Antiretroviral Therapy Outcomes Research Articles

Perceived barriers and opportunities for implementing an integrated psychological intervention for depression in adolescents living with HIV in Tanzania

BackgroundAdolescents living with Human Immunodeficiency Virus (HIV) have an increased risk of depression, negatively affecting their adherence to antiretroviral therapy (ART) and treatment outcomes. Integrating mental health care in HIV care and treatment settings improves comprehensive care. However, integration remains challenging in Tanzania, like in other high-burden and low-resource settings. The overall objective of this work is to inform the development of a psychological intervention for depression in adolescents living with HIV (ALWHIV). We describe perceived barriers and opportunities for implementing an integrated, evidence-based psychological intervention to manage adolescent depression in HIV care and treatment centers (HIV-CTC) from the perspectives of adolescents, caregivers, and healthcare providers (HCPs) in Dar es Salaam, Tanzania.MethodsTo inform intervention development and implementation, this study utilized a qualitative design through a phenomenological approach informed by the Consolidated Framework for Implementation Research (CFIR) to explore implementation barriers and facilitators in ALWHIV, HCPs, and caregivers. Forty-five in-depth interviews were conducted in three HIV-CTCs in Kinondoni Dar es Salaam. Audio records were transcribed verbatim and analyzed deductively through NVIVO software.ResultsBarriers to implementing an integrated psychological intervention to address depression in ALWHIV included (A) poor mental health awareness among caregivers, adolescents, HCPs, and policy-makers, (B) high level of stigma against mental health care, (C) poor communication between adolescents and HCPs concerning mental health care, (D) lack of contextualized intervention of proven effectiveness and guidelines of mental health care, and (E) inadequate mental health care supportive supervision and mentorship. Facilitators for implementation included supportive infrastructure, positive pressure from HIV implementing partners, tension for change, and participant’s perception of the advantage of a psychological intervention as compared to just usual HIV care and treatment counseling.ConclusionDespite several modifiable barriers to implementing a psychological intervention in HIV CTC, there were encouraging facilitators and opportunities for implementing an integrated, evidence-based psychological intervention to address depression in ALWHIV in Kinondoni Dar es Salaam, Tanzania.

Incorporating temporal dynamics of mutations to enhance the prediction capability of antiretroviral therapy's outcome for HIV-1.

In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables. We compare a model encompassing history (H) with one not using this information (NH). The H-model demonstrates superior discriminative ability, with a higher ROC-AUC score (76.34%) than the NH-model (74.98%). Wilcoxon test results confirm significant improvement of predictive accuracy for treatment outcomes through incorporating historical information. The increased performance of the H-model might be attributed to its consideration of latent HIV reservoirs, probably obtained when leveraging historical information. The findings emphasize the importance of temporal dynamics in acquiring mutations. However, our result also shows that prediction accuracy remains relatively high even when no historical information is available. This analysis was conducted using the Euresist Integrated DataBase (EIDB). For further validation, we encourage reproducing this study with the latest release of the EIDB, which can be accessed upon request through the Euresist Network.

Demographic and clinical factors correlated with clinical outcomes among people with HIV treated by antiretroviral therapy: a retrospective cohort study.

As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China's National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P < 0.05). Impressively, significantly more PWH had the higher level of baseline, peak and recent CD4 cell counts in the living group compared to those in the dead group. Due to multicollinearity effect, after excluding confounders, the following factors were found to be significantly associated with mortality by multivariate Cox regression analysis: (1) male sex (hazard ratio (HR) = 1.268 [1.032, 1.559]; P = 0.024); (2) time from HIV confirmation to ART initiation ≥ 6 months (HR = 1.962 [1.631, 2.360]; P < 0.001); (3) peak CD4 cell count: Peak CD4 < 100cells/µL group (HR = 16.093 [12.041, 21.508]; P < 0.001), 100cells/µL ≤ x < 200cells/µL group (HR = 7.904 [6.148, 10.160]; P < 0.001), 200cells/µL ≤ x < 350cells/µL group (HR = 3.166 [2.519, 3.980]; P < 0.001), 350cells/µL ≤ x < 500cells/µL group (HR = 1.668 [1.291, 2.155]; P < 0.001). Interestingly, patients in male, time from HIV confirmation to ART initiation ≥ 6 months, or peak CD4 count < 500 cells/µl had inferior clinical outcomes, in other word, a lower peak CD4 cell count significantly increased the risk of death, and peak CD4 cell was independent in predicting the overall survival of PWH. It is important to promote "early diagnosis and treatment of HIV" and regularly monitor CD4 levels in HIV/AIDS to evaluate the efficacy of ART and immune reconstitution, and optimize the ART regimen in time to further reduce the mortality of PWH.

Efficacy and safety of three antiretroviral therapy regimens for treatment-naive African adults living with HIV-2 (FIT-2): a pilot, phase 2, non-comparative, open-label, randomised controlled trial

Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches. This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per μL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants. Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group. The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen. ANRS MIE.

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.

IJCM_425A: Outcomes of Second Line Anti-Retroviral Therapy Among a cohort of people living with HIV/AIDS attending an ART Centre in Mangalore

Background: Anti-Retroviral therapy for HIV/AIDS has been effective, but the mortality rate remains to be high, resulting in the use of second line of ART treatment for better results. Objectives: 1) To estimate the number of deaths among PLHIV between the years 2011 and 2017. 2) To assess the clinical immunological and virological outcomes among these patients. 3) To find out the association of outcomes with the socio demographic characteristics. Methods: In this record-based study, medical records of PLHIV seeking treatment from an ART center associated with KMC, Attavar. between the years 2011 and 2017 were reviewed. The data was extracted using a data extraction sheet consisting of sections on demographic, clinical and treatment details of the patient. Results: The baseline median CD4 count before starting ARTs was found to be 253 (IQR 150-351). After starting second line ARTs it was found to be 461 (IQR 326-651). The correlation of CD4 count after initiation of second line ART with viral load among 34 patients measured was found to be -0.371 (P&lt;0.05). Conclusion: The study concludes that the outcomes of second line ARTs in the present study were found to be satisfactory. The average CD4 count after the initiation of ARTs was significantly high as compared to the CD4 count before the ARTs, implying that second line ARTs had a good, long-term and positive immunological outcome on PLHIV and attending a second-line ART clinic.

Adverse drug reactions, adherence, and virologic outcomes in adult patients on dolutegravir-based antiretroviral therapy at a tertiary hospital, southeast Nigeria.

To assess the adherence, adverse drug reactions (ADR), and virologic outcomes of dolutegravir-based antiretroviral therapy. This was a retrospective chart review. A tertiary health facility-based study in Abakaliki, Nigeria. Five hundred and fifteen (515) adult patients on dolutegravir were selected using a Random Number Generator. Demographic and clinical data were extracted from patients' case notes and analysed with IBM-SPSS version-25. Adherence to dolutegravir, ADRs, virologic outcome, and change in Body Mass Index (BMI) were estimated. The mean age of the patients was 45.5±10.8 years; 68.2% of them were females; 97.1% of them had good self-reported adherence. The majority (82.9%) of them reported no ADRs and among those (17.1%) that did, headache (9.7%), body-itching (3.1%), and skin rash (2.7%) dominated. Most achieved viral suppression (94.4%) and did not have detectable viral particles (57.4%). There was a significant increase in the BMI of the patients with a mean weight increase of 0.9kg, a mean BMI increase of 0.3 kg/m2, and a 2.6% increase in the prevalence of overweight and obesity. Patients on dolutegravir reported low ADRs, good self-reported adherence, and a high viral suppression rate. However, dolutegravir is associated with weight gain. We recommend widespread use and more population-wide studies to elucidate the dolutegravir-associated weight gain. None declared.

Impact Of Low-Frequency HIV-1 Drug Resistance Mutations On Antiretroviral Therapy Outcomes.

The association between low-frequency HIV-1 drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using NGS methods that accurately sample low-frequency DRMs. We enrolled women with HIV-1 in Malawi who were either ART naïve (A), had ART failure (B), or had discontinued ART (C). At entry, A and C began an NNRTI-based regimen and B started a PI-based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤ 20%. We sequenced 360 participants. Cohort B and C participants were more likely to have TF than Cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HR of 3.12 [1.58-6.18, 95% CI] and 2.38 [1.00-5.67, 95% CI] respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART. Using accurate NGS for DRM detection may benefit an additional 10% of the patients by identifying low-frequency K103N mutations.

Assessing health outcomes of ART Differentiated Care Models in Migori County, Kenya

Background : HIV remains a substantial global health challenge. In Kenya, the prevalence is approximately 6%, with Migori County experiencing notably high rates. Despite this, only a small portion of its population receive antiretroviral therapy (ART). Differentiated care, an individualized approach to HIV treatment, enhances outcomes and eases strain on health systems. This study assesses health outcomes of ART differentiated care in Migori County, Kenya, focusing on retention and viral load results for stable individuals living with HIV.&#x0D; Methodology :We employed a pre-post evaluation descriptive mixed methods study design to assess health outcomes following Differentiated Care Model (DCM) implementation. One hundred and ninety-two (192) stable HIV patients from Migori's rural sugar belt, meeting DCM inclusion criteria, were enrolled using single-stage cluster and systematic sampling. DCM outcomes were compared with the standard care model (control). Data sourced from patient records and key informant interviews were analyzed using Chi-square, Fisher's exact tests, logistic regression and thematic analysis.&#x0D; Results : We observed notable statistical significance (p &lt; 0.05) in the association between DCM and health outcomes, including patient activity at 6 and 12 months (p &lt; 0.001), transfer-out retention at 6 and 12 months (p = 0.02), loss to follow-up retention at 6 and 12 months (p = 0.006 and p = 0.005, respectively), and deceased patient retention (p = 0.033). However, the viral load suppression post-DCM did not show statistical significance.&#x0D; Conclusion : To conclude, Differentiated Care Models positively impact retention outcomes for stable HIV-positive patients, notably reducing lost-to-follow-up and deceased cases. Although not significant at 6 and 12 months, DCM shows promise in early-stage viral load suppression. Gender disparities exist in suppression rates. Patient adherence and viral load awareness are favourable

Long-term Hepatitis B and Liver Outcomes Among Adults Taking Tenofovir-Containing Antiretroviral Therapy for HBV/HIV Coinfection in Zambia.

Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia. A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers. Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.

Antiretroviral Therapy and Adverse Pregnancy Outcomes in People Living with HIV

(N Engl J Med. 2023;388:344–356) Human immunodeficiency virus (HIV) is detected in about 1.3 million pregnant individuals every year. The use of antiretroviral therapy (ART) is common in about 1.1 million (85%) of these cases. When ART is not prescribed, 15% to 30% of individuals born to those with HIV will develop HIV. Maternal zidovudine (ZDV), a 3-drug ART regimen, has been proven to reduce the number of infants who contract HIV from their mothers. ZDV decreases the rate of vertical transmission of HIV from 25.5% to 8.3%. This study aimed to show the key evidence in support of ART and to evaluate both contemporary and legacy methods of ART delivery to see how they compare.

