Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is widely prescribed as a part of the combination therapy of human immunodeficiency virus (HIV) infection because of its efficacy and good tolerability. Here, we report a case of Stevens–Johnson syndrome (SJS) secondary to nevirapine. The patient had a diffuse, exfoliating exanthema with generalized bullous eruptions that involved the face, trunk and both extremities with elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme activities. The condition improved with stoppage of nevirapine-based highly active antiretroviral therapy (HAART) regimen, so we attributed this adverse event to nevirapine. A strict vigilance of adverse drug reaction is required in HAART. Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is widely prescribed as a part of the combination therapy of human immunodeficiency virus (HIV) infection because of its efficacy and good tolerability. It bindsIn 1997, nevirapine became the first NNRTI available for the treatment of HIV infection. Its efficacy was established both for the treatment of naive patients and in oversimplification strategies. NevirapiWorld Health Organization (WHO) recommends nevirapine and efavirenz (EFV) as one of the first-line drugs. The drug is widely available and is less costly than EFV; however, a higher incidence of rash is associated with it than with EFV. The most serious toxic effects associated with nevirapine are skin reactions and liver dysfunction; both are generally mild to moderate and usually an early phenomenon, occurring during the first 6-8 weeks of therapy.Clinical studies have demonstrated that sustaining viral suppression and maintaining higher CD4 count, mostly as a result of effective combination antiretroviral therapy, delay or prevent some AIDS/non-AIDS–defining complications, such as HIV-associated kidney disease. Sustained viral suppression and immune recovery may also delay or prevent other disorders such as liver disease, cardiovascular disease, malignancies, etc.Patients infected with human immunodeficiency virus-1 (HIV-1) are at increased risk of developing severe mucocutaneous drug reactions. We report a patient infected with HIV-1 who developed Stevens-Johnson syndrome (SJS) in association with nevirapine. Written informed consent was taken from the patient for collection of her details and images.3 and a viral load of 6800 copies/mL. On the basis of National Aids Control Organization (NACO) guided regimen, stavudine (30 mg), lamivudine (150 mg) and nevirapine (200 mg) were initiated once daily in the month of May 2010 for 15 days, after which she was shifted to twice daily doses. After 3 weeks of starting HAART, she came with complaints of weakness for which she was kept in observation and treated symptomatically and then discharged without any change in HARRT regimen.A 45-year-old tribal was diagnosed with advanced HIV infection with CD4 cell count of 174 cells/mmThe patient was again admitted to Community Care Centre  affiliated to NACO’s ART centre  with history of oral ulceration for 2 days, nausea, anorexia, slight headache and fever since the previous 24 hours. After 2 days, she developed generalized skin eruption. On examination, she was non-icteric, but had a diffuse, exfoliating exanthema with generalized bullous eruption that involved the trunk, face, and both extremities. In addition, she had facial and lip swelling, oral ulceration and difficulty in opening the mouth and swallowing . The ras9/L with 63% neutrophils, 22% lymphocytes, 6% monocytes, and 9% eosinophils. Her alanine aminotransferase and aspartate aminotransferase levels were 215 U/L (10-40 U/L) and 117 U/L, (10-35 U/L), respectively. In view of severe skin eruption and impaired hepatic enzymes, the HAART regimen was withheld temporarily.At this time, her white blood cell count was 13.8 × 10The patient was treated aggressively with i.v. dexamethasone, 8 mg 6 hourly, i.v. fluids, prophylactic antibiotics, anti-allergic drugs and local treatment of lesions. Stavudine (30 mg), lamivudine (150 mg) and nevirapine (200 mg) regimen was stopped. The patient’s condition improved over the next 4–5 days. The hepatic enzymes remained elevated for 1 week. Re-challenge with nevirapine was never performed but a modified HAART regimen was started that included efavirenz instead of nevirapine, after 15 days of complete resolution of all symptoms and near normalization of hepatic enzymes. No recurrence of rash and impairment of hepatic function were recorded in subsequent follow-up.In the face of the global AIDS pandemic, advances in its treatment have been strikingly impressive, for example, patients on antiretroviral therapy now live at least 13–14 years longer than those without the therapy. But we cIdentification of a single antiretroviral drug as the cause of a drug eruption in a patient infected with HIV-1 is often difficult because monotherapy is rarely used. Although our patient was not re-challenged with nevirapine, the signs and symptoms of this patient were most consistent with nevirapine induced SJS, so we believe that nevirapine was responsible for the SJS. SJS or toxic epidermal necrolysis (TEN) has been reported to occur in 0.3% of patients taking nevirapine within the first 4–6 weeks of treatment. This was3 in women and <400/mm3 in men, and abnormal baseline transaminase levels.[Identified risk factors for developing hepatotoxicity with nevirapine are female gender, chronic hepatitis C/B virus coinfection, a CD4 count <250 cells/mme levels.Most of the drugs which are available and approved for use in HAART have some or the other adverse effect. Thus, treatment of HIV infection has become a complicated balancing act between the benefits of HIV control and the risks of drug toxicity.Antiretroviral therapy is becoming not only increasingly effective but also increasingly complex. The many adverse effects associated with therapy may cause symptoms affecting a variety of organ systems. Although current antiretroviral regimens are potent from an antiviral perspective, they often do not succeed because of patient’s poor compliance. To optimize adherence, and hence efficacy, clinicians must focus on limiting the adverse effects whenever and wherever possible and distinguishing those that are self-limiting from those that are potentially serious.In the present case, the other concomitant medication the patient was receiving was stavudine (30 mg) and lamivudine (150 mg) once daily. Both these drugs do not have an obvious association with SJS. According to Hartwig scale, the case was categorized as severe and preventability of the case was probable as per modified Schumock and Thorton scale. The causality assessment of SJS with nevirapine using Naranjo’s Causality Assessment Scale showed a score of 7. WHO Uppsala Monitoring Centre (UMC) Causality Assessment Criteria also indicated a probable association with nevirapine.10A strict vigilance on part of treating physician for the initial 2 months at least is necessary to prevent such adverse events. Nevirapine should always be started as lead-in dose (200 mg OD for the first 14 days and then 200 mg BD) to sensitize the system gradually and to avoid serious ADR. The more recent trend is application of Principles of Pharmacogenomics by which we define the particular population or a person who responds differentially to a particular drug, based on their diverse genetic make-up. This has a definite role in high precision multidrug prescription and hence gives a better outcome with fewer side effects.


To determine the prevalence of virological failure and HIV drug resistance among Chinese patients one year after initiating lamivudine-based first-line antiretroviral treatment.A prospective cohort study with follow-up at 12 months was conducted in four urban sentinel sites in China. Antiretroviral naive patients ≥18 years old were recruited. Blood samples were collected for testing CD4 cell count, viral load, and (for samples with HIV-1 RNA ≥1000 copies/ml) genotyping of drug resistance.3, which increased from 192 cells/mm3 at baseline (P<0.0001). Of the 448 remaining subjects, 394 (87.9%) had successful virological suppression (HIV RNA <1000 copies/ml). Among 54 samples with viral load ≥1000 copies/ml, 40 were successfully genotyped, and 11 were found with detectable HIV drug resistance mutations. Of these, the proportions of drug resistance to NNRTIs, NRTIs and PIs were 100%, 81.8% and 0%, respectively. Injecting drug use , CD4 count at baseline ≥350 cells/mm3 , and missed doses in the past month  were significantly negatively associated with HIV RNA <1000 copies/ml.A total of 513 patients were enrolled in this cohort, of whom 448 (87.3%) were retained at 12 months. The median final CD4 cell count was 313 cells/mmOur study demonstrates effective virological and immunological outcomes at 12 months among these who initiated first-line ART treatment. However, patients infected through drug injection, who missed doses, or with higher CD4 count at baseline are at increased risk for poor virological response. The rapid expansion of combination antiretroviral treatment (cART) has dramatically improved the prognosis of patients infected with HIV and decreased HIV/AIDS associated morbidity and mortality Since the China’s National Free Antiretroviral Treatment Program (NFATP) began in 