Background: A study of patient records in four HIV clinics in three sub-Saharan African countries examined routine clinical care patterns and variations.Methods: Clinic characteristics were described, and patient data extracted from a sample of medical records. Data on treatment, CD4 count and viral load (VL) were obtained for the last visit in the records, dates mainly between 2015 and 2017, patient demographic data were obtained from the first clinic visit.Results: Four clinics, two in Nigeria, one in Zambia and one in Uganda, all public facilities, using national HIV treatment guidelines were included. Numbers of patients and health professionals varied, with some variation in stated frequency of testing for CD4 count and VL. Clinical guidelines were available in each clinic, and most drugs were available free to patients. The proportion of patients with a CD4 count in the records varied from 84 to 100 percent, the latest median count varied from 269 to 593 between clinics. 35% had a record of a VL test, varying from 1% to 63% of patients. Lamivudine (3TC) was recorded for more than 90% of patients in each clinic, and although there was variation between clinics in the choice of antiretroviral therapy (ART), the majority were on first line drugs consistent with guidelines.  Only about 2% of the patients were on second-line ARTs. In two clinics, 100% and 99% of patients were prescribed co-trimoxazole, compared with 7% and no patients in the two other clinics.Conclusions: The wide variation in available clinic health work force, levels and frequency of CD4 counts, and VL assessment and treatment indicate sub-optimal adherence to current guidelines in routine clinical care. There is room for further work to understand the reasons for this variation, and to standardise record keeping and routine care of HIV positive patients. The implementation of standardized protocols for treatment and investigations may vary in resource constrained countries, with differences in resources available for such services. For example, the current guidelines for antiretroviral therapy (ART) requires all patients on ART to have viral load test at six months and 12 months5, implementation might vary based on availability of resources to support viral load testing. While a number of reports of current treatment and testing practice are available from resource-limited settings, these are mainly in the context of patients enrolled in research centres or in research studies8. Such settings often have substantially more resources than routine clinical practices, and as such practice patterns may differ from routine practice, where issues such as clinic and patient resources or drug stock-outs can affect care. This study was designed to explore variation in the evaluation, treatment, care and follow-up among patients diagnosed with HIV in routine care settings in low- to middle-income countries.In addition to choice of appropriate drugs, best practice management of patients with HIV requires monitoring response to treatment and disease progression. This includes tracking clinical immunological, and virological data on patients at diagnosis and on follow-up. There is a rich literature guiding HIV treatment, and guidelines are developed and updated regularly as new evidence comes to light9. There was no prior determination of the numbers of centres required or their geographical setting. A protocol was developed by those who responded  based on CD4 count, and the ART regime recorded was that started as a result of that review at that time. Data on patient demographics were those present in the records, often this would be prior to the date of entry to this study.For clinic AM, a public hospital based clinic in Uganda, the sampling frame was the register of all clients on active ART, and every third patient file was retrieved from files ordered according to clinic appointment date. The CD4 counts and ART regimes recorded were for the most recent measures in the records, and patient demographics were those in the records from their first visit.Data on individual patients were extracted from medical records, including age, gender, and baseline clinical data at diagnosis and follow-up. Clinical information included clinical, immunological and virological information on patients at diagnosis and on follow-up, prescription of ART and other drug choices. Potentially important co-infections and/or co-morbidities, identified from the literature, were coded as indicated inDetails of the tests ordered and their results, and treatments ordered were extracted from medical records. Individual patients were not contacted. Data were obtained from the records, and no attempt was made to validate the information. Missing data were recorded as missing, and not explored further.A pilot study tested the feasibility of the data collection and the method of recording on to a spreadsheet. Data were collected by a research assistant in each setting, using the spreadsheet, from examination of individual records.As a retrospective patient records study, consent was not requested from individual patients. Ethics approval was sought and obtained in each setting from the appropriate authority . Considerable care was taken not to reveal the identity of any individual and all data were de-identified. The spreadsheet for the recording of data only had an identification number, and the key to the identity of each patient was kept separately to maintain confidentiality. To further this, the clinics names and exact locations have been removed.Each centre was asked to obtain information from at least 100 patients.Stata 14.1  andR version 3.3.0 .Descriptive statistics were used to characterise the study population. Data distributions were assessed, checking for skewness and kurtosis. Data summary statistics were generated. Categorical variables were summarized using proportions while continuous variables were summarized using medians and interquartile ranges. Due to differences in data extraction across sites, no statistical analyses comparing across sites was conducted. All analyses were conducted inTen alumni expressed interest in participating, three centres were able to pilot the data collection instrument and four centres in three countries participated in the data collection for the study. Overall, data were abstracted for 600 patients.De-identified data collected from clinical records used to create Tables 2 and 3 and Figure 1Scheme used to code the data is available asClick here for additional data file.Copyright: © 2019 Musa BM et al.2019Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).Data were collected according to the standardised data collection instrument , with daThis study found modest documentation of clinical activities, with a wide variation in available clinic health work force, frequency of CD4 counts and levels and viral load assessment. The two clinics in Nigeria had markedly different caseloads. The centre with the high caseload is one of the oldest in Nigeria and provides incentives to this population of patients , Differences in case load may reflect population distribution and heterogeneity in HIV prevalence, or that patients may seek care far away from their base to avoid stigmatization. Variation in case load can lead to differences in efficiency and quality of care, and potentially could have implications for care outcomes. However determining its impact on outcome would a require a properly powered longitudinal study.5. While this guideline is based on sound evidence, it adds an unanticipated number of potential eligible patients for ART care, with attendant strain on countries with an already fragile economy. The low frequency of viral load test results might also reflect resource limitations.While most patients had a CD4 count in the records, there was a wide spread of latest CD4 counts, with both within- and between-centre variation in the CD4 counts. Only one in three patients had a record of viral load at any time during the course of treatment, and most of these had an undetectable level (<50 copies/µL). Some of the absence of viral load might be poor record keeping, and the high proportion of undetectable results might reflect an absent rather than a low test result, and hence not an indicator of treatment success. Over the years the CD4 threshold for commencing ART had been lowered, as can be seen in10. TDF/3TC/EFV drug regimens have a low pill burden, and may contribute to the low usage of second-line ART regimens.Most patients were on TDF/3TC/EFV drug regimen, which is consistent with current guideline advice for first line treatment. Only 2% of the patients were on second-line ART, varying from 9% to less than 1% between clinics. It is likely that most of the studied patients are still on a potent first line ART judging by the low second-line ART usage. Use of a regimen with a low pill burden would enhance therapy adherence and might lead to reduced need for switching patients to second line ART11.The variation in the use of co-trimoxazole, from almost universal in two clinics, to negligible in the other two clinics, is an extreme example of the variation we identified. The reason for this variation despite the guideline recommendation is not clear, but it is possible that it is a result of local clinic policy settings, possibly related to concerns about increasing antibiotic resistance. Variation in the use of co-trimoxazole has been found in other resource-limited settings, while efforts are being made to improve the rates of use12. Some discrepancy between WHO guidelines and actual implementation in practice may arise from the time it takes to implement new guidelines, or due to lack of resources to immediately initiate all patients with HIV on ART. We see considerable between-clinic variation in a number of key management strategies reported by the clinics, from the recording of CD4 counts, median CD4 counts on treatment, and treatments used. This variation is consistent with a previous survey of stated management practices in 6 sub-Saharan countries14.While each clinic reported having access to treatment guidelines, those current at the time of the data collection do not appear to have been universally followed. The guidelines also do change regularly, as shown in15, as well as to lead to worse clinical outcomes, although it is beyond the scope of our study to explore outcomes. Findings of variation from standard management practice has previously been reported from routine care settings in other parts of sub-Saharan Africa including Ethiopia16, Uganda17 and Tanzania18, mostly in single isolated centres. Here we present combined data on health system related measures across multiple sub-Saharan African HIV treatment sites. Hence, this study adds to the literature a current examination of the routine care provided to patients with HIV, rather than that in the context of a clinical trial. The study adds information from a number of centres in multiple countries, using a common protocol, of both the characteristics of the clinics and of the care given in these clinics.The management of patients in routine clinical care has been shown to differ from that seen in clinical trials21. The potential of electronic medical records to improve records could be explored22.In the absence of standardised record keeping systems, it is difficult to make clear comparisons of management and outcome in routine clinical care. Our findings suggest that there is room for further work to understand the reasons for these record gaps, and to standardise the record keeping in routine care of HIV positive patientsOur study has a number of limitations. First, this study was an analysis of data extracted from existing medical records, which are prone to error including missing data. We have found missing data where it should ordinarily not be missing. We cannot comment on other factors that may have contributed to missing data, such as whether tests were not done or if they were not recorded. A future study should perform an audit of the medical records to determine the reason for missing data and hence the potential effect on the study findings. Second, some of the variation between centres may be due to differences in patient populations which we were unable to capture, even though we selected clinics involved in routine clinical care. Third, since this is a descriptive study and not hypothesis testing, it was not feasible to determine sample size in advance. A pragmatic approach was adopted, with each centre expected to obtain information from the first 100 patients presenting over a 6-month period, or from at least 100 patients. Fourth, participation in the study was restricted to few countries, and to individual clinics, which may not be representative of the national picture in these countries. A prospective cohort study on representative samples would provide a more robust study design with more detailed quantitative data to delineate care dynamics and to provide longitudinal data to better understand how clinical practice in these settings is linked to patient outcomes.We demonstrate a wide variability in compliance with HIV treatment guidelines in four routine care settings in sub-Saharan Africa, as well as gaps in the records available. The findings of this study may provide an explanation for heterogeneous HIV treatment outcomes across sub-Saharan Africa. In spite of the limitations, these data underscore the need for an in-depth study to address compliance with HIV treatment guidelines and best practice. While electronic medical record implementation might be a challenge for many HIV care points in sub-Saharan Africa, our findings emphasize the need for more robust interim paper-based medical record keeping.Ethics approval was sought in each setting from the appropriate authority. For two of the centres, research ethics committees gave approval. In two of the centres, the ethics committees stated that they did not require formal approval from them, however approval to access records was obtained from the relevant District Health Office/r. Details for each clinic as follows:Clinic BA: Ethics approval obtained from Aminu Kano Teaching Hospital Research Ethics Committee.Clinic EV: Ethics approval obtained from Research and Ethics Committee of State House Medical Centre, Abuja.Clinic MW: University of Zambia Biomedical Research Ethics Committee contacted and advised to notify the Lusaka District Health Office (LDHO) who gave approval.Clinic AM: Eastern Uganda AIDS Support Organization (TASO) contacted who recommended no need for an approval but rather write to the Amuria District Health Officer (DHO) for permission to have access to the hospital records, which was given.Informed consent was not obtained from individual patients since this was a records study with appropriate institutional approval, strict confidentiality arrangements, and no patient contact, as stated in the manuscript.The data referenced by this article are under copyright with the following copyright statement: Copyright: © 2019 Musa BM et al.Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).10.5256/f1000research.15169.d20633323Dataset 1. De-identified data collected from clinical records used to createAll data underlying the survey responses from clinic informants for Methods: Kindly include the research question being answered. Study design needs to be made clearer in this section.Measurement of study factors: Kindly specify important co-infections and co-morbidities.Sample size consideration/selection: how were the centres selected? It is not clear how the size of 100 patients was arrived at. If the sample size and record selection was arbitrary this should be stated as a limitation of the study. What is standardised data collection? If this study is looking for variations, what of the similarities? The method section should give more background information on the centres chosen. This will include the health care worker/patient ratio, patient load and type of care provided to the patients.What are the effects of missing values on the study findings? Efforts should be made by the authors to highlight reasons for missing values. A statement on the best way to address the missing values should be stated. What is the new information that this study added to the literature?I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Referee comments in italics).Comments from Referee 3, and how we have responded and made changes (Methods: Kindly include the research question being answered. Study design needs to be made clearer in this section.Supplementary File 1) which included the Research questions as follows: 1. Among a group of patients diagnosed with HIV by a health care facility newly diagnosed between 2 and 3 years previously, what proportion have standards of care in terms of the tests and treatments they receive and follow up to 2 years after diagnosis documented in their records? 2. Among the health care facilities in which the above patients are cared, what treatment, testing and referral facilities are available? 3. What is the extent of the variation in the above measures between facilities and countries, as well as in the availability of appropriate evidence based practice guidelines? A retrospective patient cohort was created via standardized record review, and clinic characteristics determined through an online survey form.”Response: Paragraph 1 in the Methods section has been revised as follows: “Interest in participating in this study was sought among the Masters of Public Health Alumni of Peoples-uni. A protocol was developed by those who responded  ‘Interest in participating in this study was sought among the Masters of Public Health Alumni of Peoples-uni’ and (Results) ‘Ten alumni expressed interest in participating, three centres were able to pilot the data collection instrument and four centres in three countries participated in the data collection for the study.’ We have added to the sentence in the Methods section as follows: “Interest in participating in this study was sought among the Masters of Public Health Alumni of Peoples-uni. There was no prior determination of the numbers of centres required or their geographical setting.” We have added to the section on study limitations as follows: “Since this is a descriptive study and not hypothesis testing, it was not feasible to determine sample size in advance. A pragmatic approach was adopted, with each centre expected to obtain information from the first 100 patients presenting over a 6-month period, or from at least 100 patients.”Supplementary File 2), with data on treatment regimes and CD4 counts relating to the latest information in the records (dates mainly between 2015 and 2017).”We have changed the first sentence in the Discussion to the following: “Data were collected according to the standardised data collection instrument  to follow our original sentence ‘Here we present combined data on health system related measures across multiple sub-Saharan African HIV treatment sites.’ the additional sentences read: “Hence, this study adds to the literature a current examination of the routine care provided to patients with HIV, rather than that in the context of a clinical trial. The study adds information from a number of centres in multiple countries, using a common protocol, of both the characteristics of the clinics and of the care given in these clinics.” The authors have corrected minor issues in the article, though I retain my reservations around the study design and the lack of a research question.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. I am sorry that you did not make your reservations clear in your first report. With regard to the research question, we stated in the Introduction "This study was designed to explore variation in the evaluation, treatment, care and follow-up among patients diagnosed with HIV in routine care settings in low- to middle-income countries". With regard to the study design, we stated in the Discussion "Data were collected in a standardised way, with data on treatment regimes and CD4 counts relating to the latest information in the records (dates mainly between 2015 and 2017). While we initially planned to collect data on a cohort of patients enrolled two years before data collection in each clinic, this did not prove feasible and patients had presented to the clinics at variable times." There has been some improvements in the current draft and most of the issues raised have been addressed. However l was wondering whether it’s possible for the authors to comment to the patient doctor ratio with regards to co-trimoxazole distribution.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Thank you for your comments. We could not demonstrate an obvious relationship between the doctor/patient ratio and use of co-trimoxazole, although it is an intriguing suggestion. A study including a larger sample of clinics might be able to explore this further. The paper is well written, however in some instances the authors have used outdated references. In the case of Nigeria where there are 2 health facilities with different caseloads per month, the authors could also enlighten us on the impact of having a high and low case load as presented. The authors should also enlighten us on whether the records indicate the dates when the CD4 count and viral load tests were taken and when they were reported back. I suppose this of great importance since, there are reports of patients who have their blood samples taken and never receive results. 1) Is The study design appropriate and is the work technically sound? The study design wand the work is technically, as the authors endeavoured to analyse multi-country settings 2. Are sufficient details of methods and analysis provided to allow replication by others? The methods and analysis were sufficient, however in the case of Nigeria where there are 2 health facilities with different case loads per month; the authors could also enlighten us on the impact of having a high and low case load as presented. 3. If applicable, is the statistical analysis and its interpretation appropriate? The statistical analysis was appropriate, although the authors should also enlighten us on whether the records indicate the dates when the CD4 count and viral load tests were taken and when they were reported back. I suppose this of great importance since, there are reports of patients who have their blood samples taken and never receive results. 4. Are the conclusions drawn adequately supported by the results? The authors however need to address the issues that have been raised above.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Thank you for your generally positive comments. In the revised version submitted, we have added four recent references, and given further details on the dates of CD4 counts and viral load tests . We have also discussed the reasons that the two Nigerian clinics might have different caseloads and the potential impact of this. This article by Musa and colleagues uses a snapshot of patient records from four HIV clinics in Nigeria, Zambia and Uganda to describe the variability in a number of patient measures. Data are not reported longitudinally and all analysis is descriptive. The most useful part of this report is to show that ordinary clinics in countries with some of the highest HIV burdens globally do not confirm with WHO guidelines. For instance, only commencing ART when CD4 cells <350/ul. Further, the high amount of missing data in viral loads suggest there are logistical or cost challenges to routine testing.   It is perhaps unsurprising that clinics in different countries vary in their patient characteristics and levels of reporting. The variability in CD4 counts is not particularly informative as it is not linked to length of time under ART. No research questions are addressed. Table 2 should be amended as some percentage values are missing and figures are presented to different numbers of significant figures. Despite the descriptive nature of the study, the authors are to be commended on presenting hard to access data from routine health care settings in sub-Saharan Africa. I hope that they will be able to take longitudinal data in the future and better understand how clinical practice in these settings is linked to patient outcomes.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Thank you for your positive comments on the paper. In the revised version submitted, we have tried to emphasise the points you make, and have amended Table 2 as requested. Supplementary File 1) which included the Research questions as follows: 1. Among a group of patients diagnosed with HIV by a health care facility newly diagnosed between 2 and 3 years previously, what proportion have standards of care in terms of the tests and treatments they receive and follow up to 2 years after diagnosis documented in their records? 2. Among the health care facilities in which the above patients are cared, what treatment, testing and referral facilities are available? 3. What is the extent of the variation in the above measures between facilities and countries, as well as in the availability of appropriate evidence based practice guidelines? A retrospective patient cohort was created via standardized record review, and clinic characteristics determined through an online survey form.”In a later revision of the paper, paragraph 1 in the Methods section has been revised as follows to include the research question: “Interest in participating in this study was sought among the Masters of Public Health Alumni of Peoples-uni. A protocol was developed by those who responded (


Test & Treat » strategy and the wider accessibility to viral load (VL), evaluating virological success (VS) would help in meeting the UNAIDS targets by 2020 in Cameroon.After the launching of the « Cross-sectional study conducted in the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaoundé, Cameroon; data generated between October 2016 and August 2017 amongst adults, adolescents and children at 12, 24, 36 and ≥ 48 months on ART. VS was defined as < 1000 copies/mL of blood plasma and controlled viremia as VL < 50 copies/mL. Data were analysed by SPSS; p < 0.05 considered as significant.1946 patients  were enrolled ; 1841 were on NNRTI-based and 105 on PI-based therapy; with 346 patients at M12, 270 at M24, 205 at M36 and 1125 at ≥ M48. The median (IQR) duration on was 48 months (24–48). Overall, VS was 79.4% (95% CI 77.6–81.2) and 67.1% (95% CI 64.9–69.1) had controlled viral replication. On NNRTI-based, VS was 79.9% vs. 71.4% on PIs-based, p = 0.003. By ART duration, VS was 84.1% (M12), 85.9% (M24), 75.1% (M36) and 77.2% (≥ M48), p = 0.001. By age, VS was 75.6% (children), 53.3% (adolescents) and 81.1% (adults), p < 0.001.In this sub-population of patients receiving ART in Cameroon, about 80% might be experiencing VS, with declining performance at adolescence, with NNRTI-based regimens, and as from 36 months on ART. Thus, improving VS may require an adapted adherence support mechanism, especially for adolescents with long-term treatment in resource-limited settings. Despite many decades of continuous fight, Human immunodeficiency virus (HIV) is still one of the major global health issue, having claimed more than 35 million lives so far, with the WHO African Region in particular being the most affected with 25.7 million people living with HIV in 2017 .test and treat” strategy. In addition, since most of the studies focused on adult populations  years vs. 41 [IQR: 34–50] years, p < 0.001; calendar year 2011 [IQR: 2008–2013] vs. calendar year 2012 [IQR: 2009–2014], p < 0.001; and 48 [IQR: 36–48] months vs. 48 [IQR: 24–48] months, p = 0.001; respectively.According to ART duration, VS was 84.1% at 12 months (M12), 85.9% at 24 months (M24), 75.1% at 36 months (M36) and 77.2% at more 48 months (≥ M48), p = 0.001. The overall VS was 75.9% (95% CI 72.3–79.2) for males and 80.9% (95% CI 78.8–82.9) for females, p = 0.013; while overall controlled viremia was 61.4% for male and 69.4% for female (p = 0.001). There was a large variation of VS prevalence with respect to age groups for both VS thresholds (p < 0.001); with the highest prevalence of virological failure at VS ≥ 1000 copies/mL being recorded among adolescents (46.7%), followed by children (24.4%). When compared according to cART regimens, TDF + 3TC + EFV, others first line combinations, and ritonavir-boosted lopinavir (LPV/r)/atazanavir (ATV/r)-based ARV) at VS < 1000 copies/mL, patients on TDF + 3TC + EFV recorded the highest VS (83.2%) versus 71.4% on PI/r-based regimens, p < 0.001.According to circumstances of HIV diagnosis, at both VS < 50 copies/mL and VS < 1000 copies/mL, those diagnosed during PMTCT had the highest prevalence (72.9% and 85.7% respectively), followed by patients screened voluntarily (72.1% and 84.0% respectively); with patients diagnosed at birth recording the worst performance (53.7% and 61.0% respectively); p < 0.001. Figure test and treat” era in Cameroon, the overall prevalence of VS < 1000 copies/mL after at least 12 months of cART was 79.4% (95% CI 77.6–81.2); about 11% away from the 90% target set by UNAIDS by 2020. This performance is less than the 82% reported global VS performance [In this study, we aimed at estimating the prevalence of virological success per age groups, duration on cART and therapeutic line among HIV/AIDS patients in Cameroon. It shows that at the start of the “formance , with thformance ; or to aformance –19, espeThe median age (IQR) of virally suppressed patients was 42 years (34–50 years) versus 39 years (33–49 years) in treatment failure patients (p < 0.001). In fact, our result shows that children (< 10 years) and/or adolescents (10–19 years) are much less likely to achieve virological success compared to adult populations (p < 0.001). Poor ART response of HIV-infected children  compared to adult populations is well documented. This could be justified by the higher viral replication and the less efficient immune response against infections in infants –22. MoreThe lack of adherence and adequate provision of psychological supports in children and adolescents has been reported to represent the major cause of loss to follow-up and virological failure , 24. TheAccording to gender, females are more likely to experience virological success than men 80.9% vs 75.9% respectively, p = 0.013). Even though the recent CAMPHIA study reported a relatively higher VS in men than women (80.1% vs 79.2%) , 15. ThiThe treatment failure rate at VS < 1000 copies/mL was higher among patients on second line compared to first line patients . When compared according to ARV combinations  versus 75.4% and 71.4% for other first line and PI-based regimen respectively (p < 0.001). Most studies reported more than 80% VS in patients on PI based therapy –36. EvenAccording to duration on therapy, VF was associated with longer stay on cART (median year of cART start: 2011 2008–2013) versus 2012 . Similar trend was equally reported after 6 months and 48 months on cART in a review –2013 ver, 43. A sAccording to reasons/circumstances of diagnosis, the VS varied significantly among the patients (p < 0.001). The VF among patients diagnosed during consultation was 22.4%, against 16.0% in patients who undertook voluntarily testing and 14.3% in women diagnosed during PMTCT. Additional data should be collected to better understand how engaging potentially infected persons and key populations in voluntary screening may contribute in achieving also the third “90”. Contrary to other studies, we noted a higher VS among patients from Rural area compared to those in urban area (p = 0.004). The major limitation of this study is that data were not collected on whether VL was requested for routine monitoring, suspects failure or repeat testers after failure, and might have confounded our estimates. Additionally, even though the acquired HIV drug resistance among patients failing ART is still of concern in Cameroon, we could not present these data in our study because they were not performed. We therefore recommend subsequent studies to investigate other predictors to VF and acquired HIV drug resistance profile among patients failing ART in such setting.In this sub-population of patients receiving ART in Cameroon, about 8 out of 10 might be experiencing VS (with a gap of 10% below the required target set by 2020), with poorer outcomes among adolescents and those as from 36 months on cART. Furthermore, VS appears higher in females and in those treated with TDF + 3TC + EFV compared to other NNRTI-based or PI/r-based regimens. Thus, strategies towards improved monitoring of adolescents, male and long-term treated patients are crucial in maximising VS, while access to timely switch of ART and/or drug resistance would help in alleviating the burden VF and in meeting the target for ART response in RLS.


Ghana has been providing HIV and AIDS services since the identification of the first case in 1986 and added highly active antiretroviral therapy to its comprehensive care in 2003.This study aimed at assessing availability of HIV services along the continuum of HIV care in Ghana.A cross sectional study was conducted among 172 (87%) of the total 197 ART canters in Ghana. Data was collected by self-administered questionnaire and analysed using STATA version 13.Of the 172 health facilities surveyed, 165 (96%) were offering HIV testing Services (HTS) during the survey period. More than 90% of the surveyed facilities reported to offer Anti-Retroviral Treatment (ART), patient counselling, TB screening and Prevention of Mother to Child Transmission (PMTCT) services. Viral load and Early Infant Diagnosis (EID) and laboratory testing services were reported at 10 (5.8%) and 23 (13.4%) respectively. HIV testing services (HTS), PMTCT, ART, patient counselling and opportunistic infections (OI) prophylaxis services were offered at all Tertiary and Regional hospitals surveyed. EID sample collection and testing services was reported at 2 out of 27 (7.4%) of the Health Centre and/or clinics in Ghana. The common adherence assessment methodology being implemented varied by facilities which included: asking patients if they took their drugs 154 (89.5%), pill counting 131 (76.2%), use of follow-up visit 79(45.9%) and use of CD4 counts, viral loads and clinical manifestation 76 (44.2%). Challenges encountered by facilities included shortage of test reagents and drugs 122 (71%), 111 (65%) respectively and patient compliance 101 (59%).This study showed ART services to be available in most facilities. Methods used to assess patients adherence varied across facilities. Shortage of test reagents and drugs, EID sample collection and testing were major challenges. A standardised approach to assessing patient’s adherence is recommended. Measures should be put in place to ensure availability of HIV commodities at all levels. The National HIV/ AIDS/ STI Control Programme(NACP) was launched in Ghana in 1987 and since then there has been an increasing number of People Living with HIV (PLHIV) population as well as those put on Antiretroviral (ARVs). By the end of 2014, Ghana had an estimated PLHIV population of 226,460 of which 10.5% were projected to be children. The projected ART need was 139,157 for adults and 13,125 for children of which 73% and 63% respectively were projected to be on ART and a projected PMTCT coverage of 82% [Availability of HIV-related preventive, care and treatment services is essential to reduce the burden of the disease. The continuum of HIV testing, care, and treatment covers a wide range of activities which aim at early detection of HIV cases through HIV testing services, care and support, anti-retroviral therapy (ART), adherence monitoring and follow-up, regular supply of medications, adverse event monitoring and drug resistance surveillance, and clinical, immunological and virologic monitoring . HoweverLimited or incomplete availability of services along the HIV testing- care - treatment continuum can negatively affect HIV. For example, where testing services are not available, this will undermine know your status campaign which is required to achieve the 90% of people knowing their HIV status by 2020 to achieve the end AIDS in 2030 target . ShortagTo date, limited review has been undertaken on a range of service availability across the nation. Analyses of HIV service delivery have been fragmented with focus on only one component of the service such as ART , and intGhana operates a decentralized administrative structure with the country divided into ten regions with the Greater Accra region being the national capital of Ghana . The decGhana has been providing HIV and AIDS services since the identification of the first case in 1986, adding and expanding gradually services along the continuum over the past decades. The provision of the highly active antiretroviral therapy (HAART) was added to its comprehensive care in 2003. Ghana’s Prevention of Mother to Child Transmission (PMTCT) program started effectively in 2002 with two facilities offering PMTCT services in the Manya Krobo District in the Eastern Region. Since then, the country has expanded PMTCT facilities to 2748 of over 3765 health facilities providing Antenatal services. Syphilis testing is also offered to all the pregnant women visiting the PMTCT centers. This study was to cross-sectionally assess availability of HIV services along the continuum of HIV care in Ghana as a step towards improving the quality of HIV and AIDS service delivery in the country.This was a cross-sectional survey which employed the administration of questionnaires to frontline service providers with at least 1 year experience in the area of HIV service delivery.The respondents for each facility were health care providers directly involved in the provision HIV related services in their respective facilities for at least 1 year. They were made up of clinician’s nurses, midwives, data managers, pharmacist and laboratory personnel who formed the core ART team at their various facilities.We conducted our study in Ghana which is located in the West African sub-region. The country is bordered to the south of Gulf of Guinea and the Atlantic Ocean and is bordered to the west by Cote d’Ivoire, east by Togo and Burkina Faso to the north. The population of the country is estimated to be 27,000, 000 based on the 2010 Population and Housing Census Report .A health facility assessment one pager questionnaire was administered to all 197 ART sites in Ghana . Out of which one hundred and seventy-two sites (87%) responded to the questionnaire with the remaining sites opting out. The indicator selection for the questionnaire was guided by WHO’s guide to monitoring and evaluation of HIV/AIDS care and support [The study was approved by the Ethics Review Committee (ERC) of the Ghana Health Service. Permission was sought from Regional and District Directors of Health services as well as facility heads involved in the study. Informed consent was also sought and obtained from all participants. They were assured of their privacy and confidentiality. No personal identifiers were captured during data collection. The respondents were informed that they could opt-out of the study at any point and were also not obliged to respond to all the questions. Data collected was kept in a locked shelve at the secured NACP records room.The questionnaire was coded, double entered into Microsoft (MS) access by two independent data entry clerks and later transferred to Stata data analysis software for data management and analysis. Descriptive statistical method was used to present proportions of variables of interest.n = 2); Regional hospitals (n = 8); District hospitals (n = 131); Polyclinic (n = 4); Health centres (n = 19) and clinics (n = 8). However, these were later during the analysis re-categorised into three groups; teaching and regional hospitals in one group, district hospitals and polyclinics in a second group and health centres and clinics in the third group. The facilities that did not respond to the questionnaire were teaching hospitals (n = 2); Regional hospitals (n = 2); District Hospitals (n = 17); Polyclinic (n = 1); Health centres (n = 2) and clinics (n = 1) Fig. In total, one hundred and seventy-two health facilities responded to the questionnaire (87%). The type of facilities that responded included teaching hospitals  services. More than 90% of the surveyed facilities reported to offer ART patient counselling, TB screening and PMTCT services On the other hand, viral load and EID specimen collection and laboratory testing was done at only 10/172 (5.8%) and 23/172(13.4%) of all survey facilities respectively because there are only nine viral load machines located in regional/teaching hospitals. All facilities in a region share the viral load machine. Table The study found that PMTCT, HIV Testing & Counselling, ART patient counselling and Opportunistic Infections(OI) prophylaxis services were offered at all Tertiary and Regional hospitals that were surveyed. Furthermore, TB screening was reported to be offered at majority of the different type of health facilities that were surveyed. More interestingly we found that Early Infant Diagnosis (EID) sample collection and testing was done at 2 out of 27 (7.4%) of the Health Centre and/or clinics in Ghana.Various ways of assessment of adherence to HIV treatment were reported at different facilities. The commonly reported methodology of assessing adherence was by asking the patient to explain how s/he took the medication and this was reported at 89.5% of all the facilities that participated in this survey and pill counting methodology was reported at 76.2% of the facilities that were visited. In addition, about 45.9% of the respondents revealed that adherence was assessed on assumption that since the patient came back for refill that implied that s/he adhered. Furthermore, staff at 44.2% of the surveyed facilities reported that they assess adherence to HIV treatment based on patient’s CD4 count, viral load or clinical manifestation  Fig. .Fig. 3Map = 0.784 and 0.667 respectively).Furthermore, the findings were stratified by the type of health facility and we found that the proportion of the facilities reporting to manage the transfers by actively following up with other ART clinics and by following the national guideline was slightly different when compared by type of facility, however these differences were not statistically significant (Patient Loss to follow up (LTFU) poses challenges to the successful implementation of ART programs. During the health facility survey, service providers were required to describe how they prevent or manage LTFU at the facility level. About 84% of all facilities that were surveyed, care providers indicated that patient LTFU was minimised by identifying patients with poor adherence to ART and providing special counselling interventions. Service providers at 81% of the survey facilities reported that LTFU is managed or prevented through proper counselling of HIV patients on adherence prior to initiation on treatment. Furthermore, service providers at about 78% of surveyed facilities indicated that LTFU is prevented by actively reminding the patients of their next appointment date through phone calls. On the other hand, service providers at about 15% of the surveyed facilities were of the view that retention on treatment is the patients’ responsibility and thus were a personal decision while about 9% of the service providers interviewed reported that sometimes those who do not attend to their appointment dates might have gone to another ART clinic , shortage of drugs 65%) and patient compliance (59%) of the facilities. Others included inadequate on the job training and support (57%), stigma (57%), patient data capturing and reporting (23%) and high number of patients (16%). Figure % and patp = 0.113). A high proportion of respondents at the health centres and clinics reported on-the-job training and support to be a challenge when compared to respondents at teaching, regional and other hospitals . Shortage of test reagents and stock out of drugs was reported similarly across different types of health facilities . Other reported uses of the clinic routine data at facility level included tracking progress towards facility performance targets 76.7%), for tracking patients (75.0%) and for clinical discussion (75.0%)  was generally high(> 90%) among the responding facilities during the study period. The high coverage of HTC and PMTCT is a positive indicator towards the attainment of the first 90. Other approaches such as the adoption of Provider initiated testing and counselling proposed by WHO in 2007 will need to be employed to help increase the yield of testing in facilities. Despite the small number of viral load testing sites, which is similar in other resourced limited settings [Again, ART patient counselling, ART patient peer support, TB Screening and OI prophylaxis were the support services assessed by this survey. Apart from a little over half of the facilities (57%) providing peer support, the other services were largely available in the surveyed facilities. This is good for the attainment of the 3rd 90 because these services have been shown to improve patient retention on treatment, and ultimately viral suppression . The chaThe survey looked at assessment of adherence, management of patient transfers and management of client loss to follow up. From the findings it could be seen that subjective methods (Patient self-report and pill count) were largely used to assess adherence instead of objectively using viral load, CD4 counts and clinical manifestation as recommended by WHO. Although, the study found that majority (89.5%) of health facilities rely on patients self-report to determine adherence to treatment. it is important to note that self-report may not always be accurate especially in a situation where a patient thinks he/she may be scolded if they indicate that they had defaulted taking medication. It would therefore be important to complement this method with pill count and CD4 count which may be more accurate. Good health status measured by blood chemistry has also been found to correlate with adherence . CombiniThe study findings also showed that 69% of the facilities that participated in this study handle transfer in and out according to national guidelines. This is quite worrying as it will negatively affect the 2nd and eventually the 3rd 90 in the 90/90/90 global targets because adherence to treatment can’t be assured if the movement of clients is not organised.This therefore underscores the need for training of service providers in this direction. Adherence to national guidelines is essential to track progress of patients as well provide good data for decision-making. In the absence of uniformity on how patients transfer in and out is managed, it would be difficult to compare data across facilities. Uniformity in data is basis for global comparison of performance of indicators , 27.Furthermore, the study found that counselling was the main strategy used to ensure adherence by patients as this was reported by 84% of the facilities that participated in the study. About 78% of the facilities also remind patients of their next appointment day. However, about 15% of the surveyed facilities felt that it was the responsibility of the patient to adhere and hence nothing was done to ensure they adhere to treatment. This is disturbing as it might hinder the attainment of the 2nd and 3rd 90 in the 90–90-90 global agenda. It is therefore important that NACP puts in place measures to ensure all facilities stick to the national guidelines for tracking patients. Although counselling on the need to adhere to treatment may be useful especially when it is individualized , in someThe study also highlighted major challenges in HIV-related service delivery. These include logistical challenges such as shortage of test reagents (71%), shortage of drugs (65%), patient adherence (59%), lack of training and support (57%), stigma (57%), patient data capturing and reporting (23%) and high number of patients (16%). With stock out of drugs and reagents occurring in majority of the survey facilities, attainment of all the UNAIDS 90/90/90 will be significantly affected.These Shortages can be minimized through good logistical management system. Hence there will be the need to train health facilities on how to keep stock and stock management as this has been found as a forum to improve stock keeping . If thisOf all the uses that the facilities put their data to, none of the survey facilities stated the use of the data to monitor and support supplies chain management. This might be responsible for the stock out of essential commodities.This study showed ART services to be available in most facilities. Methods used to assess patients adherence varied across the health facilities. Shortage of test reagents and drugs, EID sample collection and testing came out as major challenges. With these identified challenges confronting Ghana as a resource limited country compared to other well-resourced countries, Ghana will need to put in-place concerted efforts to be able to achieve the UNAIDS 90/90/90 of ending AIDS by 2030. Measures need to be put in place to ensure availability of HIV commodities at all levels. A standardised approach to assessing patient’s adherence to treatment is recommended in all health facilities. Again the country needs to come out with a plan to scale up viral load and EID sample collection and testing at most facilities in the country.The study did not collect data on stock out related to all HIV commodities. How long these stock outs normally last and how sites manage in these situations. A qualitative research may be required in future to help identify factors that may be responsible for the shortages.


Stavudine (D4T), zidovudine (AZT), and tenofovir (TDF) along with lamivudine (3TC) are the most widely used HIV treatment regimens in China. China's National Free Antiretroviral Treatment Programme (NFATP) has replaced D4T with AZT or TDF in the standard first-line regimens since 2010. Few studies have evaluated the adherence, virological outcome, and drug resistance in HIV patients receiving first-line antiretroviral therapy (ART) from 2011 to 2015 due to changes in ART regimen.From 2011 to 2015, 2787 HIV patients were examined, with 364, 1453, and 970 patients having initiated D4T-, AZT-, and TDF-based first-line ART regimens, respectively. The Cochran–Armitage test was used to examine the trends in clinical and virological outcomes during 2011 to 2015. Logistic regression was used to examine the effects of different regimens after 9 to 24 months of ART.From 2011 to 2014–2015, adverse drug reactions decreased from 18.9% to 6.7%, missed doses decreased from 9.9% to 4.6%, virological failure decreased from 16.2% to 6.4%, and drug resistance rates also significantly decreased from 5.4% to 1.1%. These successes were strongly associated with the standardized use of TDF- or AZT-based regimens in place of the D4T-based regimen. Poor adherence decreased from 11.3% in patients who initiated D4T-based regimens to 4.9% in those who initiated TDF-based regimens, adverse drug reactions decreased from 32.4% to 6.7%, virological failure reduced from 18.7% to 8.6%, and drug resistance reduced from 5.8% to 2.9%. Compared with patients who initiated AZT-based regimens, patients who initiated TDF-based regiments showed significant reductions in adherence issues, adverse drug reactions, virological outcomes, and drug resistance. Significant differences were also observed between those who initiated D4T- and AZT-based regimens.The good control of HIV replication and drug resistance was attributed to the success of China's NFATP from 2011 to 2015. This study provided real world evidence for further scaling up ART and minimizing the emergence of drug resistance in the “Three 90” era. Therefore, important questions still focus on best practice of ART and how to successfully promote on-going treatment in LMICs.Although stavudine (D4T) and zidovudine (AZT) are not recommended as first-line therapy in well-resourced settings, these thymidine analogues, along with lamivudine (3TC), have formed the most widely used combinations in LMICs. Long-term antiviral therapy is necessary for most patients; however, incomplete viral suppression and emergence of drug resistance have been major problems to be concerned.,13 According to the World Health Organization (WHO) ART guidelines, tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. Accordingly, in 2011, the NFATP expanded the use of TDF, and 6974 patients received TDF-based regimens as first-line therapy this year; this number increased to 116,726 in 2014, accounting for about 40.1% of all patients in NFATP. The use of different ART regimens in China permitted us to conduct a comparison of TDF-based regimens versus other ART regimens in antiretroviral naive HIV-infected individuals in China.As of December 31, 2015, 760,305 people were reported HIV-infected in China, 471,140 of whom had been treated through the China National Free Antiretroviral Treatment Programme (NFATP).Due to the changes and the rapid scale-up of ART in China, the aim of this study was to evaluate the impact and consequences of NFATP guideline changes. Specifically, we investigated: the efficacy of D4T and AZT compared to TDF for HIV patients receiving first-line ART in clinical practice.22.1All subjects provided written informed consent to participate in this study. The institutional review board of the National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention (China CDC) approved this study .2.2 The surveillance protocol was adopted from the WHO recommended surveillance of HIVDR in adults receiving ART. Of 11,976 participants from the national HIVDR database, a total of 4679 patients met our eligibility criteria of having received first-line ART for 9 to 24 months. Of these, 1882 patients initiated ART before 2011 and 2010 were excluded for missing values  after 6 months of treatment since the start of the study as previously described.,16,17 Drug resistance was determined according to the HIV Drug Resistance Database Program version 8.4 . All drug resistance mutations that conferred low, intermediate, or high resistance were included.All subjects provided blood specimens for testing of CD4 cell counts, HIV-1 RNA viral load, and HIV drug resistance mutations at baseline and 12-month follow-up. Blood samples were collected by the local CDC. CD4 cell counts at enrolment were determined with flow cytometry . Plasma HIV-1 RNA levels were determined using the HIV Generic Viral Load assay  as previously described.2.4χ2 tests and Fisher exact test. Cochran–Armitaget test was used to examine the trends in clinical and virological outcomes during 2011 to 2015. Multivariable logistic regression was performed to analyze adjusted odds. P < .05 was considered statistically significant and all reported values were 2-sided. Data analyses were performed using SAS software .We performed a retrospective analysis on data from national HIV drug resistance surveys. The primary outcome variables were adverse drug reaction  guidelines.), adherence, virological outcomes, and drug resistance. The data were analyzed using unadjusted odds ratios with a test for significance according to 33.13 were 19.4%, 37.7%, and 28.3%, respectively , drug resistance, and initial ART regimens in HIV patients who initiated first-line ART during 2011, 2012 to 2013, and 2014 to 2015.P < .01). Missed doses in the past month, virological failure (HIV RNA ≥1000 copies/mL), and drug resistance decreased from 9.9% to 4.6% (P < .01), 16.2% to 6.4% (P < .01), 5.4% to 1.1% (P < .01), respectively, from 2011 to 2014–2015. Significant reductions in drug resistance of nonnucleoside reverse transcriptase inhibitor (NNRTI) (NVP or EFV), nucleoside reverse transcriptase inhibitor (NRTI), PI, NNRTI, and NRTI were also observed, respectively. It was worth noting that the rates of patients who initiated TDF-based ART were gradually increasing in the last few years   and NRTI (P < .01) class drugs, as well as multidrug resistance (MDR) to NNRTI and NRTI drugs (P < .01); however, they had higher odds of resistance to PI class drugs (P = .76)  Table .3.4P = .04) class drugs, as well as MDR to NNRTI and NRTI drugs (P = 0.04); however, they had higher odds of resistance to PI class drugs (P = .21) , ethnicity, education, sex, marital status, occupation, route of HIV transmission, and CD4 count  before ART, patients who initiated AZT-based ART had 41% lower odds of having missed doses in the past month , 75% lower odds of adverse drug reactions , and 40% lower odds of virological failure . After adjustment for age , ethnicity, education, sex, marital status, occupation, route of HIV transmission, CD4 count  before ART, and missed doses in the past month, patients who initiated AZT-based regimens had significantly lower odds of resistance to NRTI (3.5P = .03) class drugs , ethnicity, education, sex, marital status, occupation, route of HIV transmission, and CD4 count  before ART, patients who initiated TDF-based ART had 32% lower odds of having missed doses in the past month , 29% lower odds of adverse drug reactions , 30% lower odds of virological failure , and 39% lower odds of HIVDR . After adjusting for age , ethnicity, education, sex, marital status, occupation, route of HIV transmission, CD4 count  before ART, and missed doses in the past month, patients who initiated TDF-based regimens had significantly lower odds of resistance to NNRTI (4P < .01), missed dose , virological failure , and drug resistance  were observed from patients receiving ART over the study period. Significant reductions in drug resistance of NNRTI, NRTI, and PI were also observed, respectively. The results were consistent with prior studies suggesting that the reductions in virological failure and HIVDR may be partly attributable to improvements in treatment and care, such as replacement of DDI with 3TC as the first-line treatment in NFATP, changes of social demographic factors among patients,,17,19–21 and providing high-quality care to HIV/AIDS patients.Our results demonstrated significant improvements in adherence, virological outcome, and drug resistance in Chinese HIV patients receiving first-line ART from 2011 to 2015, which persisted after adjusting for other factors. In this large-scale study, significant improvements in adverse drug reaction , Cuba (22%), Papua New Guinea (16%), and South Africa (14%). A recent report from the WHO showed that the prevalence of HIVDR has increased from 11% to 29% since the global rollout of ART in 2001. So to achieve “the last 90” target of the Joint United Nations Program on HIV/AIDS (UNAIDS) , multifaceted interventions should be warranted.The virologic outcomes and HIVDR in this study were better than the outcomes of previous surveillance studies in China. The first-line ART regimen in the second edition of the NFATP Guideline in 2008 was revised to consist of TDF/AZT + 3TC + EFV/NVP, and NFATP expanded the use of TDF in 2011 according to the WHO guidelines.,26 We assessed the effects of D4T-, AZT-, and TDF-based regimens as first-line therapy in China's NFATP on ART-related adverse drug reactions, adherence, virological outcomes, and HIVDR. Virological failure decreased from 18.7% in patients who initiated D4T-based regimens to 8.6% in those who initiated TDF-based regimens, and drug resistance reduced from 5.8% to 2.9%. The results were in line with previous studies. However, consequences of TDF use remained to be determined in some LMICs, where viral load monitoring was limited. In these countries, HIVDR remained a very serious concern.,28–31This study showed that the reductions in virological failure and drug resistance since 2011 were strongly associated with the standardized use of TDF- or AZT-based regimens in place of the D4T-based regimen. This highlighted the right decision for phasing out D4T in favor of TDF for first-line ART in NFATP in the last few years. D4T was initially recommended by the WHO largely due to a lower cost than AZT. However, newer ART agents, including TDF, are effective and safer than older nucleoside reverse-transcriptase inhibitor agents, although they might be associated with nephrotoxicity. This result was consistent with our study that adverse drug reactions and adherence issues at 9 to 24 months of treatment decreased from 9.2% and 7.0% in patients who initiated AZT-based regimens to 6.7% and 4.9% in those who initiated TDF-based regimens, respectively. Improvements in adherence were largely attributable to decreased adverse drug reactions, which were a major concern with AZT/D4T treatment regimens.,34Significant differences were also observed between those who initiated AZT- and TDF-based regimens. A study from South Africa demonstrated that TDF-based regimens were associated with fewer adverse drug reactions and lower proportions of loss-from-care compared to AZT-based regimens.,19 We conducted a supplementary analysis to investigate the effects of age and sex in adherence, virological outcomes, and drug resistance among patients who initiated ART in this study. The results showed that patients over 40 years old were less likely to miss dose in the past month . However, the effect of age was not significant in virological outcomes and drug resistance. Female patients were less likely to have virological failure . However, the effect of sex was not significant in adherence (miss dose in the past month) and drug resistance. In order to learn more about the effect of age and sex in ART and develop therapies against treatment failure, further studies will be needed to confirm the effect of age and sex in adherence, virological outcomes, and drug resistance among patients who initiate ART in China.In addition to the role of ARV drugs, age, and sex were other important factors that affected adherence, virological outcomes, and drug resistance according to previous studies.,35 more factors were considered in this paper and the solution was closer to reality. However, other important confounding factors, such as viral load and the 3rd drugs which would change during the ART, were not included in this study.Our study has several limitations. First, it was limited by its cross-sectional nature; early failure and mortality were not studied. In 2015, 18.9% patients being excluded due to mortality, treatment termination and loss to follow-up likely introduced selection bias; their numbers were probably insufficient to alter the conclusions derived from multivariable modeling. Second, ART regimens prescribed differently to groups of patients with varying baseline characteristics and prognoses might give rise to selection bias. The use of specific drugs/regimens for people with specific characteristics could influence the outcomes of these drugs/regimens. This was supported by the fact that D4T users were, among other characteristics as described in Table In the end, this study confirmed that the success of ART scale-up in resource-limited settings was largely due to the introduction of a public health approach to access treatment advocated by the WHO that emphasized standardized treatment regimens that could be purchased in large quantities and delivered at scale.The authors would like to thank Yi Feng, Ruihua Kang, Yang Li, Zheng Li, Jing Zhang, Jing Hu, Yang Li, Shuai Zhao, Pi Cao, Cui He, Jenny H. His, Xiaoqin Xu, Yong Liu, Jianmei He, Hua Ling, Ping Ding, Yi Tong, Xiaobai Zou, Quanhua Zhou, Xia Wang, Yanling Ma, Bin Su, Jihua Fu, Jianmei He, Lin Chen, Xiaohong Pan, Yonghui Dong, Wei Liu, Liting Yang, Jingyun Li, Hong Shang, Ping Zhong, Hanping Li, Min Zhang, Yile Xue, Zhe Wang, Bin Su, Wei Liu, Yonghui Dong, Yanling Ma, Huiqin Li, Guangming Qin, Lin Chen, Xiaohong Pan, Xi Chen, Guoping Peng, Jihua Fu, Ray Y. Chen, Laiyi Kang and who all gave valuable comments or collected the data. We thank the patients and doctors throughout China for their consent and support for the study.Conceptualization: Pengtao Liu, Lingjie Liao, Hui Xing, Yuhua Ruan.Data curation: Lingjie Liao, Wei Xu, Jing Yan, Zhongbao Zuo, Xuebing Leng, Wei Kan, Yinghui You, Hui Xing, Yuhua Ruan.Formal analysis: Pengtao Liu, Xuebing Leng, Wei Kan, Hui Xing, Yuhua Ruan.Funding acquisition: Hui Xing, Yuhua Ruan, Yiming Shao.Investigation: Lingjie Liao, Wei Xu, Jing Yan, Zhongbao Zuo, Xuebing Leng, Jing Wang, Hui Xing, Yuhua Ruan.Methodology: Pengtao Liu, Xuebing Leng, Hui Xing, Yuhua Ruan.Project administration: Pengtao Liu, Hui Xing, Yuhua Ruan, Yiming Shao.Resources: Lingjie Liao, Wei Xu, Hui Xing, Yuhua Ruan.Software: Pengtao Liu.Supervision: Pengtao Liu, Lingjie Liao, Wei Kan.Validation: Lingjie Liao, Wei Xu, Jing Yan, Xuebing Leng.Visualization: Pengtao Liu, Lingjie Liao, Jing Yan, Xuebing Leng.Writing – original draft: Pengtao Liu, Yinghui You.Writing – review & editing: Pengtao Liu, Yinghui You, Yuhua Ruan.


This study was conducted to determine the rate of initial second-line ART regimen change and its predictors among adults living with HIV in Amhara region. A retrospective follow-up study was conducted between February, 2008 and April, 2016 at eight governmental hospitals of Amhara region. Person-times and Cox proportional hazard model were fitted to determine the rate and to identify the significant predictors of second-line treatment regimen change.A total of 897 records of patients were analyzed. The overall rate of initial second-line drug regimen change was 24.2 per 100 person years. The rate of regimen change was decreased for patients with formal education , under WHO clinical stage-III , and WHO clinical stage-IV . Patients who were taking CPT  had an increased rate of regimen change. Furthermore, the rate of regimen change was decreased for patients who were switched to second-line treatment due to virological failure , and due to drug toxicity . Therefore, addressing significant predictors to maximize the durability on the initial regimen among ART clients is essential.The online version of this article (10.1186/s13104-019-4429-3) contains supplementary material, which is available to authorized users. Globally, about 21.7 million people living with human immunodeficiency virus (HIV) were receiving antiretroviral therapy (ART) at the end of 2017 . AccordiDespite ART enables to suppress viral load and restore immune function, the emergency of drug resistance makes a significant challenge to achieve better treatment response , 8. In EPrevious studies reported that drug toxicity, treatment failure, Tuberculosis (TB) treatment and pregnancy were the main reasons of ART regimen change , 15. In A retrospective follow-up study was conducted between February, 2008 and April, 2016 in Amhara region. This study included eight governmental hospitals: namely, University of Gondar teaching and referral hospital, Felege Hiwot referral hospital, Debre Markos referral hospital, Dessie referral hospital, Debre Tabor hospital, Woldiya hospital, Finote Selam hospital, and Debre Birhan referral hospital. Records of 897 ART clients were analyzed. We excluded patients whose information on the regimen change didn’t documented.In this study, the outcome variable was time to initial second-line ART drug regimen change. Regimen change is defined as a substitution of at least one drug from the initial second-line ART regimen. Patient’s survival time were measured from the start of second-line ART up to the time of initial drug regimen changed or when patients were censored. Lost to follow-up, dead, transferred, and defaulters were considered as censored. Socio-demographic variables , treatment-related variables , body mass index (BMI), CD4 cell count, and WHO clinical stages at switch were analyzed in this study.The data was collected by trained nurses after organized a standard checklist. Charts were retrieved using patient’s medical record and ART registration numbers found in the database of health facilities. The quality of collected data was assured by using a pretested questionnaire and trained data collectors. Data completeness and consistency was also checked by supervisors on daily bases.The data were checked for completeness, coded, and entered into EPI-INFO version 7 and analyzed using R statistical software. The follow-up duration for patients who are changing their regimen was calculated from initiation of second-line ART to a substitution of at least one drug from the initial regimen. Similarly, the follow-up duration for clients who did not change their regimen (censored) was calculated from the time of initiation of second-line ART until the last visit. Descriptive statistics were computed to summarize the included variables. Person-times contributed by study participants in the follow-up period were performed to measure the rates of regimen change. Furthermore, Kaplan-Meier estimator curves were used to describe the distributions of survival times  of cohort were receive INH prophylaxis, while 16.5% of respondents were obtain TB treatment. About half (46.3%) of patients switched to second-line ART due to immunological failure, and 33.7% due to clinical failure. At the time of second-line ART initiation, nearly half (48.3%) of them were under WHO clinical stage-I, 10.5% were under WHO clinical stage-II, and 33.4% were under WHO clinical stage-I classification  of the cohort were male, and more than one-third (35.3%) hadn’t formal education. About half 49.1%) of study participants were started second-line treatment between age of 25–34 years, while 10.3% of the patients started above 45 years old. The majority (86.2%) of the respondents were performed the usual work at the initiation of second-line treatment. Nearly two-third (62.1%) of patients initiated second-line ART below CD4 count of 100 cells/mm% of studOf the total cohort who were changed the drug regimen, about three-quarter (77.80%) and 20.49% of them were changed for one times and two times respectively  had a lower rate for regimen change than patients switched to second-line ART due to clinical failure. Similarly, patients who were switched to second-line ART due to virological failure  had decreased rate of regimen change as compared to patients switched due to clinical failure. Furthermore, patients who were switched to second-line ART due to drug toxicity  had a decreased rate of regimen change than patients switched to second-line ART due to clinical failure. Variables like BMI and CD4 cell count at second-line ART initiation didn’t show any significant association with drug regimen change.This study was conducted to determine the rate and to identify the predictors of second-line ART regimen change. During the follow-up period, at least one drug from the initial second-line ART regimens was changed for nearly half  of patients. This result is comparable with a study conducted in southwest Ethiopia , reporteThe findings of this study revealed that patients who had formal education had a decreased rate of regimen change as compared to patients without any formal education. The probable reason for this result might be education enable individuals to have better understanding of antiretroviral drug adherence and good nutritional status which in turn reduces the rate of regimen change . HoweverThis study showed that patients who were under WHO clinical stage-III at the time of switch had a decreased rate for regimen change as compared to patients who were under WHO clinical stage-I. In addition, patients who were under WHO clinical stage-IV at switch were less likely for regimen change as compared to patients who were under WHO clinical stage-I.The results of this study showed that HIV infected patients who were switched to second-line ART due to the reason of immunological failure had a decreased rate of regimen change as compared to patients who were switched to second-line ART due to clinical failure. Furthermore, patients who were switched to second-line ART due to the reason of virological failure had a decreased rate of regimen change than patients who were switched to second-line ART due to clinical failure. Moreover, adults with HIV who were switched to second-line ART due to the reason of drug toxicity had a decreased rate of regimen change as compared to patients who were switched to second-line ART due to clinical failure.A high rate of initial second-line ART regimen change was observed. The rate of drug regimen change was higher for patients hadn’t formal education, being under WHO clinical stage I, taking cotrimoxazole prophylaxis, and the reason for switch to second-line ART were due to clinical failure. Therefore, addressing significant predictors to maximize the durability on the initial regimen is essential, and sustainable monitoring to reduce the rate of regimen change is also desirable.Though we have done our best to indicate the incidence rate and predictors of regimen change, it is not free from limitations. The retrospective nature of the study limited the inclusion of all possible factors that could affect the rate of regimen change. Variables such as hemoglobin level, nutritional status, and side effects were some of the plausible factors that were not measured in this study.Additional file 1: Figure S1. Kaplan-Meir curve of surviving patients on the initial regimens under second-line treatment at governmental hospitals of Amhara region (February 2008 to April 2016).Additional file 2: Table S1. Frequency of regimen change under second-line treatment among adults in Amhara egion (February 2008-April 2016) (n=527).Additional file 3: Table S2. Rates of regimen change in one year interval from second-line treatment among adults in Amhara Region (February 2008-April 2016).


Anemia is the most common hematological complication of HIV infection that has a significant impact on the quality of life and clinical outcomes. Therefore, the aim of this study was to assess the prevalence and associated factors of anemia among adult HIV positive patients on Anti-retroviral therapy at Deber Tabor hospital, northwest Ethiopia. An institution based cross-sectional study was conducted on 365 HIV/AIDS patients on ART selected using the systematic random sampling technique. Blood samples were analyzed using the Cell-DYN 1800 automated hematology analyzer to measure hemoglobin. Bivariable and multivariable binary logistic regression analyzes were employed to find the predictors at p-value < 0 .2 and 0.05, respectively.3 , inability to read and write , inadequate dietary diversity , and female sex  were significantly associated with increased odds of anemia. Therefore, routine screening of hemoglobin level, proper treatment of respondents on zidovudine based ART regimen and increasing productivity to improve dietary diversity are essential to prevent anemia.The overall prevalence of anemia was 34.0%[95% CI ]; taking Zidovudine based antiretroviral regimen , CD4 count < 200 cells/mm Anemia is a nutritional disorder resulting when the number and size of red blood cells or hemoglobin concentration falls below the cut-off value, consequently impairing the capacity of the blood to transport oxygen to the body . It is aThe most common cause of anemia worldwide is iron deficiency, resulting from prolonged negative iron balance, caused by inadequate dietary iron intake, absorption, and other nutritional deficiencies like folic acid and vitamins B12. In addition to the above causes among HIV/AIDS patients, anemia could be associated with a highly active antiretroviral therapy (HAART) like zidovudine based regimen and opportunistic infections , 7.Anemia is a common feature of HIV infection, occurring in about 35% of HIV/AIDS the patients who start antiretroviral treatment (ART) in Europe and North America , while aIn addition to variation its variability in magnitude, anemia is influenced by factors which are associated with adult HIV/AIDS patients on ART, socio demographic factors, ART regimen, and CD4 count –16. FurtAn institution laboratory based cross-sectional study was conducted from March 3 to April 3, 2017. It was conducted in Debre Tabor hospital located 667 km from Addis Ababa, the capital of Ethiopia. The hospital has 253 health professionals. From the beginning, there were 4400 HIV positive patients enrolled at the ART clinic; on average, 45 HIV positive patients attended the ART clinic per day. At the moment, there were 1980 patients on ART 1822 of whom were adults  ≥ 18 years old.To determine the sample size, we used the single population proportion formula by considering the following assumptions: a 95% confidence interval, 5% margin of error, 69% proportion of anemia  plus a 1Data was collected through a face to face interview, using a structured and pre-tested questionnaire. For the measurement of hemoglobin level, venous blood was drown from each participant in a volume of 4 ml in ethylenediaminetetraacetic acid (EDTA) vacutainer tube. All specimens were properly labeled with patient codes. Hematological parameters were determined using a Cell-DYN 1800 automated hematology analyzer , while CD4+ T cell count was collected from patient charts.In order to maintain the quality of data, training was provided to data collectors and supervisors for two days by the principal investigator. A pretest was conducted on 5% of the subjects at Debre Tabor health center. On-site supervision was performed and each copy of the questionnaire was checked for completeness and accuracy before data entry. Standard Operating Procedures (SOPs) were used according to the manufacturer’s instructions for laboratory tests. Results of hemoglobin level testing were categorized to determine anemia [(hemoglobin level < 130 g/l for men > 15 years) and < 120 g/l for non pregnant women > 15 years)] . ConcernData was cleaned, coded, and entered into Epi-info statistical software Version 7 and then transferred to SPSS version 20 for further analysis. Associations between dependent and independent variables were assessed by using the binary logistic regression, and variables with p values <0 .2 were entered into the multivariable logistic regression with a 95% Confidence Intervals. The corresponding p value of < 0.05 was considered as statistically significant at a 95% confidence interval.%) of the participants were male; 162 (44.4%) were married. The mean age of the participants was 39.26 years with (St.d ± 10.88); 325 (89%) of the participants were urban dwellers. One hundred seventy seven (48.5%) were taking zidovudine containing ART regimen, and one-fifth (22.2%) were underweight, while one-third of the study participants (34%) had adequate dietary diversity  of those whose BMI was ≥ 25 kg/m2 were so , of the participants who had less than 18.5 kg/mParticipant Hgb level was used to determine the prevalence of anemia which turned out to be 124 (34%). Of those 23 (6.3%) and 101 (27.7%) were moderate and mild, respectively. The mean hemoglobin level of the participants was 13.1 (St.d ± 1.72).In multivariable analysis; ART regimen, CD4 count, dietary diversity, educational status, and sex were found to be significantly associated with anemia at a P-value of < 0 .05.3 compared with participants with CD4 count ≥ 500 cells/mm3 . Two times more likelihood of anemia was demonstrated by participants who had inadequate dietary diversity compared with their counterparts . Female sex  and educational status that is unable to read and write  were also significant predictors of anemia among HIV/AIDS infected adults on ART ] higher among adults who took Zidovudine based ART regimen compared with TDF based regimen. Likewise, the odds of having anemia were almost 5 times higher among participants with CD4 count < 200 cells/mmA variety of hematologic abnormalities associated with HIV infection have been described in different studies. One of them stats that anemia is a major public health problem in HIV positive patients around the world, particularly in Sub-Saharan African, including Ethiopia.3, while in this study only 14.8% of the participants had CD4 count less than 200 cells/mm3. This may be an important biological implication to our finding in that the mean hemoglobin level increased with increasing CD4 count, and lower CD4 count was associated with an increased risk of anemia.The overall prevalence of anemia in this study was 34% which was in line with findings from Rwanda (29%) , Central3 were more likely to be anemic compared to CD4 count ≥ 500 cells/mm3. This is supported by studies done in Diredawa Town, Ethiopia [Patients with CD4 cells < 200 cells/mmEthiopia . This coIn this study, patients who took AZT based ART regimens were more likely to be anemic than those who took TDF-based regimens. This finding is supported by studies done in Ethiopia , Rwanda In this study, women were more likely to be anemic than men. This is supported by a study done at University of Gondar Hospital, Ethiopia . HoweverThis study also identified that the educational status was a predictor of the occurrence of anima among the study subjects. Patients who were unable to read and write were more likely to suffer from anemia than clients with higher educational level. The finding is supported by studies done in China and Nigeria , 24. TheThis study also noted that the likelihood of having anemia was higher among HIV/AIDS patients on ART with inadequate diversified diet. The explanation might be that dietary diversity is essential for nutrient adequacy as there is no single food that may contains all of the essential nutrients that are needed for good optimal health and good nutritional status. Moreover, when an individual consumes different foods or food items that promote sufficient intake of essential micronutrients from the diet and the hemoglobin level is improved .This study illustrated that anemia is a moderate public health problem among HIV infected adults on ART at Debre Tabor hospital. ART regimen, CD4 count, dietary diversity, educational status and sex were significantly associated with anemia. Therefore, the government needs to focus on routine screening, proper treatment, and increasing productivity to improve dietary diversification.In this study serum ferritin was not used as an indicator to identify iron deficiency anemia, and the data was collected in the fasting session of Orthodox Christians.


Depression is a leading cause of disability and may be associated with decreased adherence to ART. We sought to describe the prevalence of depressive symptoms and outcomes one year after screening among patients receiving ART at a large HIV Clinic in Johannesburg, South Africa.Adult (≥18) patients who had been on first-line ART between 6–18 months who could communicate in English were eligible. Depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ)-9 and a score ≥10 indicated depression.3. 7 (7%) patients were found to have symptoms of depression; 4 (4%) had symptoms of moderate depression (PHQ score of 10–14) and 3 (3%) had symptoms of moderate/severe depression (PHQ score of 15–19). Women (10%) were more likely to have symptoms of depression than men ; as were patients under the age of 30 (14%) compared to those 30–39  or ≥40 , those with lower CD4 counts at ART initiation , and those with high viral loads . No relationship between depressive symptoms and retention in HIV care one year after screening was observed.97 patients enrolled. Patients had been on ART for a median (IQR) of 8 (7–10) months, 61% were female, the median (IQR) age at enrollment was 38 (33–42) years, and the median (IQR) CD4 count at ART initiation was 154.5 (65–263) cells/mmWe found a lower prevalence of depressive symptoms compared to findings from other HIV-positive populations in South Africa but more than one-third of patients with an elevated viral load had evidence of depression. Further research on the relationship between depression, adherence, and viral failure is warranted as this may present an opportunity for early interventions to improve treatment outcomes and reduce the need for second-line treatment. First, to investigate the relationship between depressive symptoms and the result of the next viral load test (as a proxy for adherence), patients were followed from the date of study enrollment until the date of their next viral load result, for a maximum of 12 months post-study enrollment. Second, we also investigated whether retention in care differed between patients with and without depressive symptoms and present the proportion of patients alive and in care one-year after screening.Ethical approval was provided by the Human Research Ethics Committee  of the University of the Witwatersrand.3. The majority (95%) of patients were virologically suppressed with a recent viral load of <400 copies/ml; however, 5 (5%) had recently experienced an elevated viral load (>1000 copies/ml)  of 8.1 (7.3–10.0) months; 61% were female, the median (IQR) age at study enrollment was 38.2 (32.5–42.4) years, and the median (IQR) CD4 count at ART initiation was 154.5 (65–263) cells/mmpies/ml) .Depressive symptoms greater than minimal (PHQ-9 score ≥10) were identified in 7 (7%) enrolled patients, 4 (4%) of whom were identified as having symptoms of moderate depression (PHQ-9 score: 10–14) and 3 (3%) of whom had symptoms of moderate/severe depression (PHQ: 15–19). None had a score of ≥20 indicating symptoms of severe depression. Regarding the most common symptoms reported, 34% of patients reported problems with low energy in the previous two weeks, 31% reported feeling down, depressed, or hopeless, 30% reported trouble sleeping, and 26% reported appetite problems . Four , and those with high viral loads . Patients who were initiated on regimens other than tenofovir (TDF) with emtricitabine (EMT) and efavirenz (EFV) were also more likely to have evidence of depression  but no differences were observed for the presence or absence of anaemia, employment status, or country of birth (Women (10%) were more likely to report symptoms of depression compared to men ; as were patients under the age of 30 years (14%) compared to those 30–39 years  or ≥40 years , those with lower CD4 counts at ART initiation  were alive and in care one-year after screening and 1 (14%) patient had died. In comparison, 81 (90%) of the 90 patients without evidence of depression were alive and in care one-year after screening, 3 (3%) had died, 4 (4%) were lost to follow-up, and 2 (2%) had transferred to another HIV treatment facility .Three (60%) of the 5 patients who had recently experienced an elevated viral load went on to have confirmed virologic failure , and switched to a protease-inhibitor based second-line treatment regimen in a median (IQR) of 2.8 (1.2–4.7) months after the second failing viral load. The prevalence of depressive symptoms among those who failed was 67% (2/3) and 0% (0/2) among those patients who went on to suppress.We observed an overall low prevalence of depressive symptoms (7%) in this population of primarily stable and virologically suppressed HIV-positive patients on ART, which is lower than that of other studies in HIV-positive populations in South Africa 14%-62%),12]. Howe3 (63.6% vs. 47.8%).[A recent study conducted among newly-diagnosed, HIV-positive patients in Johannesburg observed a prevalence of depression of 30% using the PHQ-9 and found no association between depressive symptoms and linkage to HIV care or ART initiation.[Interpretation of our findings should be made in the context of several important factors. Our study population was primarily made up of stable patients on ART for at least 6 months and, thus, our results may not be directly comparable with other research. In addition, this study took place within a well-resourced clinic that focuses solely on HIV care and operates within a university teaching hospital in an urban setting with access to a range of services. Therefore, the experiences of patients in this setting may not be generalizable to patients accessing HIV care in a primary care setting. Furthermore, a number of different tools have been used to evaluate the presence of depressive symptoms in people living with HIV in South Africa with varying levels of sensitivity and specificity and results may not be generalizable across tools.The results of this study should be viewed in light of several limitations. First, only patients who could speak and understand English were included which may limit generalizability. While English is commonly spoken throughout South Africa, proficiency among Black South Africans (of whom just 2.9% reported English as their first language in the 2011 census) may be limited to those with several years of schooling.[This is one of the first studies to assess the prevalence of depression in primarily stable HIV-positive patients on ART in South Africa. We observed a low prevalence of depressive symptoms among virologically suppressed patients while approximately 40% of patients with a recently elevated viral load had evidence of depression. This relationship should be further explored in a larger study and, if confirmed, future work may be warranted to evaluate whether a mental health intervention could treat depression, improve adherence, and prevent the need for switching to more costly second-line treatment regimens in this population.