Outcomes of Dolutegravir-Based Antiretroviral Therapy in Thai Youth Aged 18 to 24 Years Living with HIV in Bangkok: A Retrospective Cohort Study

Objective: Dolutegravir (DTG) is recommended globally for people living with HIV. The present study aimed to describe the efficacy and safety of DTG-based regimens among youth aged 18 to 24 years. Materials and Methods: A retrospective cohort study was conducted among youth aged 18 to 24 years living with HIV at Chulalongkorn Hospital. Participants were divided into antiretroviral naïve (AN), antiretroviral experienced with treatment failure (AETF), and antiretroviral experienced and virally suppressed (AEVS). DTG was prescribed as a daily individual tablet or as part of a fixed-dose combination. The primary outcome was virological suppression defined as VL of less than 200 copies/mL within 12 months after DTG initiation. Secondary outcomes included body weight and lipid profile changes. Results: Between 2017 and 2022, 87 youth with a median age of 20.6 (IQR 19.6 to 21.9) years were initiated on DTG. Fifty-six (64.3%) were male. Twelve participants were AN, 18 were AETF, and 57 were AEVS. HIV viral suppression was 100% and 96.2% among those AN and AEVS, but only 54.5% amongst the AETF group (p&lt;0.001). CD4 lymphocyte counts increased in all groups at follow-up. Median body weight change was +0.4 (IQR –1.8 to 3.6) kg in males and +0.5 (IQR –2.8 to 1.7) kg in females. Median total cholesterol declined from 167 (IQR 142 to 186) to 152 (IQR 135 to 170) mg/dL, p=0.003. Median triglycerides declined from 83 (IQR 60 to 129) to 66 (IQR 46 to 78), p&lt;0.001. No hospitalizations or mortalities were observed in the study. Conclusion: DTG was effective and well-tolerated in youth living with HIV, with no significant weight gain and improved lipid profiles. DTG implementation among youth living with HIV should be continued. Keywords: Dolutegravir; Antiretroviral therapy; Adolescents living with HIV

Provider-led community antiretroviral therapy distribution in Malawi: Retrospective cohort study of retention, viral load suppression and costs.

Outcomes of community antiretroviral therapy (ART) distribution (CAD), in which provider-led ART teams deliver integrated HIV services at health posts in communities, have been mixed in sub-Saharan African countries. CAD outcomes and costs relative to facility-based care have not been reported from Malawi. We performed a retrospective cohort study in two Malawian districts (Lilongwe and Chikwawa districts), comparing CAD with facility-based ART care. We selected an equal number of clients in CAD and facility-based care who were aged >13 years, had an undetectable viral load (VL) result in the last year and were stable on first-line ART for ≥1 year. We compared retention in care (alive and no period of ≥60 days without ART) using Kaplan-Meier survival analysis and Cox regression and maintenance of VL suppression (<1,000 copies/mL) during follow-up using logistic regression. We also compared costs (in US$) from the health system and client perspectives for the two models of care. Data were collected in October and November 2020. 700 ART clients (350 CAD, 350 facility-based) were included. The median age was 43 years (IQR 36-51), median duration on ART was 7 years (IQR 4-9), and 75% were female. Retention in care did not differ significantly between clients in CAD (89.4% retained) and facility-based care (89.3%), p = 0.95. No significant difference in maintenance of VL suppression were observed between CAD and facility-based care (aOR: 1.24, 95% CI: 0.47-3.20, p = 0.70). CAD resulted in slightly higher health system costs than facility-based care: $118/year vs. $108/year per person accessing care; and $133/year vs. $122/year per person retained in care. CAD decreased individual client costs compared to facility-based care: $3.20/year vs. $11.40/year per person accessing care; and $3.60/year vs. $12.90/year per person retained in care. Clients in provider-led CAD care in Malawi had very good retention in care and VL suppression outcomes, similar to clients receiving facility-based care. While health system costs were somewhat higher with CAD, costs for clients were reduced substantially. More research is needed to understand the impact of other differentiated service delivery models on costs for the health system and clients.

