Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT).Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups . Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes.In the D+R- patients, the median values of peak viral load  were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment . Median peak viral load increased significantly  in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup.Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system. Cytomegalovirus (HCMV) is an important opportunistic pathogen in solid organ transplant (SOT) patients. In recipients who are HCMV IgG seronegative (R-), primary infection may be transmitted from a seropositive donor (D+). In recipients who are seropositive (R+) for HCMV, the virus may reactivate once they are given immunosuppressive drugs. In addition, a seropositive donor may re-infect a seropositive recipient with a new strain of HCMV. In the pPre-emptive therapy is used at our institution and provides useful information on the natural history of HCMV. The peakFor the current report, we focused on the D+R- subgroup of SOT patients at risk of acquiring primary HCMV infection. To control HCMV replication, these patients must mount an immune response to a new antigen while receiving immunosuppressive drugs. Under the strategy of prophylaxis, the antiviral activity of valganciclovir would be expected to additionally reduce antigen presentation. Thus, potent antiviral drugs given from the time of transplant might impair the ability of the immune system to go through the multiple rounds of cell division required to select high affinity T-cell and B-cell lymphocytes able to control HCMV replication. This could explain why some patients get end-organ disease once prophylaxis is stopped. In contrUntil July 2012, pre-emptive therapy was initiated at a viral load of 3000 genomes/ml in all of our patients. the rapiThe objective was to audit the results of this change for patients transplanted up to 30 June 2015 to determine if biomarkers of viral load were reduced in the D+R- subset, compared to the D+R- subset in the earlier cohort. Because the protocol was not changed for the D+R+ and D-R+ subgroups, we hypothesised that their viral load parameters would remain similar to those reported previously.Patients undergoing HCMV surveillance because of allogeneic transplantation of a kidney or liver were studied in a single institution. Our strategy for HCMV surveillance is described elsewhere. Briefly,Up until 1 July 2012, pre-emptive therapy was started in any patient whose viral load was equal to or greater than 3000 genomes/ml. On this date, the protocol was changed so that patients in the D+R- subset were treated when their first PCR positive result was obtained, irrespective of its value. To facilitate prompt initiation of pre-emptive therapy, D+R- patients who were due to be discharged home without having become PCR positive were given a 5-day supply of valganciclovir to be taken only if a member of the transplant team telephoned to say that they had become viraemic. In addition to the routine reporting of PCR results through the hospital’s pathology computer, laboratory staff sent an email to clinical transplant teams when a D+R- patient first had a positive PCR result. Treatment was stopped when two consecutive PCR tests reported that HCMV DNA was undetectable as long as at least 21 days of treatment had been received. The cut-off of 3000 genomes/ml was retained for initiating pre-emptive therapy in the remaining patient subgroups.For all patients, both before and after the change in protocol, episodes of viraemia that occurred after completion of treatment of the initial episode were only treated if the viral load exceeded 3000 genomes/ml.The real time PCR method used a Taqman probe and the ABI7700 thermal cycler as described elsewhere and was used to monitor all patients in both time periods. The valuHCMV viraemia was defined as detection of HCMV DNA in whole blood above the assay cut-off (200 genomes/mL). The duration of viraemia was defined as the total number of days on which HCMV DNA was detected, including repeated episodes of viraemia in the same patient. A repeat episode of viraemia was defined as the presence of HCMV DNA in whole blood detectable following the resolution of a previous episode as documented by two consecutive negative samples. Peak viral load was calculated as the highest recorded HCMV value in an individual patient. HCMV end organ disease was defined using internationally agreed criteria including histological demonstration of inclusion bodies and/or positivity for HCMV proteins by immunostaining, with the exception of HCMV retinitis which was diagnosed ophthalmologically. DurationThe primary outcome was to assess the impact of the new protocol on 3 parameters , in the D+R- transplant subgroup before and after the change in antiviral protocol. Differences between peak viral loads were assessed by Student’s unpaired t-test, because the data were normally distributed. Differences between median durations of viraemia and treatment were assessed by Mann-Whitney U test to allow for their non-parametric distribution.The secondary outcome was the proportion of D+R- patients who had episodes of recurrent viraemia assessed using the chi-squared test. In addition, comparison of the viral outcomes between the two time periods in the D-R+ and D+R+ groups were performed. As there were no changes to the protocol in these two groups, these analyses served to rule out other changes occurring over calendar time between the two protocol periods.Post-hoc analysis of the proportion of patients who developed HCMV viraemia in the 3 transplant subgroups divided by organ was performed using the two-sided chi-squared test. Comparisons of the viral parameters between the 3 patient subgroups were performed with a one way ANOVA for peak viral load and Kruskal Wallis test for durations of viraemia and treatment.For all analyses, no allowance was made for multiple comparisons and a two-sided p-value <0.05 was nominally considered as evidence of a statistically significant difference.This audit of clinical data was intended to determine if the currently used clinical protocol was working as expected as part of a quality assurance and quality improvement process. In accordance with current UK guidelines, ethical approval was not required because this audit includes only retrospective analysis of results collected for clinical management and all treatment decisions pre-dated the analysis of data. The resuWe describe the viral load parameters of a total of 960 solid organ transplant recipients, transplanted between 1989–2015, before (n = 566) and after (n = 394) a change in treatment protocol for the D+R- patients  and 534 renal . Treatment for the D+R+ and D-R+ patients remained the same throughout. The five most common indications for renal transplant before the change in protocol were diabetes, autoimmune renal disease, IgA nephropathy, idiopathic and adult polycystic renal disease. After the change in protocol these were similar: diabetes, autoimmune renal disease, IgA nephropathy, adult polycystic renal disease and idiopathic. The five most common indications for liver transplant before the change in protocol were hepatitis C, alcoholic liver disease, primary biliary cirrhosis, acute liver failure and primary sclerosing cholangitis. After the change in protocol they were similar: hepatitis C, alcoholic liver disease, acute liver failure, primary sclerosing cholangitis and non-alcoholic steatohepatitis.The HCMV-related characteristics of the patient groups transplanted in the two time periods were similar .When followed up to 12 months post-transplant under the new protocol, there were no deaths in the D+R- renal patients, none had to return to dialysis, none had HCMV end-organ disease and one had HCMV syndrome. The corresponding figures for the D+R- liver transplant patients were 3 deaths , one case of HCMV end-organ disease and no cases of HCMV syndrome.13/17 of the viraemic D+R- renal and 18/32 D+R- liver transplant patients treated under the new protocol had viral loads of less than 3000 genomes/ml at initiation of treatment; these viral loads would have been too low to trigger pre-emptive therapy under the previous protocol. The remaining viraemic patients with initial viral loads more than 3000 genomes/ml would have been immediately treated under either protocol. The median viral load on initiation of antivirals for D+R- patients under the new protocol was 1957 (range 216 to 97551 genomes/ml), compared to 11476 (range 3063–128066 genomes/ml) under the previous protocol.There was a significant reduction for the D+R- subgroup under the new protocol where the median of the peak viral load fell from 30,774 genomes/ml to 11,135 genomes/ml , with medians of D+R- 36 days, D+R+ 15 days and D-R+ 11 days.Panels D-F of Significant differences in median duration of treatment were seen between the three subgroups , a non-significant increase compared to 33/58 (57%) under the previous protocol (p = 0.0743). Under the new protocol, 26/49 (53%) developed subsequent levels of viraemia high enough to warrant treatment, compared to 16/58 (27%) under the previous protocol (P = 0.0072)Among those who had subsequent episodes of viraemia, the peak viral loads in the first peak were not significantly different (p = 0.9) when compared to those in subsequent episodes of viraemia . PreviouWe describe the viral load parameters of a total of 960 kidney and liver transplant recipients, before (n = 566) and after (n = 394) a change in treatment protocol for the D+R- patients where treatment for the D+R+ and D-R+ patients remained the same throughout. The change from old to new protocol led to a numerical reduction for all 3 parameters of viral replication in the D+R- patients: 44 to 36 days for days viraemia, 54 to 49 days for days of treatment, and 30,774 to 11,135 genomes/ml for peak viral load, but only the peak viral load changes were statistically significant . It should be noted that these later episodes are usually smaller than the initial episode so that the peak level is usually derived from the initial episode of viral load.The remaining patient subgroups were examined in the expectation that no such reduction would be seen, which would act as a control for unrecognised changes in immunosuppression as an explanation for any reduced viral load in the D+R- patients. In practice, there was a significant increase in the peak viral load for the D+R+ subgroup. While this difference remains unexplained and could represent a Type I error, it remains unlikely that the reduction in peak viral load seen in the D+R- patients was due to altered patient management.The hierarchy of risk for HCMV viral load parameters and risk of end-organ disease has consistently been reported as D+R-, D+R+ and D-R+ in the published literature., 6 We noGiven the theories of antigen presentation in pre-emptive versus prophylactic treatment in altering the natural history of HCMV disease, we were interested to see whether earlier initiation of pre-emptive therapy still provided sufficient antigen presentation to the immune system so that the number of future episodes of viraemia was not increased. In fact, we saw an increase in the proportion of patients developing subsequent episodes of viraemia, from 33/58(57%) to 36/49(73%) of patients, p = 0.0743, and in the proportion requiring treatment  although there was no change in the overall duration of viraemia or treatment needed. We interpret these results in terms of the antigenic stimulation provided to the immune system and future studies should address this hypothesis by enumerating T-cell and B-cell responses directly. If this hypothesis is confirmed, it would mean that the amount of antigenic stimulus provided to the naïve immune system of a seronegative recipient should not be reduced any further by attempting to initiate pre-emptive therapy at levels of viraemia lower than those employed here. For example, use of a more sensitive PCR method to screen and detect very low levels of viraemia in D+R- transplant patients might provide a paradoxical disadvantage to them in terms of ultimate immune control of HCMV. Given all these results, we will continue to deploy the new protocol to gain more information about the natural history of HCMV and how this could be modified for potential patient benefit. The results also illustrate the potential for evaluating prototype vaccines against HCMV for their ability to prevent second episodes of viraemia in D+R- patients managed with pre-emptive therapy.S1 File(XLSX)Click here for additional data file.


