Second-line Antiretroviral Treatment Research Articles

Population Pharmacokinetic Analysis of Dolutegravir in Treatment-Experienced Adults Living with HIV-1.

The World Health Organization has recommended the use of dolutegravir (DTG) for both first and second-line antiretroviral treatment in both adults and children down to 4 weeks of age. We developed a population pharmacokinetic(PopPK) model following oral administration of DTG 50 mg QD and 50 mg BID in HIV-infected treatment-experienced adults (607) based on pooled data from four phase 2/3 trials. DTG population pharmacokinetics are described by a one-compartment model with first-order absorption, absorption lag-time, and first-order elimination. The PopPK parameter estimates were apparent oral clearance (CL/F) = 1.00 L/h, apparent volume of distribution (V/F) = 18.9 L, absorption rate constant (Ka) = 1.99 per hour, and absorption lag time = 0.333 h, respectively. The final model included inter-individual and inter-occasion variability on apparent clearance (CL/F). Weight, smoking status, use of metabolic inducers as part of background antiretroviral therapy (ART) classified by their level of induction, use of atazanavir or atazanavir-ritonavir as part of background ART, and albumin level were predictors of CL/F; weight and albumin level were predictors of V/F; and sex and concomitant use of metal cation-containing vitamin/mineral supplements were predictors of relative bioavailability (F). The current model-based analysis suggests that the DTG dose adjustment is not required based on the demographics, laboratory values, smoking status, concomitant use of mild metabolic inducers or inhibitors in the background therapy, or use of metal cation-containing vitamin/mineral supplements because these covariate effects are not predicted to have a clinically relevant impact on safety and efficacy.

Determinants of virological failure among HIV clients on second-line antiretroviral treatment at Felege-hiwot and University of Gondar comprehensive specialized hospitals in the Amhara Region, Northwest Ethiopia: A case-control study.

Second-line HIV treatment failure has become increasing worldwide, mainly in sub-Sahara Africa including Ethiopia. Even though the problem becomes increasing, inadequate information was available about its magnitude and associated factors in the current study area. To assess the factors of second-line Anti-Retroviral Treatment virological failure among second-line ART users. Institutional-based unmatched case-control study design was conducted from September to December 2021 at Felege Hiowt and University of Gondar Comprehensive Specialized Hospitals; Amhara region, Northwest Ethiopia. A total of 216 patients (60 cases and 156 controls) were recruited by a simple random sampling technique with a 1:3 cases-to-controls ratio. Patients who had two viral load results >1000 copies/ml within a 3-month interval after taking ART drugs for at least 6 months were cases and those who had ≤1,000 copies/ mL were controls. The sample size was calculated by using Epi-Info version 7.2.4. Structured questionnaires were used to gather the required information. SPSS version 26 was used to summarize the findings. In bivariate logistic regression model, Variables with two-tailed P-value ≤ 0.25 at 95% confidence interval were transferred into multivariate binary logistic regression model and P value at ≤ 0.05 was set as statistically significant. Out of 216 patients recruited, 212 have participated with a response rate of 98.2%. From these participants, 117(55.2%) were males and 187(88.2%) were urban dwellers. Among the total respondents, 208(98.1%) had age > 24 years, 200(94.3) were at HIV clinical stage I, 72(34%) had poor ART adherence and 112(52.8) did not disclose their HIV status. Likewise, most of the patients 147(69.37) didn't use condoms. The associated factors were not disclosing HIV status (AOR = 3.4, 95% CI: 1.52-7.79), medium adherence (AOR = 3.7, 95% CI = 1.3-10.7), poor adherence level (AOR = 5.27, 95% CI: 2.2-12.5), not using condoms (AOR = 4.47, 95% CI: 1.63-12.2) and Viral load (>150 copies/ml) when switched to second-line ART (AOR = 3.56, 95% CI: 1.5-8). Non-disclosure, poor or medium adherence, not using condoms and high Viral load (>150 copes/ml) when switched to second-line ART were the main factors for second-line Anti-Retroviral Treatment virological failure. Disclosure about HIV status, using condoms and improving treatment adherence level are crucial to reduce second-line virological failure.

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.