2002, cART use has scaled up rapidly. By the end of 2012, more than 208,216 patients across the country had received free antiretroviral treatment In 2004, The World Health Organization (WHO), in collaboration with the United States Centers for Disease Control and Prevention (CDC) and through HIVResNet developed a global strategy for the assessment and prevention of HIVDR. The protocol for population-based surveillance of acquired HIVDR at sentinel ART clinics is designed to be used particularly in resource-limited countries, where decisions on ART regimens for a given patient population are made through monitoring HIVDR emergence during treatment in addition to related program factors 3; (2) World Health Organization (WHO) stage III/IV diseases, or (3) willingness to receive ART, regardless of the criteria 1 and 2. The ART regimen will be provided through the NFATP. First-line ART regimen consisted of tenofovir (TDF) or azidothymidine (AZT)+lamivudine (3TC)+efavirenz (EFV) or nevirapine(NVP) The four sentinel surveys were conducted in urban areas of China, including Jiangsu province , Guizhou province , Hunan province (Hengyang City) and Chongqing Municipality , respectively, where most of HIV infection were transmitted through heterosexual intercourse and homosexual intercourse The study was approved by the institutional review board of the National Center for AIDS/STD Control and Prevention of the China Center for Disease Control and Prevention .Data were collected using an interviewer-administered questionnaire. Each study participant was assigned a confidential identification number used to label questionnaires and blood specimens. The questionnaire was administered by trained interviewers in a private room. Questionnaires included demographic data, ART treatment and self-reported adherence data. Demographic variables included age, sex, ethnicity, education level, marital status, occupation and HIV transmission route. ART treatment variables included WHO clinical stage, initial regimen, ART distribution institution, ART refill interval, missed ART doses in the past month, ratio of on-time drug intake in the past month, and reasons for loss of treatment retention.+ T-lymphocyte count (CD4 count), HIV viral load, and HIV drug resistance mutations at baseline and 12-month follow-up. CD4 count was tested using flow cytometry  within 24 hours after specimen collection in local CDCs. Blood plasma was isolated and stored frozen at −80°C at local CDCs before transferring to NCAIDS in Beijing for testing viral load and drug resistance mutations. Plasma HIV RNA was quantified with real-time NASBA  or with COBAS  according to the manufacturers’ recommendations. For the WHO surveys, successful viral suppression was defined as HIV RNA level <1,000 copies/ml using a quality-assured viral load assay. In samples with viral load ≥1000 copies/ml, HIV drug resistance genotyping was performed at the WHO Accreditation Laboratory of NCAIDS, China CDC by using an in-house method as previously described pol gene using the Stanford University HIV Drug Resistance Database online sequence analysis tool . We included mutation results that conferred low-, intermediate-, and high- level resistance All subjects provided blood specimens for testing CD4Questionnaire and laboratory data were double-entered and compared using EpiData software . Data were then converted and analyzed using Statistical Analysis System version 9.1 . The data were analyzed using unadjusted odds ratios with a test for significance according to chi-square test and Fisher’s exact test. Variables that were significantly (p<0.05) associated with HIV RNA <1000 copies/ml at 12 months in the univariable analyses were considered for inclusion in the multivariable logistic regression model. Multivariable logistic regression was performed to examine the independent effect of each factor under consideration. All tests of significance were two-sided, with p-value <0.05 indicating that an association was statistically significant.Among 535 consecutive participants enrolled, one was less than 18 years old, three refused to participate in the study, five did not receive national free regimen, and 13 patients with baseline HIVDR were excluded from this study. Thus, 513 subjects entered this prospective cohort and provided written informed consent. The baseline and 12-month follow-up characteristics were shown in All patients received free standard first-line regimen through the NFATP, and 98.4% maintained the initial regimen at follow-up. Only 7(1.6%) patients switched to the second-line regimen during the follow-up. The initial ART regimen were AZT+3TC+NVP(59.1%), D4T+3TC+NVP(6.4%), AZT+3TC+EFV(14.4%), D4T+3TC+EFV(9.5%), 3TC+TDF+EFV(9.2%) and 3TC+TDF+NVP(1.4%). Among 65 participants who were lost to follow up, 4.9% had died, 4.9% were lost to contact, and 0.2% transferred out of the study districts .3, which increased from the median 192 cells/mm3 at baseline(P<0.0001). 14.1% reported missing doses, and 83.9% maintained ≥95% of on-time drug intake in the past month.Of the 448 patients retained at 12 month, CD4 cell count was 313 cells/mmAfter receiving ART for nearly one year, 394(87.9%) patients had plasma HIV RNA <1000 copies/ml. Among the 54 samples with viral load ≥1000 copies/ml, 40 were successfully genotyped. Of the 11 with detectable HIVDR mutations, the proportion of drug resistance to NNRTIs, NRTIs and PIs were 100%, 81.8% and 0%, respectively. Among these, 9(81.8%) patients had multi-drug resistance to NNRTIs and NRTIs. The most common NNRTIs mutation site were K103N(36.4%), Y818C/I/V(27.3%) and K101E(18.2%). As well, M184V/I(72.7%), K65R(27.3%), D67N(27.3%) were found as the most frequent mutations to NRTIs .3, and missed doses in the past month were negatively associated with virological success.The factors significantly associated with successful viral suppression at 12 month were analysed through univariable logistic regression . HIV traIn this one-year prospective follow-up survey on HIVDR at sentinel sites in four Chinese provinces, viral load suppression (HIV RNA <1000 copies/mL)was achieved at 12 months in 87.9% of treated patients, with a range from 82.9% to 93.6%. This demonstrated a rapid but successful scale up of China’s NFATP. In the 2012 WHO drug resistance surveillance guideline, viral load suppression after 12 months of ART can be graded as poor (<70%), fair (70–85%), or excellent (>85%) The drug resistance mutations identified concurred with expected mutation patterns from a treatment program based on NNRTI and NRTI class drugs. Among patients with virological failure, 11 cases (27.5%) displayed NNRTI mutations and 9 cases (22.5%) displayed NRTI mutations. No protease inhibitor (PI) mutations were identified, which affirms that the continued use of PIs as second-line therapy is still viable in China. Our HIVDR results are comparable to reported values in other developed and developing countries Our study found that injecting drug use, baseline CD4 count ≥350, and missed doses in the past month were independently associated with virological failure (HIV RNA ≥1000 copies/ml) among HIV patients receiving free first-line ART in China. Virological failure as a result of poor adherence indicates that strengthening education and counseling among HIV patients should be an important priority for HIVDR prevention in China 3 or immediately after testing) 3) at cART initiation were more likely to drop out of HIV care 3 and <350 cells/mm3were 8.9%(5/45)and 7.7%(36/468), respectively(p = 0.77). Although the difference is not statistically significant, the sample size of patients with higher CD4 cell count is small, and more data is needed to confirm the observed relationship. In general, further studies are needed to clarify the effects of early ART initiation on adherence and attrition at short-term versus long-term treatment timescales in China.Lastly, the association of higher CD4 cell count with virologic failure warrants further investigation. Recent WHO guideline changes and advocacy towards initiating ART treatment at higher CD4 levels (≤500 cells/mmThis study has some limitations. First, due to limited geographic distribution of the sentinel sites and participant exclusion criteria, these results may not be fully representative of all of China. Second, the overall retention rate at 12 months was 87.3%, but only 79.0% in Hunan province; results should therefore be interpreted with caution. Third, due to a relatively low rate of successful HIVDR sequencing, the HIVDR rate from this study is likely lower than the true drug resistance rate. Finally, a 12-month follow up survey is relatively short for the purposes of monitoring HIVDR, and more studies with long-term monitoring is recommended to provide more objective and accurate data on viral suppression, HIVDR incidence, and optimal choices of regimen.In sum, this HIVDR surveillance study in four sentinel sites across China demonstrates good virological and immunological outcomes at 12 months among these who initiated first-line ART treatment. However, patients infected through drug injection, who missed doses, or with higher CD4 at baseline are at increased risk for poor virological response. More data from these high-risk patients are needed to evaluate clinical outcomes and long-term effects of treatment.


Hematological and biochemical abnormalities are among the most common clinicopathological manifestations of HIV patients on ART. Consequently, the development and assessment of indigenous antiretroviral drugs with minimal abnormalities becomes a necessity. The objective of this investigation was to assess potential haematological and biochemical abnormalities that may be associated with the administration of Winniecure ART in HIV patients undergoing treatment in Nigeria. Fifty (50) confirmed HIV positive ART naïve patients aged 36 ± 10 were observed for haematological and biochemical responses for 12 weeks. Haematological responses were assessed thrice at 6 weeks interval using coulter Ac-T differential analyser and biochemical indicators  assayed spectrophotometrically.th week, no significant change was observed in plasma creatinine and urea concentrations while albumin levels decreased non-significantly (P > 0.002). Haematological results showed consistent reduction of ESR, eosinophil, absolute and differential lymphocytes, granulocytes and total WBC in the test subjects throughout the assessment period. Conversely, haemoglobin, platelet and PCV increased significantly (P < 0.05). At the 12th week thrombocytopenia (10.30%) and anaemia (76%) were reduced to 2% and 31% respectively while neutropenia (4.2 to 8%), leucopenia (26.8 to 30%) and lymphopenia (1 to 10%) increased. No cases of neutrophilia, lymphocytosis, eosinophilia and leukocytosis was observed.The biochemical parameters ALP (P < 0.05), ALT (P < 0.0001), AST (P < 0.001) and amylase (P < 0.05) slightly increased at the 12The drug has a reduced haematological abnormalities and normal kidney function was unaffected though there were signs of possible abnormal levels of hepatic enzymes beyond 12 weeks of treatment. The human immunodeficiency virus (HIV) is one of the most important emerging infections of this century. It is probably one of the diseases with multiple impacts on persons, families, communities and the entire society. HIV is threatening especially in sub-Saharan African countries. In Nigeria for instance the prevalence rose from 3.8% in 1993 to 5.8% in 2001 . These tIt is observed that the emergence of drug development programmes by government agencies, research establishments and pharmaceutical industries has led to many potent anti-HIV drugs called antiretrovirals . PresentIt is undoubtedly observed that the HIV drugs are without some adverse medical effects with implicit safety limitations. Certain documented side effects of these drugs include diarrhea, nausea, abnormal distribution of body fats, anemia, neutropenia and cytopenia . The neeIt is highly documented that the hematological consequences of HIV infection is dominated by peripheral blood cytopenia. This has become more common with the advent of antiretroviral therapy and related treatments for HIV-associated infections and malignancies ,15. GeneIn view of the various questions raised by end users of antiretroviral therapy such as the safety and efficacy of the drug, a careful study of some possible abnormalities that may be associated with Winniecure an antiretroviral drug used in Nigeria was investigated.+ ART subjects and 40 ± 52 for the control group were recruited for the study.Fifty confirmed HIV positive patients who were previously ART naive volunteered to take Winniecure antiretroviral therapy at a prescribed dose of 5 ml (1 tea spoonful) containing 250 mg Winniecure extract taken 3 times daily for 5 days and then 2 times daily for the period of this study (12 weeks). The study also had 100 HIV negative ART naive subjects attending clinic for the first time and this served as the study reference subjects or control group. All consenting subjects were recruited consecutively for the work. Blood samples were taken in accordance with the Nigerian National Ethics and Operational Guidelines for Research on Human subjects (NNEOGRHS). Part of the blood was collected into EDTA container to give blood-anti-coagulant concentration of 2 mg/ml of blood with sterile syringe (aseptic precautions were taken). The samples were collected at intervals of 6 weeks for the whole period of this study. A total of 150 subjects with an average age of 36 ± 10 for HIVThe inclusion criteria for enrolment of the study subjects were specified as follows; subjects must be either males or females aged 17 years and above, have confirmed laboratory evidence of HIV infection, accept to abide by the prescribed dosage of the drug, have history of no previous antiretroviral therapy (ART naive) and have CD4 cell counts between 50 and 350 cells/μl. Exclusion criteria include those with recent blood transfusion.A structured questionnaire was filled by the subjects in order to obtain demographic data and clinical history and assistance was given on request. Prior to initiation of treatment, the HIV serostatuses of the patients were reconfirmed. Plasma samples from each of the patients were tested using double rapid tests kits  and an ELISA method (Genie II HIV-1 & 2 kit). The tests used have different antigenic compositions.Parameters such as Hb, PVC, Total WBC, Differential WBC, platelet count and ESR were evaluated each time samples were collected from the subjects. Samples for ESR were analyzed using Westergren method . Blood  and <12 g/dl (women) while leucopenia as total WBC count less than 4000 cells/μl. Total platelet count <150 × 10Biochemical indicators were assessed at the first and last visits only. Commercially available kits were used to assay for the following serum enzymes: ALT, AST and amylase. Urine creatine (RANDOX) and urea (BioVision) were also determined using test kits. Bilirubin was measured directly by use of bilirubin oxidase  while alAll data analysis was done using SPSS version 17 statistical software package. Data was presented as Means ± Standard deviation (SD) and calculations done using the Student’s t-test and one-way ANOVA. Differences were considered to be of statistical significance at an error probability of less than 0.05 (P < 0.05).+ HAART group (36 ± 10) and that of the reference group (40 ± 52). A non-significantly higher  number of HIV+ females and a significant increase  in married couples amongst the HIV+ ART group were observed. However, 88% of the HIV+ ART subjects had CD4+ cells within the range of 200-350 cells/μl while 12% were between 50-200 cells/μl (Table There was no significant difference between the ages of the HIVoup 36 ± 0 and tha+ ART patients on Winniecure therapy before treatment (1st assessment) and subsequent appointments at 6 weeks interval otherwise referred to as visits in this study.Table st assessment visit and subsequent visits (treatment period)  increase in haemoglobin, platelet and packed cell volume from the 1st to the 3rd assessment visits. All values obtained here was lower than the reference value.A comparative statistical analysis was made between the 1d) Table . A consiThe concentration of these biochemical parameters; ALP , ALT , AST , amylase  and direct bilirubin was significantly increased (upper range) at the third visit though still within the acceptable normal range  at 3rd assessment visit/12th week  and anaemia (76%) in ART HIV0.30% andThe study seeks to evaluate some haematological and biochemical indicators of abnormalities in HIV infected patients administered with Winniecure chemotherapeutic agent used in the treatment of HIV/AIDS in some parts of Nigeria.HIV infection has been reported to cause diverse degree of immunopathogenesis in man  and thisThe baseline characteristics of the study population showed no significant age difference between the reference or control group with that of the test subjects. This implies a reduced variation that could emanate from the pharmacological effect of age on chemotherapeutic agent. The number of HIV infected subjects are generally reported to be higher in the female gender than in the male counterpart . The resIt is generally believed that single/unmarried young individuals are more likely to acquire HIV infection than married partners . ContrarHIV patients assessing ART have been reported to have an increased CD4 cell count, normally initiating treatment from 100-260 cells/μl baseline ,33. Star+ subjects on Winniecure treatment  observed in absolute lymphocyte and total WBC may indicate suppressive activity of the antiretroviral drug on the virus with the resultant increase in leucopenia  and lymphocytopenia . Leucopenia (a decrease in the number of white blood cells ) and Lymphopenia (decrease in lymphocyts) are the hallmarks of HIV infection and is thought to be mediated by infection of the virus with subsequent killing of CD4+ T cells. It can also be caused by certain medications such as ART [nd visit follows the pattern already reported by Stein and his colleagues [Generally, the overall White Blood Cell (WBC) count is important to monitor because elevation of WBC may indicate infection, lack of response to treatment or an abnormality. The total WBC count shows a consistent significant reduction in all the visits although the reduction at the 3rd visit was non-significant (P > 0.05). The progressive reduction  therapy causes anaemia with a significant reduction in Hb in HIV patients  even at  anaemia . The conondition . ESR incondition  have repst and 3rd visits. Using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Version 2.0 it was found that the subjects undergoing treatment are at NCI risk category 1, implying a mild neutropenia. It is of note that abnormal granulopoiesis and anti-granulocyte antibodies have been noted and described in 30-70% of HIV infected patients [rd visit may reflect the action of Winniecure on HIV infection or associated conditions. The incidence of neutropenia at the first visit (untreated patients) is consistent with other reports [A significant reduction in both differential and absolute granulocyte count was observed between the 1patients . This ispatients . The low reports  which hast to the 3rd visits. This indicates a reduced incidence of thrombocytopenia in the HIV+ ART subjects. This action maybe adduced to the activity of the administered Winniecure.An escalated and uncontrolled platelet count may indicate disease progression and may sometimes be associated with abnormal bleeding. Thrombocytopenia however, is defined as any disorder in which there is an abnormally low amount of platelets which may result due to immune system malfunction . The resst visit) to the 12 th week (3rd visit). It is of note that this increase is still within the normal laboratory reference ranges and the result however agrees with the report of Abdullahi et al. [th week thus indicating a non-significant change.Numerous studies have found that liver problems are the most common non-AIDS cause of death among people with HIV infection. Also liver-related death is one of the major causes of mortality accounting for 14-18% of all deaths in the effective antiretroviral therapy era -53. The i et al. . It is oi et al.  reportedrd visit. Though amylase increased during treatment, it is still within the normal reference range. No case of hyperamylasaemia could be established at the 12th week of administration but there could be possibility of elevated levels at long term treatment. Similarly, plasma creatinine and urea an excellent indicator of kidney function did not show any significant change in their plasma levels between 1st and 3rd visits and with the reference values. This may indicate a normal functional and intact kidney.The pancreatic enzyme amylase (71.21 ± 41.26 U/I) was mildly elevated at the 12th week/3In summary the efficacy of the drug has a reduced haematological and biochemical abnormalities with a normal kidney function. The drug seems to may have worked optimally at about 12 weeks of treatment within the period of test thereby indicating appreciative positive changes in the haematological and biochemical indices measured. These results show that the therapeutic efficacy measured on haematological and biochemical responses are accompanied by a reduction of these (parameters measured) indicators of abnormality. They also suggest possible tendency of the administered ART to drive a shift from the physiological normal ranges of haematological and biochemical (mostly liver damage) indices of healthy status to an elevated range.Admittedly, the study did not consider the intriguing possibility of symptomatic improvement, palliative benefit and CD4 count improvement of the administered drug nor its comparison with any other known antiretroviral drugs thus its limitation.Ethical clearance obtained from Emerging Health and Environment Initiative (EMHEI)/Michael Okpara University of Agriculture with reference N0: Ibeh-2010-25.The authors declare that they have no competing interests.BI: designed the work, interpreted the results. Laboratory analysis and drafting of the original manuscripts and final approval of the version. OO: involved in the project design, result interpretation and analysis laboratory analysis. UI: critical revision of draft article for suitability and intellectual content, statistical analysis and recruitment of the study population. JH: Draft and final revision of manuscript, statistical analysis and subjects recruitment. All authors read and approved the final manuscript.BI: Holds Ph.D in Medical Biochemistry, a University lecturer and currently is an Assistant Director, Medical Biotechnology Department, National Biotechnology Development Agency Abuja, Nigeria. BI is an active member of Nigerian Society of Biochemistry and Molecular Biology ( NSBMB ) and International Union of Biochemistry and Molecular Biology( IUBMB). An external examiner to two Universities and have published several papers and conference proceedings.OO: A lecturer at the Department of Biochemistry, Michael Okpara University of Agriculture. A Pharmacology expert and a Medical laboratory Scientists.UI: Holds Doctor of Optometry (OD). A biostatician and HIV programme specialist at Emerging Health and Environment Initiative.JB: A Deputy Director at National Biotechnology Development Agency.


Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD.HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase , using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms.10 HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations.We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT . There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in logIn this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs.NCT00279110?term = NCT00279110&rank = 1ClinicalTrails.gov NCT00279110  Studies evaluating the efficacy of directly administered antiretroviral therapy (DAART) for the treatment of HIV-infected individuals have yielded mixed results. A systematic review and meta-analysis of randomized trials by Ford and colleagues found no evidence overall for DAART benefit Opioid treatment programs (OTPs) provide a potential framework for DAART because patients visit multiple times each week to receive opioid agonist medication. Moreover, maintenance treatment at OTPs permits prolonged DAART, which is difficult in models based on outreach workers. Based on promising results from a non-randomized pilot study We conducted a randomized controlled trial comparing 12 months of DAART to self-administered therapy (SAT) in five Baltimore OTPs - 3 hospital associated (1 Veterans Administration) and 2 free-standing - which has been described previously We monitored adherence with electronic pill bottle monitors  for the first 2 months after subjects started antiretroviral therapy (ART). We selected a single medication for monitoring according to the following hierarchy: dosed most frequently, combination preparation, protease inhibitor, and non-nucleoside reverse transcriptase inhibitor. We gave all participants an electronic monitor for use at home. Additionally, we used separate monitors to record OTP doses for participants assigned to the DAART arm. We instructed participants on the purpose and use of the monitors and asked them to return at 1 week, 4 weeks, and 8 weeks to download data from the monitors. Research assistants did not review recorded adherence data with participants. The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Each participant provided written informed consent and the study protocol was approved by the Johns Hopkins Medicine Institutional Review Board (IRB), the University of Maryland IRB, and the Veterans Administration Research and Development Committee. This trial was registered at ClinicalTrials.gov (NCT00279110).Individuals were eligible for the study if they were 18 years of age or older, HIV seropositive, not taking ART or virologically failing therapy, and had received methadone or buprenorphine for ≥3 weeks at the OTP with no plans to discontinue. We also required verbal approval from participants’ HIV providers and confirmation of active insurance coverage for ART. Exclusion criteria included ART dosed more frequently than twice daily, use of liquid medication, and use of a regimen that was predicted to have fewer than 1.5 active drugs . The treatment assignment list was incorporated into a Microsoft Access-based program that revealed individual assignments sequentially as new participants were enrolled. The study assignment list was concealed from study staff in a password-protected file.Two pharmacies packaged medications for the DAART arm in single-dose plastic bags that were labeled with medication and dosing information. When participants attended the OTP for methadone or buprenorphine they went to a private office where a research assistant or a methadone nurse observed them take ART doses. The dose observer at each site encouraged DAART subjects to maintain adherence with self-administered doses and helped participants trouble-shoot difficulties that they were having with ART or other medical issues, but did not deliver a manual-based behavioral intervention directed at improving adherence. We gave participants take-home ART doses for weekends and (if applicable) weekdays that they were not required to attend the OTP. Participants who were taking twice-daily regimens self-administered evening doses. We provided DAART subjects with emergency doses to take if they missed a scheduled OTP visit. Participants assigned to SAT self-administered all ART doses. SAT participants were free to engage in adherence services offered by their HIV clinics or providers.10 HIV RNA, change in CD4 cell count, and acquisition of new drug resistance mutations during the intervention phase. We also measured HIV RNA and CD4 count differences at 18 months (6 months after the intervention phase) to assess the persistence of any intervention effects. Other secondary outcomes include retention to the OTP, urine drug tests positive for opiates or cocaine, self-reported emergency department use and hospitalizations, new opportunistic diseases The study’s primary outcome was HIV RNA <50 copies/mL. Specifically, we compared the average proportion of subjects in each arm with HIV RNA <50 copies/mL during the intervention phase  using a generalized estimating equation (GEE) to account for intra-subject correlation. Electronic adherence measures included overall adherence (recorded doses divided by expected doses in the monitoring period), proportions adherent above thresholds of 80% and 95%, and proportion with a 72-hour period without a recorded dose. Secondary outcomes included HIV RNA <400 copies/mL, change in logWe assessed the acquisition of new drug resistance mutations by conducting genotypic resistance tests  on paired failure and baseline samples. Failure samples were defined as the latest sample from the 3, 6, or 12 month visits in which the HIV RNA was ≥500 copies/mL. We defined new drug resistance mutations as clinically significant drug mutations listed in the International AIDS Society compendium Based on our pilot experience 10 HIV RNA. For the main two-factor model, the coefficient X1 represented the difference in the odds of viral suppression between the intervention phase and baseline in the SAT arm, while the coefficient X3 represented the difference between DAART and SAT in the odds of viral suppression during the intervention phase versus baseline. The model accounted for the intra-person dependency of observations using the generalized estimating equation (GEE) approach Analyses were based on the intent-to-treat approach. For the primary analysis and other binary outcomes, we evaluated the difference between arms using a logistic regression model with two explanatory variables: an indicator for follow-up versus baseline visits , and an interaction term between the intervention indicator  and the follow-up indicator . Note that the intervention indicator, X2, was not included in the main model considering the randomized design of the trial, which tends to balance both measured and unmeasured covariates. However, since this was a small trial we ran additional models in sensitivity analyses that adjusted for baseline values of log10 HIV RNA level and CD4 cell counts), we used linear regression GEE models to compare the average levels between the two treatment arms over follow-up, while accounting for the repeated measures design. These models included the same two factors, X1 and X3, described above. Undetectable HIV RNA values were assigned a value equal to the limits of assay detection (50 copies/mL). Estimated differences and 95% CI were based on model outputs. We compared retention to OTPs between arms using a Cox proportional hazards model for time from baseline to exit from the OTP, with results reported as a hazard ratio (HR) with 95% CI. Additional secondary endpoints measured at a single point in time were evaluated as differences in means for continuous outcomes or differences in proportions for binary outcomes. The estimated differences with 95% CI were calculated by using two-sample t-tests for means or Fischer’s exact test for proportions. In post-hoc analyses, we assessed the associations of selected factors with HIV RNA <50 copies/mL during the intervention phase with GEE logistic regression models as described above, with results reported as odds ratios (OR) and 95% CI. We assessed potential effect modification between these factors and the association between study arm and viral load suppression by combining terms in models and reporting P values for interaction terms. STATA version 12 software  was used for statistical analyses.For continuous outcomes . Research assistants observed a median of 90 doses (IQR 28–183) in DAART participants, and this varied by participants’ OTP reporting frequency at baseline . Fifty six percent (IQR 20%–79%) of expected observed doses were actually observed. Drop-out from the OTP or ART discontinuation accounted for a substantial proportion of non-observed doses. For example, when considering only the weeks in which DAART participants were retained to the intervention, 72% (IQR 56%–83%) of expected observed doses were observed. During electronic adherence monitoring in the first 2 months of the intervention, a median of 53% (IQR 33%–63%) of all doses taken by subjects in the DAART arm was observed in an OTP.The proportions of SAT and DAART subjects with HIV RNA <50 copies/mL at each visit are shown in 10 HIV RNA and CD4 cell counts, respectively. The differences between arms in log10 HIV RNA and CD4 cell changes from baseline were not statistically significant , or average change in CD4 count from baseline .At 18 months (6 months following the intervention phase) there were no significant differences between DAART and SAT in the proportions with HIV RNA <50 copies/mL , the proportions with HIV RNA <400 copies/mL , average change in HIV RNA from baseline , with no difference by study arm (data not shown). Adherence was marginal: the average adherence was 73% and only 14% were ≥95% adherent. There were no statistically significant differences in any adherence parameters between the study arms . The proFewer participants assigned to DAART (45%) than SAT (60%) met virologic failure criteria for resistance testing during the intervention phase, although the difference was not statistically significant . Among tThe estimated OTP retention at 6 and 12 months were 78% and 60% in DAART, and 83% and 73% in SAT, respectively . During the intervention phase, the average proportions with urine drug tests positive for opiates or cocaine were 0.33 and 0.37 in DAART and SAT, respectively .In post-hoc analyses, we examined the associations of selected baseline factors with the likelihood of achieving HIV RNA <50 copies/mL during the intervention phase in univariate models. Compared to ART-naïve subjects, ART-experienced subjects had similar odds of viral suppression . Compared to subjects who had attended the OTP for >12 months at enrollment, those who has attended ≤12 months had lower odds of viral suppression . Compared to subjects dosed at the OTP five or more days each week, those dosed less frequently than five days per week had lower odds of viral suppression . There was no evidence that ART-exposure status, duration of OTP attendance, or OTP dosing frequency modified the association between study arm and HIV RNA <50 copies/mL during follow-up .10 HIV RNA or in CD4 cell counts and, importantly, there were no differences between arms in electronically measured adherence. OTP retention and urine drug test results for opiates or cocaine were also similar in the two arms. Few subjects acquired new drug resistance mutations during the intervention phase, and the proportions acquiring new drug resistance were similar in the study arms.In this randomized trial of HIV-infected subjects receiving methadone or buprenorphine in OTPs, we found little evidence that DAART provided benefit compared to SAT. DAART was associated with a non-statistically significantly higher average proportion with HIV RNA <50 copies/mL during the intervention phase, the primary outcome. However, there were no differences between arms in average change in logNotably, our failure to find a benefit with DAART did not occur in the context of a high overall success rate as has been the case in some DAART trials that enrolled individuals at relatively low risk for virologic failure Our findings should be interpreted in the context of other randomized trials of DAART in similar populations. In contrast to our findings, three prior randomized trials among substance abusers reported statistically significantly higher rates of viral suppression compared with DAART compared to SAT, and two of the three trials also reported statistically significantly larger increases in CD4 cell counts with DAART There are potential explanations for the different findings of our trial and the Bronx trial. First, subjects enrolled in the Bronx study may have been more stable than those in our study. In the Bronx study, participants had been receiving methadone for a median of 10 years at enrollment, compared to a median of 11 months in our study. In a post-hoc analysis, we found that subjects who had attended the OTP for less than 1 year at study enrollment were significantly less likely to achieve viral load suppression than those who had attended the clinic for more than 1 year. Additionally, only 4% (3/77) subjects in the Bronx study left the OTP during the study, compared with 20% (21/107) in a similar time frame in our study. Second, the Bronx trial was conducted in a jointly administered network of OTPs that offered on-site medical and HIV care Despite success in some studies, it is difficult to formulate recommendations for DAART. Unlike tuberculosis, which is curable with 6 months of chemotherapy and where directly observed therapy has assumed central role, HIV treatment requires lifelong medication adherence. Existing research has not addressed the long-term effectiveness of DAART - most studies have used intervention periods of 6 months or less, and three studies where an early viral suppression benefit was observed reported that the differences between arms waned rapidly following intervention cessation Our study has limitations and strengths. First, our final sample size was small (107) and we failed to meet our revised enrollment target of 120. Consequently, results from our single trial cannot completely exclude a clinically significant difference in the study arms and our results should be interpreted in the context of other studies in this area. However, our failure to detect a statistically significant difference in viral suppression between the arms – the primary outcome - was supported by a cadre of secondary outcomes, including electronic adherence monitoring. Second, in response to lower than expected recruitment we changed our primary analysis from comparison of viral suppression at a single time point to a repeated measures analysis using GEE. While the repeated measures approach is robust and produces valid inferences, the comparison of average suppression rates may have less clinical relevance and less straightforward applicability to other work than comparison at a single time point.3 lower in the SAT arm than the DAART arm. Differences in baseline immune status and higher mortality in SAT compared to DAART may have affected the comparison of viral suppression rates. In the primary intent-to-treat analysis where missing values were ignored, higher mortality in the SAT arm may have reduced the apparent difference in viral suppression between the arms. In contrast, in the secondary intent-to-treat analysis where missing results were considered failures, differences in mortality or drop-out for other reasons would be reflected in viral suppression differences. In our analyses, the results were similar and inferences unchanged when missing values were ignored or treated as failures. Fourth, our study was conducted in Baltimore, Maryland, and may not reflect intervention efficacy in other domestic or international settings. The strengths of our study include >90% follow-up at study visits during the intervention phase, a 12-month intervention to assess longer-term efficacy, a rigorous electronic adherence monitoring protocol for both study arms, and a study assessment 6 months after the DAART conclusion to assesses post-intervention durability.Third, the median CD4 cell count at baseline was almost 100 cells/mmIn conclusion, compared to SAT, we found that rates of viral suppression were similar with DAART or SAT among HIV-infected participants attending OTPs in Baltimore. There were no differences between the arms in electronically monitored adherence, CD4 cell count change, emergency room use, hospitalizations, retention to OTP, urine drug screen results, or acquired drug resistance.Checklist S1CONSORT 2010 checklist of information to include when reporting a randomised trial.(DOC)Click here for additional data file.Protocol S1IRB-approved protocol for trial.(DOC)Click here for additional data file.


Michael Chung and colleagues show that intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure, whereas use of an alarm device had no effect. Behavioral interventions that promote adherence to antiretroviral medications may decrease HIV treatment failure. Antiretroviral treatment programs in sub-Saharan Africa confront increasing financial constraints to provide comprehensive HIV care, which include adherence interventions. This study compared the impact of counseling and use of an alarm device on adherence and biological outcomes in a resource-limited setting.p = 0.055) and 59% less likely to experience viral failure   compared to those who received no counseling. There was no significant impact of using an alarm on poor adherence  or viral failure  compared to those who did not use an alarm. Neither counseling nor alarm was significantly associated with mortality or rate of immune reconstitution.A randomized controlled, factorial designed trial was conducted in Nairobi, Kenya. Antiretroviral-naïve individuals initiating free highly active antiretroviral therapy (HAART) in the form of fixed-dose combination pills  were randomized to one of four arms: counseling (three counseling sessions around HAART initiation), alarm (pocket electronic pill reminder carried for 6 months), counseling plus alarm, and neither counseling nor alarm. Participants were followed for 18 months after HAART initiation. Primary study endpoints included plasma HIV-1 RNA and CD4 count every 6 months, mortality, and adherence measured by monthly pill count. Between May 2006 and September 2008, 400 individuals were enrolled, 362 initiated HAART, and 310 completed follow-up. Participants who received counseling were 29% less likely to have monthly adherence <80%  recent studies have shown that adherence is high in African HIV treatment programs and often better than in Western HIV clinics. For example, in a meta-analysis of 27 cohorts from 12 African countries, adequate adherence was noted in 77% of subjects compared to only 55% among 31 North America cohorts; (2) choice of antiretroviral regimens may impact on the development of antiretroviral resistance. In poor countries, most antiretroviral regimens contain non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as nevirapine or efavirenz, which remain in the patient's circulation for weeks after single-dose administration. This situation means that such patients may not experience antiretroviral resistance unless they drop below 80% adherence—contrary to the more stringent 95% plus adherence levels needed to prevent resistance in regimens based on unboosted protease inhibitors—ultimately, off-setting some treatment lapses in resource-limited settings where NNRTI-based regimens are widely used.Given that adherence may not be as crucial an issue as previously thought, antiretroviral treatment programs in sub-Saharan Africa may be spending scarce resources to promote adherence to the detriment of some potentially more effective elements of HIV treatment and management programs. Although many treatment programs currently include adherence interventions, there is limited quality evidence that any of these methods improve long-term adherence to HIV treatment. Therefore, it is necessary to identify adherence interventions that are inexpensive and proven to be effective in resource-limited settings. As adherence counseling is already widely implemented in African HIV treatment programs and inexpensive alarm devices are thought to also improve compliance, the researchers compared the impact of adherence counseling and the use of an alarm device on adherence and biological outcomes in patients enrolled in HIV programs in rural Kenya.The researchers enrolled 400 eligible patients  to four arms: (1) adherence counseling alone; (2) alarm device alone; (3) both adherence counseling and alarm device together; and (4) a control group that received neither adherence counseling nor alarm device. The patients had blood taken to record baseline CD4 count and HIV-1 RNA and after starting HIV treatment, returned to the study clinic every month with their pill bottles for the study pharmacist to count and recorded the number of pills remaining in the bottle, and to receive another prescription. Patients were followed up for 18 months and had their CD4 count and HIV-1 RNA measured at 6, 12, and 18 months.Patients receiving adherence counseling were 29% less likely to experience poor adherence compared to those who received no counseling. Furthermore, those receiving intensive early adherence counseling were 59% less likely to experience viral failure. However, there was no significant difference in mortality or significant differences in CD4 counts at 18 months follow-up between those who received counseling and those who did not. There were no significant differences in adherence, time to viral failure, mortality, or CD4 counts in patients who received alarm devices compared to those who did not.The results of this study suggest that intensive adherence counseling around the time of HIV treatment initiation significantly reduces poor adherence and virologic treatment failure, while using an alarm device has no effect. Therefore, investment in careful counseling based on individual needs at the onset of HIV treatment initiation, appears to have sustained benefit, possibly through strengthening the relationship between the health care provider and patient through communication, education, and trust. Interactive adherence counseling supports the bond between the clinic and the patient and may result in fewer patients needing to switch to expensive second-line medications and, possibly, may help to decrease the spread of resistant HIV. These findings define an adherence counseling protocol that is effective and are highly relevant to other HIV clinics caring for large numbers of patients in sub-Saharan Africa.http://dx.doi.org/10.1371/journal.pmed.1000422.Please access these Web sites via the online version of this summary at HIV treatment strategiesUNAIDS provides information about adherence to HIV treatment regimensThe American Public Health Association has information about information for patients about adherence to HIV treatmentThe US Department of Health and Human Services has HIV treatment pharmacovigilanceThe World Health Organization provides information about  The introduction of antiretroviral medications on a public health scale to treat HIV-positive persons in sub-Saharan Africa has been accompanied by concern that these actions will result in widespread viral resistance because of poor adherence Among individuals with imperfect adherence, the choice of antiretroviral regimens may impact the development of antiretroviral resistance. In resource-limited settings, most antiretroviral regimens contain non-nucleoside reverse transcriptase inhibitors (NNRTI) Given these findings, antiretroviral treatment programs in sub-Saharan Africa may be spending valuable resources promoting adherence Inexpensive adherence interventions need to be identified that are proven to be effective in resource-limited settings. Counseling is widely implemented in HIV treatment programs in Africa, but delivery of this intervention is not uniform and its impact on improving adherence is unclear. There is some evidence that early intensive counseling around the time of HAART initiation may be beneficial 3, World Health Organization (WHO) clinical stage IV disease, or a CD4 count <350 cells/mm3 with WHO clinical stage III disease The trial was conducted between May 2006 and September 2008 at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya  and S2. The study evaluated two interventions based on models of cognitive and behavioral theory to promote adherence to antiretroviral medications: intensive adherence counseling and use of a pocket alarm device In the adherence counseling intervention, trained counselors administered two counseling sessions to participants prior to HAART initiation and a third session one month after HAART initiation . CounselParticipants in the alarm device intervention received a small pocket digital alarm, the ALRT PC200 (ALR Technologies Inc), which the individual was to carry at all times for 6 mo duration. The device was programmed by the study staff to beep and flash twice a day at a time convenient to the participant when medications were to be taken. The digital alarm could not be reprogrammed or inactivated by the individual and was utilized for 6 mo after HAART initiation before being disabled by study staff.At HAART initiation, the study pharmacist explained the side effects of medications and problems associated with poor adherence in a 15-min session prior to dispensing drugs. All participants, including those in the control arm, received this educational message. Participants randomized to the control group did not receive adherence counseling or an alarm device.At enrollment, participants signed a written informed consent, had blood drawn for HIV-1 RNA levels and CD4 count, and shared information on sociodemographic characteristics, risk behavior, and distance from clinic. After initiating HAART, participants returned to the study clinic at monthly intervals with their pill bottles to pick up antiretroviral medications. At each monthly visit, the study pharmacist counted and recorded the number of pills remaining in the bottle, the visit date, whether the participant took his or her morning dose, and the number of pills dispensed that day. Participants randomized to receive an alarm device were asked if they had been using the device at each of these monthly visits, and any defective, lost, or stolen devices were replaced at this time. Blood was drawn for CD4 count and HIV-1 RNA at 6, 12, and 18 mo after HAART initiation. Participants were followed for 18 mo on HAART before exiting the study. HIV-1 RNA was measured using the Gen-Probe quantitative HIV-1 viral load assay Adherence was calculated at each pharmacy refill visit as the percentage of dispensed doses that were taken since the previous visit to the study pharmacy. Total time between the last date the participant was in the pharmacy and the participant's subsequent pharmacy visit included any missed visits to the pharmacy or time when the participant was not attending the clinic. This calculated adherence was assumed to be constant and the same as daily adherence throughout this time period. Continuous adherence and time to monthly adherence <80% and <95% were calculated p-value larger than 0.20 and therefore was dropped from the model. Accordingly, following the factorial design of the study, those who received counseling were compared against those who received no counseling and those who received an alarm device were compared against those who received no alarm. Analyses of discrete time-to-viral-failure event models were performed using SAS 9.2; all other analyses were performed using StataSE v10 (StataCorp).All analyses were modified intent-to-treat in that only individuals who initiated HAART, and therefore had pill count data collected for adherence measurement, were included in the analyses. Data from all participants were utilized in analyses until time of exit either because of completion of the study, loss to follow-up, or death. Because of the factorial design of the study, models to evaluate the study interventions were developed by first testing the statistical interaction between those who received counseling and those who received alarm. In all models, the interaction term had a Univariate comparisons were done using the Mann Whitney U test for continuous variables, and Chi square tests for binary variables. Baseline characteristics were compared between interventions and if there were statistically significant differences , then these variables were tested to see if they also related to the various outcomes of interest . If baseline variables met both criteria , then they were included in a multivariable model Analyses of time to monthly adherence <80% and <95%, viral failure, and death were performed using Cox proportional hazards models. Kaplan-Meier methods were used to create time to event graphs. Longitudinal analyses of adherence were performed using generalized estimating equations (GEE) with an exchangeable correlation matrix and robust variance estimate. Linear regression was used to assess differences in change in CD4 count.The sample size was calculated as follows. Given information from previous studies The study protocol was reviewed and approved by the institutional review boards at the University of Washington and Kenyatta National Hospital .Enrollment of participants began on May 2006 and ended on November 2006 during which time 1,096 patients were deemed eligible to receive HAART at the Hope Center . Of thes362 participants initiated HAART  and were included in analyses of the study endpoints . In thisFor all endpoint analyses, the interaction term between counseling and alarm was tested and not statistically significant. Therefore, those who received counseling  were compared to those who received no counseling  and those who received an alarm device  were compared to those who received no alarm (participants from the counseling and control arms).p = 0.002) and fewer people per household . Prior to HAART initiation, 29 (7%) participants were lost to follow-up and nine (2%) died. Monthly rent was higher among those who did not initiate HAART compared to those who did .At the end of study follow-up, there were 52 patients who were lost to follow-up and 38 deaths . In a co200 participants were randomized to the adherence counseling intervention and 164 (82%) received all three assigned counseling sessions, 21 (10.5%) received two sessions, seven (3.5%) received one session, and eight (4%) did not undergo any sessions. All of those who did not receive all three counseling sessions died or were lost to follow-up before completing the intervention.200 participants were randomized to receive the alarm device intervention and to use it for 6 mo after HAART initiation. 29 individuals died or were lost to follow-up before the pocket alarm was used. Among those who used the external reminder, 150 (88%) reported using it for 5 to 6 mo after HAART initiation: 107 (63%) reported using the alarm at all monthly follow-up visits over 6 mo, 43 (25%) reported not using the device at one visit, 11 (6%) at two visits, seven (4%) at three visits, and three (2%) at four visits. Reasons for not using the pocket alarm included: the device not working properly (72%), stolen (11%), lost (6%), no reason (6%), forgot (2%), no need (2%), and unable (1%). There were no reports of not using an alarm device because of stigma and all participants requested to keep the inactivated alarm device for use as a pocket watch after the 6-month intervention had ended.There was no harm or unintended effect recorded for either intervention.p = 0.023) compared to those who did not receive counseling, and this difference was constant over 18 mo follow-up  (p = 0.055) (p = 0.053). No significant differences were found in adherence <95% between those who received counseling and those who did not .In longitudinal analysis, adherence during the first month after initiating HAART was significantly higher among those who received counseling  . Those pp = 0.01) (p = 0.01).Participants who received counseling were 59% less likely to experience viral failure  than those who did not receive counseling  . Signifip = 0.7) (p = 0.7), and this lack of significant difference remained in multivariable modeling controlling for age at baseline (unpublished data).There was no significant difference in mortality between those who received counseling and those who did not  . There wp = 0.6), and this lack of difference continued over 18 mo follow-up  (p = 0.7), even after adjusting for baseline differences of ever having given or received money/favors in exchange for sex , death , immunological recovery , and adherence <95%  between those who received an alarm device and those who did not. These results remained unchanged in multivariable analyses and at a viral failure threshold of HIV-1 RNA ≥1,000 copies/ml (unpublished data).There was no significant difference in any of the study endpoints between those who received alarm device and those who did not . In longp = 0.3) . Those wp = 0.01) less likely to experience viral failure, demonstrating the powerful impact of this behavioral intervention on biological outcomes. Although poor adherence has been associated with plasma HIV-1 viral rebound and development of viral resistance In this randomized controlled trial comparing counseling and the use of an alarm device to improve adherence to antiretroviral medications in Kenya, participants receiving intensive early adherence counseling were 59%  less likely to experience poor adherence compared to those who received no counseling. The positive effects of counseling on adherence in this study were found immediately after HAART initiation and were sustained over 18 mo. Trained counselors provided not only didactic information but discussed barriers to good adherence and developed a relationship with participants through one-on-one interviews conducted over 2 mo. Motivating individuals to change their behavior through counseling appears to give individuals tools they need to improve their adherence Those receiving adherence counseling in this study were 29%  In summary, we found that intensive counseling on adherence to antiretroviral medications around the time of HAART initiation significantly reduced poor adherence and virologic treatment failure, while using an alarm device had no impact. Investment in careful individualized counseling at the onset of HAART appears to have sustained benefit. These findings are highly relevant to other HIV clinics caring for large numbers of patients in sub-Saharan Africa. Implementing adherence counseling or interventions that strengthen the relationship between the provider and patient through communication, education, and trust may substantially reduce the risk of antiretroviral treatment failure. Supporting the bond between the clinic and patient in this way appears to be more effective than using a device that simply reminds patients when to take their pills. Through interactive counseling and communication, fewer patients may need to switch to expensive second-line medications and the spread of resistant HIV may decrease.Text S1Trial protocol.(0.33 MB PDF)Click here for additional data file.Text S2CONSORT checklist.(0.22 MB DOC)Click here for additional data file.


Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda.A prospective cohort of HIV-infected infants receiving treatment at the Baylor-Uganda clinic was analyzed. Patients were diagnosed, enrolled and followed up at the clinic. HIV viral load, CD4 cell counts and clinical progress were assessed during follow-up. Descriptive statistical analysis and logistic regression modeling to determine predictors of treatment success were conducted.Of 91 HIV-infected infants enrolled into the cohort, 53 (58.2%) infants were female; 43 (47.3%) were 6 months of age or younger, and 50 (55.6%) had advanced HIV/AIDS disease . Eighty four infants started ART and 78 (92.9%) completed 6 months of treatments. Fifty six (71.8%) infants attained virologic suppression by month-6 of ART, and at month-12 of ART, the cumulative probability of attaining viral suppression was 83.1%. None of the baseline infant factors  predicted treatment success. There was an increase in CD4 cells from a baseline mean of 23% to 30% at month-6 of treatment (p<0.001) and by month-24 of ART, the mean CD4 percent was 36%. A total of 7 patients died while on ART and another 7 experienced adverse events that were related to treatment.Our results show that, even among very young patients from resource constrained settings, ART dramatically suppresses HIV replication, allows immune recovery and clinical improvement, and is safe. However, baseline characteristics do not predict recovery in this age group. Over the last decade, the beneficial effects of antiretroviral therapy (ART) have been reported among HIV-infected adults and children in both resource rich and resource poor countries -4. AntirThe World Health Organization (WHO) in its 2010 revision of HIV treatment guidelines recommends early initiation of ART among infants and young children . As thesThe objective of this study was to determine the virologic response to ART in a cohort of HIV-infected Ugandan infants (children less than 12 months of age) as measured by HIV viral suppression after 6 months of therapy; determine the level of immunologic recovery as measured by increase in CD4 cell counts; and determine the proportion of infants developing ART-related adverse events.For this observational cohort study, we recruited and followed HIV-infected infants who were enrolling for care and treatment at the Baylor College of Medicine Bristol Myers Squibb Children’s clinical centre of excellence at Mulago Hospital (Baylor-Uganda) in Kampala, Uganda. Baylor-Uganda is a Non Governmental Organization (NGO) involved in the prevention, care and treatment of HIV-infected children and their families in Uganda. The Foundation is donor funded and runs a clinic that offers free clinical care to all its patients. The clinic is an out-patient treatment center that operates five days a week with an average daily attendance of 170 patients. Over 90% of patients seen at the clinic are children from the age of 6 weeks to 18 years. Parents or adult caretakers constitute the remainder of the patients.At the clinic, patient care involves HIV diagnosis and treatment, nutritional rehabilitation, diagnosis and treatment of opportunistic infections, counseling and social support. Infants enrolled for care at the clinic are referred from the nearby Mulago National Referral hospital wards and from other centers involved in Prevention of Mother to Child HIV Transmission (PMTCT). Some infants are referred from HIV treatment centers within the country, and others are self referrals.Study participants were identified and recruited into the cohort from the Baylor-Uganda clinic patient population. Study participants were selected based on a criteria that required them to be clinic patients, confirmed to be HIV positive ; between 6-weeks and 12 months of age; ART naïve, but willing to start ART as soon as deemed necessary by the clinician; reside within 20 kilometer radius from the clinic; willing to be visited at home; and agree to be regularly followed-up at the clinic. Children without parents or guardians were excluded. Patients less than 6 weeks of age were not included since they were not routinely registered for care at the clinic. Based on WHO guidelines for infant diagnosis , and recFrom April 2009 to March 2012, all clinic patients that fulfilled the selection criteria were consecutively recruited into the cohort and were subsequently followed up.Before starting ART, we confirmed HIV infection in the infants by carrying out an HIV DNA Polymerase Chain Reaction (PCR) test followed 2 weeks later by a viral RNA PCR test to quantify the HIV virus in the blood. To be considered HIV infected, both tests had to confirm presence of the virus in blood.All laboratory- confirmed HIV infected infants were started on ART. Infants enrolled before July 2010 were started on ART based on the 2006 WHO guidelines for ART initiation. Based on these guidelines, all infants with CD4 cell counts below 25% or in advanced WHO clinical stages (stages 3 and 4) were considered eligible for ART and were started on treatment. Following the 2010 revision of WHO treatment guidelines, all HIV-infected infants were started on ART irrespective of their clinical stage or CD4 cell counts. A combination of 2 Nucleoside Reverse transcriptase inhibitor (NRTI) drugs and 1 Non-Nucleoside Reverse Transcriptase (NNRTI) or Protease Inhibitor was the ART combination of choice. Zidovudine (ZDV) or stavudine (D4T) combined with lamivudine (3TC) together with either nevirapine (NVP) or Lopinavir/ritonavir were the main ART drug combinations as recommended by WHO. Stavudine was preferred in patients with anemia (hemoglobin <7.5 g/dl) and Lopinavir/ritonavir was preferred in patients exposed to single dose NVP for PMTCT. Patients on rifampicin for treatment of tuberculosis were put on 3 NRTIs (ZDV or D4T + 3TC + Abacavir).Baseline measurements and tests were carried out on the date when ART was started and subsequent follow-up visits were scheduled 2, 4, and 8 weeks after starting treatment. Thereafter, patients returned to the clinic monthly, and if an appointment was missed, a home visit was carried out by trained home health workers. In addition, parents were encouraged to bring the children for medical care whenever they fell sick. At baseline and every 6 months thereafter, blood samples were drawn for complete blood count (CBC), CD4 cell count; liver function test [serum alanine amino transferase (ALT)], and HIV viral load.At every visit, physicians reviewed the infant, documented and managed any adverse events or opportunistic infections. In addition, nutritional assessment including measurement of weight and height was conducted. Anthropometric computations and comparisons were conducted using the WHO anthro software  which isAntiretroviral therapy was considered the exposure variable and the primary outcome variable was viral suppression 6 months after ART initiation. Other outcomes of interest included change in CD4 cell count; occurrence of ART-related adverse events; death during follow-up; and change in nutritional status as measured by weight-for-age, height-for-age and weight for height z-scores. Virologic suppression was defined as the attainment of HIV viral loads less than 400 copies/ml after 6 months of ART.Patients’ age, sex, WHO clinical stage, ART combination, presence of opportunistic infections and concurrent use of other medication, were considered potential confounders and were therefore documented and considered in the analysis.All patient information was recorded in structured forms and was subsequently entered into the clinics electronic medical database which is designed to check for consistency of the data.Written approval to conduct the study was granted by Makerere University College of Health Sciences’ Research and Ethics committee, Uganda National Council of Science and Technology, and Baylor College of Medicine Institutional Review Board (USA). The parents or caretakers gave written informed consent to participate in the study.t-test to compare the mean CD4 cell counts at baseline and during follow-up. Virologic suppression was categorized as ‘successful’ for viral loads less than 400 copies per milliliter and as ‘unsuccessful’ if otherwise. We used bivariate and multivariable logistic regression models to identify predictors of successful virologic suppression. Proportions of infants developing ART related adverse events were computed. For all analyses, confidence intervals (CI) were set at the 95% level and p-values less than 0.05 were considered statistically significant.Descriptive analyses of baseline and follow-up characteristics are presented as proportions, medians with inter-quartile ranges (IQR), and means with standard deviations (SD).We used the paired Of 91 HIV-infected infants enrolled into the cohort during the study period, 53(58.2%) patients were female; 43(47.3%) were 6 months of age or younger, and 57 (62.7%) were moderate or severely underweight  infants were started based on the 2006 WHO treatment guidelines and 25(29.8%) were started based on the revised 2010 treatment guidelines. Seven infants were not started on treatment because 4 of them died shortly after enrolment and 3 were lost to follow-up before ART could be initiated. Among infants that started ART, 78 (92.9%) were in active care at the end of the first 6 months of therapy; 4 patients died and 2 were lost to follow-up within the 6 month period. At the end of the study period, 70, 62 and 47 patients had received ART for at least 12, 18 and 24 months respectively.Of the 78 infants that had ART for at least 6 months, successful viral suppression was seen in 56(71.8%) infants. Twenty two 28.2%) infants continued to have detectable viremia at month-6 of treatment. In univariate and multivariable regression analysis; none of the baseline factors such as age, gender, CD4 cell percent, WHO clinical stage, choice of antiretroviral agent, weight for age or height for age z-scores could predict treatment success at month-6 of therapy  were still on first line treatment. Of these, 37(84.1%) continued to have viral suppression; and 7 patients had detectable viremia, all of whom had earlier achieved viral suppression.Altogether 7 patients were switched to second-line treatment (Abacavir + 3TC + Lopinavir/ritonavir) as a result of persistent viremia;5 out of the 7 attained viral suppression 6 months after starting second-line ART, and 2 patients were yet to complete 6 months of second-line ART.The cumulative probabilities of attaining viral suppression at month-6 and month-12 of ART were 71.8% (95% CI: 61.6-81.3) and 83.1% (95% CI: 73.8-90.5) respectively.The choice of third agent (Nevirapine versus Lopinavir/r) was not associated with risk of viremia at month-6, even after adjusting for the choice of NRTI backbone and baseline WHO clinical stage, Risk Ratio(RR)=1.1 (95% CI: 0.8-1.5), P=0.152. There was no association between WHO guideline used for patient treatment (2006 versus 2010) and risk of virologic failure at month-6 of ART; RR=1.24 (95% CI: 0.9-1.6).There was a significant increase in CD4 cells from a baseline mean of 23% SD=10.1) to 30% (SD=9.6) at month-6, P<0.001; and to 33% (SD=8.9) at month-12 of ART; . By the end of the second year of ART, the mean CD4 cell percentage rose to 36% (SD=8.05)  of the 84 patients that started ART were diagnosed with tuberculosis at baseline or shortly after ART initiation. Anti-tuberculosis treatment was started but one patient died after 5 months of ART and tuberculosis medication. One 7-month old infant was diagnosed with disseminated Bacillus Calmette-Guerin (BCG) infection 3 months after starting ART. He was treated as a case of immune reconstitution inflammatory syndrome (IRIS) and improved.At ART initiation, 54 (64.3%) of 84 patients had a WAZ-score below -2SD of the WHO reference median. This prevalence of underweight varied according to age and clinical stage of the disease. Thirty six (80%) of 45 older infants (7-12 months of age) compared to 18(46.2%) of 39 younger infants (1-6 months of age) were underweight at baseline; prevalence ratio= 1.7 (95% CI: 1.19-2.51). Of 47 infants with baseline advanced HIV disease , 36 (76.6%) were underweight; and among 37 infants with milder clinical disease , 18 (48.6%) were found to be underweight at baseline; prevalence ratio= 1.6 (95% CI: 1.09-2.27). There was no association between baseline underweight and gender or baseline CD4 cell counts.Among the 78 infants that received ART for at least 6 months, the proportion that were underweight reduced from 65.4% at baseline to 30.8% at 6 month of ART, p<0.001Eighty one patients were included in the analysis of height for age z-scores (HAZ-score). Of these, 32 (39.5%) patients had baseline HAZ-score less than -2. Twenty (46.5%) out of 43 infants aged 6-12 months compared to 12 (31.5%) out of 38 infants younger than 6 months of age were stunted; prevalence ratio=1.5 (95% CI: 0.84-2.60). Twenty three (51.1%) of 45 patients in WHO stage 3or 4 compared to 9 (25%) of 36 patients in WHO stage 1 or 2 were stunted at baseline; prevalence ratio=2 (95% CI: 1.08-3.85).There was no significant change in stunting in the first 6 month of ART. Of 75 patients that had both baseline and follow-up HAZ-score measurements, the prevalence of stunting increased from 40% at baseline to 48% after 6 months of ART, p=0.134.Of 65 patients that were included in the analysis of weight for height z-scores (WHZ-score), 22 (33.8%) had baseline WHZ-scores less than -2. However, after 6 months of ART, only 9 (13.8%) patients continued to have WHZ-scores less than -2; p=0.007.th month and 2 died in the second year of ART. The overall mortality rate among children on ART was 4.09 (95% CI: 1.95-8.58) per 100 child-years. Post mortem examinations were not carried out; however, the majority of patients that died had underlying malnutrition  patients died during the follow-up period. Four of the 11 died before ART could be initiated. All 4 patients were in WHO clinical stage 4; between 6-12 months of age at the time of death; and had been in care for 6-11.7 weeks. The illness preceding death was tuberculous pericarditis for one female infant, dysentery and lymphoma for other 2 female infants and Pneumocystis Jirovecii Pneumonia for the only male infant. Of the 7 infants that died while on ART, 4 died within the first 6 months, 1 died in the 8Within the first 6 months of ART, adverse events were reported in 7 (8.3%) of the 84 patients that started treatment. Of the seven, 3 patients developed diarrhea, 1 had nausea and vomiting, 2 had anemia and 1 developed a skin rash. One of the 3 infants with diarrhea and the one infant with nausea and vomiting were on a PI based regimen. All patients with anemia were on ZDV and the one patient with skin rash was on nevirapine. All patients that developed anemia or skin rash had ART regimen change. Patients with diarrhea, nausea and vomiting had mild and transient illness not requiring ART regimen change.In this study, which involved a cohort of HIV-infected infants receiving first-line antiretroviral therapy in an outpatient setting in Uganda, we found that 71% of infants attained virologic suppression by 6 months of ART. In general, the infants had good immune recovery and experienced low levels of drug toxicity, with only 8% of patients reporting adverse events during the study period. Our results show that, even among very young infants from resource constrained settings, ART dramatically suppresses HIV replication, allows immune recovery and clinical improvement, and is safe.In sub-Saharan Africa, the treatment of HIV-infected infants has lagged behind that of older children and adults largely as a result of delays in diagnosis , restricCompared to participants of the CHER study , infantsAmong several cohorts of HIV-infected African children currently undergoing treatment, viral suppression within the first 6 months of ART has been reported in 60% to 89% of patients -21. Our In all patients on ART, the initial rapid attainment of viral suppression is critical for the long term success of treatment. Viral suppression permits immune recovery and often delays the development of viral resistance . PersistThe immune recovery that occurred in our cohort was remarkable. The change from a baseline mean of 22% to 30% after 6 months of ART compares favorably with results seen among cohorts of children receiving treatment elsewhere in Africa . In geneDespite this general success in treatment, several children failed to attain viral suppression, even after 6-12 month of first-line treatment. We presume that these children may have been infected with mutant resistant viruses from mothers that were already on treatment with first-line ART. Though HIV resistance tests were not carried out, our conclusion is that these children may have been cases of primary HIV resistance, or cases of resistance resulting from prior use of antiretroviral agents for PMTCT. Once switched to second line ART, viral suppression was quickly attained. These results are worrying since it implies that either the mothers on treatment are passing on resistant virus to their infants, or prior administration of PMTCT medication to infants maybe contributing to the development of viral resistance. This development further limits the treatment options available for these children. With more adults accessing and failing first-line ART, these results underscore the need for HIV resistance testing among HIV-infected infants born to such adults.The viral rebound that occurred in 7 patients after initial suppression may have been due to early viral resistance or due to poor adherence to medication at the time the viral load tests were carried out.We noted a high level of acute and chronic malnutrition in this cohort and this may have been due to a combination of clinical and social factors that ultimately led to reduced caloric intake, reduced absorption and increased loss of nutrients needed for growth. This high prevalence of malnutrition underscores the need for an integrated HIV treatment approach that incorporates interventions focusing on reducing malnutrition.As reported in previous studies ,26, deatOur study had several limitations: We were not able to accurately document PMTCT history; neither were we able to carry out HIV resistance testing. In addition, we were unable to carry out postmortem examination of patients that died, and we did not measure adherence to medication though it was emphasized at every clinic visit. Despite these limitations and the possibility of failing to detect significant differences due to the small sample size, the results presented here draw attention to a vulnerable group of HIV-infected children and highlight the feasibility of treatment success even in resource constraint settings.Our results indicate that despite the high prevalence of malnutrition and the probable transmission of resistant virus from mothers to infants, treatment success for HIV-infected infants living in resource-constrained settings is possible. We recommend an integrated approach to early infant diagnosis and treatment that takes into consideration early detection of viral resistance especially among infants whose mothers received ART during pregnancy and a robust nutritional intervention plan for every infant.The authors declare that they have no competing interests.VJT participated in the design of the study, acquisition of data, data cleaning and analysis, and drafting, revision and final submission of the manuscript. MM participated is data acquisition and in the critical revision of the manuscript. ARA was involved in study design, submissions for ethical approval and critical revision of the draft manuscript. DM participated in the design of the study and acquisition of data. AM was involved in the initial design of the study and critical revision of the draft manuscript. SBK, IK and PM all participated in the initial design of the study, interpretation of the data and critical revision of the draft manuscript. AK participated in all stages of the study from design, data acquisition, interpretation of collected data, and final revision of the draft manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/13/42/prepub


To our knowledge, the antiviral activity of pegylated interferon alfa plus HAART has not been studied in patients with human immunodeficiency virus type 1 (HIV-1) coinfected with chronic hepatitis B virus (HBV).To evaluate the effectiveness of pegylated interferon alfa plus HAART in HIV/HBV treatment-naïve coinfected patients.We performed a prospective cohort study in HIV/HBV treatment-naïve coinfected patients taking care at "La Raza" National Medical Center, Mexico City. Patients were treated with Efavirenz or Lopinavir-ritonavir, each with tenofovir/emtricitabine plus pegylated interferon alfa-2b (1.5 µg/kg/week) or pegylated interferon alfa-2a (180 µg/week) during 48 weeks. HBV genetic analysis was obtained. The study had a primary measure of effectiveness assessed at 24 and 48 weeks of treatment: suppression of HIV RNA to levels below 50 IU/ml. Secondary endpoints were increased in CD4+ cells count, HBV DNA to levels below 60 IU/ml, HBeAg seroconversion (defined by the loss of HBeAg and the presence of anti-HBe antibody) and HBsAg seroconversion (defined by the loss of HBsAg and the presence of anti-HBs antibody). Cumulative incidence with 95% confidence interval (95%CI) were calculated.We enrolled 18 subjects, 1 patient discontinued treatment because adverse events related to PEG-IFN. The mean (± SD) age was 30.3 ± 6.9 years old, all patients were men. The median (interquartile range) basal CD4+ cells count was 112 (61 to 300), RNA HIV 163,000 copies/ml , DNA HBV 20,200,000 IU/ml . All patients had positive HBeAg and were negative to HDV serology. HBV genotype distribution was H 9 (52%), G 6 (35%), A 1 (6%) and F 1 (6%). Primary endpoint (RNA HIV < 50 copies/ml) was present in 100% of our patient at 24 and 48 weeks; the median increased in CD4+ cells count was 231 cells/ml at 24 weeks and 322 cells/ml at 48 weeks; cumulative incidence of secondary endpoints were: DNA HBV < 60 UI/ml was present in 8 patients [47% CI95% 26-69%)] at 24 weeks and 17 patients (100 %) at 48 weeks; HBeAg seroconversion was in 8 patients [47% CI95% 26-69%)] at 24 weeks and 16 patients [94% CI95% 73-98%)] at 48 weeks, HBsAg seroconversion was in 0 patients (0%) at 24 weeks and 6 patients [35% CI95% 17-58%)] at 48 weeks.Pegylated interferon alfa plus HAART were well tolerated and exhibited high viral effectiveness in HIV/HBV treatment-naïve coinfected patients.