Effect of the Friendship Bench Intervention on Antiretroviral Therapy Outcomes and Mental Health Symptoms in Rural Zimbabwe

Common mental disorders (CMD), which include depression and anxiety, are prevalent among people living with HIV and are associated with suboptimal antiretroviral therapy (ART) adherence. To assess the effect of a lay health worker-led psychological intervention on ART adherence, virologic suppression, and mental health symptoms. Open-label pragmatic cluster trial with 1:1 block randomization of 16 health facilities in rural Bikita, Zimbabwe. Recruitment occurred from October 2018 to December 2019, and participants were followed up for 12 months, ending in December 2020. Participants were adults aged 18 years and older, who spoke English or Shona, screened positive for CMD (Shona Symptoms Questionnaire [SSQ]-14 score ≥9), received first-line ART for 6 or more months, had no World Health Organization stage 4 disease, no psychosis, were not pregnant, and provided informed consent. Data were analyzed from March 2021 to February 2022. The Friendship Bench, consisting of 6 lay health worker-led weekly problem-solving therapy sessions and optional peer-led group support. The primary outcome was mean adherence during 2 to 6 months of follow-up, and the secondary outcomes were mean adherence during 1 to 12 months of follow-up, change in SSQ-14 and Patient Health Questionnaire (PHQ-9) scores (3, 6, 9, and 12 months), and viral load suppression (6 and 12 months). A total of 516 participants were recruited (244 in Friendship Bench and 272 in enhanced standard care facilities); 438 (84.9%) were female and the mean (SD) age was 45.6 (10.9) years. Mean (SD) adherence between 2 to 6 months was 89.9% (18.4%) in the Friendship Bench group and 87.2% (20.1%) in the control group. The intervention had no statistically significant effect on adherence between 2 to 6 months (unadjusted mean difference, 1.93 percentage points; 95% CI, -1.20 to 5.06 percentage points; P = .23), between months 1 to 12 (mean difference 0.79 percentage points; 95% CI, -2.14 to 3.71 percentage points; P = .60), or viral suppression. Declines in SSQ-14 scores from baseline to 3 months (difference, -1.65; 95% CI, -3.07 to -0.24), 6 months (difference, -1.57; 95% CI, -2.98 to -0.15), and 9 months (difference, -1.63; 95% CI, -3.05 to -0.22) were greater in the Friendship Bench than the standard care group (P < .05). There were no differences in the decline in the SSQ-14 scores from baseline to 12 months and in declines in PHQ-9 scores from baseline to 3, 6, 9, and 12 months. In this randomized trial of HIV-positive participants with CMD, the Friendship Bench intervention had no effect on adherence and viral suppression, possibly due to the absence of skill-based adherence training and a ceiling effect. ClinicalTrials.gov Identifier: NCT03704805.

TREATMENT OUTCOME OF CHEMOTHERAPY AND ANTIRETROVIRAL THERAPY AND COTRIMOXAZOLE PREVENTIVE THERAPY IN TUBERCULOSIS PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS COINFECTION

Objective: In developing countries like India, the fatality rate of tuberculosis (TB) coinfected with human immunodeficiency virus (HIV) is still at high rate and imposes significant challenge among the physicians. The present study was conducted to evaluate management outcomes of combined antiretroviral therapy (ART) and chemotherapy or cotrimoxazole preventive therapy (CPT) in TB/HIV co-infected patients. Methods: The study was conducted on 3512 confirmed TB patients who were treated with ART and CPT therapy. Out of these, HIV positive was 58 cases and HIV negative was 3414 cases. HIV cases the algorithm KHB- Statpak- Unigold were used. Patient started CPT. Results: Percentage of TB and HIV coinfection was 58 and the coinfection was greater in 20–40-year age groups and 2 times higher in PTB sputum-positive cases. Among the extrapulmonary TB cases, 76% took CPT + ART. The treatment success was 86%. Conclusion: Thus, CPT therapy must be established in all centers and compulsory HIV screening must be implicated throughout the country.

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.

Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy

Background. Up to 20% of people with HIV (PWH) who undergo virologically suppressed antiretroviral therapy (ART) fail to experience complete immune restoration. We recently reported that plasma anti-CD4 IgG (antiCD4IgG) autoantibodies from immune non-responders specifically deplete CD4 + T cells via antibody-dependent cytotoxicity. However, the mechanism of antiCD4IgG production remains unclear.Methods. Blood samples were collected from 16 healthy individuals and 25 PWH on suppressive ART. IgG subclass, plasma lipopolysaccharide (LPS), and antiCD4IgG levels were measured by ELISA. Gene profiles in B cells were analyzed by microarray and quantitative PCR. Furthermore, a patient-derived antiCD4IgG–producing B cell line was generated and stimulated with LPS in vitro. B cell IgG class switch recombination (CSR) was evaluated in response to LPS in splenic B cells from C57/B6 mice in vitro.Results. Increased plasma anti-CD4 IgGs in PWH were predominantly IgG1 and associated with increased plasma LPS levels as well as B cell expression of TLR2, TLR4, and MyD88 mRNA in vivo. Furthermore, LPS stimulation induced antiCD4IgG production in the antiCD4IgG B cell line in vitro. Finally, LPS promoted CSR in vitro.Conclusion. Our findings suggest that persistent LPS translocation may promote anti-CD4 autoreactive B cell activation and antiCD4IgG production in PWH on ART, which may contribute to gradual CD4 + T cell depletion. This study suggests that reversing a compromised mucosal barrier could improve ART outcomes in PWH who fail to experience complete immune restoration.

Strategies to improve antiretroviral therapy (ART) initiation and early engagement among men in sub-Saharan Africa: A scoping review of interventions in the era of universal treatment.

Men in sub-Saharan Africa (SSA) have lower rates of antiretroviral therapy (ART) initiation and higher rates of early default than women. Little is known about effective interventions to improve men's outcomes. We conducted a scoping review of interventions aimed to increase ART initiation and/or early retention among men in SSA since universal treatment policies were implemented. Three databases, HIV conference databases and grey literature were searched for studies published between January 2016 to May 2021 that reported on initiation and/or early retention among men. Eligibility criteria included: participants in SSA, data collected after universal treatment policies were implemented (2016-2021), quantitative data on ART initiation and/or early retention for males, general male population (not exclusively focused on key populations), intervention study (report outcomes for at least one non-standard service delivery strategy), and written in English. Of the 4351 sources retrieved, 15 (reporting on 16 interventions) met inclusion criteria. Of the 16 interventions, only two (2/16, 13%) exclusively focused on men. Five (5/16, 31%) were randomised control trials (RCT), one (1/16, 6%) was a retrospective cohort study,and 10 (10/16, 63%) did not have comparison groups. Thirteen (13/16, 81%) interventions measured ART initiation and six (6/16, 37%) measured early retention. Outcome definitions and time frames varied greatly, with seven (7/16, 44%) not specifying time frames at all. Five types of interventions were represented: optimising ART services at health facilities, community-based ART services, outreach support (such as reminders and facility escort), counselling and/or peer support, and conditional incentives. Across all intervention types, ART initiation rates ranged from 27% to 97% and early retention from 47% to 95%. Despite years of data of men's suboptimal ART outcomes, there is little high-quality evidence on interventions to increase men's ART initiation or early retention in SSA. Additional randomised or quasi-experimental studies are urgently needed.

