Year Of Antiretroviral Therapy Initiation Research Articles

Predicting mortality within 1 year of ART initiation in children and adolescents living with HIV in sub-Saharan Africa: a retrospective observational cohort study

Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV. Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria. The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001). This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings. National Institute of Health Fogarty International Center.

Ongoing High Prevalence of Severe Immune Suppression Among Children in South Africa.

Among children in Southern Africa severe immune suppression (SIS) has declined, but most continue to initiate antiretroviral therapy (ART) with SIS. Using data from South Africa, we describe SIS at ART start and on ART between 2007 and 2020, among children <5 years with a CD4%/cell count at ART start and ≥1 subsequent measure. Gap in care was defined as >9 months without a recorded visit. We defined SIS according to age and CD4%/cell count. A multistate model was used to estimate transition probabilities between 5 states: SIS on ART; Stable, not SIS; Early Gap, commencing <9 months from ART start; Late Gap, commencing ≥9 months on ART; and Death. Among 2536 children, 70% had SIS at ART start, and 36% experienced SIS on ART. An increasing proportion were age <1 year at ART initiation (2007-2009: 43% to 2013-2020: 55%). Increasingly, SIS on ART occurred after a gap, in those with SIS on ART for >1 year, and after a period of unknown immune status. Later year of ART initiation was associated with reduced transition from SIS on ART to Stable. Infants and those initiating ART with SIS were more likely to transition from Stable to SIS. Viremia strongly predicted death from both the on ART states. Increasingly SIS occurred among ART-experienced children. Those starting ART with SIS and during infancy remained especially vulnerable to SIS once on treatment. Managing ART in these children may be more complex and further reducing AIDS-related mortality is likely to remain challenging.

Determinants of Successful Human Immunodeficiency Virus Treatment Outcomes: A Linkage of National Data Sources in Malaysia.

Concerted efforts have been undertaken to reduce the human immunodeficiency virus (HIV) infection by the year 2030 in Malaysia. A situational analysis of the performance of successful HIV treatment and its determinants is vital; however, this information remains scarce. This study aimed to identify the determinants of undetectable viral load among people living with HIV (PLHIV). Newly diagnosed HIV cases (n = 493) registered under the Malaysia HIV/AIDS-related national databases from June 2018 to December 2019 were studied. The deterministic matching method was applied to link the records in two national databases (at Kuala Lumpur and Putrajaya Federal Territories Health Department, JKWPKLP HIV line-listing database and National AIDS Registry). Successful HIV treatment, an outcome variable, was measured by the undetectable viral load < 200 copies/mL after 1 year of antiretroviral therapy initiation. Logistic regression analysis was applied in the current study. Results showed that 454/493 (92.2%; 95% confidence interval [CI]: 89.8%, 94.6%) PLHIV had successful HIV treatment. Study participants had a mean (SD) age of 30 (8.10) years old, predominantly male (96.1%) and sexually transmission (99.9%). The multiple logistic regression analysis revealed two significant determinants including the timing of ART initiation (AOR = 3.94; 95% CI: 1.32, 11.70; P = 0.014) and establishment of Sexually Transmitted Infection Friendly Clinic (STIFC) (AOR = 3.40; 95% CI: 1.47, 7.85; P = 0.004). Non-significant variables included gender, education level, HIV risk exposure, and co-infections of tuberculosis and Hepatitis C. JKWPKLP is on the right track to achieving universal treatment as a prevention strategy. Reinforcement of early ART initiation and establishment of STIFC are recommended.

CD4/CD8 Ratio Recovery Among People Living With HIV Starting With First-Line Integrase Strand Transfer Inhibitors: A Prospective Regional Cohort Analysis.

We evaluated trends in CD4/CD8 ratio among people living with HIV (PLWH) starting antiretroviral therapy (ART) with first-line integrase strand transfer inhibitors (INSTI) compared with non-INSTI-based ART, and the incidence of CD4/CD8 ratio normalization. All PLWH enrolled in adult HIV cohorts of IeDEA Asia-Pacific who started with triple-ART with at least 1 CD4, CD8 (3-month window), and HIV-1 RNA measurement post-ART were included. CD4/CD8 ratio normalization was defined as a ratio ≥1. Longitudinal changes in CD4/CD8 ratio were analyzed by linear mixed model, the incidence of the normalization by Cox regression, and the differences in ratio recovery by group-based trajectory modeling. A total of 5529 PLWH were included; 80% male, median age 35 years (interquartile range [IQR], 29-43). First-line regimens were comprised of 65% NNRTI, 19% PI, and 16% INSTI. The baseline CD4/CD8 ratio was 0.19 (IQR, 0.09-0.33). PLWH starting with NNRTI- (P = 0.005) or PI-based ART (P = 0.030) had lower CD4/CD8 recovery over 5 years compared with INSTI. During 24,304 person-years of follow-up, 32% had CD4/CD8 ratio normalization. After adjusting for age, sex, baseline CD4, HIV-1 RNA, HCV, and year of ART initiation, PLWH started with INSTI had higher odds of achieving CD4/CD8 ratio normalization than NNRTI- (P < 0.001) or PI-based ART (P = 0.015). In group-based trajectory modeling analysis, INSTI was associated with greater odds of being in the higher ratio trajectory. INSTI use was associated with higher rates of CD4/CD8 ratio recovery and normalization in our cohort. These results emphasize the relative benefits of INSTI-based ART for immune restoration.

Transfer of Patients on Antiretroviral Therapy Attending Primary Health Care Services in South Africa.

Patients stable on antiretroviral therapy (ART) may require transfer between health care facilities to maintain continuous care, yet data on the frequency, predictors, and virologic outcomes of transfers are limited. Data for all viral load (VL) testing at public sector health facilities in the Western Cape Province (2011-2018) were obtained. Participant inclusion criteria were a first VL between 2011 and 2013, age >15 years at ART initiation, and >1 VL within 5 years of ART initiation, of which ≥1 was at a primary health care facility. Two successive VLs taken at different facilities indicated a transfer. We assessed predictors of transfer using generalized estimating equations with Poisson regression and the association between transfer and subsequent VL> 1000 copies/mL using generalized mixed effects. Overall 84,814 participants (median age at ART initiation 34 years and 68% female) were followed up for up to 4.5 years after their first VL: 34% (n = 29,056) transferred at least once, and among these, 26% transferred twice and 11% transferred thrice or more. Female sex, age <30 years, and first VL > 1000 copies/mL were independently associated with an increased rate of transfer [adjusted rate ratio 1.24, 95% confidence interval (CI): 1.21 to 1.26; 1.34, 95% CI: 1.31 to 1.36; and 1.42, 95% CI: 1.38 to 1.45, respectively]. Adjusting for age, sex, and disengagement, transfer was associated with an increased relative odds of VL > 1000 copies/mL (odds ratio 1.35, 95% CI: 1.29 to 1.42). Approximately one-third of participants transferred and virologic outcomes were poor post-transfer. Stable patients who transfer may require additional support to maintain adherence.

Factors Associated With Late Antiretroviral Therapy Initiation Among People Living With HIV in Southern Iran: A Historical Cohort Study.

ObjectivesLate initiation of antiretroviral therapy (ART) is associated with poor outcome among people living with HIV (PLHIV) and higher risk of transmission of infection. This study was conducted to identify the determinants of late ART initiation among PLHIV in Southern Iran.MethodsA historical cohort study was conducted on 1,326 PLHIV of ≥15 years of age who were registered with the behavioral diseases counseling center (BDCC) in southern Iran from August 1997 to March 2021. Late ART initiation was defined as a CD4 cell count <200 cells/mm3 or having a clinical AIDS diagnosis at the time of ART initiation. The required demographic and clinical data were collected from the patients' medical records. Multiple regression analysis was conducted to define late ART initiation associated factors.ResultsLate ART initiation was found among 81.9% of patients. Based on the results of the multivariate analysis, older age (odds ratio [OR] = 1.02, 95% CI = 1.00–1.04), being single (ORsingle/married = 1.80, 95% CI = 1.17–2.78), history of drug use (ORyes/no = 1.64, 95% CI = 1.02–2.62), year of ART initiation (OR2011−2013/2018−2021 = 3.65, 95% CI = 2.28–5.86), and possible route of transmission (ORdruginjection/sexual = 7.34, 95% CI = 1.16–46.21) were directly associated with the risk of late ART initiation.ConclusionsThe results show that the prevalence of late ART initiation was alarmingly high. For better infection control and better prognosis of infection, people at high risk need to be provided with timely services (e.g., diagnosis, treatment, training, and social support).

Anal cancer incidence in men with HIV who have sex with men: are black men at higher risk?

To assess differences in anal cancer incidence between racial/ethnic groups among a clinical cohort of men with HIV who have sex with men. Clinical cohort study. We studied men who have sex with men (MSM) in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who initiated antiretroviral therapy (ART) under HIV care in CNICS. We compared anal cancer incidence between Black and non-Black men and calculated hazard ratios controlling for demographic characteristics (age, CNICS site, year of ART initiation), HIV disease indicators (nadir CD4+, peak HIV RNA), and co-infection/behavioral factors including hepatitis B virus (HBV), hepatitis C virus (HCV), tobacco smoking and alcohol abuse. We studied 7473 MSM with HIV who contributed 41 810 person-years of follow-up after initiating ART between 1996 and 2014 in CNICS. Forty-one individuals had an incident diagnosis of anal cancer under observation. Crude rates of anal cancer were 204 versus 61 per 100 000 person-years among Black versus non-Black MSM. The weighted hazard ratio for anal cancer in Black MSM (adjusting for demographics, HIV disease factors, and co-infection/behavioral factors) was 2.37 (95% confidence interval: 1.17, 4.82) compared to non-Black MSM. In this large multicenter cohort, Black MSM were at significantly increased risk for anal cancer compared to non-Black MSM. Further detailed studies evaluating factors impacting anal cancer incidence and outcomes in Black men with HIV are necessary. Inclusion of more diverse study cohorts may elucidate modifiable factors associated with increased anal cancer risk experienced by Black MSM.

Multilevel Analysis of Individual and Neighborhood Characteristics Associated with Viral Suppression Among Adults with HIV in Rio de Janeiro, Brazil.

Understanding the impact of neighborhood context on viral suppression outcomes may help explain health disparities and identify future interventions. We assessed the relationship between individual characteristics, neighborhood socioeconomic context, and viral suppression using multilevel logistic regression models. Adults with HIV initiating antiretroviral therapy (ART) between 2000 and 2017, who resided in Rio de Janeiro and had an HIV-1 RNA level (viral load) measured 90-270 days after ART initiation were included. Overall, 83.9% achieved viral suppression. Participants who were older, had a higher level of education, and identified as heterosexual cisgender men and cisgender men-who-have-sex-with-men had increased odds of viral suppression. Later calendar year of ART initiation carried the strongest association with viral suppression, reflecting the increased effectiveness and tolerability of ART over time. Neighborhood socioeconomic indicators did not predict viral suppression in unadjusted or adjusted analyses, which may result from the integrated care provided in our health care facility together with Brazil's universal treatment.

Incidence and predictors of mortality within the first year of antiretroviral therapy initiation at Debre-Markos Referral Hospital, Northwest Ethiopia: A retrospective follow up study.

