 101 HAART naïve) children were included by using consecutive sampling. Stool specimen was collected and processed using direct wet mount, formol-ether concentration and modified Ziehl-Neelsen staining techniques. A structured questionnaire was used to collect data on socio-demographic and associated risk factors. CD4+ T cells and complete blood counts were performed using BD FACScalibur and Cell-Dyn 1800, respectively. The data was analyzed by SPSS version 16 software. Logistic regressions were applied to assess any association between explanatory factors and outcome variables. P values < 0.05 were taken as statistically significant.Cryptosporidium species, E. histolytica/dispar, Hook worm and Taenia species were IPs associated with CD4+ T cell counts <350 cells/μμL in HAART naive patients. The overall prevalence of anemia was 10% in HAART and 31.7% in non-HAART groups. Hook worm, S. stercoralis and H. nana were helminthes significantly associated with anemia in non-HAART patients . The prevalence of IPs in non-HAART patients was significantly associated with eating unwashed/raw fruit , open field defecation  and diarrhea . IPs significantly increased in rural residents .The overall prevalence of IPs was 37.8% where 27.8% of HAART initiated and 45.5% of HAART naive pediatric HIV/AIDS patients were infected (p < 0.05). cryptosporidium species were found only in HAART naïve patients with low CD4+ T cell counts. Anemia was also more prevalent and significantly associated with IPs in non-HAART patients. This study identified some environmental and associated risk factors for intestinal parasitic infections. Therefore, Public health measures should continue to emphasize the importance of environmental and personal hygiene to protect HIV/AIDS patients from infections with intestinal parasites and maximize the benefits of HAART.The overall prevalence of intestinal parasites significantly differed by HAART status and  Intestinal parasitic infection (IPI) is a serious public health problem throughout the world particularly in developing countries –4. In ch3, infections with opportunistic intestinal parasites result in diarrheal symptoms. With the introduction of HAART which partially restores the immune function, the incidence of opportunistic parasite infection such as cryptosporidiosis has declined  . Among pE. histolytica/dispar accounting for 10% followed by G. lamblia 7.6%, A. lumbricoides 6.3%, S. stercoralis 2.5%, Hook worm and H. nana 1.3% each  of them. Among the 79 pediatric HIV patients taking HAART, 22(27.8%) were infected with intestinal parasites. There were no opportunistic intestinal parasites detected in this group. The highest prevalent IP was .3% each .Cryptosporidium species. The most prevalent IP was G. lamblia (11%) followed by E. histolytica/dispar, Hookworm, and S. stercoralis (6.9% each), Ascaris lumbricoides (4%), Cryptosporidium species (3.96%), Taenia species (3%) and H. nana (2%)  and 4(3.96%) were infected with ana (2%) . There wana (2%) .Of the 79 study participants who were on HAART, 66 patients (83.5%) had CD4 count > 350 cells/μL and the remaining 13 patients (16.5%) had CD4 count < 350 cells/μL. Among the 13 HAART patients with CD4 count < 350 cells /μL, parasites were identified in 4 (30.8%) of them while 27.3% of those with CD4 count>350 had IPs, showing no statistically significant association with CD4+ T cell levels , Hook worm , Taenia species  and Cryptosporidium species  were significantly associated with CD4 levels < 350 cells/μL  were anemic (mean hemoglobin level 13.36±1.35g/dl) of which 4(50%) were infected with IPs. Most of anemic patients used 4c (AZT+3TC+NVP) 4(44.4%) and 4d (AZT+3TC+EFV) 2(22.3%) drug regimens. But none of the regimens showed significant association with IPIs.Hookworm, S. stercoralis and H. nana were significantly associated with anemia  of HAART naive pediatric HIV patients were anemic (mean hemoglobin level 12.89±1.9 g/dl) of which 24(75%) were infected with IPs. Whereas the presence of intestinal parasites was not significantly associated with anemia in HAART initiated patients , P = 0.15), in the non HAART group anemic patients had 4.5 times likelihood of being infected with intestinal parasites compared to non-anemic patients  . In non-h anemia .Even though distribution of anemia status was higher in females with lower CD4 +T cell counts in HAART naïve groups, it was not statistically significant regardless of HAART in relation to gender .The significantly higher prevalence of common and opportunistic intestinal parasites observed in the HAART naïve children in this study (45.5% versus 27.8%) partly signifies the value of HAART in reducing intestinal parasites through improving the immune response as also demonstrated by the lower prevalence in those with higher CD4+ T cell counts. Moreover, the observed 45.5% prevalence of intestinal parasite among HAART naive patients in this study is in line with reports from South west Ethiopia (44.8%) and Gondar (43.5%) . HoweverOn the other hand, the 27.8% prevalence of IPs detected among patients on HAART in this study is higher than that reported in Brazil 24%) and Dessie (17.6%) , 24 but % and DesStrogyloides stercoralis is an important human parasite primarily because of its potential for serious and even lethal disease in immunosuppressed patients. The prevalence of Strongyloides stercoralis is higher in non-HAART (6.9%) than patients on HAART (2.5%) in the present study which is comparable with a study done in Nigeria (6.39%) , Hookworm , and Taenia species  were non opportunistic IPs significantly associated with CD4+ T cell levels < 350 cells/μL in this study. This result agrees with a study done in Malaysia [E. histolytica/dispar) [In case of non-HAART Pediatric HIV patients, CI: 141, 5, P<0.05/dispar) .cryptosporidium species and other intestinal parasites among non-HAART patients, as is documented by other studies in Ethiopia and Nigeria [Infection with  Nigeria , 23, 24, Nigeria .Hookworm, S. stercoralis, and H. nana were associated with anemia which is in line with a study done in Veitnam [Hookworm and Trichuris trichuira were associated with anemia, but different (except for Hookworm) from a study done in Nigeria where Cryptosporidiasis, Ascariasis, Hook worm and Taeniasis were associated with anemia [Cryptosporidiasis, Taeniasis and Ascariasis in this study.The 31.7% prevalence of anemia in HAART naive patients in this study is lower than the findings from Nigeria (93.3%) . This mi Veitnam  where Hoh anemia . These dIn the present study, only 8 (10%) of HAART initiated pediatric patients were anemic from which 4(50%) are infected with IPs. However, the presence of intestinal parasites was not significantly associated with anemia in HAART initiated patients which is different from a study done in Nigerian adults where the presence of IPs was associated with anemia . In addiThe total prevalence of diarrhea detected in the present study (29.4%) was consistent with a study done in Nekemte (27%) , but lowNon-HAART initiated patients who were diarrheic, ate unwashed/raw fruit, and defecate openly had 5.2, 6.3, and 9.3 times likelihood of getting infection with intestinal parasites, respectively. Although the majority of our study participants reported that they have toilet and use pipe water for drinking, this result is almost similar to a study done in Dessie where absence of toilet, source of water and living condition were significantly associated with the presence of IPs .In this study, we have used normal saline, iodine, formol-ether concentration and modified Ziehl-Neelsen staining methods for detection of common and opportunistic intestinal parasites. We have not used water-ether sedimentation method for Microsporidia and other sensitive methods, which might result in underestimation of the prevalence of intestinal parasites.Hookworm, Strogyloides stercoralis and Hymenolopis nana were IPs associated with anemia. Open field defecation, eating raw/unwashed fruit, diarrhea and being HAART naïve significantly increased the prevalence of intestinal parasites in the study area. Public health measures, parasitological tests and large scale longitudinal studies to understand casual relationships are recommended in the study setting.The prevalence of intestinal parasites was found to be higher in HAART naïve than HAART experienced patients. High proportions of intestinal parasites were associated with lower CD4+ T cell counts in HAART naïve initiated patients. Infections with opportunistic intestinal parasites were associated with lower CD4+ T cell counts in HAART naïve patients only. Increasing the immune status of HIV infected patients with antiretroviral therapy may help to reduce acquisition of parasites. Moreover, the prevalence of anemia was higher in HAART naïve patients where helminthes like