Implementation and outcomes of dolutegravir-based first-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study

There are few data assessing the uptake of first-line dolutegravir among men and women living with HIV in low-income and middle-income countries, and subsequent clinical outcomes in non-trial settings. We aimed to determine dolutegravir uptake in women, and the effect of dolutegravir on clinical outcomes in routine care in South Africa. In this cohort study, we analysed deidentified data from adults receiving first-line antiretroviral therapy (ART) at 59 South African clinics from Dec 1, 2019, to Feb 28, 2022, using two distinct cohorts. In the initiator cohort, we used Poisson regression models to assess the outcome of initiation with dolutegravir-based ART by gender, and associations between dolutegravir use and the outcomes of 12-month retention in care and viral suppression at less than 50 copies per mL. In the transition cohort, comprising adults who received non-dolutegravir-based first-line ART in December, 2019, we used Cox proportional hazards models to assess the outcome of transition to first-line dolutegravir by gender. We then used time-dependent propensity score matching to compare the outcomes of subsequent 12-month retention in care and viral suppression between people who transitioned to dolutegravir and those who had not yet transitioned at the same timepoint. In both the initiation and transition cohort, the primary viral load analysis was an intention-to-treat analysis, with a secondary as-treated analysis that excluded people who changed their ART regimen after baseline. In the initiator cohort, between Dec 1, 2019, and Feb 28, 2022, 45 392 people were initiated on ART. 23 945 (52·8%) of 45 392 were non-pregnant women, 4780 (10·5%) were pregnant women, and 16 667 (36·7%) were men. The median participant age was 31·0 years (IQR 26·0-38·0) and 2401 (5·3%) were receiving tuberculosis treatment at time of ART initiation. 31 264 (68·9%) of 45 392 people were initiated on dolutegravir, 14 102 (31·1%) on efavirenz, and 26 (0·1%) on nevirapine. In a univariable Poisson regression model, pregnant women (risk ratio [RR] 0·57, 95% CI 0·49 to 0·66; risk difference -35·4%, 95% CI -42·3 to -28·5) and non-pregnant women (RR 0·78, 0·74 to 0·82; risk difference -18·4%, -21·6 to -15·2) were less likely to be initiated on dolutegravir than were men. In Poisson models adjusted for age, gender (including pregnancy), time, tuberculosis status, and initiation CD4 count, people initiated on dolutegravir were more likely to be retained in care at 12 months (adjusted RR 1·09, 95% CI 1·04 to 1·14; adjusted risk difference 5·2%, 2·2 to 8·4) and virally suppressed (adjusted RR 1·04, 95% CI 1·01 to 1·06; adjusted risk difference 3·1%, 1·2 to 5·1) compared with those initiated on non-dolutegravir-based regimens. For the transition cohort, on Dec 1, 2019, 180 956 people were receiving non-dolutegravir-based first-line ART at the study clinics, of whom 124 168 (68·6%) were women. The median age was 38 years (IQR 32-45), and the median time on ART was 3·9 years (2·0-6·4) years, with most people receiving efavirenz (178 624 [98·7%] people) and tenofovir (178 148 [98·4%]). By Feb 28, 2022, 121 174 (67·0%) of 180 956 people had transitioned to first-line dolutegravir at a median of 283 days (IQR 203-526). In a univariable Cox regression model the hazard of being transitioned to dolutegravir was lower in women than in men (hazard ratio 0·56, 95% CI 0·56 to 0·57). Among 92 318 propensity score matched people, the likelihood of retention in care was higher among the dolutegravir group compared with matched controls (adjusted RR 1·03, 95% CI 1·02 to 1·03; risk difference 2·5%, 95% CI 2·1 to 2·9). In the dolutegravir group, 33 423 (90·5%) of 36 920 people were suppressed at less than 50 copies per mL compared with 31 648 (89·7%) of 35 299 matched controls (adjusted RR 1·01, 95% CI 1·00 to 1·02; risk difference 0·8%, 95% CI 0·3 to 1·4). Women were less likely to receive dolutegravir than men. As dolutegravir was associated with improved outcomes, roll-out should continue, with a particular emphasis on inclusion of women. Wellcome Trust, Africa Oxford Initiative, International Association of Providers of AIDS Care, and Bill & Melinda Gates Foundation. For the isiZulu translation of the abstract see Supplementary Materials section.

Treatment Outcomes After Switching to Second-Line Anti-Retroviral Therapy: Results From the Thai National Treatment Program.

This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors.