Treat All approach, expanding antiretroviral therapy (ART) eligibility to all individuals with HIV infection, regardless of CD4+ cell count, and recommending ART be initiated within two weeks of HIV diagnosis . The Test and Treat policy was first piloted in 32 local government areas (LGAs). The primary objective of this study was to evaluate the clinical outcomes of adult patients initiated on ART within two weeks of HIV diagnosis during this pilot. We conducted a retrospective cohort analysis of patients who initiated ART within two weeks of new HIV diagnosis between October 2015 and September 2016 in eight randomly selected LGAs participating in the Test and Treat pilot study. 2,652 adults were newly diagnosed and initiated on ART within two weeks of HIV diagnosis. Of these patients, 8% had documentation of a 12-month viral load measurement, and 13% had documentation of a six-month viral load measurement. Among Test and Treat patients with a documented viral load, 79% were suppressed (≤400 copies/ml) at six months and 78% were suppressed at 12 months. By 12 months post-ART initiation, 34% of the patients who initiated ART under the Test and Treat strategy were lost to follow-up. The median CD4 cell count among patients initiating ART within two weeks of HIV diagnosis was 323 cells/mm3 . While randomized controlled trials have demonstrated that Test and Treat strategies can improve patient retention and increase viral suppression compared to standard of care, these findings indicate that the effectiveness of Test and Treat in some settings may be far lower than the efficacy demonstrated in randomized controlled trials. Significant attention to the way Test and Treat strategies are implemented, monitored, and improved particularly related to early retention, can help expand access to ART for all patients.In December 2016, the Nigerian Federal Ministry of Health updated its HIV guidelines to a  HIV continues to have a major impact on public health globally with an estimated 36.9 million people living with HIV (PLWH) including 1.8 million new infections in 2017 [Treat All guidelines in 2016 [Test and Treat strategy of initiating ART within two weeks of HIV diagnosis as part of the Treat All policy in 32 local government areas (LGAs) beginning in October 2015. To expand the Treat All approach from piloted LGAs to sites nationwide and to decrease the time to initiating ART after a positive HIV test result, the Federal Ministry of Health of Nigeria made two significant changes to their national HIV prevention and treatment guidelines in December 2016. First, CD4+ cell count thresholds for ART initiation were removed, thus expanding ART eligibility to all HIV-positive individuals, and second, ART should be initiated as soon as possible following HIV diagnosis (preferably within two weeks) [Nigeria has the second largest HIV epidemic globally . While n in 2016 . HIV treo weeks) .Test and Treat pilot, which was implemented just before the changes in national guidelines, we conducted a retrospective cohort study of patients who initiated ART within two weeks of HIV diagnosis during the pilot. The primary objectives of this study were to evaluate viral suppression and ART retention among adult patients who initiated ART within two 2 weeks of HIV diagnosis in a sample of the pilot LGAs. A secondary objective of this study was to compare these outcomes with those of patients previously diagnosed and enrolled in care in the same LGAs. Additional secondary analyses included demographic and clinical predictors of loss to follow-up (LTFU) or non-adherence to ART, time to LTFU, and odds of non-adherence to ART across the first year of treatment.To evaluate the outcomes of the Test and Treat pilot across five states in Nigeria.We conducted a retrospective cohort analysis of patients who initiated ART between October 2015 and September 2016 in eight LGAs randomly selected from the 32 which participated in the Test and Treat group). The second group included were HIV-positive patients enrolled in care before the Test and Treat pilot who then initiated ART irrespective of immunologic or clinical status during the study period. To be eligible for the study, patients had to be aged at least 16 years at the time of ART initiation and had to have initiated ART at one of the eligible sites.The study populations consisted of two groups of adult patients. The first group included newly identified HIV-positive patients who initiated ART within two weeks of diagnosis irrespective of clinical or immunological status  of the 32 LGAs were selected with a probability of selection proportionate to the number of total patients receiving ART within each LGA, according to the 2015 PEPFAR Annual Progress Report (APR). Second, we included all facilities in each of the eight selected LGAs that had at least 50 patients receiving ART according to the 2015 PEPFAR Annual Progress Report that had implemented We manually abstracted the following data from the electronic and paper medical records at the sampled facilities: outcomes of ART, demographic variables, clinical variables including functional status, HIV diagnosis information, ART initiation and subsequent visits, regimen information, baseline and subsequent laboratory measurements including viral load and CD4 cell count, co-infections and opportunistic infections, ART refill data, and support services received. All data abstractors were trained to understand the survey objectives, their roles in the evaluation, best practices for good data quality, the importance of confidentiality, and the survey instruments. Each data abstraction team had a dedicated, onsite supervisor during abstraction to perform quality checks.The evaluation study protocol and abstraction surveys were approved by the National Health Research Ethics Committee Nigeria and the Institutional Review Board of the University of Maryland, Baltimore. Because the study was retrospective, the requirements for written informed consent were waived. The study was reviewed according to the United States Centers for Disease Control and Prevention (CDC) human research protection procedures and was determined to be, and approved as, research, but CDC was not engaged.All variables were initially investigated in univariate analysis to determine frequency, distribution, and the amount of missing data for each variable. Patients were grouped by ART initiation strategy: newly diagnosed and initiated on ART within two weeks (Test and Treat), and previously diagnosed and enrolled in care.Viral load measurements for the 6-month outcome were eligible for inclusion if they were measured between 4 and 8 months after ART initiation. Viral load measurements for the 12-month outcome were eligible for inclusion if they were measured between 10 and 14 months after ART initiation. In our analysis, we defined viral suppression as a viral load test result of less than 400 HIV ribonucleic acid copies/mL, per Nigerian integrated national guidelines for HIV prevention, treatment, and care [LTFU was defined as no documented attendance at the health care facility within 90 days from the date of the missed scheduled visit to see a health care provider or to pick up medication. Kaplan-Meier methods were used to estimate the time to LTFU among Test and Treat patients by relevant clinical and demographic variables. The constancy of care engagement after ART initiation was calculated as the proportion of quarters in which a patient had at least one visit in the first year of ART . The firBecause of the frequency of missing viral load results, we used medication refill data to determine adherence to ART. Non-adherence to refill was defined as an interval between medication refills when the ratio between the number of days of pills dispensed by days between refills was less than 95%. Patients had to have at least two documented refill dates and the number of pills dispensed documented at the previous refill for inclusion in the non-adherence to refill analysis. Refills in the first 14 days of ART were excluded. Days between refill visits were calculated for all patients with a refill date and corresponding number of days’ worth of pills dispensed. The adherence rate was calculated as the (number of days’ worth of pills dispensed divided by the days between refills) multiplied by 100 . Time frTest and Treat patients, we estimated cause-specific hazards for LTFU using Cox proportional hazards with a random effect for facility and with a frailty term in the models. Patients who died or who were transferred were excluded from this analysis due to the low numbers available for a competing risks analysis. To identify independent predictors of LTFU, we used generalized linear models allowing for a binary outcome distribution using stepwise selection. Predicted probabilities were then calculated for each patient on the basis of the independent predictors and then were plotted on a receiver operator characteristics curve to calculate a c-statistic to estimate the ability of the combination of predictors to discriminate a patient who was LTFU from one who was retained. Statistical analysis was conducted using STATA 15  and SAS 9.4 .To estimate the rate of LTFU among Test and Treat patients. The remaining 604 (19%) were in the previously diagnosed and enrolled in care group. Of the patients included in the final study sample, 91% were missing documentation of a 12-month viral load measurement, and 86% were missing documentation of a six-month viral load measurement.The final study sample included 3,256 PLWH whose medical records were abstracted from 31 clinics across eight LGAs. Of these, 2,652 (81%) were 3 . The sample was 68% female and 50% married. Eighty-five percent of HIV-positive individuals in the study population did not have their partners’ HIV status documented in the medical records. Of those with partner status documentation, 49% of patients reported having an HIV-positive partner , 27–40 years). The median CD4+ cell count at ART initiation was 323 cells/mm partner .Test and Treat patients were more likely to be aged 16–24 years (p = 0.05), to have only primary or secondary school education (p<0.0001), to be unemployed (p<0.0001), to report having an HIV-negative partner (p = 0.05), to be underweight (p<0.0001), to have a baseline CD4+ cell count <200 cells/mm3 (p<0.0001), to be WHO stage III (p<0.0001), to have an ambulatory functional status (p = 0.004), to have a prior history of TB treatment (p<0.0001), and to have received ART initiation counseling (p = 0.01); Among women in the study population, those with new HIV diagnoses (Test and Treat) were more likely to be pregnant (p = 0.013). The median number of days to ART initiation after enrolment in the facility among Test and Treat patients was 0 days .Compared with patients who were previously diagnosed and enrolled in care, Test and Treat patients that had a 6-month viral load result, 79% had viral suppression (≤400 copies/mL); 79% of the 107 previously enrolled patients with 6-month viral load results also had viral suppression. Of the 204 Test and Treat patients with a 12-month viral load result, 78% were suppressed (≤400 copies/mL), compared to 84% of the 75 previously enrolled patients with a documented 12-month viral load result. There was no evidence of a difference in viral suppression outcomes at 6 months and 12 months when comparing Test and Treat patients to those previously enrolled in care  died, 128 (5%) were transferred out from the health facilities, and 903 (34%) were LTFU, compared to five (1%), 21 (3%), and 116 (19%) of the previously diagnosed patients, respectively .A total of 21,338 patient months were observed among ectively . Of the Test and Treat patients, 1,193 (45%) had at least one visit in each quarter of the first year of treatment: 411 (15%), 249 (9%), 340 (13%), and 459 (17%) had visits in three, two, one, and no quarters, respectively. Lower visit constancy was associated with an increased likelihood of LTFU (p<0.0001).Of the 2,652 Test and Treat patients. Of the 2,652 Test and Treat patients, 2,206 had at least one prescription with a corresponding number of pills dispensed and two documented refill dates. Of the total refills observed, 67% had pills to cover at least 95% of their treatment days, 10% had 85%–94% of their treatment days covered, 5% had 75%–84% of their treatment days covered, and 18% had less than 75% of their treatment days covered. The number of patients with optimal adherence to refills  decreased in the second month of treatment. In other words, non-adherence to refill was significantly higher in the second month compared with the first month. Model-based estimates of non-adherence demonstrate an increasing trend over time. Observed non-adherence to refill fluctuated from month 3 to 12, but there was no clear trend. The proportion of patients with optimal adherence remained below 70% following the first month of treatment . Higher LTFU was observed for younger patients , those who were divorced or single compared with those who were married (p<0.0001), those with a secondary education or lower compared to those with post-secondary education or above (p<0.0001), those unemployed compared to employed patients (p = 0.01), patients who were underweight compared to those who were normal or overweight at the time of ART initiation (p<0.0001), those with higher WHO clinical stage compared to those with lower WHO stage (p<0.0001), and those with an ambulatory or bed-ridden functional status compared with those with a working status (p = 0.01), those with prior history of tuberculosis compared to those without tuberculosis or those currently receiving tuberculosis treatment (p = 0.02), those without documented receipt of cotrimoxazole (p = 0.003), and those without documented pre-ART counseling  of LTFU compared with those with a CD4 count <200 cells/mm3. Higher WHO disease stage was associated with stepwise increases in LTFU rates: Stage II with an aOR of 1.95 ; Stage III with an aOR of 3.68 ; and Stage IV with an aOR of 4.49 , compared with Stage I.In predictive modelling for LTFU, stepwise regression analysis identified age group, CD4 cell count at baseline, and WHO stage at baseline as independent predictors of LTFU among patients . SpecifiTest and Treat pilot were LTFU by 1 year after treatment initiation compared to approximately one in five HIV-positive patients who had been previously enrolled in care, though this finding is limited by the fact that those previously in care were perhaps engaged with the clinic for a longer time than Test and Treat patients and had survived to benefit from the change in guidelines removing CD4 cell count thresholds. However, implementing Test and Treat nationwide following the pilot model could significantly impair Nigeria’s ability to achieve the 90-90-90 targets and move toward epidemic control. Program data also show suboptimal retention in care and ART adherence. National expectations related to counseling and follow-up including frequent contact following treatment initiation and assessment of barriers to care could be considered at the facility level. Our findings provide valuable information to HIV service delivery implementing partners to help strengthen the health system and improve implementation of Treat All nationwide.We found that approximately one in three HIV-positive patients in Nigeria who participated in the Test and Treat patients had lower baseline CD4+ cell counts and had more advanced disease at diagnosis, as evidenced by worse WHO disease stage, compared to patients who had been previously enrolled in care. This may indicate that people are still not presenting for testing until they are symptomatic, which could delay the population-level benefits of removing CD4+ cell count thresholds for treatment and the availability of rapid initiation interventions such as Test and Treat. Additionally, median ART initiation was on the day of diagnosis, and the Test and Treat patients had higher rates of LTFU than previously enrolled patients, which highlights the need for strategies to improve pre-ART counseling while balancing the drive for rapid initiation.In this study, Test and Treat patients were less likely to consistently present at the point of service for scheduled visits than previously enrolled patients. Of the patients in this sample, only 45% had a visit in each of the four quarters of the first year of ART. Routine engagement in care is an important tool for epidemic control. Consistent visits would allow clinicians and care delivery staff to provide needed services such as continued adherence counselling, assessment of clinical symptoms, diagnosis of opportunistic infections or non-communicable disease comorbidities, and general preventive services. Inconsistent presentation at the point of service delivery could also contribute to disengagement from the care continuum. A recent study of patients in central or decentralized care in North Central Nigeria found differences in visit constancy and overall LTFU depending on where ART services were offered [Test and Treat patients was much larger than has been observed in previous evaluations of ART retention outcomes conducted before the adoption of the Treat All guidelines in Nigeria [Test and Treat patients as the Treat All guidelines are implemented nationwide.We found that the  offered . In this Nigeria . Identif Nigeria , 15. OurPatients LTFU were more likely to be younger, have a higher baseline CD4 cell count, a functional status of ambulatory or bedridden, and a WHO stage of III or IV compared to patients who were still alive at the time of review. High WHO stage and bedridden status may indicate that death is the reason for LTFU for a proportion of these patients. This finding indicates the importance of offering services for patients presenting with advanced disease and the need for continued active case-finding to diagnose and treat PLWH at early stages of disease. However, death is unlikely to explain all of the LTFU as observed by Charurat et al. . The assTreat All. Differentiated care refers to flexible service models developed to meet the needs of clients and clinics, particularly as more patients initiate treatment [Treat All strategy. Community-based initiation and management of ART increases long-term retention rates in some settings [Test and Treat approaches, flexible models of care are needed [One opportunity for improving retention outcomes in Nigeria could be developing differentiated care models within the context of reatment . Servicereatment , and hassettings –21. To se needed . An evale needed . HoweverViral load is considered the gold standard for monitoring adherence to treatment. However, viral load documentation was lacking within the selected facilities, suggesting that, for the vast majority of patients, clinicians do not have access to vital information related to treatment effectiveness or an objective measure of early treatment adherence. Our evaluation did not include care processes or treatment delivery models to enable us to understand the root cause of suboptimal utilization of viral load monitoring. A full mapping of the viral load process may be warranted to determine whether viral loads are being ordered, whether viral load orders are being processed, and whether the results are being returned to the facilities and then entered into the medical records. Nigerian health officials could consider implementing an alert system to notify clinicians when a patient is due for a viral load test and could consider interventions to increase patient-led demand for viral load testing. Additionally, data systems that allow the automatic upload of facility viral load results once entered into the laboratory system may mitigate this challenge going forward. Significant investment in laboratory infrastructure has been made in Nigeria, particularly since the beginning of PEPFAR –25; howeTest and Treat as a long-term strategy for epidemic control must move beyond how quickly patients receive treatment as the primary measure of success. Early retention will be particularly important for Test and Treat to be successful. Patient and provider readiness, as well as the ability of the facility to absorb, manage, support, and follow a dramatically increased patient volume are also important factors to implement Test and Treat successfully [Given the high frequency of missing viral load results, we assessed adherence using pharmacy refill. After the first month of treatment, only approximately 30%–40% of patients refilled their prescription; the greatest increase in non-adherence to medication refill was in month 2 of treatment. Adherence to ART in the first several months is critical to control viral replication and prevent the development of drug-resistant mutations. Although actual adherence among these patients may be slightly higher due to earlier refill and thus maintenance of a buffer stock of pills, these findings suggest the need for programs to support medication adherence for patients earlier in disease progression or immediately after HIV diagnosis. essfully , 18, 26.Test and Treat has been implemented at other facilities, and it is possible that program maturity has improved retention outcomes. The amount of missing data for variables thought to be associated with LTFU precluded the use of methods such as multiple imputation to predict levels of the missing variables and thus limited their inclusion in adjusted models. Complete clinical data in patient medical records are needed for this analysis. Missing data represents a challenge not only to research and evaluation, but also the long-term longitudinal care of patients. Funders and Implementing Partners responsible for providing technical assistance at the facility level may wish to increase data quality improvement efforts to reduce the amount of missing clinical data. As programmatic reporting increasingly moves to electronic formats with direct health information exchange, data completeness checks for key indicators could be incorporated to help drive feedback to facilities to help improve data quality. Another limitation was that the study did not achieve the required sample size of 3,432 patients at a presumed 75% retention. An a priori assumption of the observed retention of 65% would have required an even larger sample size. Therefore, some important differences between comparison groups may not have met thresholds commonly used to define statistical significance. However, even without the desired power, this study still provides robust findings of significant predictors of retention and LTFU in Nigeria.Our study has several limitations. We were unable to assess whether patients classified as LTFU died after starting ART or migrated from the area. Additionally, Treat All and Test and Treat, our findings of persistent LTFU and lack of viral load results for medical decision-making underscore the importance of continuous quality improvement and monitoring patient outcomes. This is especially true given that more PLWH are now initiating ART. Continuous medical education about Treat All could help maintain the gains made toward epidemic control and avoid wasting resources. However, particular attention to early retention in the context of Test and Treat, which will be imporant Evaluating how Test and Treat strategies are implemented, monitored, and improved can help expand ART access to all successfully.In conclusion, although Nigeria, like many countries in sub-Saharan Africa, is eager to adopt and scale up The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the funding agencies. Use of trade names is for identification only and does not imply endorsement by the CDC or the U.S. Department of Health and Human Services.


Kaposi sarcoma (KS) remains a relevant malignancy in human immunodeficiency virus (HIV)-infected patients with a non-standardized management; despite past suggestions that ritonavir-boosted protease inhibitor (bPI)-based regimens could be preferable, no combination antiretroviral therapy (cART) regimen was demonstrated to outperform the others and the impact of new drugs, drug classes or paradigms was never investigated nor proven better than previous therapeutic regimes. In order to do this, we retrospectively collected data regarding HIV-infected patients with a diagnosis of KS last seen in six Italian centers after 1 January 2013. A total of 104 KS cases in 99 patients was analyzed for 945.34 patient-year follow-up (PYFU). Twenty-six patients had visceral localizations. Thirty-three patients were treated with chemotherapy, four with electrochemotherapy, and 12 with α-interferon (α-IFN). At censor, 22% received a bPI-based, 14% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, and 28% an integrase inhibitor (INI)-based standard cART, 24% a less drug regimen and 12% a mega-cART. Twelve recurrence episodes were observed in seven patients for an incidence of 1.27 per 100 PYFU. Two patients with no evidence of recurrence episodes died for other reasons. In our experience, KS recurrence episodes were infrequent. Despite the increasing use of new antiretroviral drug classes and new treatment paradigms, no excess of recurrence episodes was observed in patients receiving such cART regimens. In more than thirty years since acquired immunodeficiency syndrome (AIDS) was defined, the introduction and the subsequent optimization of combination antiretroviral therapy (cART) greatly improved its prognosis  and the Therefore, when KS is diagnosed, international guidelines recommend the rapid initiation of cART, with or without chemotherapy if indicated ,11,12,13Currently, major guidelines recommend the use of integrase inhibitors (INIs) as first line cART in the vast majority of cases ,11,12,13The aim of this study was to evaluate the incidence of recurrence episodes (REs) and the possible associations with the prescribed antiretroviral regimens.This was a retrospective, observational, multicentric study conducted in six Italian centers. Clinical and laboratory data regarding all HIV-infected patients last seen in our outpatient services after 01 January 2013 were collected; clinical history including prior exposure to cART, exposure to chemotherapy (CT), electrochemotherapy (ECT) or α-interferon (α-IFN) were also recorded. Baseline was set at the date of the diagnosis of KS, follow-up was censored at the first recurrence episode (RE) or at the last observation or 15 March 2019. A RE was defined as the appearance of a new KS lesion after prior clinical remission.HIV testing was performed by ELISA assay with Western blot confirmation. KS diagnosis was defined by skin or mucosal biopsy; all patients diagnosed with KS were staged at baseline .2 every three weeks [Liposomal doxorubicin was used for chemotherapy at the recommended dose of 20 mg/mee weeks . Intraveee weeks . Alpha-iDescriptive analysis was performed as appropriate for continuous and categorical variables; survival free from recurrence episode was estimated by Kaplan–Meier (KM) analysis. Patients with multiple REs were evaluated as a single case for descriptive statistical analysis regarding demographic characteristics and as many cases as the number of REs for the KM-estimated survival free from recurrences and descriptive analysis regarding the exposure to antiretroviral drugs. The incidence of recurrence episodes was calculated as the number of events during the total follow-up time.A total of 99 patients from six centers were enrolled. A skin or mucosal biopsy was available for all patients at baseline and at the recurrence episodes. In 26 patients, a visceral localization was found in one or more sites: 18 out of the 26 (69.2%) had oral cavity mucosal lesions, 9 (34.6) had gastric lesions, 6 (23%) had colic lesions, and 8 (30.8%) had pulmonary lesions.In seven patients the KS lesions were completely removed by biopsy; four out of the seven patients underwent chemotherapy thereafter and one of them also underwent electrochemotherapy. A total of 33 (33.3%) patients were treated with a median (interquartile range (IQR), range) of six  cycles of chemotherapy for a median (IQR) time of 5.2 (2.6–12.6) months, 4 (4%) with electrochemotherapy, and 12 (12%) with α-IFN for a median  time of 14.2  months. The remaining patients were managed with antiretroviral therapy alone.The disappearance of the cutaneous lesions was well documented in the clinical records for 62 (62.6%) patients; visceral remission was documented for all 26 patients with initial visceral localizations.Twelve recurrence episodes were observed in seven patients, four of which had multiple episodes (3/4 had two and 1/4 had three recurrence episodes), while the remaining three had just one recurrence episode, for an incidence of 1.27 per 100 PYFU. Median (IQR) time free from new episodes was 7.48 (3.19–14.05) years. Patient no. 4 was the only HIV-negative patient at the diagnosis of KS. The diagnosis was made elsewhere in July 2011 (age 47), when the biopsy of an oral cavity localization revealed KS; a few months earlier, other KS lesions of the left leg and foot had appeared. He first came to our observation on 26 March 2013 bringing negative HIV tests; CD4 cell count was 569 cells/mmc , HHV8 PCR was positive but lower than 125 genome equivalents/mL. He underwent ECT in May. He was tested for HIV infection on 19 July 2013 with negative results; CD4 cell count was 420 cells/mmc  and HHV8 PCR was 284 genome equivalents/mL. He was again tested negative for HIV infection a third time on 24 October 2013, when a new KS lesion was found in his back; HHV8 PCR was positive but lower than 125 genome equivalents/mL and CD4 cell count was 389 cells/mmc . Finally, he tested positive for HIV  on the subsequent visit on 17 December 2013; HHV8 PCR was stably positive but lower than 125 genome equivalents/mL and CD4 cell count 329/mmc . We prescribed him a mega-cART regimen as described in Patient no. 5 was diagnosed with HIV infection in 1992 (age 45). He was exposed to suboptimal NRTI-only therapy until he started an unboosted PI-based regimen in 1998 as described in Patient no. 7 was diagnosed with HIV infection in 1995 elsewhere and came to our attention in 2004, following the appearance of cutaneous lesions compatible with KS, confirmed by biopsy. Staging for organ localizations resulted negative. The patient was still naïve to antiretroviral therapy. Despite the successful introduction of cART , we witnessed the appearance of new skin lesions; hence, the patient started six cycles of CT with liposomal doxorubicin, with benefit (inactive lesions). After two years, in 2008, new purple lesions appeared despite continued virologic success ; no chemotherapy was started, and lesions disappeared with antiretroviral therapy alone. The patient is still in follow-up in our center, his cART was switched to an INI-based standard regimen (2012–2015), and then to the lamivudine plus dolutegravir LDR regimen with no further signs of KS and a stable virologic suppression.Two deaths among the 99 patients were observed: one patient died because of a sepsis two months after the KS and HIV infection were diagnosed and one patient was lost to follow-up after the first month; he was subsequently reported as dead for unknown reasons by his family. For both patients, no evidence of recurrence of KS was available. At censor, the proportion of patients receiving a boosted PI-based cART regimen had decreased while the proportion of patients receiving INI-based regimens, cobicistat-boosted regimens or LDR regimens had increased.KS remains a relevant AIDS-defining malignancy and it still represents the second most frequent AIDS-defining event among MSM in Italy  and the This study tried to describe the incidence and characteristics of KS recurrence in six major Italian centers; we choose to only insert patients who last accessed our services after 01 January 2013 in order to include patients who had the possibility to receive the newest and most recently recommended therapies. Therefore, the median calendar year of KS diagnosis was quite recent , even if the range went from 1989 to 2018. The median exposure was slightly less than two years for the newest compounds such as INIs and dolutegravir in particular, and the cobicistat booster; in this limited exposure time, we did not find any excess of recurrences in the exposed patients.The follow-up time on LDR exposure is slightly less than four years with a wide IQR and an upper limit above five years, reflecting the long time experience of our centers with this strategy; again, no excess of recurrences was observed in patients exposed to these regimens, with or without protease inhibitors and independently from the type of booster.Recurrence episodes were infrequent. As indicated in the details shown in Our study has several limitations. Firstly, it is an observational, retrospective study, so the data regarding clinical evolution and local and/or systemic therapies are often missing/incomplete and the virologic data regarding HHV8 is absent and therefore not evaluated in the majority of centers. Secondly, the follow-up time with new drugs/boosters/drug classes is limited, although almost two years seems to be a reasonable interval to try to drive some early observations. Finally, the old perception that PIs could have an advantage over other antiretroviral classes could have led to a prescription bias in the first cART regimens, but the increasing part of patients receiving new drug classes, namely integrase inhibitors, in more recent years proves that this effect is declining over time. Furthermore, the introduction of the less drug regimen did not seem to affect the control of both HIV and KS.Nevertheless, this study has the advantage to be, to our knowledge, the first to investigate the impact of the newest cART regimens and paradigms on KS; in fact, only sporadic case reports about the effect of integrase inhibitors ,20,34 arIn conclusion, in our experience KS recurrence events were infrequent. Despite the increasing use of new antiretroviral drug classes and new treatment paradigms, no excess of KS recurrence episodes was observed in patients receiving such cART regimens.


Direct comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking.Time to treatment discontinuation (TD) and virological failure (VF) were compared in a cohort of HIV+ patients on a virologically-effective ART starting lamivudine with either darunavir/r, atazanavir/r or dolutegravir. Changes in laboratory parameters were also evaluated.Four-hundred-ninety-four patients were analyzed : median age was 49 years, with 8 years since ART start. Groups differed for age, HIV-risk factor, time since HIV-diagnosis and on ART, previous therapy and reasons for switching.p < 0.001). Calendar years, HIV-risk factor, higher baseline cholesterol and an InSTI-based previous regimen predicted TD, whereas lamivudine+dolutegravir therapy and previous tenofovir use were protective. VF was the cause of TD in 6/123 cases with darunavir/r, 4/97 with atazanavir/r and 3/21 with dolutegravir. Other main reasons for TD were: toxicity , further simplification . Incidence of VF did not differ among study groups (p = 0.747). No factor could predict VF.Estimated proportions free from TD at week 48 and 96 were 79.8 and 48.3% of patients with darunavir/r, 87.0 and 70.9% with atazanavir/r, and 88.2 and 82.6% with dolutegravir, respectively (Lipid profile improved in the dolutegravir group, whereas renal function improved in the bPIs groups.In real practice, a switch to lamivudine+dolutegravir showed similar efficacy but longer durability than a switch to lamivudine+bPIs. Combination antiretroviral therapy (ART) has dramatically decreased the incidence of AIDS-defining events in the HIV-infected population . InternaAfter achieving a stable virological suppression, treatment simplification with two-drugs regimens is a switch strategy considered by both US  and EuroSo far, direct comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking. Therefore, we aimed to compare the virological efficacy, safety and durability of lamivudine plus either atazanavir/ritonavir (r), darunavir/r or dolutegravir in clinical practice.Three groups of ART-treated HIV-positive adult (≥ 18 years) patients, followed-up in a single clinical center, starting a two-drug regimen with lamivudine plus either atazanavir/r, darunavir/r or dolutegravir in a period ranging from 2008 to 2017 were retrospectively evaluated. Switching to a dual regimen was driven by current toxicity issues or need for prevention of future toxicities, and all patients had undetectable viral load at the time of regimen initiation (HIV-RNA < 50 copies/mL). Due to increasing knowledge about treatment toxicities and a greater availability of different treatment choices over time, reasons for beginning a lamivudine-based dual regimen changed in different study periods. In order to observe these changes, no exclusion criteria were selected about study population, with the exception of hepatitis B surface antigen-positive serostatus. The choice of this criterion was mainly driven by the possibility of finding patients who could inadvertently have had their three drug-regimens switched to lamivudine-based dual therapy without checking HBsAg serostatus and that could subsequently have undergone treatment discontinuation at the time of serological test availability.Data analyzed in the present study were selected from an internal observational database, which collects main clinical and demographic characteristics of every patient who gave informed consent to personal data record since the time of HIV diagnosis. The creation of the database was approved by the “Fondazione Policlinico Gemelli” Ethics Committee (protocol number: 10978/15).Main outcomes measures were time free from treatment discontinuation  and time free from virological failure , estimated by the Kaplan-Meier method and compared between groups by the log-rank test. The follow up was censored at TD, death, loss to follow-up, or last available clinical data , whichever occurred first. For the VF analysis, TD was used as an additional censoring criterion. Predictors of TD and VF were evaluated by Cox regression.Secondary endpoints were the evaluation and comparison of changes in CD4 count, blood lipids and estimated glomerular filtration rate  at different times  by using generalized linear models for repeated measures. Predictors of changes were identified by linear regression analysis.Four-hundred-ninety-four patients were eligible for the analysis: 170 started lamivudine plus darunavir/r, 141 lamivudine plus atazanavir/r and 183 lamivudine plus dolutegravir. Overall, 348 (70.4%) were male, with 49 years of median age, 12 years since HIV diagnosis and 8 years on ART. Characteristics of the study population are summarized in Table p < 0.001). Between-group comparisons showed a significant difference between darunavir/r and atazanavir/r (p < 0.001) and between darunavir/r and dolutegravir (p < 0.001), but no differences between atazanavir/r and dolutegravir , but not with lamivudine and atazanavir/r .Over 333.2 patient-years follow-up (PYFU) there were 123 discontinuations in the darunavir/r group , 97 over 461.1 PYFU (21.0 per 100 PFU) in the atazanavir/r group and 21 over 189.1 PYFU (11.1 per 100 PYFU) in the dolutegravir group. Estimated probabilities of remaining free from TD at week 48 and 96 were, respectively, 79.8%  and 48.3% (95% CI 40.7–55.9%) with darunavir/r, 87.0% (95% CI 81.3–92.7%) and 70.9%  with atazanavir/r, 88.2% (95% CI 82.9–93.5%) and 82.6% (95% CI 74.4–90.8%) with dolutegravir (log-rank p < 0.001) and atazanavir/r .After adjusting for baseline factors that were significantly different among groups, calendar period of regimen initiation (2015 or later versus 2013 and before), HIV-risk factor , higher baseline cholesterol and the use of a InSTI-based three-drug regimen before switch (versus a bPI-based three-drug regimen) were associated with TD, whereas dolutegravir use (versus bPIs), switch from tenofovir (versus other backbones) and duration of the previous regimen were protective factors (see Table p < 0.001). With darunavir/r, 6 (4.9%) interruptions were due to VF, 53 (43.1%) to toxicity , 45 (36.6%) due to further simplification, 7 (5.7%) due to drug interactions and 12 (9.8%) due to other/unknown reasons. With atazanavir/r discontinuations occurred for VF in 4 (4.1%) cases, toxicity in 38 (39.2%) , simplification in 30 (30.9%), drug interactions in 8 (8.2%), other/unknown reasons in 17 (17.5%). With dolutegravir, reasons for TD were VF in 3 (14.3%) cases, toxicity in 11 (52.4%) , simplification in 3 (14.3%) and unspecified reasons in 4 (19.0%).Reasons for TD varied among groups (p = 0.747). Potential exposure variables associated to VF were analyzed: nor immunological parameters (baseline and nadir CD4+ count), nor viral factors , nor HCV coinfection, time since HIV diagnosis and years of exposure to antiretrovirals, could predict an increased risk of VF.VF occurred in 11 patients over 319.2 PYFU (IR 3.5 per 100 PYFU) with darunavir/r, with estimated probabilities of remaining free from VF of 95.4% (95% CI 92.1–98.7) and 92.5% (95% CI 88.0–97.0) at week 48 and 96, respectively. Ten VF over 441 PYFU (IR 2.3 per 100 PYFU) occurred with atazanavir/r, with estimated probabilities of remaining free from VF of 96.1% (95% CI 92.8–99.4) and 95.1% (95% CI 91.2–99.0) at week 48 and 96, respectively. With dolutegravir, 5 VF occurred over 188 PYFU (IR 2.7 per 100 PYFU): the estimated probabilities of remaining free from VF were 97.5% (95% CI 94.8–100) and 94.5% (95% CI 89.6–99.4) at week 48 and 96, respectively. No difference in the time to VF was detected among study groups (log-rank p < 0.001).Of 494 patients, 341 had week 24 and 48 follow-up CD4 counts, 295 total cholesterol (TC) and HDL, 362 triglycerides, 369 eGFR. At baseline, groups differed for eGFR levels only, these were slightly higher in the dolutegravir group (p = 0.530) and no time-group interaction was found (p = 0.477). A previous AIDS-event  and baseline CD4 count  independently predicted CD4 change at week 48, after adjusting for type of dual regimen and nadir CD4 count.Absolute CD4 counts significantly increased in all groups from baseline to 48 weeks , with no significant changes in CD4/CD8 ratio. No differences among groups were seen at different time points  compared with lamivudine plus bPIs (time-group interaction-effect test-p = 0.006): the differences in mean change in TC/HDL between dolutegravir and atazanavir/r  and between dolutegravir and darunavir/r  were significant only at week 24. The use of dolutegravir  and baseline TC/HDL values  predicted a decreased TC/HDL at week 48, after adjusting for use of cholesterol-lowering therapy after baseline, time to start of cholesterol-lowering therapy, previous tenofovir use and cumulative time on ART.A decrease in TC/HDL ratio emerged with lamivudine plus dolutegravir , triglycerides only decreased in the latter , with a significant time-group interaction (p < 0.001). The difference in mean change of triglycerides between dolutegravir and both bPIs emerged at both week 24 (p < 0.001) and week 48 (p = 0.003). Baseline triglycerides values  and the use of dolutegravir  independently predicted a decrease in triglycerides at week 48, whereas previous tenofovir use  predicted their increase, independently from the start and time to start of a triglycerides-lowering therapy, history of myocardial infarction and cumulative time on ART.Despite a greater use of triglycerides-lowering therapies since or after baseline in the bPIs groups compared with dolutegravir group , with a significant time-group interaction (p < 0.001). The eGFR decreased in the first 24 weeks of dolutegravir use  and stabilized thereafter. Age , baseline eGFR  and the use of dolutegravir  were negatively associated with the change in eGFR at 48 weeks, after adjusting for anti-HCV positive serostatus, previous use of tenofovir, cumulative time on ART and PIs and duration of virologic suppression at baseline.Estimated GFR improved in the bPIs groups . Moreover, follow-up time of patients on dolutegravir were shorter than follow-up of patients on lamivudine plus PIs: at week 96, only 14 patients with dolutegravir were still on study, compared with 74 on darunavir/r and 88 on atazanavir/r, indicating the reduced reliability of data after the first 48 weeks of treatment for lamivudine plus dolutegravir.The main reason for TD was drug-related toxicity in all groups, but our data seem to underline an overall better tolerability of dolutegravir. Indeed, dolutegravir-treated group was independently associated with a lower discontinuation risk as compared with both darunavir/r- and atazanavir/r-treated groups. However, a series of possible study bias should be considered before drawing conclusions: some baseline characteristics also related to TD, namely the injecting drug use as a HIV-risk factor, the presence of dyslipidemia, and the previous regimen, were statistically different among groups. Patients switching from an InSTI-based regimen were at higher risk of TD. As previously found in a multicenter cohort study , this reConversely, tenofovir discontinuation was protective against TD, likely reflecting a loss of renal or bone toxicity, as observed in previous trials , 13, or Interestingly, more recent study calendar periods were increasingly associated to the risk of TD, indicating a higher propensity to change, presumably related to the availability of more alternative regimens during more recent years. Considering the more recent introduction of dolutegravir and the shorter follow-up of patients on lamivudine and dolutegravir compared with patients on lamivudine plus PIs, prospective studies are needed to fully assess the durability of this strategy over time, especially in comparison with newer treatment strategies.Blood lipids profile significantly improved after switching to lamivudine plus dolutegravir: the use of dolutegravir was associated with a reduction of TC/HDL ratio and triglycerides at week 48, independently from baseline values, use of lipid-lowering therapy and a previous tenofovir-containing regimen. Renal function apparently declined in the dolutegravir group at week 24 but stabilized thereafter, whereas an increase in eGFR was observed in the bPIs groups, independently from a previous tenofovir use, as already reported in the ATLAS-M trial . These fTo our knowledge this is the first observational study aiming to compare the durability of lamivudine-based two-drug regimens. Further strengths of our study are represented by the large sample size, the relatively long median follow-up time (1.6 years) and the lack of exclusion criteria that could have had an impact on efficacy of dual regimens . Of course, our study has important limitations, particularly in relation to its retrospective design and the lack of randomization, that hamper direct evaluation of differences among lamivudine-based dual regimens and that precluded to interpret the global efficacy of these simplification strategies. The different characteristics of study groups at baseline, partly explained by the different periods of enrolment, lead to the emergence of several important confounders: although we used multivariate models to address these issues, the strength and the generalization of our conclusions are limited.Keeping that in mind, our study adds further proof that lamivudine plus dolutegravir could represent a potential optimization strategy in virologically-suppressed patients. The improvement of the blood lipids profile can be considered another advantage of this strategy: given the increased frequency of age-related comorbidities in the HIV-infected population, lamivudine plus dolutegravir could play an important role in the next years to reduce cardiovascular diseases in this setting. Longer follow-up studies are needed to verify this hypothesis.


Antiretroviral therapy (ART) started between 7 and 12 weeks of age improves neurodevelopmental outcomes in HIV-infected (HIV+) infants, but the impact of even earlier initiation is not yet described.We assessed the early neurodevelopment of HIV+ infants who started ART within 21 days of life.Participants were enrolled from the public sector birth HIV-diagnosis programme. Inclusion criteria included the following: birth weight > 2000 g, infant commencing ART < 6 weeks and no infant cytomegalovirus disease. Antiretroviral therapy included Zidovudine/Lamivudine/Nevirapine for the first 2 weeks, the latter then replaced by Lopinavir/Ritonavir. Once body weight > 3 kg and gestational age > 44 weeks, Abacavir replaced Zidovudine. The Griffiths mental development scales (GMDS) were administered at 10–12 months.Of 29 infants assessed, 23 (79%) were girls. Mean birth weight was 3002 ± 501 g. Twenty-four mothers (83%) received ART during pregnancy. Seven (24%) infants were diagnosed HIV+ within 48 h of birth. Median [interquartile range] viral load (VL) at diagnosis was 3904 [259–16 922] copies/mL, age starting ART was 6.0 [3–10] days and age at VL suppression was 19.1 [15–36] weeks. At the GMDS assessment, nine (31%) participants had detectable VL and 26 (90%) had World Health Organization (WHO) clinical stage I disease. The GMDS was performed at a mean age of 11.5 ± 0.8 months. Mean quotients were within the average range: Global Griffiths score was 103.6 ± 10.9 and mean quotients on the subscales ranged from lowest 95.9 ± 13.4 for locomotor to highest 112.8 ± 11.3 for hearing-and-language.Preliminary findings in this small group suggest that early neurodevelopmental scores are within the normal range in infants with perinatal HIV infection who started ART at a median of 6 days. HIV encephalopathy rates range from 6% to 30%, with higher rates in low- and middle-income countries especially with delayed initiation of combination antiretroviral therapy (ART).5 These consequences place a great burden on the social and healthcare systems.HIV-infected (HIV+) children are at risk for neurodevelopmental delay. Neurologic insults develop after HIV enters the brain, creating an inflammatory state affecting neuronal and astrocyte growth and development6 and when initiated between 3 and 9 months of age, it improves clinical and neurodevelopmental outcomes.10 Nevertheless, studies describing permanent deficits or lack of catch-up suggest that prevention is better than reversal of HIVE.13 From 2016, the World Health Organization (WHO) introduced birth testing and recommended starting ART as soon as possible once HIV infection is confirmed.14 Since the report of temporary remission in the Mississippi baby after very early ART,15 there is increasing evidence that early ART in perinatally infected children improves infant outcomes.16 Early ART can limit HIV reservoir size, and when started before 2 months of age, it is associated with fewer infected and transcriptionally active cells and less infectious virus recovery.24 However, administering ART in a neonate and young infant is not easy with potential drug resistance because of under-dosing, or neurotoxicity because of overdosing.25 The long-term outcomes of very early exposure to ART are still unknown. It is therefore imperative that neurodevelopmental testing be undertaken after early ART initiation. Our aim was to determine the neurodevelopmental outcomes of perinatally HIV-infected children after initiating ART within the first 3 weeks of life.Antiretroviral therapy has decreased the incidence of HIVE,27 Inclusion criteria were the following: birth weight > 2000 g, commencing ART < 6 weeks of age and no infant cytomegalovirus (CMV) infection. Mothers or legal guardians were consented in person in their language of choice according to Good Clinical Practice standards.We report early data from a prospective descriptive study conducted in the Family Centre for Research with Ubuntu (FAM-CRU) in Tygerberg Hospital, Cape Town, South Africa, with recruitment from the Médecins Sans Frontières service in Khayelitsha and elsewhere in the public sector. Antiretroviral therapy was started as soon as HIV infection was confirmed. HIV diagnosis was made by quantitative HIV-1 viral load (VL) testing and confirmed by a qualitative HIV-1 RNA PCR. Indeterminate samples were repeated until HIV diagnosis confirmation.Participants were seen as frequently as needed until stable, monthly for 3 months and then 3 monthly. Visits included a medical examination, growth monitoring, adverse event assessment and social work support where needed. At each visit, a pharmacist calculated the percentage adherence for each drug from returned ART containers and an adherence counsellor established reasons for over or under-dosing with the parent or caregiver, offered advice on problems identified and reviewed measuring techniques. HIV viral load was performed at baseline, 3, 6 and 12 months. Undetectable VLs were reported as < 100 or < 40 copies/mL depending on the blood volume available for testing. CD4 cell counts were done at 3, 6 and 12 months. Antiretroviral therapy comprised Zidovudine, Lamivudine and Nevirapine, with Lopinavir/Ritonavir replacing Nevirapine after 2 weeks of age or gestational age of 42 weeks. Once weight exceeded 3 kg and gestational age was above 44 weeks, Abacavir replaced Zidovudine. Participants also received co-trimoxazole from 6 weeks of age.28 The GMDS assesses five subscales: locomotor, personal–social, hearing-and-language, eye–hand coordination and performance . A global score, the General Griffiths, is also calculated. Raw scores are converted into quotients, derived from norms of healthy British children, with a mean of 100 and standard deviation (s.d.) of 16. While the GMDS is neither standardised nor validated in South Africa, it is the most widely used developmental assessment tool, is considered culturally fair and is used to assess young children including those exposed to HIV.36 Vision was assessed clinically during testing and through the ability to track small cake decorations (‘hundreds and thousands’ test), which implies visual acuity of 6/24 or better.37The Griffiths mental development scales (GMDS) (0–2 years) were conducted by the same developmental paediatrician (B.L.) at 10–12 months of age.Statistical analysis was performed using Stata release 11  and Statistica 13 (software.dell.com. Dell Inc. 2015). For descriptive statistics, mean and s.d. were reported for normally distributed data and median and interquartile range (IQR) for skewed data. Guided by distribution of the data, Spearman and Pearson correlations were used to explore correlation between various parameters and neurodevelopmental outcomes. For calculating age at VL suppression, those who had not yet achieved VL suppression were assigned a date 2 days after the GMDS. Regression analysis explored the contribution of five predictors of GMDS scores: birth weight, ART start age, baseline VL, baseline CD4% and age at first VL suppression.10Descriptive data and GMDS scores were also compared to those from the early treatment arms on Children with HIV Early antiRetroviral treatment (CHER) trial participating in a neurodevelopmental sub-study who received early ART from a median of age of 7.7 weeks and were assessed by the same investigators at 11 months of age.Mothers or legal guardians were consented in person in their language of choice according to Good Clinical Practice standards. The Stellenbosch University Health Research Ethics Committee approved the study (No.: M14/07/029).Of 29 children studied, 23 (79%) were female. Mean birth weight was 3002 ± 501 g and gestation was 37.9 ± 2.3 weeks. HIV+ diagnosis was made by 48 h of birth in 7 (24%) and within 7 days of birth in 17 (59%) infants. Median [IQR] age for starting ART was 6.0 [3–10] days (range 0–21) from birth. Twenty-three achieved VL suppression at median [IQR] 19.1 [14.7–35.9] weeks of age (range 2–53) .The GMDS was performed at a mean of 11.5 ± 0.8 months (range 10.2–13.1) and scores are described in Clinical status at the time of GMDS is described in A number of demographic and exposure issues with potential to influence neurodevelopmental outcomes were identified. These included two without antenatal care, one with an unsupervised home birth and three with maternal substance abuse: two methamphetamine and one methamphetamine and alcohol (over time these children were fostered by caring relatives). Medical problems included one each of the following: congenital pneumonia of unknown aetiology, intrauterine growth retardation, neonatal jaundice above exchange transfusion levels (resolved without exchange), congenital syphilis with mild hypoxia and suspected seizure, mild birth asphyxia (low birth Apgar scores and cord blood pH = 7.17) and suspected hypoglycaemia (but glucose level not recorded) (these data not shown in any table).The following adverse events, which could negatively impact neurodevelopment, were documented before the GMDS assessment: six with otitis media (one had two episodes), six with anaemia and three with neutropenia (Zidovudine was discontinued). One infant recovered fully after treatment for suspected bacterial meningitis and another was hospitalised for 6 months with pulmonary tuberculosis. Lastly, failure to thrive because of poor feeding and insufficient caloric intake occurred in one infant.Adherence was calculated at a median [IQR] of 10 [9–11] visits. Only one participant had acceptable adherence percentages for all drugs at all visits. Three participants had poor adherence for more than half of the visits, with the rest over or under-dosing at various times. For the former, the infant would spit syrups out and caregivers were unsure how much to replace. For the latter, the caregivers either measured syrups incorrectly or were non-compliant. This prompted clinicians to encourage treatment supporters for the caregivers.r = −0.41; p = 0.03) and a negative trend with General Griffiths .Correlations between GMDS scores and possible predictors of developmental outcomes  were not significant. The five predictors of GMDS scores entered into the regression model also did not show significant relationships, that is, birth weight, ART start age, baseline VL, baseline CD4% and age at first suppression. CD8 count at the time of GMDS showed a negative correlation with personal–social  scores  and weight z-score correlated with eye–hand coordination scores . There was a positive trend between weight for age z-score and General Griffiths score .For growth parameters closest to the GMDS assessment, head circumference We compared the GMDS scores of those whose mothers had ART for prevention of mother-to-child transmission of HIV (PMTCT) and those who did not and found no difference between the groups see . There w10 apart from personal–social subscale, where the CHER cohort had mean quotients 7 points above that of the current study population (The GMDS scores achieved by this cohort were similar to those from the CHER cohort (children on ART commenced at 7 weeks of age) at a mean age of 11.3 months,pulation . Post hoSignificant differences between the two groups are shown in 34 , one co-infected with tuberculosis and one nutritional failure. Growth in participants was appropriate for weight and head circumference, but mean length z-score was −1.1.An important finding is that we identified a number of challenges within the context of perinatal HIV infection, despite good PMTCT programmes. In those perinatally infected infants, a number of secondary effects, including systemic illnesses and environmental affects, may negatively impact a child’s early neurodevelopment.43 Our findings do not suggest neurotoxicity from ART.We noted variability of ART adherence and the delay in attaining competence with ART dosing and adherence, with six children not yet suppressed at the time of GMDS assessment. Management of these young children was challenging as caregivers were non-compliant, under-skilled and found difficulty administering liquid formulations. Solid or dispersible formulations would certainly improve adherence.44 this may be because of small sample size. We were not able to determine reliable predictors for neurodevelopmental outcomes, or compare the outcomes of suppressed and unsuppressed participants. This was also hindered by time to suppression being inaccurate as VLs were only done at baseline 3, 6 and 12 months. We did not collect information on maternal health, immune status, VL or antiretroviral therapies. In the absence of South African normative data on the GMDS, a control or comparison group would have been helpful. However, we have experience in this community using the GMDS and are able to use these results for comparison32 (This work had some limitations. As multiple factors may influence outcomes, 29 children starting ART very early are too few to assess weak associations with neurodevelopmental outcomes, including our finding of lower locomotor scores compared to other subscales. More girls than boys were enrolled in the sample; although previously described,arison32 . The con46 While the number of HIV+ infants is decreasing, this population remains at high risk because of structural and behavioural challenges in providing appropriate care. As liquid Lopinavir/Ritonavir formulation is poorly tolerated, newer formulations and other alternatives such as integrase inhibitors will be better accepted. Healthcare planners should not downscale programmes according to decreasing numbers, as those failing PMTCT require a higher level of care and intensive intervention to enable benefit from early ART. With the potential of early ART to limit HIV reservoir seeding, and potential to contribute to functional cures, treatment programmes need to support these vulnerable infants and their caregivers.47 Mentor mothers as treatment supporters may decrease the burden of HIV care and consequences of developmental delay, and could be very important when planning programmes. If these needs can be met, our findings are encouraging.49Our findings are relevant to upscaling neonatal HIV identification and care.Preliminary findings in this small group suggest that despite PMTCT failure, children infected perinatally with HIV may have typical neurodevelopment if starting ART at a median age of 6 days, and similar to those starting ART at a median of 7 weeks. Good supportive care, including for ART adherence, is essential. A larger cohort that includes controls is in study and the findings at 18 months of age will inform on the influence of time to VL suppression and reservoir size and also the influence of social factors and demographic factors on neurodevelopmental outcomes. This may also allow for more precise study of locomotor outcomes.


To evaluate the effectiveness of antiretroviral therapy and the associated factors according to the type of regimen used: Single Tablet Regimen or Multiple Tablet Regimen. Prospective cohort of 440 patients  who initiated antiretroviral therapy between Jan/14 and Dec/15 at a referral service in Belo Horizonte. Efficacy was defined as viral suppression  and evaluated after six and twelve months of treatment. Sociodemographic, clinical and behavioral data were collected from clinical charts and from Information Systems. Multivariate analysis of overall effectiveness was performed by logistic regression. Most patients initiated Multiple Tablet Regimen antiretroviral therapy . At six months, overall viral suppression was 74.6%, being higher among patients who used Single Tablet Regimen . At twelve months, 83.2% of patients reached viral suppression, with no difference between groups (p = 0.93). Factors independently associated with viral suppression at six and twelve months varied, being negatively associated with effectiveness: VL ≥ 100,000 copies/ml, symptoms of AIDS, longer interval time between diagnosis and initiation of antiretroviral therapy, antiretroviral switching, smoking or current illicit drugs usage (p < 0.05). Factors positively associated with viral suppression included adherence to antiretroviral therapy and category of risk/exposure of men who have sex with men (p < 0.05). Reaching viral suppression at six months was the main predictor of effectiveness at one year (OR = 8.96 and p < 0.01). Viral suppression was high and better results were achieved for patients who used Single Tablet Regimen regimens at six months. Clinical, behavioral, and antiretroviral therapy -related factors influence viral suppression and highlight the need for interventions to increase early diagnosis and initiation of antiretroviral therapy, patient’s adherence, and to reduce illicit drugs and cigarette smoking in this population. This prevalence is higher among sex workers, injecting drug users, men who have sex with men (MSM), and persons deprived of libertySince 1996, the Brazilian Unified Health System (SUS) has offered ART as part of its care policy for people living with HIV (PLHIV),The STR have allowed the simplification of ART and the administration of a single tablet per day compared to multiple-tablet regimens (MTR). The benefits include greater patient preference, increased self-perceived health, greater adherence to ART, greater viral suppression, better laboratory parameters and reduction of associated costs,The Brazilian Ministry of Health invested over R$ 1 billion in antiretroviral drugs and the treatment of sexually transmitted diseases in 2016We aimed to evaluate the effectiveness of antiretroviral drugs in PLHIV according to the type of regimen (STR or MTR) used in the treatment and associated factors.A non-concurrent prospective cohort of patients who initiated ART between January 2014 and December 2015 at an HIV specialized service (SAE) that provides inpatient and outpatient care in Belo Horizonte, the major point of reference in Minas Gerais.Sistema de Controle Logístico de Medicamentos (Siclom – Logistic Control System of Medicines) and in HIV and AIDS reports issued by the SAE. Of those, 440 met the inclusion criteria  The data collected in medical records were: sociodemographic ; behavioral and lifestyle habits ; clinical/laboratory [possible sources of infection, hospitalizations in the previous year and after initiating ART, initial clinical classification of patient Data collection was carried out by two trained researchers using a standardized form and typed in EpiInfoPatient follow-up lasted 12 months. The initial date of therapy was determined by the first dispensation of ART to outpatients registered with Siclom or the first dispensation of ART registered in the medical record of patients who began therapy during hospitalization.Therapy effectiveness was defined as viral suppression (plasma VL < 50 copies/ml) six months after initial treatmentPatients were compared according to initial therapy regimen: STR or MTR. Categorical variables were presented by frequency distribution and quantitative variables by central tendency (mean or median) and variability . The chi-square test was used to compare the groups.The magnitude of the association between the explanatory variables and effectiveness was estimated by odds ratio with 95% confidence interval. The independent effect of the explanatory variables was evaluated by a multiple logistic regression model which included all explanatory variables that obtained p < 0.20 in the Wald test in simple regression. The goodness of fit of the multiple model was verified by the area under the Receiver Operating Characteristic curve (above 0.7). The level of significance was 5% for all analyses, performed using R software version 3.4.0.Three scenarios were constructed to evaluate the impact of missing data on the analysis outcomes: in the first, only patients with observed data were evaluated; in the second, missing data were considered as success (VL < 50 copies/ml), and, in the third, missing data were considered as failure (VL ≥ 50 copies/ml).2 = 0.99 for six months and R2 = 0.83 for 12 months). No differential loss was observed between the groups that reached viral suppression or not according to the explanatory variables.The missing data were replaced using multiple imputation by chained equations “Efetividade da terapia antirretroviral em pessoas vivendo com HIV, HIV/tuberculose, HIV/hanseníase ou HIV/leishmaniose visceral, acompanhados em Belo Horizonte”  approved by the Research Ethics Committee of Universidade Federal de Minas Gerais  and Hospital Eduardo de Menezes .This study is part of the ECOART project 3 (32.0%) and presence of AIDS-defining signs and symptoms (45.7%), although most had no record of hospitalization due to HIV in the year prior to entering the cohort (52.7%)  and the main category of risk or exposure to HIV infection was MSM (32.3%), followed by heterosexual men (30.0%). Many patients entered the cohort with advanced immunosuppression, characterized by CD4 + counts below 200 cells/mm (52.7%) .During follow-up, 60.7% of patients recorded infectious and parasitic diseases, of whom 28.9% presented HIV complications and 18.2% infections with a predominantly sexual mode of transmission. Co-infection by tuberculosis and hepatitis B or C occurred in 10.0% and 2.3% of the population, respectively. In addition, 25.9% of patients had a record of mental or behavioral disorder, the most common being depression  and anxiety .The ART was mainly initiated at outpatient level (63.6%) with regimens that combined two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) associated with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (92.0%) – mainly efavirenz (90.7%). The most common drug combination was tenofovir, lamivudine and efavirenz (85.0%), followed by zidovudine, lamivudine and efavirenz (3.6%). The interval between diagnosis and initial ART was up to 60 days for approximately half of patients (52.5%), with an average of 1.1 years . Adherence to treatment was higher in the first six months, 83.4% of patients, versus 73.4% at 12 months. At least one incident ART-related adverse reaction was recorded for 50.9% of patients and ARV switch for 23.9%. The use of illicit drugs and tobacco reduced after initial ART .The distribution of patients in the STR and MTR groups was mostly similar regarding sociodemographic, clinical, ART-related and behavioral and lifestyle characteristics. However, compared to the MTR group, patients who used STR had a higher level of education, fewer were browns, had a lower prevalence of mental disorders, more recent HIV diagnosis, and lower incidence of adverse reactions to ART and ARV switch (p < 0.05) .Viral suppression was observed for 74.6% of patients at six months of follow-up, and this percentage was higher among patients in the STR group (p = 0.035). Viral suppression results in the other scenarios followed the same trend, although statistical significance was observed only in the success scenario .At 12 months of follow-up, 83.2% of the patients reached viral suppression, with no statistically significant difference between the STR and MTR groups (p = 0.929) in all proposed scenarios. In this period, 75.2% of patients reached immunological recovery, also without differences between the groups. However, the percentage of missing data for this outcome was high (53.2%), which may compromise the interpretation of results in the proposed scenarios .Bivariate analysis with imputed data showed different factors associated with viral suppression at six and 12 months. Sociodemographic characteristics did not influence the outcome, whereas clinical variables related to disease progression and immunosuppression at the baseline were associated with lower effectiveness: presence of AIDS-defining signs and symptoms and hospitalization records in the year prior to entry into the cohort and viral load above of 100,000 copies/ml for effectiveness at six and 12 months (p < 0.05) .Among ART-related characteristics, antiretroviral drug switch was negatively associated with effectiveness at six and 12 months, while adherence was positively associated with effectiveness in both periods (p < 0.05). At six months, initiating treatment during hospitalization and use of MTR were associated with a lower probability of achieving effectiveness (p < 0.05), while initiating therapy in 2015 and diagnostic time above two months increased the likelihood of achieving viral suppression (p < 0.05). The extent of viral suppression at six months was strongly associated with achieving effectiveness at 12 months of treatment (OR = 7.78 and p < 0.001) .Tobacco use during follow-up was negatively associated with viral suppression, and illicit drug use during follow-up reduced the chance of achieving viral suppression at 12 months (p < 0.05) .Clinical, ART-related, behavioral and lifestyle factors remained in the final model associated with effectiveness in the multiple analysis with imputed data. Viral load above 100,000 copies/ml (p = 0.017) and presence of AIDS-defining signs and symptoms (p = 0.014) were associated with approximately 55.0% and 70.0% less likelihood of achieving viral suppression at six months, as were ARV switch (p < 0.001) and tobacco use during follow-up (p = 0.005). Only adherence to ART increased the chance of achieving viral suppression  .The multiple model with imputed data showed that achieving viral suppression at six months was the main predictor of effectiveness at 12 months . In addition, adherence to ART at 12 months and belonging to the MSM category increased the likelihood of achieving viral suppression (p < 0.05), while use of illicit drugs during follow-up reduced that likelihood by 66.0% .,In this Brazilian cohort study, which included only ART-naïve patients, the overall effectiveness of antiretroviral therapy was high, 74.6% at six months and 83.2% at 12 months of treatment, similar to rates in developed countries,,The characteristics of the patients included in this study are similar to the profile of PLHIV in Brazil, as published in epidemiological bulletins and other national studies,,,,Overall effectiveness at six months agrees with the results obtained by Cardoso et al.12–14, albeit with different regimen compositions.The simplified therapy regimen with daily ingestion of tablets only once a day is associated with the higher level of adherence of patients to ART and higher levels of viral suppression when using STR or absence of difference between groupsThese results reinforce the strategy of supplying generic drugs in STR in Brazil. Although the difference between groups was not statistically significant at 12 months of follow-up, there was a trend of better results for patients using this drug regarding the incidence of adverse events, switch of therapy regimens, adherence to treatment and immunological recovery, as well as higher viral suppression at six months of ART.8,15–17. Initiating ART regardless of CD4+ cell counts has been adopted in Brazil since 2013. Recent studies indicate a 50% reduction in the incidence of serious AIDS-related events, such as death and opportunistic diseases, among patients who initiate ART early (CD4+ count > 500 cells/mm3),The effectiveness of antiretroviral therapy was influenced by clinical, behavioral and ART-related factors. Among the factors that predicted effectiveness at six months, initiating treatment with high viral load and AIDS-defining signs and symptoms were negatively associated with viral suppression, as reported in previous studies,Despite knowledge of these benefits and policies introduced to increase access to diagnosis and treatment, such as expansion of testing sites and availability of quick diagnostic testsThe MSM were more likely to achieve viral suppression after 12 months of treatment compared to other risk or exposure categories. This result may reflect a greater involvement of those patients in continuous healthcare,The ARV switch and ART adherence influenced viral suppression. The ARV switch is associated with lower adherence to treatment and may be more closely related to the occurrence of adverse events and intolerance rather than virologic failure,,,The relationship between adherence to treatment and ART effectiveness is well documented in the literature,Viral suppression at six months was the main predictor of effectiveness in one year,Use of substances such as tobacco and illicit drugs during follow-up were associated with lower likelihood of achieving viral suppression. Tobacco use among PLHIV has been linked to worse clinical outcomes, such as increased viral load, reduced CD4+ cell count and increased occurrence of opportunistic infections,,,28–30 are possible strategies to improve the clinical results of these patients.The use of illicit substances among PLHIV may be related both to the actual source of infection and to diagnosis coping mechanismsThis study has limitations, such as poor accuracy of measurements collected from medical records and high percentage of missing data. The strategies used to minimize their effect were the elaboration of clinical scenarios and data imputation, with no change in the trend of results. Study strengths include the high quality of collection, the broad inclusion of confounding factors, and the robustness of the final model in both follow-up periodsThe incidence of viral suppression at six and 12 months in patients with no prior use of ART was high, with differences between patients using STR and MTR. Clinical, behavioral, lifestyle, and ART-related factors influenced viral suppression. They also demonstrated the need for interventions to improve diagnosis and the timely initiation of treatment, patients’ adherence to therapy, and the reduction of tobacco and illicit drugs use, so as to optimize treatment outcome and contribute to quality of life and reduction of HIV transmission.


Background: Nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) with boosted protease inhibitors are included in standardized first-line and second-line regimens. Recent World Health Organization (WHO) guidelines recommend a boosted protease inhibitor (PI) combined with 2 NRTIs or raltegravir as a second-line regimen.Objective: Ritonavir-boosted lopinavir (LPV/r) is known as a key second-line antiretroviral therapy (ART) in resource-limited settings. We carried out a meta-analysis to analyze virologic suppression and effectiveness of LPV/r-based second-line therapy in HIV-infected patients.Methods: In this meta-analysis, we searched randomized controlled trials and observational cohort studies to evaluate outcomes of second-line ART for patients with HIV who failed first-line therapy. A systematic search was conducted in Pubmed, Cochrane Library, and Embase from inception to January 2018. Outcomes included viral suppression, CD4 cell counts, drug resistance, adverse events, and self-reported adherence. We assessed comparative efficacy and safety in a meta-analysis. Data analysis was performed using RevMan 5.3 and Stata12.0.Results: Nine studies comprising 3,923 patients were included in the meta-analysis. The overall successful virologic suppression rate of the second-line regimen was 77% (ITT) and 87% (PP) at 48 weeks with a plasma HIV RNA load of <400 copies/mL. No statistical significance was found in CD4 cell count recoveries between LPV/r plus 2-3 NRTIs and simplified regimens  at 48 weeks (P = 0.09), 96 weeks (P = 0.05), and 144 weeks (P = 0.73). Four studies indicated that the virus had low-level resistance to LPV/r, and the most common clinically significant PI-resistance mutations were 46I, 54V, 82A/82F, and 76V; however, no virologic failure due to LPV/r resistance was detected. In addition, no statistical significance was found between the two groups in self-reported adherence , grade 3 or 4 adverse events  or serious events .Conclusions: These results suggest that the LPV/r-based regimen demonstrates efficacious and low resistance as second-line antiretroviral therapy.Both LPV/r plus 2-3 NRTIs and LPV/r plus RAL regimens improved CD4 cell counts. There was no evidence of superiority of simplified regimens over LPV/r plus 2-3 NRTIs. Millions of adults and children who are infected with HIV in resource-limited regions have access to antiretroviral therapy (ART) based on World Health Organization (WHO) guidelines .This article was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement  screened all abstracts. Two authors (Y.Q. HUANG and Y.D. LUO) obtained full-text copies of relevant publications that reported viral suppression, CD4 cell counts and other outcome results, assessed those articles for eligibility and reached a consensus on potential relevance. We included studies of HIV treatment experienced patients over 12 years old who failed first-line NRTI-based regimens and were switched to LPV/r plus 2-3 NRTI regimens. According to the following criteria, certain studies were excluded: (1) reviews and animal studies, (2) regimens without LPV/r, (3) patients living with HIV who were less than 12 years old or pregnant, (4) patients with opportunistic infections and not treated with second-line therapy, and (5) reports without baseline CD4 cell counts or viral load monitoring.According to the consensus list, one investigator extracted the data. The data included second-line ART regimens, treatment failure definition and follow-up durations of second-line treatment, viral load monitoring, baseline CD4 cell counts, adherence and drug resistance. When there was uncertainty about the data, the original study authors were contacted for clarification. Detailed data, such as study design, participant information, interventions, outcomes, and adverse events, were extracted and imported into an Excel table. A second author randomly checked 25% of all the extracted data  provided in study reports and calculated the RR for dichotomous outcomes and the 95% confidence interval (CI) when necessary. We then pooled data across the included studies and estimated their summary effect sizes. We performed all meta-analyses with RevMan 5.3  and Stata12.0 . Heterogeneity for each combined rate was assessed with a chi-square-based P = 1.00)   (ITT) and 94% (95% CI: 92–96%) (PP) in 48 weeks, while 528 patients using LPV/r plus RAL as a second-line treatment showed a virologic suppression rate of 87% (95% CI: 78–96%) (ITT) and 95% (95% CI: 90–100%) (PP) in 48 weeks , 96 weeks  and 144 weeks   and serious adverse events  , as seen from the figure, LPV/r plus RAL was superior to LPV/r plus NRTIs  Figure . In one ) Figure , fasting) Figure . The eGFs Figure .The data on LPV/r resistance primarily came from clinical trials. Only 4  for patients with virologic failure. In patients who failed all NRTIs, LPV/r plus RAL is a good option. Further study is warranted to investigate whether similar outcomes can be achieved with LPV/r plus other integrase inhibitors as second-line ART regimens.For two treatment regimens, there were no significant differences in grade 3 or 4 adverse events or serious events. In a study carried out by Cohen et al. , grades The present review has multiple limitations. To reduce the possibility of missing key studies as much as possible, we searched three scientific databases and carefully reviewed the cited references of included studies, review articles and abstracts from recent conferences. However, it should be noted that the bulk of participants in our identified literature come from sub-Saharan African countries; few studies were contributed from other regions. Due to the lack of independence between study populations, our effectiveness assessment could be biased. There were two studies with the same participants and the same baseline characteristics, and the only difference was follow-up time. Some important outcomes, including CD4 cell counts and side effects, were limited by the very low number of events.In conclusion, our meta-analysis showed that LPV/r as a second-line ART regimen had good efficacy and little drug resistance. RAL plus LPV/r as an alternative second-line regimen was not inferior to LPV/r plus NRTIs in viral suppression, immunological reconstitution, grade 3 or 4 adverse events, serious events or treatment adherence. However, it is worth noting that RAL plus the LPV/r regimen was more likely to cause dyslipidemia. Compared with RAL, LPV/r is available in resource-limited settings. In China, LPV is the first protease inhibitor prescribed. Compared with RAL, NRTIs and LPV/r are free of charge. The higher efficiency and lower side effects of LPV/r could achieve better therapeutic effect. The results of this systematic review clearly showed solid evidence that LPV/r-based ART is a preferred second-line therapy regimen and should be widely used in resource-limited countries. More clinical trials, particularly with an alternative second-line regimen of RAL plus LPV/r, are needed to better guide WHO treatment strategies and policy.YH and YL analyzed the data and wrote the manuscript. YZ, XT, and AS collected and prepared the samples. HC and YH performed the analyses. XH and YC designed the study and revised the manuscript. All authors critically revised the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Monitoring the safety of antiretroviral therapy (ART) remains a challenge in resource-constrained countries such as Eritrea due to their serious adverse drug reactions (ADRs). This study was aimed at assessing the prevalence, nature, seriousness and possible risk factors of ART associated ADRs in Halibet National Referral Hospital in Eritrea.p-value. A P-value < 0.05 was regarded as being statistically significant.A three month retrospective, longitudinal, descriptive study of patients treated with ART between September 2005 and December 2016 was conducted in Halibet National Referral Hospital. Demographic characteristics, treatment details, reaction and outcome details, laboratory investigations and other information was abstracted manually from patients’ clinical cards. Statistical analysis was conducted using both univariate and multivariate analysis and statistical significance was tested using 95% confidence intervals and/or p = 0.000).Of the 309 patients screened, 62.8% encountered at least one ADR and 29.8% of the reactions were serious with similar male to female ratio. Gastrointestinal symptoms were the most common ADR and were associated mostly with Atripla followed by AZT + 3TC + NVP drug combinations, but lipodystrophy followed by peripheral neuropathy which were both commonly associated with Stavudine and anemia associated with Zidovudine were the most serious. Patients with CD4 count below 200 were more likely to develop ADRs (ADRs associated with ART drugs in Halibet hospital were found to be highly prevalent. Furthermore, CD4 count below 200, was identified as a major risk factor that predisposes patients to ADRs. This is burdensome to resource constrained countries such as Eritrea who have limited drug options and high HIV prevalence, therefore these findings will help patients and healthcare professionals understand the nature as well as seriousness of these ADRs and identify the risks involved with ART medications which can help minimize ART associated ADRs early on. Highly Active Anti-Retroviral Therapy (HAART) has made a significant change in the lives of people living with HIV (PLWH) in decreasing AIDS-related deaths and improving quality of life . DespiteLimited study has been conducted on the adverse effect of ART in Sub-Saharan countries, such as Eritrea, despite having high prevalence of HIV. A five-month prospective study conducted in Eritrea by Russom et al. 2017  aimed atThis was a retrospective, historically longitudinal, descriptive study conducted in all eligible patients treated with ART in Halibet national referral hospital. Longitudinal data  of patients compiled between September 2005 and December 2016 in the ART clinic was abstracted from patients’ clinical cards. The HIV clinic in Halibet hospital as part of the infectious clinic gives an outpatient services to 1242 adult patients, above 18 years of age, that come from different parts of the country.The study population was PLWH/AIDS who were attending Halibet national referral hospital’s ART clinic between 2005 and December 2016. The source population covers all HIV patients in the country as the hospital provides services to all patients coming from different parts of the country. Patient cards that were hard to assess were excluded from this study since the information they presented was not enough to be evaluated. Furthermore, patients aged 60 years and above were also excluded from the study as they may have different co-morbidities and are likely to take multiple drugs which would make the causality assessment more challenging.Once a patient is diagnosed with HIV, he/she may start on HAART. HAART refers to the combination of three or more antiretroviral drugs for the treatment of HIV infection. The patients may start therapy regardless of their CD4 count under the new ART guidelines. Once patients decide to start ART, they begin with standard first-line HAART regimen which for an adult includes Atripla (Tenofovir /Emtricitabine/Efavirenz), Tenofovir/Lamivudine+Nevirapine, Zidovudine/Lamivudine+Nevirapine, Zidovudine+Lamivudine+Efavirenz, Abacavir+Lamivudine+Efavirenz, Abacavir+Lamivudine+Nevirapine. Patients who develop resistance to these first-line regimens move to a boosted protein inhibitor (PI) and two nucleoside reverse transcriptase inhibitor (NRTI) combinations as they are preferred strategy for second-line ART. In case of TDF +3TC or FTC based first-line regimen failure, AZT + 3TC + LPV/r or AZT + 3TC + ATV/r are used. For AZT + 3TC based first-line regimen failure, TDF + 3TC/FTC + ATV/r and TDF + 3TC/FTC + LPV/r are used as second-line regimens respectively. Since these are combination drugs, they do not use weight-based regimen and the same doses are given to all patients deemed as adults. In case of ADRs, specific or symptomatic relief may be given to alleviate the encountered ADRs and in severe cases the drug may be withdrawn.This study’s primary outcome measures were the nature of ADRs encountered, their prevalence, seriousness as well as the possible risk factors that predispose patients to ADRs.A sample that would ideally be representative of the patients in Halibet National referral hospital was taken. This sample was calculated using the following formula:Adjusted to the population size (population correction factor) = Where p = prevalence of ADR = 0.05.p = 1–0.05.q = complement of Z = parameter of the confidence interval = 1.96.e = margin of error = 0.05.N = population size = 1242.Three hundred nine patients were taken as sample to further decrease the margin of error.This sample was taken from the population by selecting every fifth card from the 1242 cards that were alphabetically ordered to ensure randomness. Data collection tools developed by the Eritrean Pharmacovigilance Centre for conducting similar studies were used to capture data. Demographic information of all the eligible patients attending the ART clinic during the study period was documented using a ‘Patient Listing Form’. It was used to capture demographic information of the patients regardless of their adverse drug reaction status including age, sex, number of drugs taken, availability of co-morbidities, CD4 count and so on. The second data collection tool was a comprehensive and well-structured tool for those with ADRs aimed at collecting patient demographic information, reaction details and drug details on both suspected and concomitant drugs including those taken for longer period of time to manage ADRs. Furthermore, detailed information of ADRs manifested during treatment including type of ADR, date reaction started, date reaction stopped, therapy started and stopped, dechallenge and rechallenge information, seriousness of the reactions, reaction outcome, information on other possible alternative cause(s) or explanations, management taken and treatment provided whenever available was recorded.For the purpose of this study, the definition of an ADR was based on the one developed by the World Health Organization (WHO)  WHO has Causality assessment was performed for all suspected ADRs using Naranjo probability scale . The NarResulted in death,Is life-threatening,Required hospitalization or resulted in prolongation of existing hospitalization,Resulted in persistent or significant disability/incapacity,Caused congenital anomaly/birth defect orMedically important event or reaction that required medical/surgical intervention to prevent serious outcome.Seriousness of the identified suspected ADRs was determined according to the definition of the ICH E2A guideline . Accordip-value were used. A P-value < 0.05 was regarded as being statistically significant.Data was captured into computer using an entry program developed with CSPro version 6.3.2 software package. All questionnaires were entered twice; that is 100% verification was done to eliminate keying errors during entry. Data was edited during and after data entry using CSPro and Statistical Package for Social Science version 20 (SPSS-20). Both descriptive and analytical analysis was carried out on the data using SPSS. Both univariate and multivariate analysis were carried out to measure the association of some potential risk factors and ADRs. Results were presented as percentage and frequencies as appropriate. To test statistical significance, 95% confidence intervals and/or Three hundred and nine (309) patients, 64.1% females and 35.9% males, were included in this study  of these patients were females while 66 (59.5%) were males. 44.3% of them experienced at least three ADRs with similar male to female ratio. Of these, 29.8% were found to be serious. Gastrointestinal upset (19.5%) were the most frequently reported ADR followed by non-specific symptoms (11.2%), hypersensitivity reactions (10%) and lipodystrophy (9.8%) . Those with CD4 count below 200 were about six times more likely to face ADRs compared to those with higher CD4 count , and those patients with CD4 count between 200 and 349 were also about five times more likely to develop ADRs  compared to patients with CD4 count above 349. In the regression model patients with age (35–44 years old), female gender, lower baseline body weight, and co-morbidities were tested to have statistically insignificant impact (Table p = 0.002 < 0.05). Therefore the model correctly predicts the ADR status of the patients (69.6%).Patients with CD4 count, below 200 cells/mm3, and between 200 and 348 had a statistically higher occurrence of ADRs, 65.5 and 67.9%, respectively, , while the rest occurred after 3 years (58.5%).Most of the reactions were associated with Stavudine and Zidoudine containing HAART with 75.2 and 67.5% respectively. Tenofovir and Nevirapine were similar in bringing ADRs with 54.1 and 53.5% respectively. Lamivudine is the least offending drug with 46.8%.The causal relationship that was assessed using Naranjo probability scale in majority of the suspected adverse drug reactions cases was found to be possible 393/420.  were not documented in the patients’ clinical cards and thus their contribution to ADR prevalence was left unmeasured. Furthermore, co-morbidity types were not captured by our questionnaire as it lacked to address this. In addition, the findings are from a small size and from one referral hospital, hence a bigger study needs to be conducted to solidify these findings.The findings in this study have proven that ART associated ADRs are highly prevalent and are threatening the adherence level that is much needed to ensure maximum benefit from these medications. The drugs as well as the risk factors that are mostly associated with ADR occurrence found in this study should help health professionals at all levels to foresee, identify and minimize ADR at the earliest possible time as well as to understand the need for close follow up and monitoring to avoid the occurrence of serious ADRs.