Resistance to protease inhibitors among persons living with HIV in Ghana: a case for viral load and drug resistance monitoring.

OBJECTIVE: Routine viral load and drug resistance testing are well supported in most resource-rich settings and provide valuable benefits in the clinical care of PLWH in these communities. Undoubtedly, there exist financial and political constraints for the scale-up of viral load and drug resistance testing in Sub-Saharan Africa. To achieve the global UNAIDS 95/95/95 targets, there is the need to bridge this inequity in patient care and allow for a universal approach that leaves no community behind. METHODS: Venous blood from 96 PLWH on second-line ART from Korle-Bu Teaching Hospital were collected and processed into plasma for CD4+ T- cell and viral load assessments. Ribonucleic acid (RNA) was extracted from stored plasma and the protease gene amplified, sequenced and analyzed for subtype and drug resistance mutations using the Stanford HIV drug resistance database. RESULTS: Out of the 96 PLWH, 37 experienced virological failure with 8 patients' samples successfully sequenced. The predominant HIV-1 subtype identified was CRF02_AG (6/8, 75.0%) with 12.5% (1/8) each of CFR06_cpx infection and one case unable to subtype. The major PI resistance mutations identified were; M46I, I54V, V82A, I47V, I84V and L90M. CONCLUSIONS: Persons living with HIV who had experienced virologic failure in this study harboured drug resistance mutations to PI, thus compromise the effectiveness of the drugs in the second line. Resistance testing is strongly recommended prior to switching to a new regimen. This will help to inform the choice of drug and to achieve optimum therapeutic outcome among PLWH in Ghana.

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021.

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4-2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Time to Treatment Failure and Its Predictors Among Second-Line ART Clients in Amhara Region, Ethiopia: A Retrospective Follow-Up Study.

Background: Second-line antiretroviral treatment failure has become a major public health issue, and the time to treatment failure among second-line ART clients varies globally, and the Sub-Saharan African region having a high rate of second-line ART treatment failures. In addition, after the ART treatment guideline changed there is limited information on Ethiopia. Therefore, this study aimed to assess time to treatment failure and its determinants among second-line ART clients in Amhara Region, Ethiopia. Methods: A multi-centered retrospective follow-up study was conducted. A random sample of 860 people on second-line ART was selected by using a computer-generated simple random sampling technique from January 30, 2016, to January 30, 2021, at the University of Gondar Compressive Specialized Hospital, Felege Hiwot Compressive Specialized Referral Hospital, and Debre Tabor Compressive Specialized Referral Hospital, in Amhara region, Ethiopia. Data was captured using a checklist. Results: A total of 81 (9.4%) ART clients developed second-line treatment failure, with a median follow-up time of 29 months with an interquartile range (IQR: 18, 41]. The risk of second-line treatment failure is higher among patients aged 15 to 30 years (adjusted hazard ratio (AHR) = 2.01, 95% confidence interval (CI): [1.16, 3.48]). Being unable to read and write (AHR = 1.312, 95% CI: [1.068, 1.613]), and poor ART drug adherence (AHR = 3.067, 95% CI: [1.845, 5.099]) were significant predictors of second-line ART treatment failures. Conclusion: In the current study, the time to second-line ART treatment failure was high compared with a previous similar study in Ethiopia. Factors like being younger age, ART clients who are not being able to read and write, and having poor ART drug adherence was significant predictors of second-line ART treatment failure.

Second-Line Antiretroviral Treatment Outcomes and Predictors in Tigray Region, Ethiopia.

