By September 2016, approximately 653,865 people in China were living with HIV/AIDS (PLWHA) and 492,725 people were receiving antiretroviral therapy (ART). PLWHA frequently experience discrimination in all domains of their personal and social lives. The World Health Organization includes discrimination in its list of social determinants of health factors that have been linked to poor physical and psychological health. This paper identifies the family support enjoyed and discrimination faced by people infected with HIV and examines the effect they have on patients’ quality of life (QOL) as they undergo ART in China.-treated patients with HIV in Guangxi Province using a questionnaire survey at baseline, 6, 12, and 24 months, starting in 2010. Descriptive analysis was used to describe the demographic characteristics  of participants. Generalized estimating equations (GEE) were employed to examine the relationships between family support, discrimination, and QOL.We conducted this observational cohort study of ARTn = 281) of patients received family support at baseline, here defined as the initiation of ART, 91.8% (n = 244) received family support 6 months into ART, 95.5% (n = 220) at 12 months, and 94.3% (n = 230) at 24 months. The proportion of patients who did not feel discriminated against by their families was 87.2% (n = 274) at baseline, 90.4% (n = 229) 6 months into ART, 90.0% (n = 210) at 12 months, and 94.5% (n = 219) at 24 months. Patients’ overall QOL scores were positively associated with having received family support , not feeling discriminated against by their families  or discrimination from patients themselves, including never experiencing fear of abandonment by family .In the study, 90.4%  contains supplementary material, which is available to authorized users. Please see Additional file www.ncstdc.org). The average annual growth in the rate of 15 to 24 year old students infected with HIV reached 35% in 2015, and 65% of these students infected with HIV were 18–22 years old and studying at universities. This may be because young students’ minds are open but they lack sexual knowledge and have limited capacity for self-examination and self-awareness . Reliability and validity of the structured questionnaires were examined using Cronbach’s α coefficient and the results (α = 0.946) demonstrated that the questionnaire exhibited high reliability and validity. The quantitative questionnaire surveys were conducted at four points in time including baseline of initial ART, and after 6, 12, and 24 months of ART.Before data analysis, different surveys and variables were checked for logic using SAS, covering ranges, consistency, logical relationships, and other factors. Whenever such checks revealed errors, original hard copy questionnaires and medical records were revisited for final confirmation and correction. Some participants gave answers of “I don’t know” or made no response at all. These were treated as “no”. All data from different sites were merged into a unified dataset based on the variables in the questionnaire using SAS 9.1.Sample size calculations were based on the following assumptions: Significance  was set to 5%; power (beta) to 90%; desired changes in QOL over time to 0.8 for all QOL domains; 20% was allowed for loss to follow up. Given these considerations and calculations, it was determined that a sample size of approximately 300 people infected with HIV was adequate. About 40% of the cohort participants were from Guangxi CDC ART clinic in Nanning City, 30% from the 4th Nanning Hospital ART Clinic, 20% from Pingxiang People’s Hospital ART Clinic, and about 10% from Guigang City People’s Hospital and Guilin 3rd People’s Hospital.Descriptive analysis was used to describe the demographic characteristics  of participants. Generalized estimating equations (GEE) with standardized counselling sessions were used to analyse the effect of family support and discrimination on patients’ overall quality of life.A total of 332 subjects were recruited for the study. 267 (80.4%), 260 (78.3%), and 246 (74.0%) continued to participate at the 6-month, 12-month, and 24-month periods, respectively  disclosed their HIV positive status to family before receiving ART and this proportion increased to 96.7% at the 24-month mark. Among those who had disclosed their HIV positive status to their family, most of them were satisfied with their decision to disclose; 90.4% of patients had received family support at baseline, 91.8% at 6 months, 95.5% at 12 months, and 94.3% at 24 months-significantly higher than that at baseline. Most patients (55.2% and 84.5%) had received encouragement as well as psychological, financial and physical care support from their families at the baseline and at the 24-month survey.Participants’ perception of family support increased over time. The proportion of patients who did not feel discriminated against by their families was 87.2% at baseline, 90.4% at 6 months, 90.0% at 12 months, and 94.5% at 24 months. At baseline, 28.1% of the patients reported not visiting family because they thought they would not be welcomed, and the rate significantly decreased to 13.3% at the time of the 24 month survey. The rate of patient fear of abandonment by family significantly decreased from 20.7% at baseline to 8.4% at 24 months  although family income was found to vary slightly across different periods.GEE analysis revealed that nearly all of the family factors were significantly closely associated with overall quality of life scores of the patients. Among these factors, whether the patient has disclosed his or her HIV status to family, whether the family provided supports, and whether the patients were satisfied or very satisfied with their decision to disclose their HIV-positive status to family were associated with higher overall quality of life scores. These results remind us that in order to improve overall patient quality of life, especially in the context of Chinese culture, we must actively provide counselling services to encourage patients to disclose their HIV status to their families earlier. Because families can only provide the support that their HIV-positive relatives need if they know that it is needed, disclosure to family members is imperative, and strategies to encourage people infected with HIV to disclose their health conditions to family after diagnosis must be developed. For example, the community, especially clinicians who work with families affected by HIV, need to address the discrimination and stigma issues associated with disclosure in order to increase social support in an attempt to reduce any negative emotional impact that disclosure may have on people infected with HIV. In addition, many studies have suggested that, in general, there is a positive relationship between income and quality of life , 35. In In this study, most participants disclosed their HIV status to family members and the rates increased significantly from 81.3% at baseline to 96.7% at 24 months. More than 90% of the participants received support from their families and the proportion remained high at 12-months and 24-months. These results indicated that, as has been found in Chinese culture, family were the people the patients were most likely to trust and to play the most important role in providing support . TherefoThe present study has some limitations that should be acknowledged. The respondents were recruited solely among individuals actively seeking routine medical care. Those who did not keep regular clinic appointments or peer organization visits could not be included. The results of this study may not be generalizable to all HIV-positive people in China. Moreover, the face-to-face interviews, the assessment of readiness with regard to family and peer support and the administration of the questionnaire by the research team may have led to social desirability biases or affected QOL scores and related results. Nurses, counsellors, and research staff were trained to conduct the interviews in a non-judgmental and objective way and the changes over time were consistent across study sites. Missed observations due to participants dropping out of the study or missed appointments could have caused outcome bias. However, a weighted GEE method was used based on the bias parameters regarding missing data, and the cases of demographics and experiences of the initial participants who left the study were analysed. Overall the results indicated that the participants who left the study could be representative of the entire population studied. In this way, the attrition rate may not have affected the results. Self-reporting data may also have introduced bias. We did not identify any specific association between young men and the fact that about 15% of all people infected with HIV are young people aged 15 to 24. Further research focusing on family support and young people is urgently needed.Family support and either no or very limited discrimination was found to contribute to QOL among people infected with HIV, which tended to improve significantly as ART continued. Strategies to improve and strengthen family support and care for PLWHA and promote HIV screening among high-risk populations should be developed and implemented by both policy makers and researchers. For example, the community, especially clinicians who work with families affected by HIV, must encourage high-risk individuals to undergo HIV testing regularly and to address discrimination and stigma associated with disclosure in order to encourage early initiation of ART and increase the QOL of PLWHA.


The progression of Human Immunodeficiency Virus (HIV) within host includes typical stages and the Antiretroviral Therapy (ART) is shown to be effective in slowing down this progression. There are great challenges in describing the entire HIV disease progression and evaluating comprehensive effects of ART on life expectancy for HIV infected individuals on ART.We develop a novel summative treatment benefit index (TBI), based on an HIV viral dynamics model and linking the infection and viral production rates to the Weibull function. This index summarizes the integrated effect of ART on the life expectancy (LE) of a patient, and more importantly, can be reconstructed from the individual clinic data.The proposed model, faithfully mimicking the entire HIV disease progression, enables us to predict life expectancy and trace back the timing of infection. We fit the model to the longitudinal data in a cohort study in China to reconstruct the treatment benefit index, and we describe the dependence of individual life expectancy on key ART treatment specifics including the timing of ART initiation, timing of emergence of drug resistant virus variants and ART adherence.We show that combining model predictions with monitored CD4 counts and viral loads can provide critical information about the disease progression, to assist the design of ART regimen for maximizing the treatment benefits. Human immunodeficiency virus (HIV), the pathogen causing acquired immune deficiency syndrome (AIDS), exhibits highly complex interaction with human immune system , 2. HIV There has been substantial progress in modelling antiretroviral intervention, with particular success in predicting long-term viral dynamics –17. A chEstimating the LE is important to inform the patients of their prognosis at the individual level, and to predict the future demographic and socioeconomic impact of HIV/AIDS at the population level. Several studies have investigated the prolonged LE of patients due to ART in high-income countries or resource-constrained settings at the population level –28, usinThe model Let T(t),T∗(t) and V(t) be the concentrations of uninfected target CD4 T cells, productively infected cells, and free virus at time, respectively. We adopt the classic HIV viral dynamics model , is what we want to find, and denoted by Te. Then Te−Tm gives the prolonged LE due to ART, indicates the integrated treatment benefits. Based on the feasibility of four roots we can provide the formula of Te and one of the possible cases is discussed in the following. Note that here Td is set to be equivalent to or greater than the Te. Due to the fact the extension of the life by ART has been increasing, we then assume that the LE of patients with ART can be as long as the average LE of individuals without infection.The smallest one of real roots B2≥0 and t1 and Te can be defined as Let η or τ50 or Tr) affect the prolonged LE, and consequently the disease progression. In particular, This formula shows how the drug efficacy  or model  to produce the whole disease progressions without or with ART.Based on above definitions and analyses, we can see that the natural HIV disease progression is defined in the interval ,Formulation of DA To describe the effects of DA on treatment benefit, we further extend the TBI to include the adherence rate , and also to include various patterns of randomly or regularly missed doses. Assuming that once patients take doses daily, which will contribute to the function TBI, while the TBI keeps at a day for doses missing. Let Da be a set of days when doses are missed, then we have Ti], with integer i∈. The daily treatment benefit functions are as follows. Denote the time intervals i+1 days, when drug doses are missed during treatment intervals , respectively. Let Ts), then we have where τ(t)) at i-th interval Ti]. So we have the revised drug efficacy and sensitivity as the following: A cohort study in China  has indir1>1 and close to 1, r2<1 and close to 1. Since no reliable information of how DA influences on the time of emergence of resistant virus variants, we simply do not consider the effects of DA on time of emergence of resistant strain here.with w1) and LE for various regular adherence patterns at a given adherence rate of 90%. Figure Te) and the duration of drug on. We conclude that a long duration of drug on (and consequently a long duration of drug off due to the fixed DA rate) could yield slightly longer LE by about 100 days. A repeat of the above with low drug efficacy and decreased sensitivity due to imperfect adherence gives a short LE . For a given adherence 60% (or 90%), the mean LE is 16.6944 (or 23.2532) years with range of 271 (177) days. Similarly, lower drug efficacy and decreased sensitivity in such a scenario give a shorter mean LE.T1000) and duration of viral suppression (T1000−Ts) show great variance for different adherence patterns, especially for 85 and 65% adherence  are estimated by fitting the proposed model to the data together with information on first data point and/or the date of death for the death cases. All estimated parameter values for 15 patients are listed in the Tables η=0.605) and sensitivity (τ50=383.85) are both low, and this resulted in a small and slow increase of TBI over time and very insignificant increase in the prolonged LE (Te−Tm=20.96 days). Other data fits (not reported here) further confirms that the first-line ART for patient 3 barely delayed the disease progression. For the patient 4 with the first recorded CD4 counts of 40 cells/ μl, we constructed the TBI . Patient 2 had the longest LE on the first-line ART among the four death cases, which was associated with late emergence of drug-resistant virus variants and great drug efficacy and sensitivity. The TBI for patient 8 increased with the fastest speed and latest time of emergence of drug resistant variants . The TBI shown in Fig. The TBI can be reconstructed based on the estimated parameter values for all 15 patients, as shown in Fig. TBI Fig. a and cants Fig. c. FigurIt is known that HIV infection typically results in a vast replication of virus during the acute phase. The viral load then becomes much lower and approaches a quasi-steady state, and finally increases significantly after the development of AIDS , 35. TheWe have also shown that our model can be used to predict the LE of an HIV infected individual and the time of virological failure. The accurate description of the entire HIV disease progression makes it possible to use this model to predict the transmission probability at different stages based on viral loads, and this is important when we consider new infections generated by a particular infected individual. Our model can also be used to determine the timing of infection for an infected individual based on individual parameters, monitored data on CD4 cell counts and viral loads, which is difficult to get. This estimation of the infection time for each infected individuals provides vital information on estimating new infections at the population level. In addition, the knowledge about the timing of infection for HIV-infected individuals in various communities enables effective contact tracing and facilitates treatment resource allocation.Te) and prolonged LE (Te−Tm), in agreement with those in previous studies [Simulating the proposed model shows early initiation of ART can result in long LE  to summarize the integrated effect of ART in terms of prolonged LE. Moreover, this TBI can be reconstructed from clinical data with predicting the time of virological failure. Our model can be used to determine the timing of infection for an infected individual based on individual parameters, monitored data on CD4 cell counts and viral loads. Main results show that combining model predictions with monitored CD4 counts and viral loads can provide critical information about the disease progression, to assist the design of ART regimen for maximizing the treatment benefits.


WHO hepatitis B guidelines recommend testing all new HIV patients, treating them accordingly or providing immunization. At the Infectious Diseases Institute (IDI) following an audit done in 2012, only 46% patients had been screened for hepatitis B with variable management plans therefore new internal guidelines were implemented. This study describes the uptake of hepatitis B screening and management of patients with hepatitis B and HIV con-infection after the implementation.Data included for all HIV positive patients in care at IDI by October 2015. Data are expressed as median with interquartile range (IQR) and percentages were compared using the chi square test. Statistical analysis was performed using STATA version 13. The IDI laboratory upper limit of normal for alanine aminotransferase (ALT) and aspartate aminotransferase (ASTs) was 40 IU/ml.Number of hepatitis B screening tests increased from 800 by 2012 to 1400 in 2015. By 2015 8042/8604(93.5%) patients had been screened for hepatitis B. Overall hepatitis B positive were 359 (4.6%). 166 (81.4%) hepatitis B positives were switched to a tenofovir (TDF) containing regimen.Our study confirms the importance of screening for hepatitis B and of using ART regimens containing tenofovir in hepatitis B co-infected patients. Whilst our program has made improvements in care still 18.6% of patients with hepatitis B were not on tenofovir regimens, 98.1% had no hepatitis B viral loads done. Clinicians should recognize the potential for hepatitis B in HIV positive patients and the importance of early diagnosis and treatment to ensure optimal management of cases and follow up. Chronic viral hepatitis is an increasing cause of morbidity and mortality among HIV confected persons, including those on ART, as persons with HIV continue to live longer –3. The cChronic hepatitis B virus infection affects 5–20% of the 36 million people living with HIV worldwide, and the burden of HIV- hepatitis B co-infection is greatest in low and middle income countries, particularly in sub-Saharan Africa. Globally it is estimated that 2.6 million are HIV- hepatitis B co-infected . The WorUganda is highly endemic for hepatitis B infection, with a seroprevalence for hepatitis B positivity of around 10%, based on a national hepatitis serosurvey in 2005 , 16. As Whilst access to HIV care is becoming widely available in Sub-Saharan Africa, in diagnosis and treatment of viral hepatitis co-infection there remains a big disparity between resource rich and poor settings. Limitations such as the availability of further investigations and medication can be challenging in these settings to provide individualized care for more complex patients, such as those with co-infection –24.An audit conducted in September 2012 among newly registered patients at the Infectious Diseases Institute – a large urban HIV clinic in Kampala, Uganda showed a low uptake of hepatitis B screening and variable management of those diagnosed Hepatitis B positive . In respThis study describes the impact on uptake of hepatitis B testing, assesses whether new guidelines and the introduction of the hepatitis B specialty clinic increased hepatitis B screening uptake and improved clinical management.The Infectious Diseases Institute (IDI) is an HIV center of excellence  located In 2010, routine hepatitis B testing was first introduced, followed in 2012 by establishment of a dedicated hepatitis B clinic and clinic guidelines. The new guidelines were written by a team of three doctors, the quality manager and approved by the senior Physician who is also the head of the Prevention, Care and Treatment (PCT) department. One staff training session was conducted and the guidelines were implemented starting 1st September 2012. The hepatitis B clinic is held every Friday, staffed by doctors, nurses, counselors, laboratory technician, and pharmacist.IDI has an electronic patient management system (ICEA)  and sincSince September 2012, in accordance with the new IDI clinic guidelines, all newly registered HIV patients are tested for hepatitis B surface antigen, while those already registered in care are tested during their routine clinic appointments. ART naive hepatitis B positive patients are prepared to start ART with two pre-ART counselling sessions. In hepatitis B positive patients already on a zidovudine (AZT) based ART regimens, zidovudine (AZT) is substituted for tenofovir (TDF) if the viral load is undetectable, or switched to a second line regimen containing tenofovir (TDF), if viral failure is confirmed. Free hepatitis B testing and treatment is provided, but additional investigations including hepatitis B DNA viral load and fibro scan to help stage liver disease and monitor response to treatment; ultrasonography and alpha-fetoprotein measurement to screen for hepatocellular carcinoma; and endoscopy to screen and manage varices due to hepatitis B infection related complications need to be paid for by the patient. However, these are expensive and beyond the financial means of many of our patients.This analysis includes all adult (≥18 years) HIV patients in current care at IDI from January 2002 to October 2015, with censorship at lost to follow up (LFU), transfer, or death. For each patient we recorded demographic, clinical, ART status, hepatitis B status, liver function test results, clinical management decisions regarding use of tenofovir containing ART regimen, and clinical outcomes . We also describe the number of patients tested each year, and compared the clinical characteristics and outcomes between those who tested hepatitis B positive and negative.Two audits were undertaken for this study; the first was done in September 2012 and looked at newly enrolled patients, the second was undertaken in October 2015 following the establishment of the hepatitis B-HIV clinic.P values were found using Cochran-Armitage test for trend. We used an IDI laboratory upper limit of normal for alanine aminotransferase (ALT) and aspartate aminotransferase (ASTs) of 40 IU/ml. We used the t test for comparison of parametric continuous variables, Wilkinson rank sum test for non-parametric variables and chi square and fisher’s exact tests for categorical variables. Statistical analysis was performed using STATA version 13.We describe the number of patients tested each year and compared baseline characteristics  in hepatitis B positive and negative patients and described the clinical outcomes in hepatitis B positive patients. Data are expressed as median with interquartile range (IQR) or number and percentages as appropriate for . Proportion of hepatitis B co-infected patients already on a TDF containing ART regimen at the time of test are described. To show trends of for patients tested before and after guideline implementation, we used proportion of patients tested for hepatitis B compared to the number of patients who registered in the period. In the first audit, 1753 patients were reviewed. Of these only eight hundred seven patients (46%) received hepatitis B testing. Twenty-nine (3.6%) of those tested were hepatitis B positive, of which 8/29 (27.6%) were not started on ART; of note five of those had CD4 count < 500 cells/μL. Of 21 who started ART, eighteen (62.1%) were prescribed TDF-3TC containing regimens, three (10.3%) on ART regimens not known to have activity against hepatitis B. 19/29 (65.5%) patients had baseline liver function tests (LFTs) checked. No patients had follow up LFTs.During the repeat audit in October 2015, there were 8042 (93.5%) active HIV infected patients screened for hepatitis B at IDI. Of these,2984(37.1%) were male, with median age 31 years (IQR: 26–35), majority in WHO stage 3 and 4; 4608(57.3%). 7416(92.2%) were initiated on ART and were on first line ART regimen 6930 (86.2%). There has been a marked increase in the uptake of testing per year from 611 tests in 2010, to 909 in 2012 and now 1500 in 2015. Overall, 8042 (93.5%) of 8604 current HIV infected patients have been screened for hepatitis B with the largest number of patients being screened between 2014 and 2015. Figure p < 0.001).The proportion of patients screened for hepatitis B compared to the number of patients newly registered in the clinic was higher after the implementation of the new guidelines (2141(79.3%) of 2700 versus 5901 (28.4%) of 20,774 before the guidelines Table P < 0.0001) and to have a lower median CD4 count at hepatitis B test (423 cells/μL) (IQR 269–600) versus 483 cells/μL (IQR 325–657). In addition, hepatitis B positive had been on ART for shorter period  vs  days) at the time of the hepatitis B test.Those who were hepatitis B positive, were more likely to be male (52.6%) versus (36.4%) .There was no difference in median age at 38 (IQR) or in WHO stage 3 and 4 (61.3%). Three hundred thirty-seven (93.9%) of the hepatitis B positives ever used ART with a median time on ART seventy-four days from hepatitis B test (IQR 27–399). Two hundred fifty-four (75.4%) patients started ART before the hepatitis B test date, eighty-one (24.1%) after the test and two (0.5%) on the day of the test. The proportion of deaths (6.5%) was higher among the hepatitis B positives as compared to the hepatitis B negative population (2.3%) .The median time from testing positive for hepatitis B test to death was 143 days (IQR 15–242). Hepatitis B positive patients were on ART for shorter period prior to testing  as compared to the hepatitis B negative patients  days) at the time of the hepatitis B test. Hepatitis B positive had lower CD4 count: 423 cells/μL, (IQR: 269–600) compared to hepatitis B negative patients 483 cells/μL , Figure 337 (93.9%) had been started on ART, while 22 (6.1%) had not been started not on ART at the time of the analysis. Of the 22 not on ART - most died , four (18.2%) were lost to follow up, seven (31.8%) had been transferred out while three (13.6%) were active in care. One patient of those active in care had documented evidence that they refused to initiate ART while two had results returned before their scheduled return clinic appointments date. Overall 259(76.9%) had been initiated on ART prior to their hepatitis B test, and 78 (23.105%) after.One hundred thirty-three of 337 (39.4%) patients were already on a TDF containing ART regimen at the time of test, 166 of 337 (49.3%) were subsequently switched to TDF within median of 3.7 months (IQR 1.8–6.3) from hepatitis B test, and 38 (11.2%) were never switched. The most commonly documented reason for not switching was that the viral load was ˂1000 copies/ml for 24 (92.3%) hepatitis B patients.By October 2015, two hundred ninety nine (83.3%) of 359 patients were on a TDF based regimen.Overall 285 (79.6%) hepatitis B positives had an HIV viral load done with 253 (70.7%) of patients with viral load VL˂1000 copies/ml. Patients who never had an HIV viral load done 74(20.4%), 24 (32.9%) patients were active in care, 17 (23.4%) were dead, 4 (5.5%) were lost from care while twenty eight (38.4%) had been transferred out to other health care providers.Liver enzymes tests (ALTs) were done for 249 (69.4%) patients with 205 (82.3%) of patients having normal alanine aminotransferase levels. Patients with Aspartate transaminase (ASTs) test done were 86 (24%) most of which (61.6%) had results in normal ranges.Patients with hepatitis B DNA viral loads done were 7(1.9%) while 250 (69.6%) patients had an ultra sound scan done.Overall twenty three (6.5%) of the hepatitis B positives died, of these 9(39%) were those who had never been initiated on ART.Our findings show the striking impact of the introduction and implementation of a series of clinic activities to support the provision of effective hepatitis B care in an HIV clinic. There was a progressive increase in the uptake of hepatitis B testing particularly over the preceding four years 79.3%, with now almost universal testing of all HIV infected patients at IDI. It also shows the direct impact of knowledge of hepatitis B status on ART regimen choice with 299(83.3%) of 359 patients who were identified as positive on a TDF regimen as recommended in WHO guidelines  and consThis scale up and response was largely achieved as a result of results through actions taken in response to the findings of the first audit in 2012 showing a low uptake of testing . These aOur study showed that hepatitis B occurred in 359(4.6%) patients; slightly lower than the general hepatitis B seroprevalence for Kampala regions (5.3%) reported in the 2005 national serosurvey , 29, 30.p value <0.0001).  among the hepatitis B positives compared to the negatives patients 179 (2.3%, Further investigations and management of hepatitis B patients is still a challenge. IDI has access to hepatitis B, hepatitis C and E testing only. Further investigations that would be standard in resource rich settings are not available. Additional tests including liver function tests and ultra sound scans for hepatitis B patients were not done for all the patients. Only 1.9% of patients were able to have a hepatitis B DNA viral load. In Uganda generally extensive medical investigations are expensive and beyond the financial means of IDI and many of the patients. In our settings, diagnosing chronic liver disease and hepatitis infection is currently a challenge without external funding and availability of appropriate diagnostic investigations. There are also limited drug combinations for those with drug resistance and for more complex patients, such as those with co-infection.Clinicians should recognize the potential for hepatitis B in HIV positive patients and the importance of early diagnosis and treatment to ensure optimal management of cases and follow up. Effective prevention and treatment of hepatitis B virus infection is an important public health priority with effective ART being associated with lower incidence of hepatitis B infection.The Ugandan government is making progress in prioritizing hepatitis B screening. We advocate for further budgetary allocation for the implementation of hepatitis B treatment, management and long term screening for liver cancer. In the future additional funding is still required to increase management for complex patients with HIV-hepatitis B co-infection and its complications.


Whether the non-inferior efficacy and safety results of switching virologically suppressed HIV-1-infected patients from nevirapine immediate-release (NVP-IR) to NVP extended-release (NVP-XR) demonstrated in the TRANxITION study conducted in Europe and North America are also applicable to virologically suppressed HIV-infected Taiwanese patients remains unknown. We evaluated the comparative safety and efficacy of continuing NVP-IR versus switching to NVP-XR in virologically suppressed HIV-infected Taiwanese adults receiving combined antiretroviral therapy (cART) regimens.n = 49) and those being switched to NVP-XR (n = 35). Demographic characteristics, clinical variables, and laboratory findings were compared. Therapeutic drug monitoring of steady-state plasma NVP concentrations and genotype analysis of CYP2B6 516 were also performed in 22 participants. The primary endpoint was continued virological suppression at the end of the study. Secondary endpoints were time to loss of virological response and adverse events.We conducted a retrospective cohort study at Kaohsiung Veterans General Hospital from April 1, 2013, to March 31, 2015. Eighty-four virologically suppressed HIV-infected adults receiving NVP-IR cART were split into two groups: those continuing with NVP-IR (P = 0.72). Cox regression analysis indicated that there were no significant differences between NVP regimens for time to loss of virological response . Furthermore, there were no significant differences in adverse events between these two groups. In the 22 participants, there was a non-significantly lower level of steady-state plasma NVP concentrations in the NVP-XR group than in NVP-IR recipients . The prevalence of CYP2B6 516 GT was 86.6%, and there was no significant difference in the distribution of CYP2B6 516 between these two groups.During a mean follow-up of 18.4 months, the NVP-XR group demonstrated similar success at maintaining virological response compared with the NVP-IR group  contains supplementary material, which is available to authorized users. Nevirapine immediate-release (NVP-IR) has been used with a high level of efficacy and safety since its introduction in 1996 in the United States and 1998 in Europe as a potent non-nucleoside reverse transcriptase inhibitor (nNRTI) used in combined antiretroviral therapy (cART) . Howevertrough ≤ 3 mg/mL compared with patients who had higher trough concentrations [Nevirapine is pharmacologically characterized by a strong relationship between NVP trough plasma concentrations and virological response, , 14 and trations , 14.CYP2B6 may influence the metabolism of NVP, with the variant CYP2B6 516 GT polymorphism resulting in reduced clearance of NVP compared with CYP2B6 516 GG [CYP2B6 516 GT polymorphisms, resulting in a 15.3% reduced clearance of NVP compared with patients with CYP2B6 516 GG [trough compared with patients with CYP2B6 516 GT. Furthermore, a recent prospective study of 227 HIV-infected, treatment-naïve patients conducted in China recommends a higher target therapeutic Ctrough (3.9 μg/mL) of NVP for Chinese patients than the currently recommended level (3.0 μg/mL), which is predominately from the results of studies among Caucasian and African American patients [However, in routine clinical practice, optimal plasma concentrations of NVP are reached in only 27.8% patients . The sig6 516 GG . In a 2N6 516 GG . This di6 516 GG . However6 516 GG  which matrough with 400 mg NVP-XR once daily compared with 200 mg NVP-IR twice daily [In addition, previous PK studies of NVP have demonstrated a lower Cce daily , 12, 23.CYP2B6 516 were also performed in some participants.The current study, conducted at a large teaching medical center in southern Taiwan, was designed to evaluate the efficacy and safety of switching virologically suppressed Taiwanese patients from 200 mg NVP-IR twice daily to 400 mg NVP-XR once daily. Therapeutic drug monitoring of plasma NVP concentrations and genotype analysis of This study is composed of two parts: a retrospective analysis of the efficacy and safety of switching virologically suppressed patients from 200 mg NVP-IR twice daily to 400 mg NVP-XR once daily, and a prospective analysis of the impact of CYP450 polymorphisms on plasma concentrations of nNRTI. In the first part of the study, we retrospectively examined data collected from April 1, 2013, to March 31, 2015, at Kaohsiung Veterans General Hospital (KVGH), a 1200-bed, general and tertiary care hospital located in southern Taiwan. Prior to April 2013, only NVP-IR was available at KVGH. Once NVP-XR became available at KVGH in April 2013, all patients receiving NVP-IR were queried by their physician regarding their willingness to switch to NVP-XR. Because HIV-infected patients regularly visit our infectious diseases department every 1–3 months, we retrospectively screened all HIV-infected patients who were receiving NVP-IR-containing cART during the period from April 1, 2013 to June 30, 2013. Inclusion criteria for virological suppression were patients who were receiving NVP-IR plus two nucleos(t)ide reverse-transcriptase inhibitors, for a preceding minimum of 18 weeks, with undetectable (<50 HIV-1 RNA copies/mL) HIV-1 viral load (VL) in the previous 1–4 months [For the second part of the study, we evaluated the impact of CYP450 polymorphisms on plasma concentrations of nNRTI by high-performance liquid chromatography (HPLC) in HIV-infected patients, beginning in January 1, 2014. Inclusion criteria were patients who were receiving the same nNRTI-containing cART for at least 14 days. We excluded patients who were also receiving medications other than antiretroviral agents, those who were aged <20 years, and those who did not adhere to cART. For patients who were eligible and agreed to participate, a steady-state plasma sample was obtained before administration of the next dose of nNRTI. Finally, we matched those patients enrolled in the prospective part of our study to those in the retrospective analysis.The two parts of this study were approved by the KVGH ethics committee (VGHKS14-CT7–22 and VGHKS14-CT2–13) and adhered to the principles of the Declaration of Helsinki. Informed consent was obtained from participants who underwent therapeutic drug monitoring of plasma nNRTI concentrations and genotype analysis of CYP450 polymorphisms.For each enrolled patient, the following information was extracted for analysis from computerized hospital records and chart reviews: demographic characteristics, risk factors for HIV infection, comorbidities, and cART regimen. Laboratory testing included hemograms, biochemical profiles, plasma viral load, and CD4+ T cell counts at baseline and at each follow-up visit. Viral load was determined using the Roche COBAS Amplicor assay prior to 2008 and the Roche COBAS TaqMan assay subsequently. Adverse events (AE) were also recorded. Liver function abnormalities were graded according to definitions of the Division of Acquired Immunodeficiency Syndrome (DAIDS).Virological suppression was defined as HIV RNA ≤50 copies/mL. A virological blip was defined as an isolated detectable HIV RNA signal after a period of suppression, followed by a return to virological suppression . VirologThe primary end point was the proportion of patients with continued virological response with VL <50 HIV-1 RNA copies/mL at the end of the study. Patients were classified as treatment failures at the first occurrence of virological failure or a change in NVP regimen because of AEs or other reasons, death, or loss to follow-up (LTFU),  which waA steady-state plasma sample was obtained from all participants before administration of the next dose of NVP. Blood samples were centrifuged immediately after collection, and plasma was removed and stored at −20 °C until analysis. We used an HPLC technique with UV detection for analysis of NVP concentrations, as previously described . For eacCYP2B6 gene was amplified by polymerase chain reaction (PCR). The primers 5′ CTTGACCTGCTGCTTCTTCC 3′ and 5′ TCCCTCTCCGTCTCCCTG 3′ were used to amplify a 204-bp fragment. PCR products were digested with BsrI restriction enzyme . Digestion products were then loaded on a 2% agarose gel and separated by gel electrophoresis [Genomic DNA was isolated from peripheral blood using the PureLink Genomic DNA Mini Kit . Exon 4 of the phoresis , 27.2 or Fisher’s exact tests, and continuous variables were compared using the independent t-test or Mann–Whitney U test. All tests were two-tailed, and P < 0.05 was considered significant. The TLOVR of these two groups was analyzed using a Kaplan–Meier survival curve, and the influence of the NVP regimen (NVP-IR twice daily vs. NVP-XR once daily) on the TLOVR was investigated using Cox regression that was adjusted for age, sex, history of AIDS, cART regimen, and duration of virological suppression.All statistical analyses were performed using IBM SPSS software, version 22.0 . Categorical variables were compared between the two groups using the χn = 1), receiving a regimen that contained 400 mg NVP-IR once daily (n = 2), switching from NVP-IR to NVP-XR (n = 2), or had a change of the NRTI backbone (n = 1) between July 1, 2013, and March 31, 2015  whereas most patients in the NVP-XR group received abacavir and lamivudine (Kivexa®) . Regarding the third drug of cART before entering the study, 24 of 35 patients (68.6%) in the NVP-XR group received an off-label regimen with 400 mg NVP-IR once daily, and all 49 patients in the NVP-IR group received 200 mg NVP-IR twice daily.The baseline demographic characteristics and comorbidities of the two participant groups are shown in Table P = 0.72) (Table P = 0.23). There were no differences in CD4+ count changes between the two groups .Compared with those in the NVP-IR group, virologically suppressed HIV-infected participants in the NVP-XR group demonstrated more or less similar success at maintaining virological response during the mean follow-up time of 18.4 months . A Cox model adjusted for age, sex, history of AIDS, cART regimen, and duration of virological suppression demonstrated a non-significant difference between the NVP regimens with respect to hazard ratios (HR) for TLOVR  . There was one case (2.9%) of grade 4 aspartate transaminase/alanine transaminase levels in the NVP-XR group.There were no significant differences in AEs between the NVP-XR and NVP-IR groups Table . ObserveCYP2B6 516 polymorphisms on plasma concentrations of NVP from January 1, 2014 to December 31, 2014. A total of 22 patients   . There was no significant difference in the distribution of CYP2B6 516 between these two groups . Additionally, these patients only received antiretroviral agents and did not take any other prescribed medicine concomitantly. Finally, genotype analysis of CYP2B6 516 in 15 patients also revealed no significant difference in CYP2B6 516 polymorphisms between these two groups.We believe that there was no obvious selection bias between patients receiving NVP-XR and NVP-IR who also underwent therapeutic drug monitoring of steady-state plasma NVP concentration in the current study. Compliance, drug–drug interactions, and differences in pharmacokinetics are critical factors that influence the plasma concentrations of antiretroviral drugs . Our pattrough levels in both groups compared with other studies conducted in the Netherlands, [CYP2B6 516 GT in our study population (86.6%) compared with other reports of Han Chinese, [CYP2B6 516 GT in the current study requires further verification in a larger Taiwanese population.Surprisingly, however, our study demonstrated higher Cerlands,  Germany,erlands,  and Canaerlands, . This diChinese,  CaucasiaChinese,  and TaiwChinese, . Our finP < 0.0001) [P = 1.00) for the NVP-XR group compared with the NVP-IR group. The relationship between viral blip and virological failure in Taiwanese patients requires further investigation in a larger population.Maximal and durable suppression of plasma HIV viral load has now been established as the primary aim of antiretroviral treatment for both treatment-naïve and treatment-experienced patients . However 0.0001) . In our The current study has several limitations and biases inherent to retrospective cohort studies, the first being selection bias. Second, there were significant differences in cART backbone drugs between the NVP-XR and NVP-IR groups. However, the CNA30024 study comparing the durability of viral effect and the safety profile of triple therapy with either abacavir or zidovudine, combined with lamivudine and efavirenz, demonstrated similar virological suppression (HIV RNA ≤ 50 copies/mL) in treatment-naïve patients at week 48 (abacavir group vs. zidovudine group: 70% vs. 69%) . Third, trough levels in both groups compared with other studies conducted among Caucasian populations may be due to the high prevalence of CYP2B6 516 intermediate/low metabolizers in the present study.In this retrospective study, we found that switching from cART regimens with twice-daily doses of 200 mg NVP-IR to a once-daily dose of 400 mg NVP-XR appeared nearly as safe and effective as continuing NVP-IR in virologically suppressed HIV-infected Taiwanese patients. Our findings of higher CAdditional file 1:P = 0.926). (DOCX 14 kb)Multivariate analysis of treatment failure in 84 virologically suppressed HIV-infected patients. In Cox regression, the hazard ratios for TLOVR between NVP regimen (NVP-XR vs. NVP-IR) was 0.940  and heavier  than the 26 patients not enrolled in the retrospective analysis of the current study. There were no significant differences between these two groups in sex, height, the steady-state plasma NVP concentration, and genotype analysis of CYP2B6 516. (DOCX 15 kb)Comparison of demographic characteristics, steady-state plasma concentration of NVP, and genotype analysis of Additional file 3:CYP2B6 516 of 22 virologically suppressed, HIV-infected patients enrolled in this study, by NVP regimens. There were no significant differences between NVP-XR and NPV-IR in age, sex, height, weight, steady-state plasma NVP concentrations, and genotype analysis of CYP2B6 516. (DOCX 15 kb)Demographic characteristics, steady-state plasma concentration of NVP, and genotype analysis of Additional file 4:CYP2B6 516. Three cases  participating in genotype analysis of CYP2B6 516 in the current study are shown. Lane M represents a size marker. After digestion with BsrI restriction enzyme, wild-type GG (case B) is visible as one band of 152 base pair. Heterozygous GT (case C) is visible as two bands (152 base pair and 204 base pair); homozygous mutant TT (case A) is visible as one band of 204 base pair. (PPTX 122 kb)PCR-restriction fragment length polymorphism analysis of


Switch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90′ of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005.Retrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of ≥50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients.p = 0.009). Patients switched after 12 months of of virologic failure were more likely to experience CD4 decline and/or further VL increases.The cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs ≤ 5000 copies/ml, patients with VLs = 5001–10,000 copies/ml had an aHR = 1.81 (95% CI = 0.9–3.6), and patients with VLs > 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9–6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 ≥ 100 cells/ul . Mortality in patients not switched to second-line ART was 11.9%, compared to 1.2% for those who switched (Intervention strategies that aid clinicians to promptly switch patients to second-line ART as soon as virologic failure on 1st line ART is confirmed should be prioritized.The online version of this article (doi:10.1186/s12879-017-2680-6) contains supplementary material, which is available to authorized users. The World Health Organization (WHO) recommends switching from first- to second-line antiretroviral therapy (ART) for HIV patients with virologic failure  to avertAnalyses of rates and determinants of switching to second-line ART have largely been estimated for the entire patient population on ART rather than restricted to patients with proven virologic failure. Studies for overall ART populations reported switching rates of 2.6–3.3/100 person years (pys) , 10. FacUsing data from the Rakai Health Sciences Program (RHSP) Clinical Cohort Study, which monitors HIV care programs, we retrospectively assessed the rate and factors associated with switching from first- to second-line ART among HIV-infected adults with virologic failure 6 months after ART initiation, and evaluated the impact of delayed switching on immunologic, virologic, and mortality outcomes.We conducted a retrospective study of HIV-infected adults initiated on ART between June 2004 and June 2011 in the RHSP clinical cohort, in south-central Uganda. Since 2004, RHSP, with funding from the President’s Emergency Plan for AIDS Relief (PEPFAR), has provided free ART using a community-based decentralized service-delivery model. First-line ART regimens consisted of two nucleoside/nucleotide reverse transcriptase inhibitors  and one non-nucleoside reverse transcriptase inhibitor , while second-line consisted of ritonavir-boosted lopinavir with 2 NRTIs. After ART initiation, participants were seen weekly for the first month, then biweekly for 2 months and monthly thereafter, with adherence and HIV risk reduction promotion at all visits, and CD4 and VL monitoring every 6 months. In 2005, RHSP initiated bi-annual routine VL monitoring to identify patients experiencing virologic failure. Interventions to address virologic failure included intensified adherence counseling, peer support, and switching to second-line ART . DecisioWe included all HIV-infected adults aged 18 years or older who had been on ART for at least 6 months. Operational definitions of virologic failure changed over time so we defined virologic failure based on the current WHO guidelines [central if care was received at the large, fixed-location referral clinic/laboratory at the RHSP main facility in Kalisizo, or peripheral if care was received at one of 16 HIV treatment clinics conducted by visiting RHSP staff once every two weeks at local government health center facilities, year of ART initiation categorized as 2004–2007 or 2008–2011 to indicate scale-up and stabilized implementation phases of the ART program, WHO stage at ART initiation , CD4 count at ART initiation (<100 or ≥100 cells/ul); characteristics at time of VF: CD4 count (<100 or ≥100 cells/ul), viral load , year of VF and status of virologic failure prior to VF.The primary analysis explored the risk factors of switching to second-line ART among patients confirmed to have VF. The primary outcome was a switch to second-line ART after first occurrence of VF defined as the change from an NNRTI-based regimen to a ritonavir-boosted, lopinavir-based regimen, and the primary exposure was time from VF to switching to second-line ART. The secondary analysis focused on patients that switched to second-line ART during the study to evaluate the risk of immunologic decline, virologic increase or death associated with delay in switching to second line ART. We defined an event of immunologic decline as decrease in CD4 count up 50 cells/ul from the CD4 at the time of virologic failure, and event of virologic increase as an increase of viral load count ≥0.5 log10 copies/ml from the VL at the time of virologic failure. We considered deaths that occurred in patients switched to second-line ART. In this analysis, the exposure of interest was time from VF to immunologic decline or virologic increase or death, compared among patients switched 0–6 months, 7–12 months, 13–24 months, ≥25 months.. Other exposure variables of interest included characteristics at ART initiation; age in years , gender, type of ART treatment clinic defined as p-value ≤0.15 in the univariate analysis were included in multivariate analyses. In addition, age and gender were maintained in the multivariate analysis irrespective of their statistical significance to ensure adjustment for any age or gender related confounding. Analysis was performed using STATA 14.0 .For the primary analysis, person time of observation was computed from the date that the second consecutive (confirmatory) VL of VF was >1000 copies/ml to the time of switching to second-line ART if switched or censored at the last available clinic visit if lost to follow-up or at time of death or administratively censored on April 01, 2014 if not switched, whichever occurred first. Then we used competing risk models to estimate the cumulative incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of switching to the second-line ART regimen following VF, treating death as a competing risk [Of 3036 HIV-infected adults who had initiated ART between June 2004 and June 2011, we identified 124 (4.1%) who met the criteria for virologic failure. A median of 5.6 months (IQR = 5.1–5.6) elapsed between the first and second (confirmatory) failing VL. The median confirmatory failing VL was 13,835 copies/ml  at a median time of 16.7 months (IQR = 11.6–22.7) from ART initiation. At time of ART initiation, 53% of clients were aged 25–34 years, 60% were female, 71% were on niverapine first-line based regimens and 37% has a CD4 count less than 100 cells/ul at ART initiation. While at time of virologic failure 91% has a CD4 count greater than 100 cells/ul, 58% had viral loads of greater than 10,000 copies/ul and 54% had achieved virologic suppression prior to virologic failure  patients with virologic failure were switched to second-line ART at a rate of 49/100 pys (95% CI = 39.1–60.4). The median timing of switching to second-line ART was 8.1 months (IQR = 3.7–17.0) after virologic failure detection. The cumulative incidences of switching at 6, 12, and 24 months after virologic failure were 30.2% (95% CI = 22.8–39.3), 44.6% (95% CI = 36.1–54.1), and 65.0% (95% CI = 55.7–74.2), respectively.In univariate analyses, significant predictors of more rapid switching to second-line ART were younger age, lower CD4 at ART initiation, and higher VL at the time of virologic failure diagnosis Table . In the The rate of switching was also increased with higher VL at the time of virologic failure; compared to patients with VLs ≤ 5000 copies/ml, patients with VLs of 5001–10,000 copies/ml had an aHR of 1.81 and a 95% CI of 0.9–3.6, and patients with VLs > 10,000 copies/ml had an aHR of 3.38 and a 95% CI of 1.9–6.2. Cumulative incidence curves generated from the adjusted competing risk models show a steep increase in the rate of switching in the first three years and consistent differences in the rates of switching by the level of viral load at virologic failure. Corresponding cumulative incidence at 2 years was 40%, 60%, and 80%, respectively .Eight deaths occurred among the 124 patients with confirmed virologic failure (6.5%), of which 6 occurred in patients who had not yet switched to second-line ART and 2 were among patients who had been switched to second line ART, translating into mortality rates of 11.9% and 1.22%, respectively . Patients switched in 0–6 months had an incidence rate of 5.5/100 pys (95% CI = 2.5–12.3), while the incidence rate was 13.6/100 pys (95% CI = 6.5–28.5) among patients switched in 7–12 months, 16.0/100 pys (95% CI = 8.6–29.7) among patients switched in 13–24 months and 19.4/100 pys (95% CI = 9.2–40.7) among patients switched after 24 months since virologic failure. In the adjusted analysis, compared to patients who were switched within 6 months of confirmed virologic failure, patients who switched within 7–12 months and 13–24 months had a non-significantly different hazard ratio of 2.21 (95% CI = 0.4–13.7) and 2.76 [Table When the end point was virologic increase defined as an increase of 0.5 log 10 copies/ml above VL at time of virologic failure, 24 patients reached the end point in 270.1 person years of observation  . Patients switched in 0–6 months had an incidence rate of 3.7/100 pys (95% CI = 1.4–9.9), those switched in 7–12 months had an incidence rate of 1.3/100 pys (95% CI = 0.2–9.4) while those switched in 13–24 months and 25 or more months had incidence of 15.2/100 pys (95% CI = 7.9–29.3) and 36.4(95% CI = 19.6–67.8) respectively. In the adjusted analysis, compared to patients who were switched within 6 months of confirmed virologic failure, patients who switched within 7–12 months had a non-significantly different hazard ratio of 0.32 (95% CI = 0.0–3.6), while those switched in 13–34 and 25 months or more experienced significantly higher hazard rate of developing virologic increase  and aHR = 10.13, 95% CI = 1.7–59.3 respectively) [Table Lastly, we evaluated the risk of the composite endpoint associated with timing to switch to second-line ART. The Two deaths occurred in patients that switched to second line, the overall incidence rate was 20.2/100 pys (95% CI = 15.0–27.2). Patients switched in 0–6 months had an incidence rate of 10.4/100 pys (95% CI = 5.6–19.3), while the incidence rate was 13.7/100 pys (95% CI = 6.5–28.7) among patients switched in 7–12 months, 36.4/100 pys (95% CI = 21.9–60.3) among patients switched in 13–24 months and 45.8/100 pys (95% CI = 25.3–82.6) among patients switched after 24 months since virologic failure. In the adjusted analysis, compared to patients who were switched within 6 months of confirmed virologic failure, patients who switched within 7–12 months had a non-significantly different hazard ratio of 1.06 (95% CI = 0.3–3.9), while those switched with 13–24 months experienced significantly higher hazard rate of dying or developing immunologic or virologic decline , as did those who switched after 24 months  [Table We assessed the rate of switching to second-line ART after confirmed virologic failure, identified predictors of regimen change, and explored the impact of delayed switching on immunologic, virologic, and mortality outcomes. We found that switching to second-line ART regimens after virologic failure was delayed beyond 12 months in 55% of patients, which was consistent with reports from other settings , 12. SwiWe also found that delay in switching to second-line ART beyond 12 months compared to switching within first six months following virologic failure was associated with more than a 5-fold increased risk of developing either immunologic decline, virologic increase or death. Therefore, delayed switching is not only associated with death as previously documented , 12, 16,The goal of effective anti-retroviral therapy is to dramatically reduce the risk of death and morbidity due to HIV, tremendous gains in reaching this goal globally have been achieved. Our results and others , 15 showWe found the rate of switching to be 49/100 pys, indicating that up to 51/100 pys are spent on failing first-line regimens after confirmed virologic failure. This finding highlights an important gap that has potential to undercut the gains made in the context of test and start all HIV infected programing that aims to reduce the time of unsuppressed HIV viral load from onset of HIV infection . TherefoThere are several factors that could have caused delayed switching in our study. First, as suggested by our findings, it is likely that clinicians were likely to switch sicker patients more rapidly. Secondly, a big part of the study period occurred when the criteria for virologic failure were 10,000 copies/ml and then later 5000 copies/ml . ThirdlyOur rates of switching are not directly comparable to most other studies that report rates of switching to second-line for all patients on ART, rather than for those with confirmed virologic failure. Reported rates