Acquired Immunodeficiency Syndrome (AIDS) is one of the most fatal infectious diseases in the world, especially in Sub-Saharan Africa, including Ethiopia. Even though Antiretroviral therapy (ART) significantly decreases mortality overall, death rates are still highest especially in the first year of ART initiation. To assess the incidence and predictors of mortality within the first year of ART initiation among adults on ART at Debre-Markos Referral Hospital, Northwest Ethiopia. A retrospective follow-up study was conducted among 514 newly enrolled adults to ART from 2014 to 2018 at Debre-Markos Referral Hospital. Patients' chart number was selected from the computer using a simple random sampling technique. Data were entered into EPI- INFO 7.2.2.6 and analyzed using Stata 14.0. The mortality rate within the first year was computed and described using frequency tables. Both bivariable and multivariable Cox-proportional hazard models were fitted to show predictors of early mortality. Out of 494 patient records included in the analysis, a total of 54 deaths were recorded within one year follow-up period. The overall mortality rate within 398.37 person years (PY) was 13.56 deaths/100 PY with the higher rate observed within the first three months. After adjustment, rural residence (Adjusted Hazard Ratio (AHR) = 1.97; 95% CI: 1.05-3.71), ≥ 6 months pre-ART duration (AHR = 2.17; 95% CI: 1.24-3.79), ambulatory or bedridden functional status at enrolment (AHR = 2.18; 95% CI: 1.01-4.74), and didn't take Cotrimoxazole preventive therapy (CPT) during follow-up (AHR = 1.88; 95% CI: 1.04-3.41) were associated with early mortality of adults on ART. Mortality within the first year of ART initiation was high and rural residence, longer pre-Art duration, ambulatory or bedridden functional status and didn't take CPT during follow-up were found to be independent predictors. Hence, giving special attention for patients from rural area and provision of CPT is crucial to reduce mortality.

Role of CD4/CD8 ratio on the incidence of tuberculosis in HIV-infected patients on antiretroviral therapy followed up for more than a decade.

The role of CD4/CD8 ratio on the incidence of tuberculosis (TB) in patients on antiretroviral therapy (ART) is unknown. Thus, we sought to determine whether the CD4/CD8 ratio was associated with development of TB in a cohort of HIV infected individuals on ART followed up for more than a decade in the setting of sub-Saharan Africa (SSA). The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 15 years. Clinical data were collected in retrospective manner. Patients with an AIDS defining illness or a CD4 count <200 cell/μL were started with a combination of ART. The participants have clinic visits every 6 months and/or as needed. Poisson regression models were used to identify factors associated with development of incident TB. Kaplan-Meier curves were used to estimate the probability of incident TB while on ART. A total of 347 patients with a median duration of follow-up on ART of 11.5 (IQR: 10.0-12.5) years were included. Incident TB developed in 47 patients during the 3259 person-years of follow-up, the majority (76.6%) occurred within five year of ART initiation. On univariate analysis, poor ART adherence (RR:2.57, 95% CI: 1.28-5.17), time-updated CD4 cell count of lower than 200 (RR: 4.86, 95%CI 2.33-10.15), or CD4 cell count between 200 and 500 (RR: 4.68, 95% CI: 2.17-10.09), time-updated CD8 cell count lower than 500 (RR: 2.83 95% CI 1.31-6.10), or CD8 cell count over 1000 (RR: 2.23, 95% CI: 1.12-4.45), time-updated CD4/CD8 ratio of less than 0.30 (RR: 6.00, 95% CI: 2.96-12.14), lack of normalization of CD4 T-cell count (RR: 6.13, 95% CI: 2.20-17.07), and virological failure (RR: 2.35 (95% CI: 1.17-4.71) were all associated with increased risk of incident TB. In multivariate analysis, however, time-updated CD4/CD8 ratio of less than 0.30 (adjusted RR: 4.08, 95% CI: 1.31-12.68) was the only factor associated with increased risk of developing incident TB (p = 0.015). Similar results were obtained in a sensitivity analysis by including only those virally suppressed patients (n = 233, 69% of all patients). In this group, CD4/CD8 ratio of less than 0.30 was associated with development of incident TB (adjusted RR: 4.02, 95% CI: 1.14-14.19, p = 0.031). Overall, the incidence rate of TB in patients with an updated CD4/CD8 ratio of less than 0.30 was more than 5-fold higher when compared with those with a ratio more than 0.45. Low CD4/CD8 ratio is independently associated with an increased risk of incident TB despite viral suppression. CD4/CD8 ratio may serve as a biomarker for identifying patients at risk of TB in patients on ART in the setting of SSA.

Impact of sickle cell disease on presentation and progression of paediatric HIV: a retrospective cohort study.

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. The study was a retrospective cohort study (study period 2004-2018). Cases of HIV+and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV+controls without SCD (HIV+/SCD-). Thirty-five HIV+/SCD+subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD+had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P=0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD+and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD+cohort (P=0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD+cohort showed a more rapid rise and higher total CD4 count (P=0.012, regression analysis). The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD+achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

Predictors of lost to follow-up in a \u201ctest and treat\u201d programme among adult women with high-risk sexual behavior in Kampala, Uganda

BackgroundImmediate uptake of antiretroviral therapy (ART) after an HIV-positive diagnosis (Test and Treat) is now being implemented in Uganda. Data are limited on lost to follow-up (LTFU) in high-risk cohorts that have initiated ‘Test and Treat’. We describe LTFU in a cohort of women of high-risk sexual behaviour who initiated ART under “Test and Treat”.MethodsWe performed a retrospective cohort study of participant records at the Good Health for Women Project (GHWP) clinic, a clinic in Kampala for women at high-risk of HIV-infection. We included HIV positive women ≥18 years who initiated ART at GHWP between August 2014 and March 2018. We defined LTFU as not taking an ART refill for ≥3 months from the last clinic appointment among those not registered as dead or transferred to another clinic. We used the Kaplan-Meier technique to estimate time to LTFU after ART initiation. Predictors of LTFU were assessed using a multivariable Cox proportional hazards model.ResultsThe mean (±SD) age of the 293 study participants was 30.3 (± 6.5) years, with 274 (94%) reporting paid sex while 38 (13%) had never tested for HIV before enrolment into GHWP. LTFU within the first year of ART initiation was 16% and the incidence of LTFU was estimated at 12.7 per 100 person-years (95%CI 9.90–16.3). In multivariable analysis, participants who reported sex work as their main job at ART initiation (Adjusted Hazards Ratio [aHR] =1.95, 95%CI 1.10–3.45), having baseline WHO clinical stage III or IV (aHR = 2.75, 95% CI 1.30–5.79) were more likely to be LTFU.ConclusionLTFU in this cohort is high. Follow up strategies are required to support women on Test and Treat to remain on treatment, especially those who engage in sex work and those who initiate ART at a later stage of disease.

Predictors of mortality among adult people living with HIV/AIDS on antiretroviral therapy at Suhul Hospital, Tigrai, Northern Ethiopia: a retrospective follow-up study

BackgroundEthiopia is striving to achieve a goal of “zero human immune deficiency virus/acquired immune deficiency syndrome (HIV/AIDS)-related deaths.” However, little has been documented on the factors that hamper the progress towards achieving this goal. Therefore, the ultimate aim of this study was to determine predictors of mortality among adult people living with HIV/AIDS on antiretroviral therapy (ART).MethodsA retrospective follow-up study was employed on all adult HIV/AIDS patients who started ART between January 1 and December 30, 2010, at Suhul Hospital, Tigrai Region, Northern Ethiopia. Data were collected by trained fourth-year Public Health students using a checklist. Finally, the collected data were entered into SPSS version 16. Then after, Kaplan-Meier curves were used to estimate survival probability, the log-rank test was used for comparing the survival status, and Cox proportional hazards model were applied to determine predictors of mortality.ResultsThe median follow-up period was 51 months (ranging between 1 and 60 months, inter-quartile range (IQR) = 14 months). At the end of follow-up, 37 (12.5%) patients were dead. The majority of these cumulative deaths, 19 (51.4%) and 29 (78.4%), occurred within 3 and 4 years of ART initiation respectively. Consuming alcohol (adjusted hazard ratio (AHR) = 2.23, 95% CI = 1.15, 4.32), low body weight (AHR = 2.38, 95% CI = 1.03, 5.54), presence of opportunistic infections (AHR = 2.18, 95% CI = 1.09, 4.37), advanced WHO clinical stage (AHR = 2.75, 95% CI = 1.36, 5.58), and not receiving isoniazid prophylactic therapy (AHR = 3.00, 95% CI = 1.33, 6.74) were found to be independent predictors of mortality.ConclusionThe overall mortality was very high. Baseline alcohol consumption, low body weight, advanced WHO clinical stage, the presence of opportunistic infections, and not receiving isoniazid prophylactic therapy were predictors of mortality. Strengthening behavioral and nutritional counseling with close clinical follow-up shall be given much more emphasis in the ART care and support program.

Lessons for test and treat in an antiretroviral programme after decentralisation in Uganda: a retrospective analysis of outcomes in public healthcare facilities within the Lablite project.

We describe the decentralisation of antiretroviral therapy (ART) alongside Option B+ roll-out in public healthcare facilities in the Lablite project in Uganda. Lessons learned will inform programmes now implementing universal test and treat (UTT). Routine data were retrospectively extracted from ART registers between October 2012 and March 2015 for all adults and children initiating ART at two primary care facilities (spokes) and their corresponding district hospitals (hubs) in northern and central Uganda. We describe ART initiation over time and retention and use of Cox models to explore risk factors for attrition due to mortality and loss to follow-up. Results from tracing of patients lost to follow-up were used to correct retention estimates. Of 2100 ART initiations, 1125 were in the north, including 944 (84%) at the hub and 181 (16%) at the spokes; children comprised 95 (10%) initiations at the hubs and 14 (8%) at the spokes. Corresponding numbers were 642 (66%) at the hub and 333 (34%) at the spokes in the central region (77 [12%] and 22 [7%], respectively, in children). Children <3y of age comprised the minority of initiations in children at all sites. Twenty-three percent of adult ART initiations at the north hub were Option B+ compared with 45% at the spokes (25% and 65%, respectively, in the central region). Proportions retained in care in the north hub at 6 and 12mo were 92% (95% CI 90 to 93) and 89% (895% CI 7 to 91), respectively. Corresponding corrected estimates in the north spokes were 87% (95% CI 78 to 93) and 82% (95% CI 72 to 89), respectively. In the central hub, corrected estimates were 84% (95% CI 80 to 87) and 78% (95% CI 74 to 82), and were 89% (95% CI 77.9 to 95.1) and 83% (95% CI 64.1 to 92.9) at the spokes, respectively. Among adults newly initiating ART, being older was independently associated with a lower risk of attrition (adjusted hazard ratio [aHR] 0.93 per 5y [95% CI 0.88 to 0.97]). Other independent risk factors included initiating with a tenofovir-based regimen vs zidovudine (aHR 0.60 [95% CI 0.46 to 0.77]), year of ART initiation (2013 aHR 1.55 [95% CI 1.21 to 1.97], ≥2014 aHR 1.41 [95% CI 1.06 to 1.87]) vs 2012, hub vs spoke (aHR 0.35 [95% CI 0.29 to 0.43]) and central vs north (aHR 2.28 [95% CI 1.86 to 2.81]). Independently, patient type was associated with retention. After ART decentralisation, people living with human immunodeficiency virus (HIV) were willing to initiate ART in rural primary care facilities. Retention on ART was variable across facilities and attrition was higher among some groups, including younger adults and women initiating ART during pregnancy/breastfeeding. Interventions to support these groups are required to optimise benefits of expanded access to HIV services under UTT.

LB9. The Effect of Initiating Integrase Inhibitor-based vs. Non-Nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy on Progression to Diabetes among North American Persons in HIV Care

BackgroundIntegrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) has been implicated in greater weight gain than other regimens among people with HIV, but there is little evidence about its role in serious clinical outcomes proximal to weight gain. We therefore examined the impact of initial ART regimen class/drug on incident diabetes mellitus (DM) in a large North American HIV cohort.MethodsTreatment-naïve adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART from January 2007 to December 2016 in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Individuals were followed until date of incident DM (HgA1c >6.5%, diabetes-specific medication, DM diagnosis along with diabetes-related medication, or random glucose measure ≥200 mg/dL), virologic failure, regimen core switch, cohort close (through December 2016), death date, or loss to follow-up (≥12 months with no contact before cohort close). Cox regression stratified by site and adjusting for age, sex, race, HIV transmission risk, year of ART initiation, and baseline weight, CD4+ cell count, and HIV-1 RNA yielded adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident DM by ART class and INSTI drug.ResultsAmong 21,516 eligible ART initiators, 10,553 (49%) started NNRTIs, 6,677 (31%) PIs, and 4,286 (20%) INSTIs, with median follow-up of 3.0, 2.4, and 1.6 years, respectively. Among INSTI initiators, 21% started dolutegravir (DTG), 28% raltegravir (RAL), and 51% elvitegravir (EVG). Overall, 669 (3%) developed DM. Patients differed by all characteristics except baseline body mass index and HIV-1 RNA. Those starting INSTIs vs. NNRTIs had increased risk of incident DM (HR = 1.22; CI: 0.95–1.57) similar in magnitude as for PI vs. NNRTI initiators (HR = 1.25; CI: 1.05–1.49) (figure). Among INSTIs, starting RAL- vs. NNRTI-based ART was associated with a 50% increased risk of DM (HR = 1.50, CI: 1.11–2.03).ConclusionInitiating ART with INSTI- or PI- vs. NNRTI-based regimens may confer increased risk of incident DM, though risk is heterogeneous among INSTIs. Further research is needed to determine whether this elevated risk can be attributed to weight gain. DisclosuresKassem Bourgi, MD, Gilead Sciences (Grant/Research Support), Joseph J. Eron, MD, Gilead Sciences (Consultant, Grant/Research Support), Janssen (Grant/Research Support), Merck (Consultant), ViiV Healthcare (Consultant, Grant/Research Support), M. John Gill, MB, ChB, MSc, Gilead (Board Member), Merck (Board Member), Viiv (Board Member), Michael Silverberg, PhD, MPH, Gilead (Grant/Research Support). Other Authors: No reported disclosures.

Long-term loss to follow-up in the TREAT Asia HIV Observational Database (TAHOD).

With earlier antiretroviral therapy (ART) initiation, time spent in HIV care is expected to increase. We aimed to investigate loss to follow-up (LTFU) in Asian patients who remained in care 5 years after ART initiation. Long-term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression. Under the 12-month definition, the LTFU rate was 2.0 per 100 person-years (PY) [95% confidence interval (CI) 1.8-2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub-hazard ratio (SHR) 1.64; 95% CI 1.17-2.31] compared with 31-40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16-2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06-2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self-reported adherence ≥ 95%, and in those living in high-income countries. The 6-month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9-3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006-2009: SHR 2.38; 95% CI 1.93-2.94; and 2010-2011: SHR 4.26; 95% CI 3.17-5.73) compared with 2003-2005. The long-term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6-month analysis, but not the 12-month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia.

The shift in tuberculosis timing among people living with HIV in the course of antiretroviral therapy scale-up in Malawi.

IntroductionAlthough the use of antiretroviral therapy (ART) reduces HIV‐associated tuberculosis (TB), patients living with HIV receiving ART remain at a higher risk of developing TB compared to those without HIV. We investigated the incidence of TB and the proportion of HIV‐associated TB cases among patients living with HIV who are receiving ART.MethodsThe study used TB registration and ART programme data collected between 2008 and 2017 from an integrated, public clinic in urban Lilongwe, Malawi. ART initiation was based on either WHO clinical staging or CD4 cell count. The CD4 thresholds for ART initiation eligibility was initially 250 cells/μL then changed to 350 cells/μL in 2011, 500 cells/μL in 2014 and to universal treatment upon diagnosis from 2016. Using TB registration data, we calculated the proportion of TB/HIV patients who were already on ART when they registered for TB treatment by year of TB registration. ART registration data were used to examine TB incidence by calendar year of ART follow‐up and by time on ART.ResultsThe overall proportion of TB/patients living with HIV who started TB treatment while on ART increased from 21% in 2008 to 81% in 2017 but numbers remained relatively constant at 500 TB cases annually. The overall incidence rate of TB among patients on ART was 1.35/100 person‐years (95% CI 1.28 to 1.42). The incidence of TB by time on ART decreased from 6.4/100 person‐years in the first three months of ART to 0.4/100 person‐years after eight years on ART. TB incidence was highest in the first month on ART. The annual rate of TB among patients on ART rapidly decreased each calendar year and stabilized at 1% after 2013. Although the risk of developing TB decreased with year of ART initiation in univariable analysis, there was no significant association after adjusting for sex, age and reason for ART eligibility.ConclusionsThe decline in TB incidence over calendar years suggests protective effects of early ART initiation. The high TB incidence within the first month of ART highlights the need for more sensitive tools such as X‐ray and GeneXpert to identify patients living with HIV who have clinical and subclinical TB disease at ART initiation.

Short Communication: Relationship Between Contraindicated Drug-Drug Interactions and Subsequent Hospitalizations Among Patients Living with HIV Initiating Combination Antiretroviral Therapy.

Persons living with HIV (PLWH) are at an increased risk of contraindicated drug-drug interactions (XDDIs), which may result in deleterious outcomes. Study objectives were to (1) compare the frequency of hospitalizations between patients with and without XDDIs and (2) determine if XDDIs are independently associated with hospitalizations in PLWH. A retrospective cohort study was performed among PLWH receiving care at the Upstate New York Veterans' Healthcare Administration or University of New Mexico Truman Health Services from 2000 to 2013. Hospitalization was defined as an admission to an inpatient hospital facility for ≥24 h. Of the 1329 patients evaluated, 149 (11.2%) patients were hospitalized within 1 year of antiretroviral therapy initiation. A significantly higher proportion of patients with XDDIs were hospitalized compared with those who did not have XDDIs (20.3% vs. 10.2%, risk ratio: 1.98, 95% confidence interval [CI]: 1.35-2.91, p = .001). In the multivariate Cox proportional hazards regression analyses, XDDIs were independently associated with hospitalizations (hazard ratio [HR]: 1.58; 95% CI: 1.00-2.48; p = .05), after adjustment for CD4 < 242 cells/mm3 (HR: 2.38; 95% CI: 1.72-3.33; p < .001), protease inhibitor (PI)-based regimen (HR: 1.35; 95% CI: 0.97-1.89; p = .08), recreational drug use (HR: 2.58, 95% CI: 1.85-3.58, p < .001), and non-HIV medications ≥10 (HR: 1.62; 95% CI: 0.97-2.69; p = .07). In this study an increased risk of hospitalization was observed among PLWH with XDDIs compared with those without XDDIs. This relationship persisted after adjustment for CD4 count, use of a PI-based regimen, recreational drug use, and number of non-HIV medications.

A decade of antiretroviral therapy in Uganda: what are the emerging causes of death?

BackgroundThe roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa.MethodsWe used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death.ResultsOf the 559, (386, 69%) were female, median age 36 years (IQR: 21–44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21–163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi’s Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%).ConclusionDespite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.

Outcome of antiretroviral therapy: a longitudinal study in Nalgonda district, Telangana

Background: India is among the list of countries with highest HIV prevalence. Retention in care is vital to maintain good health and obtain antiretroviral therapy (ART) medicines on time. The objectives of the study were to study the clinico-demographic profile of study population and to study the outcome of ART after one year of treatment initiation.Methods: This is an observational follow up (longitudinal) study done on 142 patients which included all newly diagnosed (diagnosed on or after 1st January 2012), sero positive, adult patients, enrolled at an ART centre and started on treatment during the months of December 2012, January 2013, February 2013, using a pre-designed, pre-tested questionnaire. They were visited again a year after ART initiation and outcome was assessed along with determinants of poor outcome.Results: Mortality at the end of one year was 9.15%, rate of loss to follow up (LFU) was 7.6%.Therefore a total of 73.2% cases were retained in care and 26.8% were disengaged from care (LFU and dead) after one year of ART initiation. Risk factors found to have significant association with being disengaged from care were male sex, unmarried/widowed/divorced/separated individuals, lower socio economic status, illiteracy, unskilled occupation, spouse status negative for HIV, presence of addictions like alcoholism, smoking, experience of drug side effects, early WHO clinical stage, presence of opportunistic infections and low CD4 counts.Conclusions: Many of the risk factors are amenable for intervention and may be incorporated to strengthen the programme.