Introduction: Ethiopia has one of the highest HIV burdens in sub-Saharan Africa. Despite the fact that second-line antiretroviral therapy (ART) has been available for more than ten years, studies on its effectiveness are scarce. Objective: To assess treatment outcomes and predictors of unfavorable outcomes in HIV patients receiving second-line ART at Ayder Comprehensive Specialized Hospital and Mekelle Hospital. Materials and Methods: An institution-based retrospective cohort study was conducted in two hospitals in Tigray Region, Ethiopia. We evaluated 192 patients aged ≥15 years who were switched to second-line from November 2009 to May 2020 after failure of first-line ART. The primary outcome was the time from the initiation of second-line ART to the occurrence of unfavorable treatment outcomes (treatment failure, death, and loss to follow-up). We performed Kaplan-Meier survival estimates to calculate the cumulative incidence rates of unfavorable outcomes. Results: The mean age (SD) at the initiation of second-line ART was 39 (10.03) years, and the median CD4 cell count was 121 cells/microL. During a median follow-up of 4.6 years, 24 (12.5%) patients had died, 11 (5.7%) patients were lost to follow up, and 47 (24,4%) patients were experienced treatment failure. The incidence rates for unfavorable outcomes were 7.8 per 100 patients/years. Predictors for unfavorable outcomes were body mass index (BMI) <18.5 (adjusted hazard ratio [aHR] = 2.51, 95% confidence interval (CI): 1.27-4.95) and CD4 counts ≤100 cells/microL (aHR = 1.74, 95% CI: 1.09-2.79). Despite the failure of second-line ART, none of the patients received third-line ART. Conclusion: The incidence rate of unfavorable treatment outcomes for second-line ART was found to be high. A low BMI and a low baseline CD4 count were significant predictors of unfavourable outcomes and should be given special consideration in HIV care. A third-line ART regimen should also be considered for people who have failed second-line ART.

Time to Viral Re-suppression and Its Predictors among Adults on Second-Line Antiretroviral Therapy in South Wollo Zone Public Hospitals: Stratified Cox Model.

Background: Even though there are many patients on second-line antiretroviral therapy (ART) in Ethiopia, there is a paucity of evidence on the rate of viral resuppression and its predictors. Therefore, this study aimed to determine a time to viral resuppression and identify predictors among adults on second-line ART in South Wollo public hospitals, northeast Ethiopia. Methods: A retrospective-cohort study design was employed using patients enrolled in second-line ART from August 28, 2016 to April 10, 2021. Data were collected using a structured data-extraction checklist with a sample size of 364 second-line ART patients from February 16 to March 30, 2021. EpiData 4.6 was used for data entry and Stata 14.2 was used for analysis. The Kaplan-Meier method was used for estimating time to viral resuppression. The Shönfield test was used to check the proportional-hazard assumption, and the "no interaction" stratified Cox assumption was checked using the likelihood-ratio test. A stratified Cox model was applied to identify predictors of viral resuppression. Results: Median time to viral re-suppression in patients on a second-line regimen was 10 (IQR 7-12) months. BeingFemale (AHR 1.31, 95% CI 1.01-1.69), low viral load count at switch (AHR 1.98, 95% CI 1.26-3.11), normal-range BMI at switch (AHR 1.42, 95% CI 1.03-1.95), and lopinavir-based second-line regimen (AHR 1.72, 95% CI 1.15-2.57) were significant predictors of early time to viral resuppression after stratification by WHO stage and adherence level. Conclusion: Median time to viral re-suppression after switching to second-line ART was 10 months. In the stratified Cox model, female sex, baseline viral copies, second-line regimen type, and BMI at switch were statistically significant predictors of time to viral resuppression. Different stakeholders working on the HIV program should maintain viral resuppression by addressing significant predictors, and ART clinicians should consider ritonavir-boosted lopinavir based second-line ART for newly switched patients.

Effectors of Hyperlipidemia among HIV/AIDS patients with second-line antiretroviral therapy based on register data.

OBJECTIVE: In this study, we aimed to determine the prevalence and effectors of hyperlipidemia among people living with HIV/AIDS (PLWHA) and taking second-line antiretroviral therapy (ART) using registry data in central China. METHODS: We conducted a cross-sectional study and collected information of PLWHA on second-line ART during 2018 from two medical registries. Hyperlipidemia was defined according to the 2016 Chinese guidelines for the management of dyslipidemia in adults. Univariate and multivariate logistic regression analyses were performed to explore the influencing factors of hyperlipidemia. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2886 PLWHA taking second-line ART were included in this study, and 978 (33.9%) had hyperlipidemia. Female patients, those with hyperglycemia, and patients with CD4+ cell counts >500 cells/µL had a higher prevalence of hyperlipidemia with 37.0%, 49.0%, and 41.3%, respectively. Multivariate analysis showed that CD4+ cell count 350-500 cells/µL (OR=1.72, 95% CI: 1.26-2.38), CD4+ cell count >500 cells/µL (OR=2.49, 95% CI: 1.85-3.38), and FPG >6.2 mmol/L (OR=2.08, 95% CI:1.64-2.65) were risk factors for hyperlipidemia. Male sex (OR=0.72, 95% CI: 0.61-0.85) and Hb <110 g/L (OR=0.59, 95% CI: 0.45-0.76) were protective factors against hyperlipidemia. CONCLUSIONS: PLWHA on second-line ART had a higher prevalence of hyperlipidemia. Gender, CD4+ cell count, FPG, and hemoglobin were influencing factors of hyperlipidemia.

Joint Modeling of Incidence of Unfavorable Outcomes and Change in Viral Load Over Time Among Adult HIV/AIDS Patients on Second-Line Anti-Retroviral Therapy, in Selected Public Hospitals of Addis Ababa, Ethiopia.

Background: In Ethiopia, second-line anti-retroviral therapy (ART) for HIV/AIDS patients was started some years ago; however, few studies have reported the unfavorable outcomes of second-line ART. Therefore, this study aimed to assess the incidence and predictors of unfavorable outcomes and their association with change in viral load among adult HIV/AIDS patients on second-line treatment at selected public hospitals in Addis Ababa, Ethiopia. Methods: A retrospective follow-up study was conducted at selected public hospitals in Addis Ababa, Ethiopia, on 421 HIV/AIDS patients on second-line ART from 2016 to 2021. Cox proportional hazard models with a linear mixed effect model were jointly modeled using the JM package of R software with time-dependent lagged parameterizations, and a 95% confidence interval was used to select significant variables. Results: Overall, 89 HIV/AIDS patients developed unfavorable outcomes. The incidence density was 7.48/100 person-years (95% CI: 6.08, 9.2). Secondary and tertiary educational level (AHR=0.47, 95% CI: 0.25, 0.89, and AHR=0.27, 95% CI: 0.1, 0.72), CD4 count less than 100 cells/mm3 (AHR=2.15, 95% CI: 1.21, 3.83), poor adherence (AHR=3.59, 95% CI: 1.73, 7.49), and TB comorbidity (AHR=2.23, 95% CI: 1.21, 4.14) at the start of second-line ART were significant predictors of incidence of unfavorable outcome. Time-dependent lagged value viral load was significantly associated with the risk of unfavorable outcome (AHR=1.28, 95% CI: 1.01, 1.63). Conclusion: In the study area, the incidence of an unfavorable outcome of second-line ART was high. Secondary and tertiary educational level, CD4 count less than 100 cells/mm3, poor adherence, and TB comorbidity at the start of second-line ART were significant predictors of incidence of unfavorable outcomes. Thus, strengthening routine viral load measurement, increase patient adherence, intensive counseling, and strong TB screening are needed in the study setting.

Social support, perceived stigma, and depression among PLHIV on second-line antiretroviral therapy using structural equation modeling in a multicenter study in Northeast Ethiopia.

BACKGROUND: Depression has a multitude of clinical and public health consequences for HIV patients. The magnitude of HIV patients who failed first-line antiretroviral treatment and switched to second-line therapy is becoming a growing public health concern. However, unlike first-line therapy, to date, little attention has been given to mental health problems in such patients, particularly in the era of the COVID-19 pandemic. Thus, this research was conducted to determine the magnitude of depression and its determinants among HIV patients on second-line antiretroviral therapy. METHODS: A multi-centered cross-sectional study was conducted on 714 HIV patients on second-line therapy who were selected via systematic random sampling. Data were collected in personal interviews as well as document reviews. The nine-item patient health questionnaire score was used to assess depression, while the three-item Oslo Scale was used to assess social support. The associations between exogenous, mediating, and endogenous variables were identified simultaneously using structural equation modeling. Statistical significance was declared at a P-value less than 0.05, and the effect sizes were presented using 95% CI. RESULTS: Depression was reported in 27.7% of HIV patients on second-line therapy [95% CI: 24.7-31.1%]. Social support has a direct [[Formula: see text] = - 0.9, (95% CI: - 1.11 to - 0.69)] and indirect [[Formula: see text] = - 0.22, (95% CI: - 0.31 to - 0.13)] negative effect on depression. Perceived stigma was a mediator variable and significantly associated with depression [[Formula: see text] = 0.40, (95% CI: 0.23-0.57)]. Co-morbid illness [[Formula: see text] = 0.49, (95% CI: 0.35-0.63)], high viremia [[Formula: see text] = 0.17, (95% CI: 0.08-0.26], moderate and high-risk substance use [[Formula: see text] = 0.29, (95% CI: 0.18-0.39)], and not-workable functional status [[Formula: see text] = 0.2, (95% CI: 0.1-0.31)] were all positively associated with depression. CONCLUSIONS: This study revealed that there was a high prevalence of depression among HIV patients on second-line antiretroviral therapy. Social and clinical factors were associated with depression risk. As a result, screening, prevention, and control strategies, including psychosocial support, should be strengthened in routine clinical care.

Time to Switch to Second-Line Anti-Retroviral Treatment and Its Predictors Among HIV Infected Adults with Virological Failure in Northwest Ethiopia: A Retrospective Follow-Up Study.

Background: HIV treatment failure is a devastating public health challenge worldwide. Low rates and delays in switching are associated with increased death and second-line failure. But the time to switch and predictors are not well studied in Ethiopia. Therefore, this study assessed the time to switch to second-line ART and its predictors among HIV-infected adults with virological failure in Northwest Ethiopia. Methods: An institution-based retrospective follow-up study was conducted from Oct 1/2016 to Feb 28/2020 in Northwest Ethiopia. Secondary data were extracted through a predefined extraction tool from 427 HIV-infected adults, which were selected by systematic random sampling. Kaplan-Meier with log rank test was done to identify the survival time and compare survival time among different categorical independent variables. The Cox proportional hazard model was fitted and variables having a p-value of less than 0.05 with a 95% confidence level were identified as a predictor of time to switch to second-line ART and interpreted accordingly. Results: A total of 288 (67.45%) HIV-infected adults were switched to second-line ART with a median time of 162 days (IQR: 35,682). The risk of switching is higher among HIV infected adults with viral RNA of 60,000 copies/mL or more at failure (AHR=1.80, 95% CI: 1.31-2.48), ≥8 years duration on first-line ART (AHR: 2.31, 95% CI: 1.62, 3.29) and enhanced adherence counseling of 4 to 6 sessions (AHR: 1.28, 95% CI: 1.01, 1.63), and lower with 4 or more missed appointments (AHR: 0.49, 95% CI; 0.28, 0.84) and no history of 1st line regimen change (AHR: 0.53: 95% CI: 0.41,0.69). Conclusion: The median time to switch to second-line ART following 1st line virological failure is about 162 days, higher than other related studies. But switching was higher in patients with high viral RNA copies, missed appointments, longer duration on first-line ART, and the number of enhanced adherence counseling. So, intervention strategies that aid patients to have timely switch without due delays as soon as virologic failure should be prioritized.

The role of health facility and individual level characteristics on medication adherence among PLHIV on second-line antiretroviral therapy in Northeast Ethiopia: use of multi-level model.

BACKGROUND: Medication adherence plays a pivotal role in achieving the desired treatment outcomes. The proportion of HIV patients on second-line antiretroviral therapy is becoming a growing public health concern. However, to date, little attention has been given to second-line antiretroviral medication adherence. Moreover, the association between health facility characteristics and medication adherence has yet not been tested. Thus, this research was conducted to determine the magnitude of medication adherence and examine the role of facility-level determinants among HIV patients on second-line ART. METHODS: A cross-sectional study was conducted on 714 HIV patients on second-line therapy who were selected via systematic random sampling in twenty public health facilities. Medication adherence was measured using the six-item Simplified Medication Adherence Questionnaire (SMAQ) tool. Data were collected in a personal interview as well as document reviews. A multi-level binary logistic regression was used to uncover individual and facility-level determinants. The effect size was presented using an adjusted odds ratio (AOR), and statistical significance was declared at a P value less than 0.05. RESULTS: The magnitude of optimal medication adherence among HIV patients on second-line antiretroviral therapy was 69.5% (65.9-72.7%). Medication adherence was positively associated with the use of adherence reminder methods [AOR = 3.37, (95% CI 2.03-5.62)], having social support [AOR = 1.11, (95% CI 1.02-1.23)], and not having clinical depression [AOR = 3.19, (95% CI 1.93-5.27). The number of adherence counselors [AOR = 1.20, (95% CI 1.04-1.40)], teamwork for enhanced adherence support [AOR = 1.82, (95% CI 1.01-3.42)], and caseloads at ART clinics were all significantly correlated with ARV medication adherence at the facility level. CONCLUSIONS: A large proportion of HIV patients on second-line antiretroviral therapy had adherence problems. Both facility-level and individual-level were linked with patient medication adherence. Thus, based on the identified factors, individual and system-level interventions should be targeted.

Treatment Failure and Associated Factors among Individuals on Second Line Antiretroviral Therapy in Eastern Uganda: A Retrospective Cohort Study.

BACKGROUND: ART failure is a growing public health problem and a major threat to the progress of HIV/AIDS control. In Uganda however, little is documented on treatment outcomes and their associated factors among individuals on second line ART regimen. The rapid scale-up of ART over the past has resulted in substantial reductions in morbidity and mortality. However, as millions of people must be maintained on ART for life, individuals with ART treatment failure are increasingly encountered and the numbers are expected to rise. This could be attributed to factors such as sub-standard regimens, limited access to routine viral load monitoring, treatment interruptions, suboptimal adherence, among others. The purpose of this study was to estimate 5-year cumulative treatment failure and the associated factors among individuals on second line ART regimen Eastern Uganda. MATERIALS AND METHODS: A retrospective analysis of 541 records of HIV positive individuals, switched to second line ART regimen from January 2012 to December 2017. Inferential statistics including the Chi square test and multivariable logistic regression analysis was applied to determine associations of treatment failure against of the selected demographic, laboratory and clinical factors was performed. Associations between treatment failure and the predictors was based on a P-value of less than 5% and confidence intervals level of 95%. RESULTS: We reviewed 541 records of individuals on second line ART regimen, of which 350 (64.7%) were female, 226 (41.8%) were married, and 197 (36.4%) were older than 35 years. The mean age at ART initiation was 30 years (SD = 14.8), while the mean weight at ART initiation was 47 kg (SD = 18.6), (range 4-97 kg). The overall proportion of treatment failure was 23%. The cumulative mortality risk for 5 years was 12.4% and the mortality rate was 2.5 deaths per 100 individuals per year. The odds of developing treatment failure among individuals switched to ATV/r-based regimen were 44% lower as compared to individuals who were switched to LPV/r (ORadj0.56, 95% CI 0.35-0.90, P = .016). while the odds of experiencing treatment failure among individuals that used AZT at ART initiation were 43% lower as compared to individuals that used a TDF based regimen at ART initiation (ORadj0.57, 95% CI 0.33-0.98, P = .041). CONCLUSION: The 5 year cumulative incidence of treatment failure in a cohort of 541 individuals was 23%. The type of protease inhibitor (PI) used in second line regimen and use of AZT at ART initiation were significantly associated with treatment failure. Our study also shows that the cumulative mortality risk while on second line ART regimen was 12.4% while the mortality rate was 2.5 deaths per 100 individuals per year. Given the high level of treatment failure among individuals on second line ART regimen, yet the current ART protocols limits the use of third line ART regimens to only regional referral hospitals, the Ministry of Health should strengthen the surveillance systems for identifying individuals failing on second line ART regimen even at district hospitals and lower health facilities to facilitate timely switch to optimal regimen. The Ministry of health through the Quality Improvement Division should conduct routine onsite support supervision to sites offering ART to ensure that treatment guides and other standard of care like timely switch to appropriate regimens among others are being adhered to. Knowledge gaps identified can also be addressed through onsite Continuous Medical Educations.

Predictors of failure on second-line antiretroviral therapy with protease inhibitor mutations in Uganda.

INTRODUCTION: Failure on second-line antiretroviral therapy (ART) with protease inhibitor (PI) mutations (VF-M) is on the rise. However, there is a paucity of information on the factors associated with this observation in low-income countries. Knowledge of underlying factors is critical if we are to minimize the number of PLHIV switched to costly third-line ART. Our study investigated the factors associated with VF-M. METHODS: We conducted a matched case-control analysis of patients' records kept at the Joint Clinical Research Center, starting from January 2008 to May 2018. We matched records of patients who failed the second-line ART with major PI mutations (cases) with records of patients who were virologically suppressed (controls) by a ratio of 1:3. Data analysis was conducted using STATA Version 14. Categorical variables were compared with the outcomes failure on second-line ART with PI mutations using the Chi-square and Fisher's exact tests where appropriate. Conditional logistic regression for paired data was used to assess the association between the outcome and exposure variables, employing the backward model building procedure. RESULTS: Of the 340 reviewed patients' records, 53% were women, and 6.2% had previous tuberculosis treatment. Males (aOR = 2.58, [CI 1.42-4.69]), and patients concurrently on tuberculosis treatment while on second-line ART (aOR = 5.65, [CI 1.76-18.09]) had higher odds of VF-M. ART initiation between 2001 and 2015 had lower odds of VF-M relative to initiation before the year 2001. CONCLUSION: Males and patients concomitantly on tuberculosis treatment while on second-line ART are at a higher risk of VF-M. HIV/AIDS response programs should give special attention to this group of people if we are to minimize the need for expensive third-line ART. We recommend more extensive, explorative studies to ascertain underlying factors.

Prevalence of nonsuppressed viral load and associated factors among HIV-positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population-based nationally representative surveys.

INTRODUCTION: The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months. METHODS: We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART. RESULTS: We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART. CONCLUSIONS: Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence.

Determinants of Virologic Failure Among Adults on Second Line Antiretroviral Therapy in Wollo, Amhara Regional State, Northeast Ethiopia.

BACKGROUND: Treatment failure among the population on second line antiretroviral therapy is a major public health threat. In Ethiopia there has been limited research done on second line treatment failure. OBJECTIVE: To identify determinants of virologic failure among adults on second line antiretroviral therapy in six public hospitals of Wollo, Amhara regional state, northeast Ethiopia. METHODS: An institution-based unmatched case-control study was conducted from February 1, 2020 to April 30, 2020 on a total of 377 clients in six public hospitals of Wollo, Amhara regional state, northeast Ethiopia. Clients whose viral load result >1,000 copies/mL in two consecutive results at least 3 month apart were cases, while ≤1,000 copies/mL were controls. The sample size was calculated by using Epi-Info version 7. Cases (94) and controls (283) were selected using a simple random sampling method in a ratio of cases-to-controls of 1:3. The model fitted and binary logistic assumptions were fulfilled with 95% confidence level and P-values<0.05 were taken as statistically significant. RESULTS: Virologic failure was predicted by poor adherence (AOR=6.060, 95% CI=2.837-12.944), not disclosing their HIV status (AOR=4.178, 95% CI=1.431-12.198), OI (AOR=4.11, 95% CI=1.827-9.246), CD4 count <100 cells/mm3 (AOR=3.497, 95% CI=1.233-9.923) and 100-350 cells/mm3 (AOR=5.442, 95% CI=2.191-13.513), low BMI <16 kg/m2 (AOR=7.223, 95% CI=2.218-23.520), and young age 15-29 years (AOR=2.898, 95% CI=1.171-7.170). CONCLUSION AND RECOMMENDATIONS: Determinants of second line ART virologic failure were patients who had poor adherence to ART, not disclosed, opportunistic infection, low CD4 counts <350 cell/mm3, low BMI (<16 kg/m2), and young age 15-29 year patients. Social support, disclosing their HIV status, and getting early treatment for any opportunistic infection is crucial to patients.

The Impact of Delayed Switch to Second-Line Antiretroviral Therapy on Mortality, Depending on Definition of Failure Time and CD4 Count at Failure.

Little is known about the functional relationship of delaying second-line treatment initiation for human immunodeficiency virus-positive patients and mortality, given a patient's immune status. We included 7,255 patients starting antiretroviral therapy during 2004-2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting of marginal structural models. The nonlinear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation. We adjusted for measured time-varying confounding by CD4 count, viral load, and visit frequency. Five-year mortality was estimated to be 10.5% (95% CI: 2.2, 18.8) for immediate switch and to be 26.6% (95% CI: 20.9, 32.3) for no switch (51.1% if CD4 count was <100 cells/mm3). The hazard of death was estimated to be 0.37 (95% CI: 0.30, 0.46) times lower if everyone had been switched immediately compared with never. The shorter the delay in switching, the lower the hazard of death-delaying 30-59 days reduced the hazard by 0.53 (95% CI: 0.43, 0.65) times and 60-119 days by 0.58 (95% CI: 0.49, 0.69) times, compared with no switch. Early treatment switch is particularly important for patients with low CD4 counts at failure.

Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings.

BACKGROUND: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). METHODS: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. RESULTS: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. CONCLUSIONS: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.

Determinants of Viral Resuppression or Persistent Virologic Failure After Initial Failure With Second-Line Antiretroviral Treatment Among Asian Children and Adolescents With HIV.

Of 56 children with perinatally acquired human immunodeficiency virus (HIV) who had been prescribed second-line protease inhibitor-based antiretroviral therapy and had ≥1 previous episode of viral failure (HIV RNA, ≥1000 copies/mL), 46% had ≥1, 34% had ≥2, and 23% had ≥3 consecutive episodes of viral failure during the 2 years of follow-up. Two of these children experienced a major protease inhibitor mutation.

Incidence of tuberculosis in HIV-infected adults on first- and second-line antiretroviral therapy in India.

BACKGROUND: Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. METHODS: We estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India. RESULTS: 4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86-5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01-2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02-1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13-2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58-5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen. CONCLUSION: Risk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.

Body mass index variation over time and associated factors among HIV-positive adults on second-line ART in north-west Ethiopia: a retrospective follow-up study.

OBJECTIVES: This study aimed to assess the evolution of body mass index (BMI) of HIV-positive adults on second-line antiretroviral therapy (ART) over time and factors affecting it in north-west Ethiopia. DESIGN: An institution-based retrospective follow-up study was conducted using data extracted from 1016 patient cards from February 2008 to February 2016. SETTING: Eight referral hospitals from Amhara region, Ethiopia were included. PARTICIPANTS: HIV patients who started second-line ART. OUTCOME MEASURES: Change in BMI since starting second-line ART. RESULTS: Five hundred and thirty-eight (52.95%) participants were males and the median age of the participants was 33 years (IQR: 28; 39). The median follow-up time was 18 months (IQR: 5.2; 32.2). The average change of BMI showed linear increase over time. The amount of BMI increment or decrement according to each variable was shown as ß coefficients. Treatment duration (ß=0.013, 95% CI 0.004 to 0.022), isoniazid prophylaxis (ß=0.87, 95% CI 0.32 to 1.42), cotrimoxazole prophylaxis (ß=0.63, 95% CI 0.08 to 1.19), ambulatory functional status (ß=-1.16, 95% CI -1.95 to 1.31), bedridden functional status (ß=-1.83, 95% CI -2.47 to 1.21), WHO stage III (ß=-0.42, 95% CI -0.65 to 0.20), WHO stage IV (ß=-0.62, 95% CI -1.02 to 0.22), CD4 count (ß=0.001, 95% CI 0.0008 to 0.0015), and time interaction of variables like tertiary educational status (ß=0.02, 95% CI 0.01 to 0.04), ambulatory functional status (ß=0.03, 95% CI 0.01 to 0.05) and WHO stages III (ß=0.01, 95% CI 0.007 to 0.02) were found to be significant predictors. CONCLUSION: The BMI of patients has shown linear increment over the treatment time. Factors affecting it have been identified but its effect on cardiovascular disease needs further study.

Second-line antiretroviral therapy failure and characterization of HIV-1 drug resistance patterns in children in Mali.

INTRODUCTION: In recent years, children born to HIV-infected mothers have been receiving antiretroviral treatment (ART) with limited or no virologic monitoring, which increases the likelihood of development and accumulation of drug resistance mutations, which itself may limit the effectiveness of future ART. The objective of this study was to evaluate the prevalence of resistance mutations in children infected with HIV-1 experiencing virological failure to second-line ART in the Pediatric Department of Gabriel Touré Hospital in Mali. METHODS: Children aged from 5 to 18 infected with HIV-1 on second-line antiretroviral therapy and whose viral load was greater than 1000 copies/mL after observance reinforcement were enrolled. The protease and reverse transcriptase genes were sequenced with ViroSeq®. The results were interpreted according to the last version of the Stanford algorithm in 2018. The study was approved by the Ethics Committee of the Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako (Mali). RESULTS: Of 216 children, 33 (15.3%) who had a viral load (VL)>1000 copies/mL in second line were recruited and included in the study. The median plasma viral load was 77,000 copies/mL [IQR (28,000-290,000)] and the median CD4 cell count was 310 cells/mm3 [IQR (152-412)]. The median age was 12 years; 48.5% of patients were treated with a combination of stavudine/lamivudine/nevirapine (Triomune®) for first-line treatment and 60.6% with abacavir/lamivudine/lopinavir/ritonavir for the second-line ART. The median treatment duration was 8.5 years [range, 3-13]. Of the 33 children whose treatment failed, the predominant HIV-1 subtype was CRF02_AG (66.7%). The prevalence of resistance to ART classes was 60.61% (20/33) to nucleoside reverse transcriptase inhibitors (NRTIs), 54.51% (18/33) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 51.52% (17/33) to protease inhibitors (PIs). Of the patients studied, 90.9% were exposed to lopinavir/ritonavir (LPV/r) but only 15.2% (5/33) developed resistance to LPV/r. CONCLUSIONS: This study demonstrated that LPV/r remains active in most patients after second-line ART failure. In children whose second-line ART fails, particular attention should be paid to their ART and adherence history when considering the next treatment option.