of switching in analyses of all patients on ART in various settings range from 2.6 to 4.2/100 pys –11. UsinThe main limitation to our retrospective analysis was that definition of virologic failure and switching practices may have changed over time as VL monitoring became part of national guidelines as the gold standard to identify treatment failure. It is likely that our definition of virologic failure could have resulted in an under estimate of the rate of switching to second line because previous switching practices could have been more relaxed and therefore not flag some of the patients as virologically failed. We performed a sensitivity analysis using a VL threshold of 5000 copies/ml on two consecutive measurements and found that the rate of switching was slightly higher, but there was no change in the findings from our multivariate analysis outcomes (data not shown). Additionally, we found that the time period (2004–2007 vs. 2008–2011) did not have an effect on the rates of switching irrespective of virologic criteria, implying there were not any time-dependent differences in the switching patterns.Our study findings can inform the scale-up and optimization of routine VL monitoring in sub-Saharan Africa. In Uganda, the Ministry of Health implemented centralized routine VL monitoring in 2014 and has focused on ensuring access to VL testing for patients on ART, as well as improved turnaround time for returning VL results to the clinics .Timely switching of patients failing on first line ART to second line ART regimens can be subjective and delayed. Worsening of immunologic and virologic status of patients may be avoided if switched promptly within first six months of confirmed virologic failure. Implementation strategies that support clinicians to promptly switch patients to second-line ART as soon as virologic failure is confirmed on first-line regimens should be prioritized as routine viral load is scaled up in sub-saharan Africa. Successful interventions will ensure the maximum health benefits are achieved from among patients globally receiving life-saving antiretroviral therapy.Additional file 1: Table S1.Risk factors of Immunologic decline among HIV infected adults failing on first line ART and switched to second line ART. Cox proportional MSM model of the time to event of immunologic decline defined as decrease in CD4 count ≥50 cells/ul above CD4 count at virologic failure. (DOCX 17 kb)Additional file 2: Table S2.Risk factors of virologic increase among HIV infected adults failing on first line ART and switched to Second line ART. Cox proportional MSM model of the time to event of virologic increase defined as increase in viral load ≥0.5 log 10 copies/ml above viral load at virologic failure. (DOCX 16 kb)Additional file 3: Table S3.Risk factors of Immunologic decline, virologic increase or death among HIV infected adults failing on first line ART and switched to Second line ART. Cox proportional MSM model of the time to event of composite endpoint defined as reaching immunologic decline or virologic increase as defined in a and b above, or dying. (DOCX 16 kb)


Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004–2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART. Socioeconomic position—an aggregate of resources including education, employment, income and wealth that interact but are not interchangeable—is linked to health outcomes in a variety of diseases and settings.–4 Among Scale-up of ART and viral load monitoring in sub-Saharan Africa is recent and limited and, as Despite an incomplete understanding of the interplay between socioeconomic position and ART outcomes, a myriad of interventions have been proposed and implemented by NGOs and even ministries of health in sub-Saharan Africa to address financial and social barriers to successful ART., 32 FurtThis prospective cohort study enrolled HIV-infected ART-naïve Ugandan adults ≥18 years of age who initiated ART between April 2004 and April 2005 at the Infectious Disease Institute clinic in Kampala, Uganda. Participants were followed for ten years. Eligibility criteria included at least two previous clinic visits, stable residence within 20 kilometers of Kampala, CD4 count <200 cells/μL or WHO stage IV disease, and written informed consent. At enrollment, we assessed HIV progression with baseline CD4 count, and we measured disability with the Karnofsky performance scale, which predicts mortality in HIV-infected persons. A KarnofAt cohort enrollment, we interviewed participants to record baseline socioeconomic characteristics. Self-reported monthly household income was converted to USD and categorized as above or below 1 USD/day. We assessed: 1) highest level of schooling completed ; 2) household income ; 3) employment status  and 4) housing description (brick or mud). Self-employment was defined as the state of working for oneself, such as growing/creating products to sell or owning a small business, without an employer.Clinic visits were scheduled every 6 months and participants were classified as lost to follow-up if they missed a clinic visit and were unreachable by telephone and home visit. Deaths were recorded and confirmed through medical record review and interviews with participants’ next of kin. HIV-1 viral load was measured in all participants at enrollment and afterwards every 6 months . Virologic treatment failure was defined as either lack of initial virologic suppression (at least one measurement below 400 copies/mL after ART initiation) or, after achieving initial suppression, two consecutive measurements >1000 copies/mL or one measurement >5000 copies/mL among patients who had no follow up measurement., 37We described baseline cohort clinical and socioeconomic characteristics stratified by sex. For categorical variables we compared proportions using the chi-square test and for continuous variables we compared medians using the Kruskal-Wallis test. We used Kaplan-Meier survival methods to calculate survival time and time to treatment failure stratified by baseline socioeconomic characteristics. Patients who died were followed up to known date of death or date of last clinic visit if death date unknown. Patients who were lost-to-follow-up were censored on last visit date, while all patients alive at ten years were administratively censored on the date of their ten-year clinic visit. For treatment failure, follow-up time began at the month six clinic visit or the first date of viral suppression and was calculated until the date of viral failure among those who failed. Among patients who died, who were lost-to-follow-up or who completed ten years of ART without failure, follow-up time was calculated until the date of death, the last visit seen or the ten-year clinic visit, respectively.p ≤0.25 in univariate analysis. Robust standard errors were used to account for within-patient correlation. Analysis was performed using Stata version 12 .To estimate the predictive associations between socioeconomic variables and mortality and virologic treatment failure, we performed Cox proportional hazard regression for each outcome (1) mortality, 2) treatment failure and 3) composite outcome of mortality and treatment failure) including demographic and socioeconomic variables as well as baseline and time-varying CD4 count and functional impairment (Karnofsky score). We developed a multivariable model that included age, gender and other variables that reached p = 0.001). At baseline, 49% (n = 272) were unemployed, 46% (n = 257) had a primary school education or less, 68% (n = 378) reported no regular household income or income below the poverty line of USD <1/day, and 33% (n = 187) lived in a mud house. Women had lower socioeconomic indicators than men (p<0.001) except in housing, which did not differ (p = 0.32). Of 553 participants with CD4 count measured at enrollment, 53% (n = 292) had a CD4 count <100 cells/μL. Participants with CD4<100 were more likely unemployed (55%) than those with higher CD4 >100 cells/μL . At baseline, 34% (189/559) were functionally impaired with a Karnofsky performance scale <80. Compared to participants with no functional impairment, a larger proportion of those with a Karnofsky <80 were unemployed  and receiving no regular income or any income <1 USD/day . After ten years, 6% (n = 31) of participants were lost to follow-up. In Kaplan-Meier analysis, sex and employment status were associated with loss to follow-up, with men and unemployed individuals most likely to be lost from the cohort.We enrolled a total of 559 adults starting ART between April 2004 and April 2005. Demographic, socioeconomic and clinical characteristics at enrollment separated by gender are presented in p<0.01), among participants with Karnofsky <80 indicating baseline functional impairment (p<0.01), and among participants who were unemployed at enrollment (p<0.01). In the univariate proportional hazard regression age >40 years compared to a reference age <30 was associated with poorer survival, while Karnofsky score >80 and CD4 100–200 cells/μL compared with <100 were associated with improved survival  of participants were alive and in care at our clinic and 23% (n = 127) had died with 63% (n = 80) of deaths in the first year of HIV therapy. Kaplan-Meier survival analysis showed higher cumulative probability of death among participants with baseline CD4<100 cells/μL  were still alive and had at least one viral load measurement after 6 months of ART. Over the ten year period 23% (107/472) met the definition of virologic treatment failure, including 7% (33/472) who never achieved viral suppression during the first 24 months after initiating ART. In the univariate proportional hazard regression, we observed no significant association between any baseline characteristics and virologic failure . The measure of higher household income, separate from employment status, may have captured a risk factor related to decreased adherence and poor outcomes. Of note, the cohort subset with income >1USD/day, which exhibited the highest relative rate of viral failure, also had the highest self-reported medication adherence. Further research is needed to better understand the interplay between household income and ART outcomes.Substantial variation in the cohort’s socioeconomic characteristics provided enough diversity to test for outcome differences. The long follow-up period with rigorous outcome ascertainment and low loss-to-follow-up of 6% also contribute to the results’ validity. Our inclusion of baseline CD4 count and functional impairment in the analysis enabled us to avoid the potential confounding of clinical status at the time of ART initiation. The different associations observed between various socioeconomic characteristics and outcomes reinforces the finding that socioeconomic position consists of separate factors that have distinct relationships with health and healthcare. Of note, formal education level was found to be unrelated to ten-year incidence of mortality or virologic failure. This finding is encouraging to HIV providers and ART programs serving populations with low levels of formal education. The ratio of women to men in this cohort represented the ratio of women and men enrolled at the Infectious Diseases Institute and in the country, likely due to higher HIV prevalence in women and more HIV screening in women, especially during antenatal care. We observed significant socioeconomic differences between women and men. However, we found no significant association between sex and any outcome, leading to the conclusion that sex alone was not predictive of survival or viral failure.Existing literature widely encourages socioeconomic interventions for HIV patients , 31, 39 Several limitations of our data collection and analysis are worth mentioning and merit further research Although we used broad categories to measure socioeconomic variables, limitations exist with patient self-reported information. Our baseline measurement of socioeconomic position upon enrollment is a common method and may be sufficient for assessing relatively static characteristics such as education and housing material in adults., 9, 28 HS1 FileTable A. Risk factors for all-cause 10-year mortality in a Ugandan cohort with baseline AIDS receiving ART (N = 559). Table B. Risk factors for 10-year virologic treatment failure in a Ugandan cohort with baseline AIDS receiving ART (N = 472).(DOCX)Click here for additional data file.