Schistosoma sp. infection has been shown to interact with HIV-1 by modifying susceptibility to the virus and impacting AIDS outcome, but very little is known about the potential impact of Schistosoma sp. infection on the efficiency of antiretroviral treatment (ART) in HIV-1 infected individuals. One study suggested increased immunological failure in patients infected with schistosomes compared to those uninfected. To our knowledge, no report exists on the virological response to ART in schistosome-infected individuals. In addition, viral load in HIV-1 infected individuals changes over the course of the HIV infection. This study assessed the impact of HIV-1/Schistosoma sp. co-infections on viral load in people with immunological failure on ART, taking into account the duration of HIV-1 infection.3 after 1 year of ART). Patients were also tested for schistosome infection by microscopy for ova in urine and stool and by circulating anodic antigen (CAA) levels in serum. The duration of HIV-1 infection was calculated using baseline CD4+ T-cell (CD4) counts determined at enrollment. Univariable and multivariable analyses were conducted to compare viral loads in schistosome infected and uninfected patients.We enrolled HIV-1 infected Tanzanian adults over 18 years of age who had used first line ART for more than 6 months and were identified to have immunological failure by the WHO criteria (50% drop from peak CD4 count, or CD4 count equal to or below baseline after 6 months of ART, or CD4 count below 100cells/mmA total of 188 patients were enrolled. After univariable analysis, female sex, lower peak CD4 counts, lower current CD4 counts, anemia, and shorter time infected with HIV-1 were all significantly associated with higher viral load. Schistosome infection was not associated with viral load even after adjusting for sex, current CD4 counts and duration of HIV-1 infection.The current study of HIV-infected patients with immunological failure on ART suggests that once ART is introduced, ART is the dominant driver of viral load and schistosome infection may no longer have an impact. Schistosoma sp. and HIV are co-endemic globally and an estimated 6 million individuals are co-infected worldwide  years, which is similar to what was found using HIV surveillance data .We modeled decay by the square-root function , which mImmunological failure was defined as either a confirmed 50% drop from peak CD4 count (if known) during current treatment or as a CD4 count equal to or below baseline after 6-months of ART, or as a CD4 count below 100cells/mm3 after 1 year of ART as per WHO guidelines . Poor ARFrom August to December 2014, we screened 237 outpatients who were diagnosed with immunological treatment failure while using first-line ART. Of these, 31 were using a stavudine-containing regimen, 10 had been on ART for less than 6 months, 6 did not want to participate in the study, and viral load testing failed on 5 patients. Thus we enrolled and analyzed data from a total of 188 patients.p = 0.005). 79/188 (42.0%) of patients had > 1000 viral copies/mL. Among those with viral loads < 1000 copies/mL, 94 (86.2%) were virologically suppressed with viral loads < 20 copies/mL. 85/173 (49.1%) had either a microscopy positive test or a positive CAA test for Schistosoma sp. (Table The median age was 41.0 [36.0–46.5] years and 116 (61.7%) of participants were female. The majority of participants resided in urban areas , were employed and selling food , and had completed only primary education . 63/87 (72%) of anemic patients were female .These results need to be considered in light of some limitations. The study included only people with immunological failure, implying that our cohort has overall low CD4 count and thus high viral loads. In addition, as immunological failure is also associated with specific host and viral genetics , 39, ourIn conclusion, our study suggests that schistosome infection does not impact viral load in HIV-1 infected patients immunologically failing on ART, likely due to the major effects of ART on viral load once ART is initiated.


HIV with HBV co-infection can result in greater HIV-related immunosuppression, morbidity and mortality. Currently, there are few studies to evaluate direct treatment effects on mortality and attrition rates between first-line antiretroviral therapy (ART) based-on tenofovir (TDF) and/or lamivudine (3TC) in a real-world setting. We used Cox proportional hazard models to evaluate direct treatment effects of the first-line ART containing stavudine (d4T), azidothymidine (AZT) and TDF on death and attrition among HIV patients with HBV coinfection. A total of 3912 patients met study eligibility criteria. The overall mortality rate and attrition rate was 2.85 (95% CI: 2.55–3.16) and 8.87 (95% CI: 8.32–9.41) per 100 person-years, respectively. The ART containing TDF had a significantly lower risk of death  when compared to the ART containing d4T, but the risk of death was not significantly different when compared to the ART containing AZT . Patients with HIV/HBV coinfection receiving the ART containing TDF had significantly lower risk rates of attrition compared to those receiving the ART containing d4T  or AZT . Compared with the ART containing d4T, the ART containing AZT was significant and not significant associated with a lower risk of death and attrition, respectively. The ART containing TDF had significant effects on both of death and attrition among HIV patients with HBV coinfection. Most developing countries have now initiated ART treatment programs, with countries such as South Africa and Brazil being the earliest adopters, many of these programs were scaled-up after the 2003 recommendation of the Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO) “Three by Five” initiative5. One such program was China’s National Free Antiretroviral Treatment Program (NFATP) which began as a pilot in the early 2000s, and was scaled-up in 20037. By the end of 2016, a total of 489,411 HIV patients across the China were receiving free antiretroviral treatment8. Many observational cohort studies have found that the NFATP has successfully increased life expectancy, decreased AIDS-related morbidity and mortality, and had significant effects on viral suppression, drug resistance and treatment for HIV prevention among Chinese HIV patients17. As of 2017, there are an estimated 21 million HIV patients receiving antiretroviral therapy worldwide, enabling them the opportunity to live full and productive lives18.Since 1996, the availability of combination antiretroviral therapy (ART) has dramatically reduced HIV-related mortality and morbidity and improved the quality of life for patients20. Due to HIV and HBV sharing similar pathways of transmission, many people living with HIV are co-infected with HBV, many of whom reside in Asian countries such as China22. HIV and HBV co-infection can greatly increase HIV-related immunosuppression, morbidity and mortality relative to either infection alone. The nucleoside reverse transcriptase inhibitors such as 3TC and TDF are effective for treatment of both HIV and HBV20. The World Health Organization (WHO) recommends initiation of ART for HIV/HBV co-infected patients and the NFATP recommended to switch the first-line regimen from didanosine to 3TC in 200824. After that, the first-line regimens were AZT/d4T + 3TC + NVP in China. Patients with HBV treated only with 3TC quickly develop resistance so TDF is typically given in combination26. In 2012, TDF/AZT + 3TC + EFV/NVP regimens were introduced as the first-line treatments of the NFATP24. Patients with HIV and HBV coinfection treated with antiretroviral therapy containing TDF/3TC demonstrated the safety and effectiveness of the regimen29. However, there are currently few studies to investigate associations between ART based-on TDF and/or 3TC with direct treatment effects. We used the NFATP database from China to evaluate treatment effects of the ART containing D4T (d4T + 3TC + NVP), AZT (AZT + 3TC + EFV/NVP) and TDF (TDF + 3TC + EFV/NVP) on death and attrition among patients co-infected with HIV/HBV in an observational cohort study.HIV and hepatitis B virus (HBV) infection is estimated at 35 million and 400 million worldwide respectivelyA total of 41,071 patients with HIV initiated combination antiretroviral therapy between 2010 and 2014 in Guangxi, China. Many patients  were excluded due to no HBV infection , no HBV testing results , lack of follow-up data (5 patients had no follow up besides baseline visit), being less than 18 years old (82), and not initiating a standard first-line treatment regimen (377). A total of 3,912 patients met study eligibility criteria and entered this observational cohort study analysis among patients with HIV/HBV coinfection.Table Among all study patients, 315 deaths occurred, 253 patients stopped ART, and 726 patients were lost to follow-up. A total of 11042.40 person-years were followed. The overall mortality rate was 2.85  per 100 person-years among all study patients. The mortality rate was 4.42(95% CI: 3.50–5.34), 2.44 (95% CI: 1.95–2.93) and 2.58 (95% CI: 2.16–2.99) per 100 person-years among all study patients initiating ART containing D4T, AZT and TDF, respectively  per 100 person-years among all study patients. The attrition rate among all study patients initiating the ART containing D4T, AZT, and TDF was 9.31(95% CI: 7.98–10.64), 10.14(95% CI: 9.14–11.14) and 7.84 (95% CI: 7.12–8.57) per 100 person-years respectively  and AZT (AZT + 3TC + EFV/NVP) in our study. In China, initial ART regimens include 3TC as it is effective against both HIV and HBV. Our study findings also support reports that suggest the use of 3TC as a backbone of cART (combination ART) when treating patients with HIV who also test positive for HBsAg31.In this observational cohort study, we found the overall mortality rate was 2.85 per 100 person-years among patients with HIV/HBV coinfection starting ART between 2010 and 2014 in Guangxi, China. The low mortality rate in our study was comparable to treatment effects seen in other developing and developed countries32. TDF entered the antiretroviral market in 2002, which is a safe, efficacious, and cost-effective alternative to AZT and d4T-based ART regimens33. TDF was active against HBV and an important component of HBV suppressive ART which alone seems to lower HBV DNA as effectively as 3TC + TDF26. Currently, the WHO recommends HBV/HIV co-infected patients start an ART regimen containing TDF and China’s NFATP uses TDF + 3TC + EFV/NVP as the current initial first-line regimens24. Compared with the ART containing D4T in our study, the ART containing AZT was significant associated with lower death. This study results support China’s NFATP to remove D4T due to side effects and efficacious24. Prior to this study, there was no observational data to support these recommendations in a real-world cohort.Our large observational cohort study found that the ART containing TDF (TDF + 3TC + EFV/NVP) was significant associated with lower mortality risk among patients with HIV/HBV coinfection. The comparison with AZT-containing regimens shows a reduction in the mortality risk although it is not statistically significant. Previous studies have not reported such a direct effect of TDF-based regimens on mortality amongst patients with HBV/HIV co-infection35. Compared with the ART containing D4T (d4T + 3TC + NVP) and AZT (AZT + 3TC + EFV/NVP), the ART containing TDF (TDF + 3TC + EFV/NVP) was associated with lower attrition risk among patients with HIV/HBV coinfection in this study. TDF has replaced both D4T and AZT in China, due to its more favorable toxicity profile, dosing, and cost-effectiveness24. The D4T regiment has salient side effects which can affect treatment outcomes. These findings also provide additional evidence to strongly support China’s NFATP initiating TDF + 3TC + EFV/NVP among all HBV/HIV co-infected individuals since 2012, as advised by WHO guidelines24. Considering moderate attrition, it is essential that adherence is promoted amongst patients with HIV/HBV and physicians providing HIV care and ART receive comprehensive education and training to further improve clinical outcomes.Our study showed the overall attrition rate was 8.87 per 100 person-years among all study patients, which was higher than that in high-income settings, but lower than that in other low-income settingsOur results should be interpreted within the limitations of this observational cohort study. First, selection bias of study participants in this cohort study may have been an issue, although we used the adjusted models to control for potential confounders. Due to our study did not include HIV diagnosed individuals but did not initiate ART, it is possible that individuals with poorer health-seeking behaviors were underrepresented in the study. Second, HBV infection was tested using an HBsAg ELISA which may not represent active HBV status. This definition could lead to overestimation of HBV infection, which may reduce statistical significance. Third, patients who were lost to follow-up might have different treatment outcomes compared to patients who remained in the study, such as high mortality and viral load rebound due to stop ART treatment. Fourth, due to this cohort study being conducted in Guangxi, study results might not be fully representative of China or other countries providing ART.36. Based on comprehensively considering different mortality and attrition rate among HIV patients received the ART containing D4T, AZT and TDF (TDF + 3TC + EFV/NVP). We believe these findings demonstrating the utility of ART regimens containing TDF in a prospective observational cohort in China and will help optimize first-line antiretroviral therapy among patients with HIV/HBV coinfection in China and other countries.In conclusion, this is the first large-scale observational cohort study in a low- or middle-income countries to assess the effects of initial ART regimen on death and attrition in HIV patients with HBV coinfection. China aims to achieve the UNAIDS “90-90-90” target for significant reductions in HIV-related mortality and HIV new infection37.This observational cohort study was conducted in the Guangxi Zhuang Autonomous Region of southwest China. In 2016, Guangxi represented 10% of the total number of nationally reported HIV cases and this region has accumulated the third highest number of HIV cases reported in China. Heterosexual transmission was the main mode of transmission accounting for 93% of reported HIV cases in Guangxi24. Physicians administering the ART at the local hospitals manage case report forms at the time of initiating ART and follow-up at 0.5, 1, 2, 3 months, and every 3 months thereafter. The case report forms are uploaded into a web-based database hosted by China Centre for Disease Control (China CDC). Eligibility criteria for this study included: (1) HIV patients that were over 18 years old; (2) had positive HBV surface antigen results at the time of ART initiation; (3) initiated free first-line ART between 2010 and 2014; and (4) provided informed consent. The NFATP treatment criterion since 2010 requires at least one of the following: (1) WHO disease stage 3 or 4 (CD4 count of ≤350 cells/μL); (2) willingness to receive ART irrespective of other criterion, such as high CD4 count when initiating ART24. In China, the first-line regimens of AZT/d4T + 3TC + NVP were changed to TDF/AZT + 3TC + EFV/NVP in 2012, as recommended by WHO24. This study was approved by the institutional review board of the Guangxi Center for Disease Control and Prevention. All research methods in this study were carried out in accordance with the approved guidelines.Patients with HIV/HBV co-infection from the NFATP database were collected from 2010 to 2016, the characteristics of this database have been previously described3) before ART, WHO clinic stage before ART, initial ART regimen, current ART regimen, year of ART initiation). Follow-up characteristics were evaluated at every 3-months and included death or attrition. Variables collected at each follow-up included transferals to another clinic, cessation of ART, loss to follow-up, duration of ART, and survival status, which were obtained from hospital records or having clinic doctors’ call family members to inquire about death. HBV infection was defined as positive serum samples for Hepatitis B surface antigen (HBsAg) which was tested using an HBV ELISA. Samples were tested for antibodies to HCV by ELISA6.The NFATP observational cohort study included baseline and follow-up characteristics. Baseline characteristics included demographic variables  and clinic variables , the first-line ART containing AZT (AZT + 3TC + EFV/NVP) and the first-line ART containing TDF (TDF + 3TC + EFV/NVP). We used Cox proportional hazard models to evaluate treatment effects of initial ART regimen on death and attrition , respectively. Competing risks for cause-specific hazard models were censored accordingly [9.10]. The adjusted models were used to control for potential bias. The following covariates of the adjusted model were included demographic variables  and clinic variables . And then, the adjusted model for sub-group analysis of death and attrition was used to compare the ART containing AZT with the ART containing TDF, respectively. A two-sided p-value less than 0.05 was regarded as statistically significant for all analyses. We did the analyses with Statistical Analysis System .


The World Health Organization recommends rapid (≤ 7 days) or same-day initiation of antiretroviral treatment (ART) for HIV-positive patients. South Africa adopted this recommendation in 2017, but multiple clinic visits, long waiting times, and delays for laboratory tests remain common. Streamlined approaches to same-day initiation that allow the majority of patients to start ART immediately, while ensuring that patients who do require additional services receive them, are needed to achieve national and international treatment program goals.The SLATE II (Simplified Algorithm for Treatment Eligibility) study is an individually randomized evaluation of a clinical algorithm to reliably determine a patient’s eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. It differs from the earlier SLATE I study in management of patients with symptoms of tuberculosis (under SLATE II these patients may be started on ART immediately) and other criteria for immediate initiation. SLATE II will randomize (1:1) 600 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa. Patients randomized to the standard arm will receive standard-of-care ART initiation from clinic staff. Patients randomized to the intervention arm will be administered a symptom report, medical history, brief physical exam, and readiness assessment. Symptomatic patients will also have a tuberculosis (TB) module with lipoarabinomannan antigen of mycobacteria test. Patients who have satisfactory results for all four components will be dispensed antiretrovirals (ARVs) immediately, at the same clinic visit. Patients who have any negative results will be referred for further investigation, care, counseling, tests, or other services prior to being dispensed ARVs. Follow-up will be by passive medical record review. The primary outcomes will be ART initiation in  ≤ 7 days and retention in care 8 months after study enrollment.SLATE II improves upon the SLATE I study by reducing the number of reasons for delaying ART initiation and allowing more patients with TB symptoms to start ART on the day of diagnosis. If successful, SLATE II will provide a simple and streamlined approach that can readily be adopted in other settings without investment in additional technology.NCT03315013. Registered on 19 October 2017.ClinicalTrials.gov, The online version of this article (10.1186/s13063-018-2928-5) contains supplementary material, which is available to authorized users. In its 2017 revision of the global guidelines for HIV care and treatment, the World Health Organization (WHO) called for rapid or same-day initiation of antiretroviral treatment (ART) for eligible patients testing positive for HIV, with rapid initiation defined as starting treatment within 7 days of diagnosis  and KenyThe WHO’s justification for its recommendation was to increase the number of patients starting ART, in particular by reducing loss to care between diagnosis and treatment initiation . In manyWe previously conducted two studies on same-day treatment initiation in South Africa. The first was the RapIT trial, which relied on point-of-care test instruments to determine patient eligibility under the prevailing CD4 count threshold. RapIT demonstrated that offering same-day initiation could meaningfully increase uptake of ART and viral suppression , but theEnrollment for SLATE I was completed in July 2017 in South Africa and April 2018 in Kenya. While follow-up to primary outcomes for that study is still underway, the baseline results indicated a number of potential improvements to the original algorithm. Most important, under SLATE I, exactly half (149/298) of intervention arm patients in South Africa (and 40% in Kenya) were deemed not eligible for same-day initiation for one or more of the reasons mentioned above. Of the 149 South African patients not eligible, nearly three quarters , and 83% of ineligibles in Kenya, had at least one symptom of TB , with orOther aspects of the SLATE I algorithm that were identified as overly restrictive included screening patients out for any self-reported use of recreational drugs, any previous default from ART, or self-reported logistical barriers to maintaining adherence. Each of these criteria ended up screening out patients whom study clinicians believed could safely have been offered same-day initiation.SLATE I was designed to address the concerns of clinicians and program managers in 2015, when the algorithm was first proposed . In viewThe purpose of the SLATE II algorithm is to allow clinics to initiate ART in a streamlined, patient-centered way that minimizes the time required for both patients and staff, reduces loss to follow-up prior to treatment initiation, and increases the proportion of patients who are eligible for same-day initiation. For those who would benefit from additional care or support, the algorithm remains conservative in referring these patients back to standard care, where additional services can be provided.SLATE II is an individually randomized, non-blinded, pragmatic evaluation of the effect of the revised SLATE algorithm on ART initiation and retention in care compared to routine standard care, conducted at primary health clinics in South Africa. Many of the procedures are identical to those in SLATE I, which is described in detail elsewhere . Here weLike SLATE I, SLATE II tests a clinical algorithm that streamlines and structures the information required from patients before ARVs are dispensed for the first time. The algorithm consists of four “screens”: symptom report, medical history, brief physical examination, and readiness assessment. Patients who “screen in”—have satisfactory responses to all four screens—can then be dispensed ARV medications on the spot, without any further steps or delays. Initiation of ART immediately after completing the four SLATE screens, without any further services required, is labeled “immediate” initiation in this study. Patients who screen out, i.e., have at least one unsatisfactory response on a screen, are referred for further services, such as a laboratory test, more intensive physical examination, or counseling, before ARVs are dispensed.Table The most important difference between the SLATE II and SLATE I algorithms concerns the detection of tuberculosis. As explained above, a large proportion of SLATE I patients who would otherwise have been eligible for immediate ART initiation screened out due to the presence of TB symptoms and the fear that starting ART in patients with active TB would cause unmasking of immune reconstitution inflammatory syndrome (IRIS) , 14. VerAs described in the shaded boxes in Fig. In addition to having a LAM test, symptomatic patients are also asked in-depth questions about the duration and severity of their symptoms, and concerns are investigated during the physical exam. Any patient with a positive LAM test, TB symptoms that are severe or of long duration, or other clinical indications of TB is screened out and referred back to standard care for further TB testing. Patients who have negative LAM results and milder symptoms are not screened out due to TB but are given an information card about TB that reminds them to return to the clinic right away if their TB symptoms worsen or new symptoms appear.Mycobacterium tuberculosis (MTB)/resistance to rifampicin (RIF) testing are available electronically the next day, though it is typically several days before clinics receive and record these results. For SLATE II intervention arm patients, study staff access the electronic NHLS portal the next working morning to check results. Any patient with a positive test is then contacted by study or clinic staff  and asked to return to the clinic to initiate TB treatment as soon as possible.After completing all four SLATE II screens, all intervention arm patients, symptomatic or not, are asked for a sputum sample for TB testing. In South Africa, samples are sent to a National Health Laboratory Service (NHLS) lab on the day they are provided, and results from Xpert SLATE II has two primary outcomes. For primary outcome 1, we will estimate the proportion of patients in each arm (baseline and intervention) who initiate ART within 7 days of study enrollment. SLATE I allowed up to 28 days to achieve this outcome, but current global and South African recommendations both call for initiation within 1 week of a patient’s first clinic visit. A patient who has not initiated within 7 days will be regarded as failing to achieve this primary outcome. Secondary outcomes, as described below, will also allow proportions of patients initiating ART at any interval after study enrollment to be assessed.and are alive, in care, and retained on ART 8 months after study enrollment. Eight months was selected for SLATE I to allow up to 1 month to initiate ART, 6 months of follow-up after treatment initiation, and up to 1 month to return for the 6 months routine clinic visit. We retained the full 8-month period for SLATE II to allow comparison of results between the two studies.For primary outcome 2, we will estimate the proportion of all patients in each arm who initiate ART within one month (28 days) Although viral suppression is preferable to retention in care as a measure of ART success, we are not confident that all the study sites will consistently perform routine viral load tests at 6 months, and viral suppression will be considered as a secondary outcome. To allow for the irregularity of clinic visits, we will allow any clinic visit between 5 and 7 months after treatment initiation  to represent the 6 months visit. Other secondary outcomes are described in Table Study patients will be randomized 1:1, using block randomization in blocks of six, to the intervention arm or standard care arm. Blinding is not possible in a pragmatic evaluation such as SLATE, as each arm will follow very different procedures post-randomization.SLATE II is powered on the first primary outcome (initiation within 7 days) but will allow enrollment to increase as needed to achieve the first secondary outcome (initiation within 14 days for TB suspects). Using results of the SLATE I study and conservatively assuming that time to initiation will decrease under standard care in response to the new WHO and South African guidelines mentioned above, we estimate that 60% of treatment-eligible patients will be initiated on ART within 7 days in the standard arm, and we consider an increase to 75% to be programmatically important. Using an α of 0.05, power of 90%, 1:1 randomization, and an uncorrected Fisher’s exact test will require a minimum sample size of 200 patients per arm. We increased our total sample size to 600 to ensure sufficient power if our estimate for the standard group is too low and to allow stratification in the analysis.2RO) of the University of Witwatersrand, the study will employ at each site a Public Health Nurse; this is the professional cadre that initiates patients onto ART in South Africa. Study nurses will be trained on study procedures but have no additional clinical training or qualifications beyond what is typical in routine clinic settings. Each site will also have two study assistants, who will be responsible for screening for study eligibility, obtaining informed consent, administering the baseline questionnaire, and performing other non-clinical tasks.SLATE II will be conducted in the same three public sector clinics in Gauteng Province of South Africa as was done in SLATE I. All three serve urban informal settlements typical of peri-urban settings. Under our local partner, the Health Economics and Epidemiology Research Office  who have tested positive for HIV, either at the current clinic visit or previously, and have not yet initiated ART. Pregnant women will be excluded, as procedures for initiating and managing pregnant women on ART differ from those for non-pregnant adults. Patients who intend to receive further HIV care at a different clinic rather than the study site will also be excluded, as will those who are determined by study staff to be physically, mentally, or emotionally unable to consent. We note that these study eligibility criteria will allow enrollment of patients at varying points in the HIV care cascade. Some will be enrolled a few moments after having their first positive HIV test, while others will have been aware of their HIV status and potentially attending pre-ART monitoring visits for several years. The study sample will thus reflect the full range of ART-eligible patients presenting at South African clinics.Site staff will refer patients with HIV to the study assistant for study screening and consent. Patients will be screened consecutively in the order in which they are referred. All patients who are found eligible for the study will be asked for written informed consent  and completed on tablet computers.For the primary analysis, the two main sources of study data will be case report forms (CRFs) and patients’ routine medical records. The SLATE CRF will be programmed in REDCap Mobile  will be made available in de-identified format following closure of the protocol in a publicly available repository, to be identified in papers published from the study. Data obtained from the study sites  will not be owned by the study and cannot be made publicly available by the authors.Our primary analysis will be an intention-to treat comparison of treatment initiation ≤ 7 days and retention at 8 months by study arm. We will first look for baseline differences between treatment arms in characteristics that predict the outcome to ensure baseline comparability. We will then compare the intervention to the standard arm as a simple comparison of proportions and calculate risk differences with corresponding 95% confidence intervals. If we identify any baseline imbalances, we will use adjusted log-binomial and linear regression models to control for any potential confounding.We will also look for absolute effect measure modification by important potential modifiers. The main modifier of interest for SLATE II is baseline TB symptoms. We will also look for modification by demographic and clinical characteristics , CD4 count, site). Our analysis for effect modification will use a simple stratification of the primary analysis by the potential modifier and report crude risk differences and risk ratios and their corresponding 95% confidence intervals.Analytic methods for secondary outcomes are described in Table We anticipate that the SLATE II study will have four main limitations. First, in order to reach the target sample size in the desired timeframe, there will be heterogeneity in the population enrolled, with some patients who have already made several pre-ART visits and others who were diagnosed with HIV on the day of study enrollment. Second, ART-eligible patients who visit the study clinics but are determined by study staff to be too emotionally distraught  or physically ill to be asked to participate in a study will be excluded, which may shift the study sample toward patients who are physically or emotionally healthier than the overall population. Third, by drawing blood samples for standard arm patients who would otherwise be too far back in the clinic queue, we are slightly enhancing standard care. We expect this to affect a very small number of patients, however, and the degree of enhancement is minimal. And fourth, as in most operational research studies, we will have little control over what happens in the non-intervention arm. With the advent of the recommendation of same-day initiation in November 2017 and the introduction of “fast track” initiation under the 2015 National Adherence Guidelines , 28, theWith global funding for HIV control plateauing  but the The SLATE II algorithm improves on SLATE I by attempting to distinguish between TB-symptomatic patients who do have TB and those who do not. The existing TB symptom screen is both non-sensitive and non-specific, resulting in delays in ART initiation for a large number of patients who do not have TB and failing to identify a small number of patients who do. SLATE II addresses these limitations with detailed questions and a LAM test for patients with symptoms and by requesting a sputum sample from all patients, regardless of symptoms. To minimize any risk of IRIS created by initiating mildly symptomatic patients on ART before TB test results are available, the study includes both additional information for symptomatic patients and active tracing of anyone with a positive TB test. SLATE II also allows immediate initiation for some categories of patients who automatically screened out under SLATE I but may be among those who can benefit most from same-day initiation, such as previous defaulters and those reporting logistical problems in making clinic visits.Like SLATE I, SLATE II has the potential to reduce the time and resources that both providers and patients must invest in ART initiation, while also diminishing the likelihood that patients will be lost from care between diagnosis and treatment initiation. If it can do so without jeopardizing outcomes after starting ART, then SLATE II will offer national HIV programs and providers an improved and easily adapted approach to an important component of HIV care.ClinicalTrials.gov NCT03315013, registered October 19, 2017,The trial status details are as follows: Protocol Version 1.0, October 5, 2017; enrollment start date March 14, 2018; enrollment completion date September 18, 2018. https://clinicaltrials.gov/ct2/show/NCT03315013.Additional file 1:SLATE II screens. (PDF 67 kb)Additional file 2:SLATE II protocol. (PDF 2300 kb)Additional file 3:Ethics approvals. (PDF 553 kb)Additional file 4:Informed consent form. (PDF 134 kb)Additional file 5:SPIRIT checklist. (PDF 507 kb)


Generic drugs may help to support antiretroviral treatment. We want to assess the efficacy and safety at 24 weeks of the change of coformulated (abacavir + lamivudine + dolutegravir) to (abacavir + lamivudine) coformulated as a generic pharmaceutical specialty + dolutegravir.® to a generic pharmaceutical specialty co-formulated tablet (abacavir + lamivudine) plus Tivicay® was made. Demographic, viroimmunological characteristics and the Charlson index were collected. Six months after switching, efficacy and safety were evaluated.Between February and June 2017, switch from TriumeqSwitch was made in 93 patients, with a mean age of 47 years, after six months there were five patients (5.4%) with viral loads between 50 and 400 copies, no patient had viral loads of greater amount. There were 2 interruptions due to toxicity (2.15%), in relation to symptoms of the central nervous system. There were no differences in the amount of years with HAART, nor in the previous months with the STR regimen based on abacavir + lamivudine + dolutegravir, nor in the Charlson index. The effective saving in 2017 derived from the change in these 93 patients was € 125.512.The change from a regimen of abacavir + lamivudine + dolutegravir seems to be safe and effective at 24 weeks. Highly active antiretroviral therapy (HAART) based on the combination of three drugs remains the model of treatment for HIV infection. To maintain the long-term efficacy of HAART, adequate adherence over time is required –3. SinglThe emergence of generic drugs in the Spanish market has posed a scenario in which it is possible to save costs at the expense of breaking STR regimes. In this context, the generic of abacavir + Lamivudine (ABC + 3TC) was commercialized in mid-2016. This allowed to have a regimen with ABC 600 mg + LMV 300 mg and dolutegravir (DTG) 50 mg more cost effective than ABC + 3TC + DTG in STR, which led to the possibility of modifying the treatment of patients undergoing treatment with the STR of ABC + 3TC + DTG to the combination of a generic pill of ABC + 3TC with a pill of dolutegravir. We report in this study the early experience (at 24 weeks) of the STR break of ABC + 3TC + DTG and its replacement by a two-tablet regimen based on a generic co-formulation of ABC 600 mg + 3TC 300 mg along with another DTG tablet 50 mg.A transversal retrospective analysis was made in order to examine the evolution 24 weeks after switching the antiretroviral treatment in Costa del Sol Hospital. This is a second level hospital in the southeast of Spain, with a reference population of about 400,000 inhabitants. A population of approximately 1000 patients infected with HIV is followed on a regular basis. In Spain, the economic cost of antiretroviral treatment against HIV is fully borne by the Public Health System, so that antiretroviral medication is only dispensed in hospital pharmacies. In February 2017, a systematic switch was made to the HAART of those patients under treatment with the ABC + 3TC + DTG STR to the combination of a generic co-formulation of ABC + 3TC together with another DTG tablet. Once the change was decided, it was agreed that, at the next medical visit, the prescription of the STR regimen would be changed to 2 tablets. In the Pharmacy Service, the Pharmacist reinforced the information that the doctor had given to the patient, explaining the change of HAART consisting of the modification of the number of tablets maintaining the same combination of active ingredients. In the next visit to the Pharmacy Service after the change of HAART it was verified that the patient was taking the medication correctly, as well as the absence of incidents related to it.Since then, the prescriptions of ABC 600 mg + 3TC 300 mg + DTG 50 mg have been administered in a two-tablet regimen. Clinical follow-up did not change after the modification of the regimen, but there was a specific follow-up by the Pharmacy area.The cost of the combination of ABC + 3TC + DTG after the break of the STR tablet is 25% cheaper than the STR. For each patient, the number of days from the change in treatment to December 31, 2017 has been calculated and multiplied by the cost difference between the two alternatives. The sum of this cost difference is the total saving since the measure began to be implemented until December 31, 2017.The demographic and viroimmunological variables were extracted from the electronic records of the hospital, while the start data of the different antiretroviral treatments were extracted from the pharmacy’s computer system. The records were only made available to the authors. Quantitative data are shown as mean and 95% CI, and qualitative variables as percentages. SPSS 20.0 was used to analyse data.Between February and May 2017, we proceeded to change from the STR ABC + 3TC + DTG to the generic co-formulation of ABC + 3TC together with another DTG tablet in 93 patients. The mean age was 47 years (95% CI: 45–49), with 76% of males. The level of studies was of secondary in 75%, university students in 10% and the rest with elementary studies. The mean of the Charlson index was 1.76 (95% CI: 1.23–2.30) and that of the infection age of 12.33 years (95% CI: 10.53–14.12). 48% were men who had sex with men, 34% heterosexuals and 16% intravenous drug users. 29% had suffered an AIDS event throughout the course of their disease and a quarter had suffered an AIDS event.The mean time using HAART was 9.6 years (95% CI: 8.14–11.11), and the median number of previous ART was 1, with a median of viral failures of 0 (range: 0–2) and a median of changes due to toxicity of 1. Near 40% of patients had active smoking, 7.5% had active alcohol consumption and 5% had active drug use. 55% did not take other mediations besides ART, while 16% took statins (the most common medication after ARVs), 11% ACE inhibitors and 10% antidepressants. The most frequent comorbidities were depression and dyslipidemia (both with 11.8%), followed by High Blood Pressure (10.8%).At the time of the change, two patients (2.2%) had viral loads between 50 and 400 copies/mL, while at 24 weeks of the change, 5 (5.4%) had viral loads between 50 and 400 copies/mL, one of these patients was detectable at the time of treatment change. Specifically, they presented values of 65, 92, 103, 118 and 259 copies/mL. Treatment was not changed in any case, remanining all of them undetectable in the next control (week 28). In the case of these patients, there were no differences in the CD4 at the time of the change, nor in the previous years with ART or the time with the STR of ABC + 3TC + DTG. The average of the Charlson index was 1.68 in the undetectables at week 24 and 3.2 in the detectable, without the difference being significant.Before the change, the average of months with the STR of ABC + 3TC + DTG had been 12.46 (IC95%: 11.11–13.82). The adherence measured in Pharmacy before and after the change was 98%. At week 24, generic drugs were suspended in two cases (2.15%), due to toxicity (at weeks 13 and 18). The toxicity was due to symptoms of the central nervous system: a worsening of migraine and a burning mouth syndrome. In these two cases of toxicity, treatment was changed to (ABC + 3TC) + raltegravir (RTG).Patients who discontinued due to toxicity had a higher Charlson index than the rest, although it did not reach statistical significance (2.34 vs. 1.74). No differences were observed in baseline CD4 or in the previous months with the STR of ABC + 3TC + DTG . Although it did not reach statistical significance, the mean time with ART was higher in those who stopped due to toxicity (16 vs 9 years).n = 93), has been estimated at € 154,652 , taking into account only the medication expenses.During 2017, there was a saving of € 125,512 with the change from one tablet per day to two tablets per day in a single shot. The estimated savings for the year 2018 of all these patients  + DTG were 2.15%, only attributable to toxicity. There are multiple studies that have compared antiretroviral treatments in STR versus regimens of more than one tablet, almost all of them retrospective and, always based on combinations of TDF + FTC + EFV, with very poor representation of other third agents such as rilpivirine (RPV) or elvitegravir (EVG) , but theNo cases of interruption of the new treatment regimen due to virological failure were described, considering possible blips the five cases of viral load> 50 and < 400 copies/mL. The adherence measured in Pharmacy was not compromised either, although it is certain that, in previous studies, regimens of more than one tablet have been associated with less adherence than those of multiple tablets, with the risk of selective adherence. This fact was not observed in our cohort. On the other hand, the two cases of toxicity were related to CNS symptoms, although patients had previously tolerated the use of the ABC + LMV + DTG co-formulated tablet. It could be that both clinicians and patients were especially vigilant in the identification and interpretation of new symptoms after the change of formulations, but it could also be the case that generic pharmaceutical specialties include different percentages of impurities, as has already been possible evidenced in other fields of Medicine –17. NowaIn our experience at 24 weeks, the change from a coformulated specialty to a regimen of two tablets with the same components does not seem to have compromised the efficacy of the treatment, providing considerable financial savings. The longer term experience (at least 48 weeks) and in greater number is necessary to confirm this type of actions.


Lipo-accumulation of the dorsocervical fat pad  is a complication observed in people living with human immunodeficiency virus (HIV). We described the clinical outcome of people living with HIV with “buffalo hump” treated by excisional lipectomy.From April 2013 to March 2018, medical records of people living with HIV, who received care in our hospital have been evaluated. Among them, patients with dorsocervical fat accumulation treated by excisional lipectomy have been retrospectively assessed.Nine patients with “buffalo hump” among 2886 people living with HIV  were included. Eight were women with a mean age of 47.9 ± 8.0 years old . Most of them have been infected by blood transfusion  and the mean duration of HIV infection was 14.1 ± 5.5 years . The mean duration for antiretroviral therapy was 8.8 ± 2.1 years . The mean pre-ART CD4+ T cell count was 91.3 ± 76.5 cells/μL  and 477.4 ± 271.8 cells/μL  at the time of surgery. All 9 patients underwent excisional lipectomy of their hypertrophied dorsocervical fat pad. The mean size of the excised specimens was 14 × 11 × 6 cm. The median follow-up time was 24 months , all 9 patients reported satisfaction with their results, with no recurrence has been observed.Corrective surgery used to treat localized fat accumulations in people living with HIV with “buffalo hump” showed a favorable effect and can therefore be considered when necessary. Whereas drugs such as integrase inhibitors may avoid lipo-accumulation related syndrome and should be given to people living with HIV in China. The prevalence of HALS in patients on ART has been reported to be 10% up to 40%.,3 Areas of adipose hypertrophy or lipo-accumulation (LA) include the dorsocervical region , the anterior neck, the upper torso, and the abdomen, whereas lipoatrophy occurs in the face and the limbs. In severe cases, LA can be disfiguring, which can cause stigma and discrimination, leading to risks of poor adherence, medication discontinuation, and treatment failure. Surgical or cosmetic corrective treatment is the only intervention with almost immediate esthetical result, as well as the change of classes of ART when possible. Herein, we described the clinical manifestations and treatment outcome in HIV-infected patients with dorsocervical fat accumulation treated by excisional lipectomy in 1 Chinese clinical center.Life of persons living with human immunodeficiency virus (HIV) has improved since the introduction of antiretroviral therapy (ART). Nevertheless, as these individuals are receiving ART for long-term, complications are increasingly reported, including the HIV-associated lipodystrophy syndrome (HALS), which is characterized by abnormal fat metabolism and tissue deposition. Several characteristics, such as older age, white race, low body weight, low nadir CD4+ T cell count, long duration of ART and exposure of protease inhibitors (PIs), or some nucleoside reverse transcriptase inhibitors (NRTIs) have been identified as risk factors for HALS.22.1Zhongnan Hospital of Wuhan University is the largest referral hospital for HIV/AIDS care in Hubei Province, central China. From April 2013 to March 2018, medical records of people living with HIV (PLWH) who received care in our hospital have been evaluated. Among them, we identified 9 patients presenting with dorsocervical fat accumulation treated by excisional lipectomy. Age, sex, weight, height, body mass index (BMI), duration of HIV infection, mode of HIV acquisition, CD4+ T cell count, ART regimens, serum levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and fasting blood glucose (FBG) were collected. Evaluation of liver steatosis was assessed by echography or computed tomography (CT). Patients information on coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and human papillomavirus (HPV) were also collected.2.2This clinical study was conducted according to the principles expressed in the Declaration of Helsinki. The Ethical approval was granted by the Ethics Committee of Zhongnan Hospital of Wuhan University (NO.2018055).2.3Continuous variables were described as means, medians, and ranges. We used SPSS 16.0  to perform all statistical analyses.33.12. The liver radiological examination showed steatohepatitis in 2 patients, whereas cirrhosis has been detected in 1 patient associated with HBV and HCV coinfection. The results of the laboratory examinations revealed a 2 to 3-fold increase of the serum TG over normal values in 8 PLWH (89%), and 1 (11%) had an increased fasting glucose. The mean pre-ART CD4+ T cell count was 91.3 ± 76.5 cells/μL  and 477.4 ± 271.8 cells/μL  at the time of surgery.From a total of 2886 PLWH  hospitalized in our center between April 2013 and March 2018, 9 of them had dorsocervical fat accumulation  were included. Eight were women with a mean age of 47.9 ± 8.0 years old  . Whereas now it is well established that each class of drugs has a different effect on fat metabolism, even drugs of the same class may have different effects. In addition, combination of certain drugs acts synergistically to cause dyslipidemia.–15 For nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), dyslipidemia has been associated with exposure to stavudine, zidovudine, and abacavir, whereas tenofovir and lamivudine showed minimal or even a favorable lipid influence. In the NNRTIs, efavirenz has been associated with increases in TC and TG, whereas rilpivirine has been shown to have less effect on lipids compared with efavirenz. Among PIs, lopinavir, ritonavir, and nelfinavir have been associated with lipo-accumulation whereas atazanavir has limited effect. The integrase inhibitors (INIs) class have a little or no effect on lipid, which makes it one of the best choices for patients. Most of our patients had been treated by the combination of 2 NRTIs and 1 NNRTI drugs and no PIs have been used, as recommended by the Chinese therapeutic guideline proposed for first-line choice regimen. Our findings further revealed that patients with dorsocervical fat pad under NRTIs and NNRTI regimens had a significantly greater increased plasma levels of TG than TC. The relationship between changes in body fat and lipid levels is not yet well understood because alterations in the lipid profile do not clearly correlate with body tissue fat deposition. Proposed hypotheses including local effects of increased glucocorticoid production, inhibition of adipocyte differentiation, impaired activity of glucose transporters, mitochondrial toxicity, and more recently the effect of gut dysbiosis.–22 In recent years, as the number of HIV infections continues to increase and the duration of ART prolonged, the utilization of PIs  as the second-line treatment in China is increasing. Apart of the morphologic changes, accompanied cardiovascular diseases in this population may also increase, and prevention of these conditions has become a concern. At the same time, other classes of antiretroviral drugs such as integrase inhibitors, which has been proposed by World Health Organization (WHO) and has been widely used in western countries should be integrated as first-line treatment in China.As one of the manifestations of HALS, dorsocervical fat accumulation called “buffalo hump” can become painful with lager size, leading to restricted neck movement, and can be associated with abdomen fat accumulation leading to sleep apnea.–25 Is the women more prone to “buffalo hump” formation than men? We think one of the reasons for this discrepancy is the lack of consensus on diagnostic criteria of HALS. The diagnosis is usually based on the patient's self-report of regional body fat changes and physical examination. But it is obviously that an individual's awareness and acceptance of body fat gain may be different. For example, an obese person may not be as concerned with increasing central adiposity, in contrast the women maybe more conscious to their body image and more eagerly to seek for medical attention. In the literature, the formation of “buffalo hump” was merely associated with the infection of HIV. Since in our study, 7 out of the 9 patients have been infected by blood transfusion, 1 patient has been coinfected with HBV whereas the HBVDNA was negative as a result of ART, but 5 out of 9 patients has been coinfected with HCV, which were not the case in other studies, so, does HCV play a synergistic role with HIV in the formation of “buffalo hump,” or especially has an influence on the women should be exploited further.Interestingly, we noticed that even more male PLWH were initially included in our study , however, in the group of patients with reported “buffalo hump” underwent surgery, there were far more women than men , whereas the patients were mainly men in other studies.P = .001). In an Indian cross-sectional study, the mean duration of ART was 5 years for the development of fat redistribution group. In our study, the average time of HIV infection was 14.1 ± 5.5 years  and the average time of duration for antiretroviral therapy was 8.8 ± 2.1 years , which was much longer than the other studies. Tracking the causes, we found that since it remains difficult to accurately define HALS, many clinicians did not make an early diagnosis, and some patients may have been treated surgically late. Hence, in resource-limited regions, apart from ART switching and lifestyle change strategies, the surgical treatment in patients with dorsocervical fat pad are still the cornerstone of the management.,25,28 Although the cosmetic and functional results of the surgery are often fulfilled, the main drawback is recurrence of the fat accumulation, with a reported relapse rate up to 50% over a follow up of 12 to 30 months. In our study, during a median of 24 months  of follow-up, all 9 patients reported satisfaction with their results, there have been no recurrences reported, and the CD4+T cell count were stable for all the patients at the time of follow-up with the viral load under detectable level. This may benefit from drug switch from d4T to TDF. Additionally, our relatively short follow-up time of certain patients could not be ignored, so the long-term effect of surgery needs further observation.A study including 72 patients from the Asia-Pacific region showed that the patients receiving ART for >3.8 years had a significantly higher prevalence of HALS than those receiving ART for <3.8 years (16% vs 5%; odds ratio [OR], 4.01; ,31 making passage of the lipoplasty cannulas into the region quite difficult, some studies recommended excisional lipectomy in order to maximal remove the fibrous fatty tissue and theoretically reduce the rate of recurrence.,32 Taking together, we suggested to use excisional lipectomy as the primary treatment, with liposuction added when necessary for better contouring of the periphery of the excision, especially when the fat pad is >10 cm.Although 2 surgical options for the treatment of dorsocervical fat pad are proposed which including traditional surgical dermolipectomy and non-invasive ultrasound-assisted liposuction. While the “buffalo humps” are usually composed by fat tissue that is hard, with trabecules and fibrous as shown in our study,5Globally, corrective surgery used to treat dorsocervical fat accumulations in patients experiencing considerable physical or psychological discomfort shown a favorable effect and can therefore be considered when necessary. Whereas more drugs with favorable lipid profile should be used to PLWH in the country like China and more prevention strategies should be initiated to control the metabolite effect of ART.The authors thank Prof. Quanyan Liu from the Department of General Surgery and Dr. Yueying Li from the Department of Pathology, Zhongnan Hospital of Wuhan University, for their assistance with this project. The authors thank all study participants. J-PR is the holder of the Louis Lowenstein Chair in Hematology and Oncology, McGill University and William Turner award from the McGill University Health Centre.Conceptualization: Xi-en Gui, Qian Cao, Jean-Pierre Routy.Data curation: Song Chen, Xi-en Gui, Qian Cao.Formal analysis: Song Chen, Xi-en Gui, Qian Cao, Jean-Pierre Routy.Funding acquisition: Qian Cao.Methodology: Song Chen, Qian Cao, Jean-Pierre Routy.Software: Song Chen.Supervision: Xi-en Gui, Qian Cao, Jean-Pierre Routy.Validation: Song Chen, Xi-en Gui, Qian Cao, Jean-Pierre Routy.Writing – original draft: Song Chen, Qian Cao.Writing – review & editing: Xi-en Gui, Qian Cao, Jean-Pierre Routy.


Over 90% of Human Immunodeficiency Virus (HIV) infected individuals will be on treatment by 2020 under UNAIDS 90–90-90 global targets. Under World Health Organisation (WHO) “Treat All” approach, this number will be approximately 36.4 million people with over 98% in low-income countries (LICs).Pretreatment drug resistance (PDR) largely driven by frequently use of non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine, has been increasing with roll-out of combined antiretroviral therapy (cART) with 29% annual increase in some LICs countries. PDR has exceeded 10% in most LICs which warrants change of first line regimen to more robust classes under WHO recommendations. If no change in regimens is enforced in LICs, it’s estimated that over 16% of total deaths, 9% of new infections, and 8% of total cART costs will be contributed by HIV drug resistance by 2030. Less than optimal adherence, and adverse side effects associated with currently available drug regimens, all pose a great threat to achievement of 90% viral suppression and elimination of AIDS as a public health threat by 2030. This calls for urgent introduction of policies that advocate for voluntary and compulsory drug licensing of new more potent drugs which should also emphasize universal access of these drugs to all individuals worldwide.The achievement of United Nations Programme on HIV and AIDS 2020 and 2030 targets in LICs depends on access to active cART with higher genetic barrier to drug resistance, better safety, and tolerability profiles. It’s also imperative to strengthen quality service delivery in terms of retention of patients to treatment, support for adherence to cART, patient follow up and adequate drug stocks to help achieve a free AIDS generation.The online version of this article (10.1186/s40249-019-0573-1) contains supplementary material, which is available to authorized users. Please see Additional file In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and partners launched the 90–90-90targets. The 90–90-90 global targets by UNAIDS call for 90% of all people living with human immunodeficiency virus (HIV) to know their status, 90% of all people diagnosed with HIV infection to be on combined antiretroviral therapy (cART) and 90% of all people receiving cART to have suppressed the virus by 2020 . In a reRoutine viral load monitoring, more potent drugs with fixed dose combinations with higher genetic barrier to DR and adherence support are among areas of emphasis for rapid scale up and better care of patients . HoweverOver the last two decades, access to ART by HIV infected patients in countries most hit by HIV epidemic has increased. Contrary to high income countries (HICs), most HIV patients in LICs have access to the type of ART with high pill burden, side effects, and easily counteracted by resistance. These have translated into frequent drug switches which are not sustainable, and therefore likely to have a huge impact to achieving 90–90-90 goal and ultimate target of eradicating HIV by 2030.The commonly used NNRTIs in FL, (NVP/EFV), and (LPV/r) based SL therapy in LICs, have low genetic barrier to drug resistance compared to second generation NNRTIs, rilpivirine (RPV) and ETR. High-level resistance between these drugs has been reported  which reAdherence to treatment is critical to a successful treatment response and may be influenced by cART. It reverses occurrence of mortality, cART related morbidity, hospital visits, and improves immunological benefit of using ART. Improved adherence correlates with increased CD4 count  and is tThe available cART in LICs is complex and associated with huge pill burden, short, and long-term medication side effects. Adherence was reported to be around 40% in a recent adolescents study in 23 sub-Saharan Africa countries . The stuaidsinfo.nih.gov/guidelines). HIVDR resulting in VF in second line failures in LICs, has been attributed to poor adherence other than LPV/r activity [Though LPV/r is associated with more adverse gastrointestinal effects than ATV/r or darunavir/ritonavir , it stilactivity . In addiactivity .Globally, over 10.1% of HIV infected patients have baseline drug resistance  and it iThe most ART associated challenges in LICs are mainly rooted on HIV drug resistance among other factors like the scarcity of treatment options for HIV infected patients in LICs more so on those failing salvage therapy. Several recommendations can be made on how to address these challenges and improve the lives of people living with HIV in LICs.Firstly, patent licences should be closely monitored, and local drug manufacturers be encouraged. Drug price is a major factor contributing to lack of access to these drugs especially due to patent restrictions. Third line therapy may be 18 times and seven times more expensive than FL and SL treatment . HoweverHIV integrase inhibitor, DTG has shown superior genetic barrier to resistance and potency in patients with DRMs to RAL and elvitegravir. Once daily dosage of DTG can be given to patients initiating cART and those failing RAL-based cART as once or twice daily dosage depending on presence of integrase strand transfer inhibitors (INSTIs) mutations more so Q148K/R/H. National Institutes of Health consultation recommends the use of tenofovir alafenamide fumarate (TAF) which has less bone and kidney toxicity, and DTG, which may help reduce drug resistance and improve adherence in LICs .The compound patent for DTG is expected to expire in 2026 and with licenses on adults and pediatric formulations available to all LICs through Medicines Patent Pool and ViiV Healthcare, market competition of local manufacturers will likely increase access of drug in this setting. The initiative by International drug purchase facility (UNITAID) to enrol DTG in some LICs of Kenya, Uganda and Nigeria  should bNeural tube birth defects in children born to mothers who were exposed to DTG during pregnancy still raises concern to the safety of using DTG in pregnant mothers. In a study that compared the birth outcomes between 1729 pregnant women on DTG based ART and 4359 mothers on EFV in Botswana, found no significant differences in the individual outcomes of stillbirth, neonatal death, preterm birth, very preterm birth, small for gestational age, or very small gestational age, and severe side effects between patients on DTG or EFV based ART .In a recent study looking at neural tube defects with DTG treatment in women who started DTG from the time of conception, 426 (0.94%) infants born from mothers who were initiated on DTG at conception, had neural birth defects of encephalocele, myelomeningocele and iniencephaly compared to 11 300 (0.12%) infants born to mothers on non-DTG regimen at conception . In sameP < 0.001) [ETR is largely patented in developing countries and with patent restrictions in leading manufacturing nations of India, China and Brazil, no generic form is available. The patent on novel compound expires in 2026 which is far beyond 2020 target and therefore more advocacies required. DRV has high genetic barrier to resistance and is effective in patients with multidrug resistant viruses  and was < 0.001) . In contSecondly, access to single pill formulations, drugs with high genetic barrier to resistance, and those with promising results in clinical trials, should be made a priority. Indeed, high TDR prevalence and lack of baseline resistance testing call for robust ART for patients starting on treatment. RPV approved for treatment of NNRTIs-naïve patients is more tolerable and allows simplification due to its single pill formulations of TDF/FTC/RPV, and TDF/TAF/RPV which improves adherence and general response to treatment. ETR is approved for use in NNRTIs experienced patients and has shown high potency to both wild type and NNRTIs resistant virus . HoweverDoravirine being tested in once daily doravirine/3TC/TDF combination, is more tolerable, has high efficacy, and activity against viruses with resistant mutations K103 N and Y181C . It was Thirdly, HIV drug resistance surveillance should be emphasized as HIV drug resistance is one of indicators of ART program. The impact of HIVDR has been attributed to be 15.6% of AIDS deaths, 9.4% of new infections and 7.9% of ART costs from 2017 to 2021 . TherefoMuch as the global burden of HIVDR especially in LICs is known and mitigation strategies well stipulated, most of these countries are struggling to implement these strategies due to mostly inadequate resources and lack of political will by governments in some countries. As a result, there is insufficient monitoring of emerging drug resistance. The early warning indicators by WHO for drug resistance provide alternative way of monitoring for emerging drug resistance in this setting. They include offering optimal treatment and according to the guidelines, checking for percentage of patients with loss of follow up after 12 months, looking at percentage of patients retained on ART at 12 months, patients with on time pill pick up/ clinic appointment, drug stock outs, and looking at patients under viral load monitoring and suppression . DespiteThe availability of more potent ART in LICs is of utmost importance if UNAIDS 2020 and 2030 goals are to be realized and sustained not only in HICs but also in LICs. Countries that have embraced these targets will have to provide treatment to the increasing numbers of newly infected individuals expected to be 800 000 annually from 30 million in 2017 to 36.4 million in 2025 . In counAdditional file 1:Multilingual abstracts in the five official working languages of the United Nations. (PDF 357 kb)


The New York City HIV Care Coordination Program (CCP) combines multiple evidence-based strategies to support persons living with HIV (PLWH) at risk for, or with a recent history of, poor HIV outcomes. We assessed the comparative effectiveness of the CCP by merging programmatic data on CCP clients with population-based surveillance data on all New York City PLWH. A non-CCP comparison group of similar PLWH who met CCP eligibility criteria was identified using surveillance data. The CCP and non-CCP groups were matched on propensity for CCP enrollment within four baseline treatment status groups . We compared CCP to non-CCP proportions with viral load suppression at 12-month follow-up. Among the 13,624 persons included, 15∙3% were newly diagnosed; among the 84∙7% previously diagnosed, 14∙2% were consistently suppressed, 28∙9% were inconsistently suppressed, and 41∙6% were consistently unsuppressed in the year prior to baseline. At 12-month follow-up, 59∙9% of CCP and 53∙9% of non-CCP participants had viral load suppression . Among those newly diagnosed and those consistently unsuppressed at baseline, the relative risk of viral load suppression in the CCP versus non-CCP participants was 1.15 (95%CI:1.09–1.23) and 1.32 (95%CI:1.23–1.42), respectively. CCP exposure shows benefits over no CCP exposure for persons newly diagnosed or consistently unsuppressed, but not for persons suppressed in the year prior to baseline. We recommend more targeted case finding for CCP enrollment and increased attention to viral load suppression maintenance. The goal of HIV treatment is to achieve viral load suppression (VLS), which occurs when the amount of viral load (VL) circulating in the body is very low (no higher than 200 HIV RNA copies/μL). The HIV HIV care continuum outcomes remain suboptimal throughout the US . In 2013A first step toward strengthening the HIV care continuum is to address immediate barriers to adherence and to improve short-term outcomes among PLWH who are under-engaged with HIV medical care and treatment. HIV affects vulnerable and marginalized populations, and PLWH have higher rates of mental illness, substance use disorders, and unstable housing, all serious and often co-occurring barriers to achieving desired HIV outcomes , 7. ReseWe conducted an observational study to assess the comparative effectiveness of a comprehensive HIV care coordination intervention on VLS outcomes among persons in New York City (NYC) with documented barriers to HIV care and treatment engagement .In December 2009, with Ryan White Part A funding, the NYC Department of Health and Mental Hygiene (DOHMH) launched the HIV Care Coordination Program (CCP) to support persons at high risk for, or with a recent history of, poor HIV care outcomes.website   as of the date of a CD4 count <200 [exhibiting poor ART adherence as of March 31, 2012, defined as not achieving VLS or not having any VL tests reported in the first 12 months after ART initiation  [experiencing viral rebound ; or 6) registering a high VL  from December 1, 2008 to March 31, 2013.Using information from the Registry, we identified persons as eligible for enrollment in the CCP if they were 1) unt <200 ; 4) exhissed VL) ; 5) expeeligibility window , or 4) inconsistently suppressed .After constructing this eligible non-CCP-enrolled population, we prepared to match persons in the non-CCP PLWH comparison group to those in the CCP group using baseline treatment status, propensity scores, and enrollment/pseudo-enrollment dates. Given that 12-month VLS outcomes would be expected to differ by baseline treatment status/engagement, we created four mutually exclusive baseline treatment status groups: 1) newly diagnosed (in the 12 months prior to enrollment/pseudo-enrollment date), 2) consistently suppressed , 3) consistently We used logistic regression to estimate the propensity for enrollment in the CCP within each of the above 4 groups. We combined two baseline treatment status groups, groups 3 and 4, for one propensity score model, because we hypothesized the propensity of enrollment in the CCP would be influenced by the same potential confounders for these two groups; when we estimated the propensity for enrollment with individual models for groups 3 and 4, the effect estimates from the pooled model did not differ from the effect estimates from the individual models. We report the results for the pooled model because we were able to match a greater proportion of CCP enrollees, enhancing generalizability. Subsequent matching occurred within each of the four groups.a priori hypothesized and measured confounders and used backward selection to identify the model with the lowest value of Akaike’s Information Criterion (AIC). The variables that we suspected were confounders of the relationship between CCP enrollment and the VLS outcome were sex, race/ethnicity, age at enrollment/pseudo-enrollment, country of birth, HIV transmission risk, year of diagnosis, baseline VL, baseline CD4, successful linkage to HIV care within three months of diagnosis, presence of an AIDS diagnosis within one year of HIV diagnosis, number of VL laboratory tests reported in the year prior to enrollment/pseudo-enrollment, residential ZIP code at enrollment/pseudo-enrollment, HIV prevalence and poverty level within ZIP code at enrollment/pseudo-enrollment, and interaction terms for baseline CD4 and baseline VL, baseline CD4 and race, sex and risk, and year of diagnosis and risk. Per the American Community Survey, poverty level within the residential ZIP code at enrollment/pseudo-enrollment was classified as high (poverty greater than the median poverty level for a given year of enrollment/pseudo-enrollment) versus low. HIV prevalence was based on aggregated NYC HIV surveillance data for the ZIP code by year of enrollment/pseudo-enrollment, and was classified as high  versus low.For the three propensity score models, we started with a model that included all of our Within each of the four baseline treatment status groups, we matched on propensity scores and enrollment/pseudo-enrollment dates (± 3 months). We used a 1:1 'greedy' match technique, and the match algorithm proceeded sequentially from 8 to 1 decimal places of the propensity score , 30. We The VLS outcome was based on the last VL laboratory result reported to the Registry in the 12 months following the enrollment/pseudo-enrollment date, and was dichotomized as ≤200 or >200 copies/μL. Persons with no VL in the Registry for the entire 12-month follow-up period were classified as not having VLS. While rare, 1∙3%  of the CCP and 5∙4%  of the non-CCP PLWH were missing a VL result. We used a GEE model with binary error distribution and identity link to estimate the difference in proportion of CCP and non-CCP participants with VLS, accounting for the matched-pairs design. The arithmetic difference was expressed in percentage point units. We used a GEE model with binary error distribution and log link to estimate the relative effect of the CCP on VLS, accounting for the matching. Absolute differences and relative risks were estimated with the GENMOD procedure in SAS version 9∙3  The absolute and relative effect of the CCP was estimated for each of the four baseline treatment status groups.From December 1, 2009 to March 31, 2013, a total of 7,337 persons enrolled in the CCP; of those, 7,058 (96∙2%) were still living 12 months after enrollment. Of the 62,828 non-enrolled PLWH who were eligible for enrollment in the CCP, 91∙9%  were assigned a pseudo-enrollment date; 74∙8%  had an HIV-related laboratory test in NYC in the two years following their pseudo-enrollment date; and 10∙8%  were matched to a CCP enrollee, allowing us to include 96∙5%  of CCP clients eligible for this analysis .unsuppressed in the year prior to enrollment. Only 31∙3% were virally suppressed at the time of last reported lab measurement prior to enrollment/pseudo-enrollment, and the median CD4 count was 314 cells/μL (IQR 150–506), with 31∙8% having CD4<200 cells/μL.Prior to propensity score matching, the CCP and non-CCP groups differed substantially by measured demographic and clinical characteristics . After punsuppressed in the year prior to enrollment/pseudo-enrollment ; RR:1∙32 (95%CI 1∙23–1∙42)). No differences in VLS were observed among persons with consistent VLS or with inconsistent VLS in the year prior to enrollment/pseudo-enrollment ; RRconsistent VLS = 1∙01 (95%CI 0∙98–1∙04); and 62∙2% vs. 62∙3%; ADinconsistent VLS = -0∙10 (95%CI: -3∙08–2∙88); RRinconsistent VLS = 0∙99 (95%CI: 0∙95–1∙05), respectively).By twelve months after enrollment/pseudo-enrollment, 59∙9% of the CCP group and 53∙9% of the non-CCP comparison group were suppressed on their most recent VL test . The prounsuppressed in the year prior to enrollment. Previously, we have shown a positive CCP effect using a single-group pre-post assessment, in which the proportion of CCP enrollees with VLS increased from 32.3% in the year prior to enrollment to 50.9% in the year after enrollment.[unsuppressed throughout the year prior to enrollment, as only 42.5% had achieved VLS on their last VL measurement.Using a surveillance-based method for comparison group selection in an observational effectiveness study, we found New York’s Ryan White CCP intervention to have a significant positive effect on VLS for newly diagnosed persons and for previously diagnosed persons who were consistently rollment., 14 Howerollment. A strengThere was a high prevalence of advanced HIV disease in the cohort (31∙8% had CD4<200 cells/uL), with a substantial proportion of persons not suppressed on their last VL measure in the 12-month follow-up period (43∙1%). This likely reflects the persistence of major barriers to care and treatment engagement in our study population. For the sample of 7,058 CCP clients alive at 12-month follow-up, we previously described the baseline prevalence of psychosocial barriers, including unstable housing (22∙1%), low mental health functioning (30∙0%), and self-reported recent hard drug use (15∙1%); half of CCP clients  had documentation of at least one of these barriers at the time of enrollment, and only 24∙4% of the 3,556  were documented as having none of those barriers at last assessment in the 12 months post-enrollment [This proportion remains high because fully resolving psychosocial barriers takes time and repeated efforts., 35 FurtPLWH who were in the consistently suppressed or inconsistently suppressed baseline groups have already by definition experienced some treatment success and were thus previously engaged in medical care and adhering to treatment to some degree. While the CCP may work better than usual care for PLWH with initial hurdles to ART access and adherence, the lack of a significant short-term CCP effect among the two groups with prior evidence of viral suppression suggests that the CCP is not more effective than usual care at helping people who have already established HIV care and treatment adherence to re-establish or maintain that adherence over a 12-month period. Among PWLH who were consistently or inconsistently suppressed throughout the prior year, the comprehensive and intensive approach of the CCP may not typically be needed , and thus may not offer a real advantage over other forms of support available under NYC usual care.Additionally, the NYC epidemic has shown substantial improvements in VLS over time , likely linkage assistance and/or have been unable to achieve suppression at all during the past year, case management under this care coordination model is more effective than usual care at achieving VLS.Case management interventions vary significantly in design and target population, making cross-study comparisons difficult. RandomizCohort studies of case management interventions have evaluated VLS outcomes and reported null results., 20 In aStrengths of our study include the use of a population-based data source to rigorously derive a contemporaneous observational comparison group, which was large enough to identify a non-CCP PLWH match (similar with regard to measured factors) for 96∙5% of the CCP sample. Additionally, deriving outcome information in an identical manner for CCP and non-CCP recipients from the longitudinal and population-based HIV Registry ensured that it was highly complete across the cohort and over time, regardless of care location or changes in care provider within NYC. Finally, our method’s explicit attention to matching on enrollment/pseudo-enrollment dates controlled for secular trends of increasing VLS in NYC over time.Our study has several limitations. First, uncontrolled or poorly controlled confounding may exist, as this was an observational study. Since our propensity models were limited to variables available in the NYC HIV Surveillance Registry, we were unable to directly account for psychosocial factors known to be associated with poor VLS , which may have been differential by arm even after propensity matching. Second, we were not able to describe or account for services or service delivery models received in the non-CCP comparison group, and we were not able to describe non-CCP services received in the CCP group. Third, we excluded CCP enrollees who had died in the first 12 months after enrollment, and exclusion of cohort members with late-stage disease and/or rapid disease progression may bias estimates. The CCP unsuppressed in the year prior to the start of follow-up, suggesting the program may be effective at helping with initial hurdles to ART access and adherence. However, the absence of an effect among previously diagnosed persons with any suppression in the year prior to enrollment indicates the program confers no advantage over usual care for resuming or maintaining recent adherence. Efforts to refine CCP service delivery in NYC could better target for enrollment those newly diagnosed and those consistently unsuppressed, and also enhance strategies for restoring and maintaining viral suppression  among PLWH who have had prior treatment success.[New York’s Ryan White CCP intervention has shown a positive short-term effect on VLS among newly diagnosed PLWH and those who were consistently virally  success. Future sS1 Table(DOCX)Click here for additional data file.