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. 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. 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. 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 anti-retroviral treatment failure and its predictors among patients with HIV in Ethiopia: A systematic review and meta-analysis.

Antiretroviral therapy (ART) treatment failure remains a major public health concern, with multidimensional consequences, including an increased risk of drug resistance, compromised quality of life, and high healthcare costs. However, little is known about the outcomes of second-line ART in Ethiopia. Therefore, this systematic review and meta-analysis aimed to determine the incidence and determinants of second-line ART treatment failure. Articles published in PubMed, Google Scholar, Science Direct, and Scopus databases were systematically searched. All observational studies on the incidence and predictors of treatment failure among patients with HIV on second-line ART were included. A random-effects model was used to estimate the pooled incidence, and subgroup analysis was performed to identify the possible sources of heterogeneity. Publication bias was checked using forest plot, Begg's test, and Egger's test. The pooled odds ratio was also computed for associated factors. Seven studies with 3,962 study participants were included in this study. The pooled incidence of second-line antiretroviral treatment failure was 5.98 (95% CI: 4.32, 7.63) per 100 person-years of observation. Being in the advanced WHO clinical stage at switch (AHR = 2.98, 95% CI: 2.11, 4.25), having a CD4 count <100 cells/mm3 (AHR = 2.14, 95% CI: 1.57, 2.91), poor drug adherence (AHR = 1.78, 95% CI: 1.4, 2.25), and tuberculosis co-infection (AHR = 2.93, 95% CI: 1.93, 4.34) were risk factors for treatment failure. In conclusion, this study revealed that that out of 100 person-years of follow-up, an estimated six patients with HIV who were on second-line antiretroviral therapy experienced treatment failure. The risk of treatment failure was higher in patients who were in an advanced WHO clinical stage, CD4 count <100 cells/mm3, and presence tuberculosis co-infection. Therefore, addressing predictors reduces the risk of treatment failure and maximizes the duration of stay in second-line regimens.

Active tuberculosis incidence among treatment failure experienced patients in North Wollow Zone: A multicenter historical cohort.

In Ethiopia, tuberculosis (TB) is a significant cause of death among individuals living with HIV, especially in resource-limited areas and those who have experienced treatment failure. However, there is the paucity of data regarding TB among treatment failures experienced people living with HIV. This study aimed to estimate the rate and identify predictors of tuberculosis among patients who received second-line treatment in North Wollo, Northeast Ethiopia. A retrospective follow-up study was conducted on 474 HIV-infected patients who experienced treatment failure. The study period ranged from January 2015 to September 30, 2021. The incidence of TB was assessed using a Cox proportional hazard regression model, after ensuring that all assumptions were met. Factors associated with active TB were determined by analyzing adjusted hazard ratios and 95% confidence intervals. In a study of 474 HIV-positive patients on second-line antiretroviral treatment, we found an incidence rate of 3.6% with 17 new cases of TB observed over 4412.4 persons per year (PPY). The overall incidence density rate was estimated to be 0.39 cases per 100 PPY (95% CI: 0.239-0.618). Regarding the occurrence of active TB in second-line patients, WHO clinical treatment stage (T3 and T4), missed isoniazid preventive therapy had a significantly higher risk (AHR: 13.225, 95% CI: 2.894-60.434, p = 0.001), while being married was associated with a lower risk (AHR: 0.203, 95% CI: 0.045-0.907, p = 0.001). A high incidence of active TB was observed shortly after initiating second-line antiretroviral treatment. Factors such as being in the WHO clinical treatment stage (T3 and T4) and marital status were determinants for active TB. To improve overall survival rates, it is vital to enhance early TB screening and implement effective isoniazid preventive therapy.

Evaluating Second-line ART Efficacy in Pediatric HIV1 Infections: A Study at Albert Royer Children's Hospital

Introduction: In developing countries, around 15% of children infected with the Human Immunodeficiency Virus (HIV) have access to early diagnosis, and 28% are eligible for antiretroviral treatment (ART). The evaluation studies carried out in Senegal have been limited to children on first-line ART. The main objective of our study was to evaluate the efficacy of second-line ART.&#x0D; Methodology: Data were collected at 3 different sites. This was a retrospective, longitudinal and analytical study, conducted from March 4 to August 28, 2015. The study population consisted of 65 HIV1-infected children. BD FACSCountTM Flow Cytometer for TCD4 lymphocyte counting. For genotyping, 2 sets of PCRs were required. Data were entered and analysed using Word/Excel 2013 and Epi-info7 software.&#x0D; Results: We had 43 boys and 22 girls, giving a sex ratio of 1.95. The extreme ages were 5 and 15 years, and the mean age was 11.43 years. The majority belonged to stage 4 and 2 of the WHO classification. The clinical evolution was favourable in 86.15%, unfavourable in 3.07% and unspecified in 10.76%. We found 9 genotypes and recombinant forms; 80% of the strains were sequenced.&#x0D; Discussion: The general aim of ART is the same as in adults. Clinical stages were not specified in 15.38% of cases. In total, 58.46% had an excellent immunovirological response. We conclude from this that a good IR doesn’t mean a good immunovirological evolution. Initiation of ART should be guided by genotyping.&#x0D; Conclusion-Recommendations: ART reduced morbidity and mortality. Our study showed a virological failure rate of 21.53% and an IR rate of 86.15%.

Prevalence of HIV-1 drug resistance among patients with high viral loads while on second-line antiretroviral treatment in Butha-Buthe and Mokhotlong, Lesotho

Prevalence of HIV-1 drug resistance among patients with high viral loads while on second-line antiretroviral treatment in Butha-Buthe and Mokhotlong, Lesotho

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

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. To assess treatment outcomes and predictors of unfavorable outcomes in HIV patients receiving second-line ART at Ayder Comprehensive Specialized Hospital and Mekelle Hospital. 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. 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 ≤100cells/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. 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.

Virological Failure and its Predictors among Human Immunodeficiency Virus Infected Individuals on Second Line Antiretroviral Treatment in North-East Ethiopia, 2021.

Acquired Immune Deficiency Syndrome (AIDS) becomes a manageable chronic disease due to the presence of effective prevention, diagnosis, treatment, and care accesses. Viral load cascade analyses are important to identify gaps in HIV/AIDS treatment and care for quality improvements OBJECTIVE: Time to Virological Failure and its Predictors among HIV Infected Individuals on Second Line Antiretroviral Treatment (SLART) in North-East Ethiopia, 2021 METHODS: Institution-based retrospective follow-up study was conducted on 474 HIV-infected individuals who were on SLART between September 2016 and April 2020. A universal sampling technique was used to recruit study participants. Data were entered by EpiData-3.3.1 and analyzed by STATA-14. Cox proportional hazard assumptions were checked to determine the effect of predictor variables on Virological Failure (VF). The study was conducted from February 01-April 30/ 2021 RESULT: The rate of Virological Failure (VF) in this study was 15.4% with an incidence rate of 4.93 per 100 person-years. As participants' age and duration of ART use increased by one year the hazards of VF was reduced by 2.9% (AHR: 0.971, 95%CI: 0.945, 0.995) and 10.6% (AHR: 0.894, 95%CI: 0.828, 0.963) respectively. The hazards of VF were twice higher among those who were on a non-protease inhibitor-based regimen. Individuals who had a history of Making Enhanced Adherence Counseling (EAC) sessions during SLART had three times more risk to develop VF (AHR:3.374, 95%CI:1.790, 6.361) CONCLUSION AND RECOMMENDATIONS: The rate of VF among SLART users was high. Keeping SLART users on PI-based regimens may improve virological outcomes in HIV care and treatment. Making EAC sessions effective in promoting better ART adherence might reduce VF. This article is protected by copyright. All rights reserved.

Recycling Tenofovir in Second-line Antiretroviral Treatment With Dolutegravir: Outcomes and Viral Load Trajectories to 72 weeks.

Recycling tenofovir and lamivudine/emtricitabine with dolutegravir (TLD) after failure of non-nucleoside transcriptase inhibitor first-line antiretroviral therapy is more tolerable and scalable than dolutegravir plus optimized nucleoside reverse transcriptase inhibitors. Studies have demonstrated TLD's efficacy as second line, but long-term follow-up is limited. ARTIST is a single arm, prospective, interventional study conducted in Khayelitsha, South Africa, which switched 62 adults with 2 viral loads >1000 copies/mL from tenofovir, lamivudine/emtricitabine, and an non-nucleoside transcriptase inhibitor to TLD. We report efficacy to 72 weeks and, in a post hoc analysis, evaluated viral load trajectories of individuals with viremic episodes. Virologic suppression was 86% [95% confidence interval (CI) 74 to 93], 74% (95% CI: 61 to 84), and 75% (95% CI: 63 to 86) <50 copies/mL and 95%, 84%, and 77% <400 copies/mL at week 24, 48, and 72, respectively, with 89% (50/56) resistant (Stanford score ≥15) to tenofovir and/or lamivudine preswitch. No participants developed integrase-inhibitor resistance. Of the 20 participants not suppressed at week 24 and/or 48, 2 developed virologic failure, 1 switched regimen (adverse event), 2 were lost to follow-up, 1 missed the visit, 1 transferred out, 9 resuppressed <50 copies/mL with enhanced adherence counseling, and 4 remained viremic (3 with <200 copies/mL) at week 72. Recycling NRTIs with dolutegravir was effective for most participants to 72 weeks. Most with viremia did not develop virologic failure and subsequently suppressed with enhanced adherence counseling or continued to have low-level viremia. No integrase-inhibitor resistance was detected despite low-level viremia in a minority of participants.

Second-Line Antiretroviral Treatment Outcome in HIV-Infected Patients Coinfected with Tuberculosis in Pakistan.

Tuberculosis (TB) coinfection in human immunodeficiency virus- (HIV-) infected patients is considered a risk of antiretroviral therapy (ART) failure. Coadministration of antitubercular therapy (ATT) with ART is another challenge for TB management. The study was aimed at investigating contributing factors affecting treatment outcomes in HIV-/TB-coinfected patients. Cross-sectional. Setting. Samples were collected from the Pakistan Institute of Medical Sciences Hospital Islamabad. Subject and Methods. Clinicodemographic and immunovirological factors between the two groups were compared. The Student t-test and chi-square test were applied to compare outcome variables, and logistic regression was applied to determine the effect of TB on virological failure (VF). Main Outcome Measures. TB coinfection did not increase VF even in univariate (p = 0.974) and multivariate analysis at 6 and 12 months of 2nd-line ART start. ARV switching was significant (p = 0.033) in TB-coinfected patients. VF was significantly high in ATT-coadministered patients along with a viral load of ≥1000 (p = 0.000). Sample Size and Characteristics. We recruited seventy-four HIV patients on 2nd-line ART; 33 coinfected with TB were followed for at least 12 months. In HIV-/TB-coinfected patients, CD4 count, CD4 gain, and VF remained comparable to HIV patients with no TB infection. ATT significantly affects the treatment outcome, suggesting drug-to-drug interactions. These factors are important to revisit the therapeutic guidelines to maximize the benefit of dual therapy in resource-limited settings.

A prospective study to estimate the incidence and pattern of adverse drug reactions to first-line antiretroviral therapy (tenofovir, efavirenz, and lamivudine).

Antiretroviral drugs are efficacious but are associated with long-term toxicities, drug interactions, and emergence of drug resistance. To study the incidence and pattern of adverse drug reactions in human immunodeficiency virus (HIV) patients receiving first-line antiretroviral therapy (ART) (tenofovir, efavirenz, and lamivudine (TEL) which was introduced by NACO in 2013. A prospective, single-center observational study that included 135 treatment-naive HIV patients who were started on fixed drug once-daily regimen (TEL). At baseline, detailed clinical history, body weight, waist-hip ratio, complete blood count, liver and renal function test, CD4 cell count were performed. Clinical monitoring for cutaneous, neuropsychiatric, and gastrointestinal side effects was done every month along with laboratory monitoring and anthropometric measurement for every 6 months. CD4 counts were measured at baseline and end of the study at 12 months. Out of 135 participants, 89 (65.9%) were males and 46 (34%) were females. The mean age and the mean duration of illness at inclusion were 35.10 ± 8.97 years and 1.2 ± 0.6 years, respectively. The mean increase in weight at baseline and at 12 months (57.55 ± 6.56 to 64.04 ± 8.2) was statistically significant (95% confidence interval [CI]: 4.35-8.62, P < 0.001). The mean CD4 counts at baseline were 309.73 ± 118.44 and increased after 12 months of treatment to 421 ± 129.4 which was statistically significant (95% CI: 81.54-140.99, P < 0.001). The mean difference in platelet count was statistically significant between baseline and 12 months (95% CI: 10.32-46.13, P = 0.002). The mean difference in serum urea levels at baseline and at 6 months (95% CI: 0.60-1.61, P < 0.001) as well as 12 months were statistically significant (95% CI: 0.08-1.03, P = 0.02). The mean increase in serum creatinine at baseline (0.75 ± 0.12) and at 12 months (0.97 ± 0.16) was also significant (95% CI: 0.21-0.28, P < 0.001). There was a significant difference between mean creatinine clearance at baseline and at 12 months (109.9 ± 13.75 to 99.33 ± 12.52, P < 0.0001). One patient discontinued treatment due to adverse effects while two patients were shifted to second-line antiretroviral treatment. Small sample size, single-center study and short follow-up period, long-term toxicities were not appreciated. Fixed drug combination with TEL as a first-line ART for HIV is a safe regime as we observed minimal side effects with current regimen.

Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar: A retrospective cohort study.

IntroductionDespite HIV viral load (VL) monitoring being serial, most studies use a cross-sectional design to evaluate the virological status of a cohort. The objective of our study was to use a simplified approach to calculate viraemic-time: the proportion of follow-up time with unsuppressed VL above the limit of detection. We estimated risk factors for higher viraemic-time and whether viraemic-time predicted mortality in a second-line antiretroviral treatment (ART) cohort in Myanmar.MethodsWe conducted a retrospective cohort analysis of people living with HIV (PLHIV) who received second-line ART for a period >6 months and who had at least two HIV VL test results between 01 January 2014 and 30 April 2018. Fractional logistic regression assessed risk factors for having higher viraemic-time and Cox proportional hazards regression assessed the association between viraemic-time and mortality. Kaplan-Meier curves were plotted to illustrate survival probability for different viraemic-time categories.ResultsAmong 1,352 participants, 815 (60.3%) never experienced viraemia, and 172 (12.7%), 214 (15.8%), and 80 (5.9%) participants were viraemic <20%, 20–49%, and 50–79% of their total follow-up time, respectively. Few (71; 5.3%) participants were ≥80% of their total follow-up time viraemic. The odds for having higher viraemic-time were higher among people with a history of injecting drug use (aOR 2.01, 95% CI 1.30–3.10, p = 0.002), sex workers (aOR 2.10, 95% CI 1.11–4.00, p = 0.02) and patients treated with lopinavir/ritonavir (vs. atazanavir; aOR 1.53, 95% CI 1.12–2.10, p = 0.008). Viraemic-time was strongly associated with mortality hazard among those with 50–79% and ≥80% viraemic-time (aHR 2.92, 95% CI 1.21–7.10, p = 0.02 and aHR 2.71, 95% CI 1.22–6.01, p = 0.01). This association was not observed in those with viraemic-time <50%.ConclusionsKey populations were at risk for having a higher viraemic-time on second-line ART. Viraemic-time predicts clinical outcomes. Differentiated services should target subgroups at risk for a higher viraemic-time to control both HIV transmission and mortality.

Survival analysis of long-term HIV/AIDS cases aged 15 years and over under antiretroviral treatment in Henan Province from 2002 to 2020

Objective: To analyze the survival and influencing factors of HIV infections and AIDS cases (HIV/AIDS) aged 15 years and over who had received antiretroviral treatment (ART) for more than 10 years in Henan Province. Methods: In this retrospective cohort study, data of HIV infections and AIDS cases in Henan province were collected from the AIDS Prevention and Control System between January 1, 2002 and December 31, 2020. This study included 20 256 participants alive after 10-year ART with complete baseline and follow-up information, such as demographic characteristics, CD4+T lymphocyte count and viral load. Cox proportional risk regression model was used to analyze influencing factors of HIV/AIDS survival. Results: A total of 20 256 participants were followed up for 82 738.2 person-years, with an average follow-up of 4.1 person-years, of which most cases were blood transmission (85.5%) and married (71.2%). The male to female ratio was 1∶1.06 and the age at 10 years of ART was (51.2±8.7) years old. About 88.5% of HIV/AIDS patients received ART in village/township treatment institutions. Overall, there were 2 030 deaths during this period, among which 1 897 were due to AIDS-related diseases (93.5%) and the case fatality rate was 9.4% (1 897/20 256). Cox proportional risk regression model showed that participants aged 40-54, 55-69, and ≥70 years had a higher risk of death compared to those aged 25-39, with adjusted HRs (95%CI) of 1.57 (1.19-2.08), 3.78 (2.86-4.99), and 6.17 (4.33-8.79), respectively. Participants with the initial CD4+T lymphocyte count about 200-349/μl and<200/μl had a higher risk of death compared to those with initial CD4+T lymphocyte count ≥350/μl, with adjusted HRs (95%CI) of 1.81 (1.61-2.04) and 3.64 (3.20-4.15), respectively. Participants with the initial viral load outcome ≥1 000 copies/ml had a higher risk of death compared to those with the initial viral load outcome<1 000 copies/ml, with adjusted HRs (95%CI) of 1.73 (1.52-1.97). Participants receiving the second-line ART had a lower risk of death compared to those receiving the first-line ART, with adjusted HRs (95%CI) of 0.12 (0.11-0.14). Conclusion: From 2002 to 2020, the survival rate of HIV/AIDS treated with ART for more than 10 years is high in Henan Province. Age, CD4+T lymphocyte count and viral load are influencing factors of HIV/AIDS survival.

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.

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.

BackgroundHIV 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.MethodsAn 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.ResultsA 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).ConclusionThe 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.

Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

BackgroundChildren with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART).MethodsWe conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non–dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan–Meier method. Safety was assessed.ResultsFrom September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor–based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, –0.08; 95% confidence interval, −0.14 to −0.03; P=0.004). Treatment effects were similar with first- and second-line therapies (P=0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P=0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P=0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P=0.01).ConclusionsIn this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.)

The influence of HIV infection and antiretroviral treatment on pulmonary function in individuals in an urban setting in sub-Saharan Africa.

BackgroundWith the roll-out of antiretroviral treatment (ART), the life expectancy of people with HIV and, hence, morbidity from non-communicable diseases, including pulmonary diseases, have increased.ObjectivesThis research study aims to investigate whether HIV infection and ART use are associated with pulmonary function, given the high frequency of pulmonary infections, including tuberculosis (TB), associated with HIV.MethodAdults living with HIV (ART-naïve, on first- or second-line ART), and age and sex matched HIV-negative controls were included in a cross-sectional study in Johannesburg, South Africa. Spirometry was performed to determine lung function, measuring the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and the FEV1/FVC ratio before (pre), and after (post), short-acting bronchodilator. The association of HIV infection and ART use with pulmonary function was analysed using linear regression models, adjusting for age, gender, body surface area (BSA), employment, education, smoking and TB.ResultsOverall, 548 participants (62% women) were included with a mean age of 38 (standard deviation [s.d.] 9.5) years. No effect of HIV or ART on post-FEV1 was observed in adjusted analysis. Additional adjustment for TB resulted in a higher post-FEV1 in participants on ART compared with HIV-negative participants, whereas TB was associated with a lower FEV1. No effect of HIV and ART on post-FEV1/FVC was observed.ConclusionHIV infection and ART use were not associated with reduced pulmonary function in this urban African population. Tuberculosis showed a mediating effect on the association between HIV, ART and pulmonary function.

Predictors of impaired pulmonary function in people living with HIV in an urban African setting.

BackgroundStudies have associated HIV with an increased risk of obstructive lung disease (OLD).ObjectivesWe aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population.MethodA cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal.ResultsThe 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (β = –0.003, P < 0.01), male sex (β = –0.016, P = 0.03) and history of TB or pneumonia (β = –0.024, P < 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47–4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64).ConclusionOur data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia.