Second-line Antiretroviral Therapy Research Articles

Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial

Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and <14 kg). Children weighing less than 14 kg starting first-line or second-line ART were enrolled in seven HIV treatment centres in South Africa, Uganda, and Zimbabwe. Randomisation, which was computer generated by the trial statistician, was stratified by first-line or second-line ART and three weight bands. Dispersible 5 mg dolutegravir was dosed according to WHO weight bands. The primary outcome was the Kaplan-Meier estimated proportion of children with virological or clinical failure by 96 weeks, defined as: confirmed viral load of at least 400 copies per mL after week 36; absence of virological suppression by 24 weeks followed by a switch to second-line or third-line ART; all-cause death; or a new or recurrent WHO stage 4 or severe WHO stage 3 event. The primary outcome was assessed by intention to treat in all randomly assigned participants. A primary Bayesian analysis of the difference in the proportion of children meeting the primary outcome between treatment groups incorporated evidence from the higher weight cohort (≥14 kg) in a prior distribution. A frequentist analysis was also done of the lower weight cohort (<14 kg) alone. Safety analyses are presented for all randomly assigned children in this study (<14 kg cohort). ODYSSEY is registered with ClinicalTrials.gov, NCT02259127. Between July 5, 2018, and Aug 26, 2019, 85 children weighing less than 14 kg were randomly assigned to receive dolutegravir (n=42) or standard of care (n=43; 32 [74%] receiving protease inhibitor-based ART). Median age was 1·4 years (IQR 0·6-2·0) and median weight 8·1 kg (5·4-10·0). 72 (85%) children started first-line ART and 13 (15%) started second-line ART. Median follow-up was 124 weeks (112-137). By 96 weeks, treatment failure occurred in 12 children in the dolutegravir group (Kaplan-Meier estimated proportion 31%) versus 21 (48%) in the standard-of-care group. The Bayesian estimated difference in treatment failure (dolutegravir minus standard of care) was -10% (95% CI -19% to -2%; p=0·020), demonstrating superiority of dolutegravir. The frequentist estimated difference was -18% (-36% to 2%; p=0·057). 15 serious adverse events were reported in 11 (26%) children in the dolutegravir group, including two deaths, and 19 were reported in 11 (26%) children in the standard-of-care group, including four deaths (hazard ratio [HR] 1·08 [95% CI 0·47-2·49]; p=0·86). 36 adverse events of grade 3 or higher were reported in 19 (45%) children in the dolutegravir group, versus 34 events in 21 (49%) children in the standard-of-care group (HR 0·93 [0·50-1·74]; p=0·83). No events were considered related to dolutegravir. Dolutegravir-based ART was superior to standard of care (mainly protease inhibitor-based) with a lower risk of treatment failure in infants and young children, providing support for global dispersible dolutegravir roll-out for younger children and allowing alignment of adult and paediatric treatment. Paediatric European Network for Treatment of AIDS Foundation, ViiV Healthcare, UK Medical Research Council.

Adaption of an ongoing clinical trial to quickly respond to gaps in changing international recommendations: the experience of D2EFT

A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART.

Durability of switched therapy after failure of WHO-recommended antiretroviral therapy regimens in a resource-limited setting.

The study investigated the durability of switched therapy and factors associated with the viral rebound among patients on second-line antiretroviral therapy (ART) in Uganda. A retrospective dynamic cohort of adults initiated on second-line ART after virological failure to first-line ART. Patients on second-line treatment for at least 6 months between 2007 and 2017 were included. Patients were followed, until they experienced a viral rebound (viral load ≥200 copies/ml). Cumulative probability of viral rebounds and factors associated with viral rebound were determined using Kaplan-Meier methods and Cox proportional hazard models. One thousand, one hundred and one participants were enrolled of which 64% were women, the median age was 37 years [interquartile range (IQR) 31-43]. The preswitch median CD4 + cell count and viral load were 128 cells/μl (IQR 58-244) and 45 978 copies/ml (IQR 13 827-139 583), respectively. During the 4190.37 person-years, the incidence rate of viral rebound was 83.29 [95% confidence interval (CI) 74.99-92.49] per 1000 person-years. The probability of viral rebound at 5 and 10 years was 0.29 (95% CI 0.26-0.32) and 0.62 (95% CI 0.55-0.69), respectively. The median rebound-free survival was 8.7 years. Young adults (18-24 years) [adjusted hazard ratio (aHR) 2.49, 95% CI 1.32-4.67], preswitch viral load at least 100 000 copies/ml (aHR 1.53, 95% CI 1.22-1.92), and atazanavir/ritonavir (ATV/r)-based second-line (aHR 1.73, 95% CI 1.29-2.32) were associated with an increased risk of viral rebound. Switched therapies are durable for 8 years after failure of recommended regimens. A high preswitch viral load, ATV/r-based regimens, and young adulthood are risk factors for viral rebound, which underscores the need for more durable regimens and differentiated care services.

Suboptimal immune recovery and associated factors among people living with HIV/AIDS on second-line antiretroviral therapy in central China: A retrospective cohort study.

The introduction and scale-up of antiretroviral therapy (ART) have contributed to significantly improved patients with acquired immune deficiency syndrome (AIDS) quality of life and prolongs their survival. This has occurred by suppressing viral replication and recovering the CD4 cell count. However, some patients do not normalize their CD4 cell count, despite suppression of the viral load (VL). Patients with suboptimal immune recovery (SIR), as defined by a VL < 400 copies/ml with a CD4 cell count of<200 cells/μl, after ART initiation, exhibit severe immune dysfunction and have a higher risk of AIDS and non-AIDS events. In recent years, People living with HIV/AIDS (PLWHA) with first-line ART failure began to gradually switch to second-line ART. This study aimed to examine the prevalence and factors affecting SIR among PLWHA who switch to second-line ART in rural China. A 1-year retrospective cohort study was conducted among PLWHA who switched to second-line ART between January 2009 and December 2018. All patients with a VL < 400 copies/ml after 1 year of second-line ART were included. SIR was defined as a CD4 cell count <200 cells/μl and a VL < 400 copies/ml after 1 year of second-line ART. The data collected from medical records were analyzed by univariate and multivariate analyses. A total of 5294 PLWHA met the inclusion criteria, 24 died, and 1152 were lost to follow-up after 1 year of second-line ART. Among 4118 PLWHA who were followed up, 3039 with a VL < 400 copies/ml had their data analyzed, and the prevalence of SIR was 13.1%. The patients' mean age at recruitment was 47.6 ± 8.1 years and 45.3% were men. A total of 30.7% of patients were HIV-positive for >8 years and 88.2% were receiving ART before starting second-line ART for >3 years. The mean CD4 cell count was 354.8 ± 238.2 cells/μl. A multivariable analysis showed that male sex, single status (unmarried or divorced), and a low CD4 cell count were risk factors for SIR among PLWHA with second-line ART. The prevalence of SIR among PLWHA who switched to second-line ART in this retrospective cohort study is lower than that in most other studies. Several factors associated with SIR include male sex, marital status, and CD4 cell count levels in PLWHA.

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.

BackgroundIn 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.MethodsA 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.ResultsOverall, 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).ConclusionIn 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.

Incidence and Predictors of Virological Failure Among Adult HIV/AIDS Patients on Second-Line Anti-Retroviral Therapy, in Selected Public Hospital of Addis Ababa, Ethiopia: Retrospective Follow-Up Study.

IntroductionVirological suppression for persons living with HIV (PLHIV) on antiretroviral therapy (ART) reached 85% at the end of 2018, still falling short of the UNAIDS target of 95%. In Ethiopia, there were studies on treatment failure focusing on viral suppression and immunological failure of ART users, but none of them have addressed virological failure for second-line regimens.ObjectiveThis study was aimed to estimate the incidence and predictors of virological failure among HIV patients who were switched to second-line ART at the selected public hospitals in Addis Ababa.MethodsAn institutional-based retrospective follow-up study was conducted from September 2018 to January 2021 at public hospitals in Addis Ababa. The sample size was determined by using the Schoenfeld formula. Data entry were done by Epi Data version-4.6.0.0 and exported to R-software version-4.1.0 for analysis. Kaplan–Meier methods were used to compare the survival estimates. Cox proportional hazard model was used to identify predictors of virological failure and model adequacy was checked by using the Cox–Snell residuals plot.ResultsOverall 44 (12.22%) HIV/AIDS patients developed virological failure with incidence density of 3.57/1000 Person-Month (PM) with 95% CI of [2.65–4.79]. Age >45 years (AHR=0.36, 95% CI: 0.12–0.99), CD4 count <100cell/mm3 (AHR=3.02, 95% CI: 1.17–7.78), TB co-infection (AHR=2.48, 95% CI: 1.10–6.33), ATV/r-based second-line regimen (AHR=0.27, 95% CI: 0.11–0.70), and poor adherence at the start of second-line ART (AHR=6.18, 95% CI: 1.93–19.76) were the significant predictors of virological failure.ConclusionA high incidence of virological failure was noticed. The rate of virological failure was higher for patients who had poor ART adherence, small CD4count, and TB co-infection. Therefore, targeted HIV care interventions shall be provided to young ages and efforts stepped up to improve adherence to ART, which helps to increase immunity and suppress viral replication. In addition, prevention and early detection of TB co-infection are crucial to the patients.

Prevalence of HIV-associated Co-infections and Clinical Characteristics among HIV/AIDS Outpatients in the Context of Dolutegravir Roll-out Program in Vietnam

The prevalence of significant HIV-associated co-infections and clinical data of HIV/AIDS outpatients in the context of dolutegravir (DTG) transition are sparsely reported in Vietnam. Treatments of HIV co-infection, including antifungals, anti-tuberculous drugs, and direct-acting antiviral agents for viral hepatitis C, potentially challenge the efficacy of DTG-based therapies in terms of drug-to-drug interactions. We conducted a single-center, cross-sectional study between June and October 2020 in Ho Chi Minh City, Vietnam. HIV-infected outpatients were enrolled in the study when they attended the clinic to receive medical consultations and antiretroviral therapy (ART). Descriptive analyses were performed to describe the data. A total of 406 HIV-infected participants were enrolled in the study. The prevalence of HIV co-infected with chronic viral hepatitis B and C were 9.9% and 10.6%, respectively. Approximately 22.2% of HIV-infected patients had a history of tuberculosis treatment, and roughly 9% of participants experienced invasive fungal infections, mainly cryptococcosis, taralomycosis, and Pneumocystic jirovecii pneumonia. History of sexually transmitted diseases accounted for 40.4%. At the time of DTG transition, roughly 93% of patients were clinically stable, with a median CD4 count of 603 cells/µl. Two-thirds of HIV-infected patients achieved viral suppression (HIV viral load threshold &lt; 20 copies/ml). A total of thirteen (3.2%) patients were ongoingly undertaking protease-inhibitors-based second-line ART regimens. The ART adherence was assessed at 92.1%. The prevalence of HIV-associated co-infections is still high in the context of DTG transition in Vietnam. More effort is needed in order to achieve the UNAIDS 90-90-90 targets.

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

BackgroundDepression 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.MethodsA 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.ResultsDepression was reported in 27.7% of HIV patients on second-line therapy [95% CI: 24.7–31.1%]. Social support has a direct [widehat{beta } = − 0.9, (95% CI: − 1.11 to − 0.69)] and indirect [widehat{beta } = − 0.22, (95% CI: − 0.31 to − 0.13)] negative effect on depression. Perceived stigma was a mediator variable and significantly associated with depression [widehat{beta } = 0.40, (95% CI: 0.23–0.57)]. Co-morbid illness [widehat{beta } = 0.49, (95% CI: 0.35–0.63)], high viremia [widehat{beta } = 0.17, (95% CI: 0.08–0.26], moderate and high-risk substance use [widehat{beta } = 0.29, (95% CI: 0.18–0.39)], and not-workable functional status [widehat{beta } = 0.2, (95% CI: 0.1–0.31)] were all positively associated with depression.ConclusionsThis 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.

Treatment failure, death, and predictors among PLWHIV on second-line antiretroviral therapy in Dessie Comprehensive Specialized Hospital, northeast Ethiopia: A retrospective cohort study.

BackgroundThe proportion of HIV patients on second-line antiretroviral therapy is becoming a growing public health concern, especially in a low-income country setting. However, unlike first-line therapy, to date, very little is known about the outcomes of second-line therapy in the Ethiopia context. Thus, this study was conducted to determine the rate of treatment failure, death, and their predictors among HIV patients receiving second-line therapy.MethodsA retrospective cohort study was conducted on 642 people living with HIV in Dessie Comprehensive Specialized Hospital from October 2016 to November 2019. Poisson and competitive risk survival models were computed to explore predictors of treatment failure and death, respectively.ResultsDuring follow-up period, 39 (6.87%, 95% CI: 5–9.2%) of 568 patients had second-line treatment failure with 4.07 per 100 person-year rate of failure. Being on anti-TB treatment [Rate ratio, RR = 2.57 (95% CI: 1.25–5.25)], not having optimal medication adherence [RR = 2.29 (95% CI: 1.09–4.78)], and not timely switched [RR = 5.89 (95% CI: 1.36–25.54)] were positively associated with treatment failure. Similarly, 44 (6.85%, 95% CI: 5–9%) of 642 patients died with 4.5 per 100 person-year rate of death. Being on advanced clinical condition [Sub distribution Hazard ratio, SHR = 2.49 (95% CI: 1.31–4.74)], not having optimal medication adherence [SHR = 2.65 (95% CI: 1.31–4.74)], lower CD4 cell counts, and high viral load measurement were positively associated with death.ConclusionsA significant number of patients had failed to respond to second-line therapy. A large number of patients had also died. Patient medical profile and monitoring practice were associated with treatment failure and death. Hence, patient-centered monitoring and interventions should be strengthened, besides treatment switch.

Recurrent pneumothorax in a human immunodeficiency virus-positive patient with multidrug-resistant tuberculosis: a rare case of bronchopleural fistula: a case report

BackgroundHuman immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and multidrug-resistant tuberculosis has become a major public health threat. There is a paucity of data on severe complications of multidrug-resistant tuberculosis in the context of human immunodeficiency virus coinfection despite the increasing prevalence of multidrug-resistant tuberculosis/human immunodeficiency virus coinfection and the complexity of multidrug-resistant tuberculosis treatment. This report describes a rare case of complicated multidrug-resistant tuberculosis in a human immunodeficiency virus-positive individual.Case presentationA 39-year-old human immunodeficiency virus-positive Ugandan male on anti-retroviral therapy for 6 years, who had recently completed treatment for drug-susceptible tuberculosis from a public hospital, presented to the tuberculosis ward of Mulago National Referral Hospital with worsening respiratory symptoms including persistent cough with purulent sputum, fever, right chest pain, and shortness of breath. On admission, a diagnosis of drug-resistant tuberculosis was made following a positive sputum Xpert MTB/Rif test with rifampicin resistance. Culture-based tuberculosis tests and line probe assay confirmed multidrug-resistant tuberculosis. The patient was given multidrug-resistant tuberculosis treatment that included bedaquiline, isoniazid, prothionamide, clofazimine, ethambutol, levofloxacin, and pyrazinamide and switched to second-line anti-retroviral therapy that included tenofovir/lamivudine/lopinavir/ritonavir. Chest X-ray revealed a hydro-pneumothorax, following which a chest tube was inserted. With persistent bubbling from the chest tube weeks later and a check chest X-ray that showed increasing pleural airspace (pneumothorax) and appearance of a new air–fluid level, chest computed tomography scan was performed, revealing a bronchopleural fistula in the right hemithorax. The computed tomography scan also revealed a pyo-pneumothorax and lung collapse involving the right middle and lower lobes as well as a thick-walled cavity in the right upper lobe. With the pulmonary complications, particularly the recurrent pneumothorax, bronchopleural fistula, and empyema thoracis, cardiothoracic surgeons were involved, who managed the patient conservatively and maintained the chest tube. The patient continued to be ill with recurrent pneumothorax despite the chest tube, until relatives opted for discharge against medical advice.ConclusionsComplicated human immunodeficiency virus-related multidrug-resistant tuberculosis is not uncommon in settings of high human immunodeficiency virus/tuberculosis prevalence and is often associated with significant morbidity and mortality. Early diagnosis and treatment of multidrug-resistant tuberculosis, with rigorous monitoring for human immunodeficiency virus-positive individuals, is necessary to prevent debilitating complications.

AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST): protocol for a randomised controlled trial

Background: Dolutegravir has superior efficacy and tolerability than lopinavir-ritonavir in second-line antiretroviral therapy after failure of a first-line non-nucleoside reverse transcriptase inhibitors-based regimen, when dolutegravir is accompanied by at least one fully active nucleoside reverse transcriptase inhibitor (NRTI). Resistance testing to select NRTIs is not feasible in low- and middle-income countries due to cost and limited laboratory capacity. Evidence suggests that recycling tenofovir plus lamivudine or emtricitabine backbone with dolutegravir could provide an effective second-line option. This study aims to determine the virologic efficacy of tenofovir-lamivudine-dolutegravir (TLD) with and without a lead-in supplementary dose of dolutegravir (to counteract the inducing effect of efavirenz) in patients failing a first-line regimen of tenofovir-emtricitabine-efavirenz (TEE). Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled, Phase II trial, comparing TLD fixed dose combination daily with a lead-in supplementary 50 mg dolutegravir dose versus matching placebo taken 12 hours later for the first 14 days, in patients failing a first-line TEE regimen. The trial will be set in two primary care clinics in Khayelitsha; a large, peri-urban informal settlement in Cape Town, South Africa. We will enrol 130 participants, with follow-up to 48 weeks. The primary endpoint is proportion achieving viral load <50 copies/mL at week 24 using a modified intention-to-treat analysis and the U.S. Food and Drug Administration snapshot algorithm. Secondary endpoints include virologic suppression at weeks 12 and 48, time to suppression, emergence of dolutegravir and new NRTI resistance mutations, safety, and tolerability. Discussion: Impaired viral fitness due to NRTI resistance mutations and dolutegravir’s high barrier to resistance provide rationale for switching patients from a failing TEE regimen to TLD; however, clinical evidence regarding virologic efficacy is lacking. This study provides estimates of such a strategy’s early virologic efficacy with and without a supplementary dolutegravir dosing. Registration: ClinicalTrials.gov NCT03991013 (19/06/2019).

Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.

Background:We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda.Methods:This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE.Results:Median time on ART was 86.4 months (interquartile range [IQR], 44.8–130.2 months), and median CD4 count at ART initiation was 311 cells/mm3 (IQR, 197–484 cells/mm3). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022–10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028–0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016–0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084–0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198–5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435–7.278], p = 0.005).Conclusion:The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

Quality of life and associated factors among people receiving second-line anti-retroviral therapy in Johannesburg, South Africa

BackgroundStudies which examine quality of life (QOL) provide important insights that are needed to understand the impacts of HIV/AIDS anti-retroviral treatment (ART), comorbid conditions and other factors on the daily activities of people living with HIV/AIDS (PLH). This study aimed to determine the inter-relationships between clinical factors, behavioural, socio-demographic variables and QOL among PLH.MethodsThe secondary analysis used data collected from 293 people living with HIV/AIDS (PLH) receiving second-line ART in Johannesburg in a clinical trial which evaluated the non-inferiority of ritonavir-boosted darunavir (DRV/r 400/100 mg) compared to ritonavir-boosted lopinavir (LPV/r) over a 48 week-period. Physical functioning, cognitive and mental QOL were measured using the Aids Clinical Trial Group questionnaire. Exploratory factor analyses were used to examine the structure, the relationships between and the construct validity of QOL items. Structural equation models which tested the a priori-hypothesised inter-relationships between QOL and other variables were estimated and goodness of fit of the models to the data was assessed.ResultsPatients on darunavir presented with lower pill burden. Older patients and women were more likely to report lower QOL scores. Pill burden mediated the effects of age, sex and treatment regimen on physical functioning QOL and adverse effects; the effects of age, sex, treatment regimen and adverse effects on cognitive QOL; and the effects of sex on mental QOL.ConclusionQOL among PLH is associated with socio-demographic and clinical factors. Therefore, QOL could be enhanced by considering PLH characteristics, clinical factors such as regimen side-effects profile, management of comorbid conditions and mitigating risks such as potential adverse drug-to-drug interactions among patients on ART.

Disengagement From HIV Care and Failure of Second-Line Therapy in Nigeria: A Retrospective Cohort Study, 2005-2017.

Understanding the correlates of disengagement from HIV care and treatment failure during second-line antiretroviral therapy (ART) could inform interventions to improve clinical outcomes among people living with HIV (PLHIV). We conducted a retrospective cohort study of PLHIV aged >15 years who started second-line ART at a tertiary center in Nigeria between 2005 and 2017. Participants were considered to have disengaged from care if they had not returned within a year after each clinic visit. Cox proportional hazard models were used to investigate factors associated with: (1) viral failure (HIV-1 RNA >1000 copies/mL), (2) immunologic failure (CD4 count decrease or <100 cells/mm3), and (3) severe weight loss (>10% of bodyweight), after >6 months of second-line ART. Among 1031 participants, 33% (341) disengaged from care during a median follow-up of 6.9 years (interquartile range 3.7-8.5). Of these, 26% (89/341) subsequently reentered care. Disengagement was associated with male gender, age <30 years, lower education level, and low CD4 count at second-line ART initiation. Among participants with endpoint assessments available, 20% (112/565) experienced viral failure, 32% (257/809) experienced immunologic failure, and 23% (190/831) experienced weight loss. A lower risk of viral failure was associated with professional occupations compared with elementary: adjusted hazard ratio 0.17 (95% confidence interval 0.04 to 0.70). Adverse outcomes were common during second-line ART. However, reengagement is possible and resources should be allocated to focus on retaining PLHIV in care and providing services to trace and reengage those who have disengaged from care.

Game-changing study of second-line HIV treatment

When a randomised controlled trial has relevant clinical and public health implications and is going to change WHO's guidelines on second-line antiretroviral therapy (ART) in Africa and other resource-limited settings, it deserves to be called game-changing. It is the dream of every researcher.

Antiretroviral therapy uptake and predictors of virological failure in patients with HIV receiving first-line and second-line regimens in Johannesburg, South Africa: a retrospective cohort data analysis

ObjectiveThis study described the demographics, treatment information and identified characteristics associated with virological failure and being lost to follow-up (LTFU) for patients with HIV on first-line and second-line antiretroviral therapy...

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

BackgroundMedication 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.MethodsA 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.ResultsThe 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.ConclusionsA 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.

Detection of HIV Virologic Failure and Switch to Second-Line Therapy: A Systematic Review and Meta-analysis of Data From Sub-Saharan Africa.

BackgroundThe late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a systematic review and meta-analysis to determine if the recognition and response to VF in the region has improved.MethodsWe searched for studies reporting CD4 count at confirmed VF or at switch to second-line antiretroviral therapy (ART). Using a random-effects metaregression model, we analyzed temporal trends in CD4 count at VF—or at second-line ART switch—over time. We also explored temporal trends in delay between VF and switch to second-line ART.ResultsWe identified 26 studies enrolling patients with VF and 10 enrolling patients at second-line ART switch. For studies that enrolled patients at VF, pooled mean CD4 cell count at failure was 187 cells/mm3 (95% CI, 111 to 263). There was no significant change in CD4 count at confirmed failure over time (+4 cells/year; 95% CI, –7 to 15). Among studies that enrolled patients at second-line switch, the pooled mean CD4 count was 108 cells/mm3 (95% CI, 63 to 154). CD4 count at switch increased slightly over time (+10 CD4 cells/year; 95% CI, 2 to 19). During the same period, the mean delay between confirmation of VF and switch was 530 days, with no significant decline over time (–14 days/year; 95% CI, –58 to 52).ConclusionsVF in Africa remains an event recognized late in HIV infection, a problem compounded by ongoing delays between VF and second-line switch.

Higher Risk of Mortality and Virologic Failure in HIV-Infected Patients With High Viral Load at Antiretroviral Therapy Initiation: An Observational Cohort Study in Chongqing, China.

BackgroundViral load (VL) is a strong predictor of human immunodeficiency virus (HIV) disease progression. The aim of this study was to evaluate the effect of high baseline VL on antiretroviral therapy (ART) outcomes among HIV-infected patients.MethodsThis retrospective study observed HIV-infected patients who had baseline VL test at ART initiation between 2015 and 2019 in Chongqing, China. Cox proportional hazards regression and logistic regression models were used to evaluate the effects of baseline VL on Acquired immunodeficiency syndrome (AIDS)-related mortality and virologic failure, respectively.ResultsThe cohort included 7,176 HIV-infected patients, of whom 38.7% had a baseline VL ≥ 100,000 copies/mL. Of the patients who died during follow-up, 58.9% had a baseline VL ≥ 100,000 copies/mL. Compared with a baseline VL < 10,000 copies/mL, ART initiation at VL ≥ 100,000 copies/mL was significantly associated with the AIDS-related death (adjusted hazard ratio, AHR = 1.4) and virologic failure (adjusted odds ratio, AOR = 2.4). Compared with patients with a baseline VL < 10,000 copies/mL, patients on the recommended first-line regimen with a VL ≥ 100,000 copies/mL at ART initiaition had higher mortality rate (5.1 vs. 1.7 per 100 person-years), but there was no significant difference in the mortality accoding to the initial VL level among patients on second-line ART (2.8 vs. 2.7 per 100 person-years). ART initiation ≤ 30 days after HIV diagnosis was associated with a lower risk of AIDS-related death (AHR = 0.6).ConclusionsART initiation with VL ≥ 100,000 copies/mL was associated with a significantly greater risk of mortality and virologic failure. Optimizing the ART regimen and initiating ART early may help to reduce mortality effectively among patients with a high baseline VL. VL testing for all HIV patients is recommended at HIV diagnosis or on ART initiation.

Effects of Chinese Medicine on the Survival of AIDS Patients Administered Second-Line ART in Rural Areas of China: A Retrospective Cohort Study Based on Real-World Data

Objectives Chinese medicine (CM) improves the symptoms of patients with acquired immune deficiency syndrome (AIDS) and prolongs their survival. This real-world study aimed to evaluate the effects of CM on the survival of AIDS patients administered second-line antiretroviral therapy (ART). Methods We conducted a retrospective cohort study of the medical records of patients with AIDS who switched to second-line ART between January 2009 and December 2014. Patients were divided into ART and CM + ART groups. Propensity score matching (PSM) was performed to correct for biases between groups. Kaplan–Meier analysis and the log-rank test were used to compare survival rates, and Cox regression models were employed to identify factors significantly associated with survival. Results The study population (n = 4180) was comprised of the CM + ART group (n = 855) and the ART group (n = 3325). After 1 : 2 PSM, 855 patients in the CM + ART group and 1699 in the ART group were selected for analysis. Patients in the CM + ART group were followed for 4246.8 person-years, and the mortality rate was 2.12/100 person-years. Patients in the ART group were followed for 8381.2 person-years, and the mortality rate was 2.91/100 person-years. Cox regression model analysis revealed that patients in the CM + ART group survived significantly longer than those in the ART group (hazard ratio: 0.73 and 95% confidence interval: 0.57–0.93). Gender, age, symptoms, CD4 cell counts, and viral loads were independently associated with the survival of AIDS patients treated with second-line ART. Conclusions CM significantly improved the survival rate of AIDS patients treated with second-line ART.