Supplemental Digital Content is available in the text An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterization of both natural viral control and the effect of ART on viral control after treatment interruption.Analysis of transient viral control in recent seroconverters in the Short Pulse AntiRetroviral Therapy at Acute Seroconversion trial.n = 292) and identified periods of control (plasma HIV RNA < 400 copies/ml for ≥16 weeks off therapy) in 7.9% of ART-naive participants, and in 12.0% overall. HIV DNA was measured by qPCR, and HIV-specific CD8+ responses were measured by enzyme-linked immunosorbent spot assay (ELISpot). T-cell activation and exhaustion were measured by flow cytometry.We compared untreated and treated HIV seroconverters  and higher CD4+ cell counts (P < 0.05) than noncontrollers. Among controllers, the only difference between the untreated and those who received ART was higher baseline HIV RNA in the latter (P = 0.003), supporting an added ART effect.At baseline, future controllers had lower HIV DNA, lower plasma HIV RNA, higher CD4Consideration of spontaneous remission in untreated individuals will be critical to avoid overestimating the effect size of new interventions used in HIV cure studies. Strategies to achieve an HIV cure by implementing interventions to deplete the HIV reservoir – a pool of latently infected cells containing transcriptionally repressed viral DNA – are entering clinical trials. In the absence of a validated biomarker to prove cure, a key outcome measure in these studies is the time to detection of viral RNA, or ‘viral rebound’, in plasma after stopping antiretroviral therapy (ART) in an analytic treatment interruption –5.Patients with primary HIV infection (PHI) are of particular interest, as with lower reservoir sizes –9 and prThe ‘Short Pulse AntiRetroviral Therapy at Acute Seroconversion’ (SPARTAC) trial ,21 was aSPARTAC (EudraCT number: 2004-000446-20) was a multicentre randomized controlled trial of short-course ART  initiated during PHI .Within this ‘at risk’ group, we identified controllers who experienced a period of remission which was defined for all as HIV RNA less than 400 copies/ml, on two measurements at least 16 weeks apart, with the period of remission starting within 1 year of randomization or ART cessation . We included participants who experienced a viral blip of any magnitude at a single time point. Time of viral rebound was the first of at least two consecutive measurements more than 400 copies/ml.n = 200) by a previously described qPCR assay  markers on CD42 or Fisher–Freeman–Halton exact test as appropriate. Continuous variables were compared across three groups using the Kruskal–Wallis test or analysis of variance (ANOVA). Pairwise comparisons were made using Mann–Whitney or Student's t test. Duration of viral control was assessed using Kaplan–Meier estimates. For all tests, P values less than 0.05 were considered statistically significant. Analyses were performed using R version 3.2.2. Plots were drawn using GraphPad Prism  version 6.0f.Categorical variables were compared using χMost studies of virological control have focused on ‘elite’ and PTCs ,26,27. WOur analysis included 292 of 366 participants recruited to the SPARTAC trial who had sufficient HIV RNA sampling and, if treated, were virologically suppressed prior to treatment interruption. Time on ART is analysed ‘as received’ rather than according to randomization arm and stratified as 0, 12 or less or more than 12 weeks of ART. Throughout this analysis, HIV RNA measurements less than 400 copies/ml are considered ‘suppressed’ as this was the lower limit of detection for assays conducted at South African and Ugandan trial sites. As such, this was the lowest HIV RNA threshold that could be applied across all samples.n = 80 ≤ 12 weeks; n = 86 > 12 weeks) and underwent treatment interruption, 25 (15.1%) experienced viral remission in the subsequent year.Considering these participants, regardless of ART use, 35 of 292 (12.0%) experienced a period of suppressed viraemia (HIV RNA < 400 copies/ml) of at least 16 weeks while off therapy and are termed ‘controllers’ for this report. Of the 126 participants who did not receive immediate ART, 10 (7.9%) experienced a period of spontaneous viral control within 1 year of randomization. Among individuals who received short-course ART . In our previous analysis of viral rebound in only the treated participants in SPARTAC, longer treatment duration was significantly associated with slower viral rebound within 12 weeks of stopping ART consistent with these findings [PTCs have been almost exclusively identified among individuals who initiated ART during PHI, suggesting an impact of early ART on long-term viral control . We founfindings .A strength of this analysis is the ability to quantify viral remission among treated and untreated individuals with PHI in a well characterized and frequently sampled randomized study. Several studies of ART initiated during PHI have demonstrated the presence of individuals who transiently control viral replication post-treatment interruption –35. NoneP = 0.22; log rank). Interestingly, when just considering the controllers, untreated participants were more likely to experience sustained control more than 104 weeks (7/10) compared with the treated controllers for whom rebound was more evenly distributed over the assessment period, and which may have implications for the underlying mechanisms.We next looked to see whether the duration of viral control varied between controllers who did or did not receive ART. There were more participants with over 1 year of remission among those receiving more than 12 weeks ART compared with 12 weeks or less or no ART [13  vs 3 (3.8%) vs 8 (6.3%), respectively (Table + T-cell counts (median 700 vs 557 cells/μl), lower plasma HIV RNA (median 2.70 vs 4.59 log10 copies/ml), higher CD4+-to-CD8+ ratio (median 0.77 vs 0.52) and lower total HIV DNA [mean 3.35 vs 3.85 log10 copies/106 CD4+ T cells , future controllers had more favourable baseline clinical characteristics with higher CD4+ cell counts, CD4+ : CD8+ ratios and HIV DNA levels to those who controlled following treatment interruption, but had significantly lower baseline HIV RNA than those who had received more than 12 weeks ART [median 2.30 vs 3.82 log10 copies/ml, respectively . We found no evidence for demographic differences between untreated and treated controllers in terms of sex, viral subtype, country of origin and age  and activation  at baseline also did not differ between treatment groups (data not shown).Next, we compared the demographic and immunological characteristics of untreated and treated controllers : T. Peto (Chair), A. McLaren (in memoriam), V. Beral, G. Chene, J. Hakim. Co-ordinating Trial Centre: Medical Research Council Clinical Trials Unit, London . Central Immunology Laboratories and Repositories: The Peter Medawar Building for Pathogen Research, University of Oxford, UK . Central Virology Laboratories and Repositories: Jefferiss Trust Laboratories, Imperial College, London, UK . Clinical Endpoint Review Committee: N. Paton, S. Fidler. Investigators and Staff at Participating Sites: Australia: St Vincents Hospital, Sydney (A. Kelleher), Northside Clinic, Melbourne (R. Moore), East Sydney Doctors, Sydney (R. McFarlane), Prahran Market Clinic, Melbourne (N. Roth), Taylor Square Private Clinic, Sydney (R. Finlayson), The Centre Clinic, Melbourne (B. Kiem Tee), Sexual Health Centre, Melbourne (T. Read), AIDS Medical Unit, Brisbane (M. Kelly), Burwood Rd Practice, Sydney (N. Doong), Holdsworth House Medical Practice, Sydney (M. Bloch), Aids Research Initiative, Sydney (C. Workman). Coordinating Centre in Australia: Kirby Institute University of New South Wales, Sydney . Brazil: Projeto Praca Onze, Hospital Escola Sao Francisco de Assis, Universidade federal do Rio de Janeiro, Rio de Janeiro . Italy: Ospedale San Raffaele, Milan , Ospedale Lazzaro Spallanzani, Roma . South Africa: Cape Town: Desmond Tutu HIV-1 Centre, Institute of Infectious Diseases, Cape Town . Johannesburg: The Wits Reproductive Health and HIV-1 Institute, University of Witswatersrand, Hillbrow Health Precinct, Johannesburg , Contract Laboratory Services, Johannesburg Hospital, Johannesburg . Kwazulu-Natal: HIV-1 Prevention Unit, Medical Research Council, Durban . Uganda: Medical Research Council/Uganda Virus Research Institute, Entebbe . Spain: Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona . UK and Ireland: Royal Sussex County Hospital, Brighton , St James's Hospital, Dublin , Regional Infectious Diseases Unit, Western General Hospital and Genitourinary Dept, Royal Infirmary of Edinburgh, Edinburgh , Chelsea and Westminster Hospital, London , Homerton Hospital, London , Mortimer Market Centre, London , North Middlesex Hospital , Royal Free Hospital, London , Barts & the London NHS Trust, London , St Marys Hospital, London , Birmingham Heartlands Hospital, Birmingham . Imperial College Trial Secretariat: S. Keeling, A. Becker. Imperial College DSMC Secretariat: C. Boocock. .We thank the participants of SPARTAC. The SPARTAC Trial Investigators: Trial Steering Committee: Independent Members – A. Breckenridge (Chair), P. Clayden, C. Conlon, F. Conradie, J. KaldorThe SPARTAC Trial was funded by The Wellcome Trust (grant no. 069598/Z/02/Z), J.F. is funded by the Medical Research Council, G.M. is funded by the Nuffield Department of Medicine, the Clarendon Fund and the General Sir John Monash Foundation.Author contributions: Conceived and designed the experiments – G.M., W.S., K.P., S.F., J.F. Performed the experiments – G.M., M.G., J.W., J.M., E.L. Analysed the data – G.M., W.S., K.P., J.F. Contributed reagents/materials/analysis tools: P.G. Wrote the article: G.M., W.S., K.P., S.F., J.F.There are no conflicts of interest.


Although tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) and zidovudine (ZDV)/lamivudine (3TC)/efavirenz (EFV) are used as preferred first line regimen, their head-to-head comparison in terms of their efficacy and tolerability was limited. This review aimed to synthesize the best available evidence on the comparative efficacy and tolerability of the two regimens. Seven sites and databases in addition to Google search until August 20, 2016, were searched. Only randomized clinical trials conducted on adult population were included in this study. Our primary outcome was viral load suppression while secondary outcomes were death and tolerability. Undetectable viral load is defined as <50 Human Immunodeficiency Virus (HIV) ribonucleic acid (RNA) copies/ml. Joanna Briggs institute meta-analysis of statistics assessment and review instrument (JBI-MAStARI) and critical appraisal and data extraction tool were applied for critical assessment and data extraction, respectively. We performed a random effect meta-analysis to pool the relative risk (RR) for viral load suppression (<50 HIV RNA copies/ml and <400 HIV RNA copies/ml), tolerability, and death.I2 = 0%) higher than zidovudine arm. Similarly TDF arm is superior in viral load suppression to <400 HIV RNA copies/ml . Moreover, TDF based regimens were more likely to be tolerated than ZDV based regimens ). However, forest plot of death shows that it was not significant . Data was extracted from four articles, which included a total of 2381 participants. We found superior viral load suppression among tenofovir (TDF) arm compared to zidovudine (ZDV) arm. Tenofovir arm achieves viral load <50 HIV RNA copies/ml  ,  The use of TDF/FTC/EFV as first line regimen for naïve HIV-1 infected adult patient showed superior viral load suppression and tolerability as compared to ZDV/3TC/EFV. In order to compare the death outcome of both ZDV/3TC/EFV and TDF/FTC/EFV further research is needed. Since its advent in 1986, Human Immunodeficiency Virus (HIV), as a causative agent for Acquired immunodeficiency syndrome (AIDS), became one of the greatest threats to public health . In 2015With the continued scale-up of access to ART, at the end of 2015, the global ART coverage reached 46%. It was increased from 24% in 2010 to 54%, in eastern and southern Africa .Because of rapidly emerging scientific understanding of HIV treatment, care, and the dynamic scale-up efforts in resource limited settings, the WHO guidelines are updated routinely every few years. So the 2013 WHO ART guideline brought TDF based regimens in clinical practice, together with ZDV based regimens , 9. TherEven though the current treatments are largely manageable, issues of tolerability and efficacy continue to be a concern, especially when combination therapy has been taken . LiteratThe fractions of evidence on which ART guideline is revised need to be organized for further synthesis. Systematic reviews serve as the basis for compiling and assessing the evidence upon which these recommendations are updated. The two previously published systematic reviews comparing the tolerability and efficacy of TDF versus ZDV based regimens were unable to show the true picture of the two currently recommended first line combination ART regimens. In addition a review by Omeje and Okwundu 2012  includedAfter having a common search strategy, all six authors independently and systematically searched to identify articles on tolerability and treatment outcomes of TDF and ZDV based regimens published until August 20, 2016. All authors searched each database on the same day to be consistent. Search terms included HIV, tenofovir, and zidovudine with their MeSH terms.In order to identify articles published in the English language that compare TDF and ZDV based regimen, we searched the PubMed, EMBASE, Scopus, Google Scholar, Mednar and Natural Standard alternative medicine, and Clinical Trials.Gov. We did the initial search for articles on July 11–18, 2016, and updated the results on August 20, 2016.Articles were eligible for inclusion if they contain only randomized clinical trials which included a head-to-head comparison of tenofovir based regimen with zidovudine based regimens among treatment naïve adult (age ≥ 18 years) HIV-1 infected patients. From both regimens the nucleoside reverse transcriptase inhibitors (NRTI) backbone other than comparison of interest can be either lamivudine or emtricitabine. Lamivudine and emtricitabine are comparable in efficacy and safety. There were no restrictions on publication date and country of focus.We excluded articles that contained only nevirapine based regimens from nonnucleoside reverse transcriptase inhibitors (NNRTI) or compared nevirapine based regimens with efavirenz based or protease inhibitor based regimens to minimize risk of confounding.https://doi.org/10.1155/2017/5792925). Any discrepancies that come up between the commentators will be decided through discussion or with a third reviewer.Besides above-mentioned inclusion criteria, papers that meet the inclusion criteria are critically appraised by two independent reviewers for methodological validity using standardized critical appraisal instruments from the Joanna Briggs institute meta-analysis of statistical assessment and review instrument (JBI-MAStARI)  ribonucleic acid (RNA) copies/ml.We extracted the evidence from original articles if they assessed at least one of the following outcomes: viral load suppression, death, and tolerability. Viral load suppression to either below <400 HIV RNA copies/ml or to undetectable levels (<50 HIV RNA copies/ml) was considered as primary outcome while secondary outcomes were death and tolerability. We extracted outcome using the similar data extraction tool of JBI-MAStARI (Appendix  II). All results were taken out by two independent reviewers to avoid extraction error.We entered data into review manager 5.3 for analysis and we did a random effect and fixed-effect meta-analysis to pool the relative risk (RR) of the outcomes. We performed a random effect meta-analysis to pool the relative risk (RR) for viral load suppression (<50 HIV RNA copies/ml and <400 HIV RNA copies/ml), tolerability, and death.P value, effect size, and heterogeneity (I2) were constructed. P values less than 0.05 were considered statistically significant.Forest plot containing RR, 95% confidence intervals (CI), A total of 1566 articles were identified from the different databases. After removal of duplicates and removal of articles by title and abstract thirty-eight full text papers were identified for eligibility. Twenty-two of the papers were rejected due to not meeting the inclusion criteria, and the rest 16 of them were examined for relevance. Of the 16 articles, we excluded 12 articles by critical appraisal. Four articles were included in the final meta-analysis .2 = 0.00, Chi2 = 0.48, df = 2 (P = 0.78); I2 = 0%, with test for overall effect of Z = 5.05  (P < 0.00001)  with 1 : 1 in the treatment and control group was extracted for determining the viral load suppression to less than 400 HIV RNA copies per milliliter. The numbers of patients who achieved this viral load suppression in the two arms were found to be 540 (76.81%) and 453 (64.44%) in treatment and control groups, respectively. Test of overall effect showed 1.19 times likelihood of achieving viral load suppression to less than 400 HIV RNA copies/ml in TDF arm compared to ZDV arm,  without heterogeneity: Tau0.00001) .2 = 0.00, Chi2 = 0.20, df = 2 (P = 0.90); I2 = 0%, with test for overall effect of Z = 3.14(P < 0.002) (Similarly data of 1408 patients (703 from TDF/FTC/EFV and 705 from ZDV/3TC/EFV) in 1 : 1 in both groups was obtained for assessing the viral load suppression to undetectable levels (HIV RNA < 50 copies/ml). The numbers of patients who achieved this viral load suppression in the two arms were found to be 495 (70.41%) and 442 (62.69%) in treatment and control groups, respectively. Test of overall effect showed 1.12 times more likelihood of achieving undetectable viral load suppression of TDF arm compared to ZDV arm,  without heterogeneity: Tau< 0.002) .I2 = 0%) among the studies may empower synthesizing the best evidence for concluding more likelihood of viral load suppression to any extent (whether to undetectable levels (<50 HIV RNA copies/ml) or to <400 HIV RNA copies/ml) among patient treated with TDF/FTC/EFV compared to those treated ZDV/3TC/EFV regimen. Therefore TDF/FTC/EFV has statistically superior efficacy profile in preventing virologic failure than ZDV/3TC/EFV combination ART regimen.The observed homogeneity ; I2 = 0%, and the test for overall effect showed that Z = 0.32 (P = 0.75) (Data of 1858 patients (920 from TDF/FTC/EFV (treatment) and 938 from ZDV/3TC/EFV (control)) with nearly 1 : 1 in the treatment and control group was obtained for assessing the mortality outcome. The number of patients who died in the two groups was calculated to be 21 (2.3%) and 24 (2.6%) in treatment and control groups, respectively. The cumulative RR between the two arms did not confer any statistical significance,  without heterogeneity: Tau = 0.75) .I2 = 0%) among the studies may empower synthesizing the best evidence for concluding the absence of risk difference in mortality among patient treated with TDF/FTC/EFV and ZDV/3TC/EFV regimens. Therefore the two arms have statistically equivalent efficacy profile in preventing death; however, clinically significant mortality differences may exist.The observed homogeneity ; I2 = 51%, Z = 2.70 (P < 0.007) (I2 = 51%) among the studies may empower synthesizing the best evidence for concluding more tolerability among patient treated with TDF/FTC/EFV than ZDV/3TC/EFV combination ART regimen  with nearly 1 : 1 in the treatment and control group. The numbers of patients who tolerated the regimens until the end of the study were calculated to be 1063 (89.86%) and 1008 (84.14%) in TDF/FTC/EFV and ZDV/3TC/EFV arms, respectively. Test of overall effect revealed 1.06 times likelihood of tolerating TDF arm as compared to ZDV arm, , Chi< 0.007) . The obs regimen .We included three clinical trials that enrolled a total of 1408 participants, four clinical trials that enrolled a total of 2381 participants, and three clinical trials that enrolled a total of 1858 participants for determining efficacy, tolerability, and mortality, respectively.P = 0.002), and viral load suppression to <400 HIV RNA copies/ml . This finding contradicted the pervious meta-analysis and systematic review [Z = 2.70, P < 0.007, I2 = 51%). This finding is similar to the previous studies [In this meta-analysis, we found superiority viral load suppression among the TDF/FTC/EFV arm as compared to ZDV/3TC/EFV arm in achieving undetectable viral load (<50 HIV RNA copies/ml) ; this result was similar to the previous systematic review . This miThe strength of this study includes head-to-head comparison of the two regimens, homogeneity of included studies, use of only randomized clinical trials for evidence synthesis, and determining efficacy in terms of viral load suppression, which is considered as the gold standard of efficacy measurement. The limitation of this was due to the fact that pooling of the results measured on different follow-up periods, 48, 96, and 144 weeks, on the same population might affect the result.The use of TDF/FTC/EFV as first line regimen for naïve HIV-1 infected adult patient showed superior viral load suppression and tolerability as compared to ZDV/3TC/EFV. In order to compare the death outcome of both ZDV/3TC/EFV and TDF/FTC/EFV further research is needed.The Joanna Briggs institute meta-analysis of statistical assessment and review instrument (JBI-MAStARI) is developed by Adelaide University, Australia. The critical appraisal contains all necessary components to appraise clinical trial articles.