Antiretroviral Therapy Treatment Research Articles

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.

Discovery of long non-coding RNAs in naïve CD4+ T cells in response to initiating antiretroviral therapy at acute or chronic phase of HIV-1 infection

Long non-coding RNAs (lncRNAs) have gained prominence due to their involvement in various cellular processes, but their specific roles remain elusive. Dysregulation of lncRNAs has been implicated in the pathogenesis of several diseases. In this study, we aimed to shed light on the role of lncRNAs in individuals infected with human immunodeficiency virus type 1 (HIV-1) by examining their changes in the expression patterns related to the initiation of antiretroviral therapy (ART) during acute or chronic phases of infection, compared to healthy controls. We found 316 differentially expressed (DE) lncRNAs in patients receiving long-term ART, shedding light on their potential roles. We also observed interactions between these DE lncRNAs and specific microRNAs (miRNAs). Some of these miRNAs, such as hsa-miR-574-5p, hsa-miR-765, hsa-miR-6165, hsa-miR-1207-5p, and hsa-miR-378i, are associated with cancer progression or suppression, while others, including hsa-miR-328-5p, hsa-miR-4753-3p, and MiR-664, play roles in immune system regulation. Furthermore, our study revealed substantial enrichment in distinct Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as axon guidance, PI3K-Akt signaling, and MAPK signaling pathways. Although our results indicate possible molecular processes impacted by the discovered lncRNAs, we cannot explicitly establish causality or specific connections between lncRNAs and genes in these pathways, fostering more specific studies. Furthermore, Gene Ontology (GO) analysis highlighted terms such as cytoskeletal protein binding, ion channel function, synaptic processes, neuron projection, and the somatodendritic compartment, underscoring the relevance of lncRNAs in these cellular components within the context of HIV-1 infection and ART treatment. In conclusion, our study emphasizes the need for further exploration of lncRNAs as potential biomarkers and therapeutic targets in HIV-1-infected patients, with a particular focus on CD4+ T cells. Understanding the functions of lncRNAs in these contexts may pave the way for novel treatment strategies and improved patient outcomes, aligning with the broader goals of our research.

Real-World Effectiveness of Dolutegravir/Lamivudine in People With HIV-1 in Test-and-Treat Settings or With High Baseline Viral Loads: TANDEM Study Subgroup Analyses.

Dolutegravir/lamivudine (DTG/3TC) was first approved by the US Food and Drug Administration in 2019 for the treatment of antiretroviral therapy (ART)-naive people with HIV-1 based on results from the pivotal GEMINI-1/GEMINI-2 trials. Around that time, immediate initiation of treatment upon diagnosis was recommended in the US Department of Health and Human Services guidelines. Here we report results from 126 treatment-naive people with HIV-1 who initiated DTG/3TC as part of a test-and-treat strategy (n = 61) or with high baseline viral loads (HIV-1 RNA ≥ 100,000 copies/ml; n = 16) from the TANDEM study. TANDEM was a US-based, retrospective chart review study that included a cohort of 126 individuals aged ≥ 18years with no prior history of ART who initiated DTG/3TC before September 30, 2020, and had ≥ 6months of follow-up. Test-and-treat was defined as ART initiation shortly after diagnosis without available viral load, CD4 + cell count, or HIV-1 resistance data. Outcomes included virologic suppression (HIV-1 RNA < 50 copies/ml; overall and by baseline viral load) and discontinuations. Analyses were descriptive. Among 61 individuals who initiated DTG/3TC in a test-and-treat setting (median [interquartile range (IQR)] treatment duration, 1.3 [0.9-1.7] years), 57 (93%) achieved virologic suppression, and 51 (84%) remained suppressed; 1 (< 1%) individual discontinued DTG/3TC due to persistent low-level viremia. The most common healthcare provider (HCP)-reported reason for initiating DTG/3TC was avoidance of long-term toxicities among individuals in the test-and-treat subgroup. Of 16 treatment-naive individuals with high baseline viral loads (median [IQR] treatment duration, 100,000-250,000 copies/ml: 1.2 [0.8-1.8] years; > 250,000 copies/ml: 1.0 [0.7-1.1] years), 14 (88%) achieved virologic suppression, 13 (81%) remained suppressed, and none discontinued DTG/3TC. Patient preference was the most common HCP-reported reason for initiating DTG/3TC in this subgroup. Results demonstrate real-world effectiveness of DTG/3TC, with few discontinuations, in people with HIV-1 in test-and-treat settings or with high baseline viral loads.

Hypercalcemia as a rare manifestation of immune reconstitution inflammatory syndrome (IRIS) in a person living with Human Immunodeficiency Virus (HIV) with disseminatednontuberculous mycobacteriosis.

Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV). A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8kg within the last 2weeks. Laboratory findings included serum hypercalcemia of 3.27mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18Fluoro-D-glucose positron emission computed tomography (18FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered. Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment.

Steroid-Induced Progressive Multifocal Leukoencephalopathy (PML) in HIV Patient: A Paradoxical Effect

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the central nervous system predominantly found in patients with acquired human immunodeficiency syndrome (AIDS). Case Presentation: This report details a case involving a male HIV-positive patient with PML who discontinued his highly active antiretroviral therapy (HAART) treatment 10 days after being diagnosed with HIV. The patient had no history of neurological symptoms either before or after his HIV diagnosis until he was administered corticosteroids. Notably, he began experiencing ataxia shortly after starting dexamethasone. Progressive multifocal leukoencephalopathy was diagnosed through polymerase chain reaction (PCR) testing for the John Cunningham virus (JCV) in the cerebrospinal fluid (CSF). The PML lesions were confined to the cerebellum. Conclusions: The occurrence of neurological symptoms (activation of JCV) after administering corticosteroids to a patient with HIV-who had not received any antiretroviral treatment for 4 years-raises a critical question: Is the use of corticosteroids, which are a primary treatment for immune reconstitution inflammatory syndrome (IRIS), a double-edged sword in CNS-IRIS?

Role of ART and PrEP treatments in a stochastic HIV/AIDS epidemic model

In this paper, a stochastic HIV/AIDS epidemic model is presented to study the synthetic effect of ART (antiretroviral therapy) and PrEP (pre-exposure prophylaxis) treatments among MSM ( men who have sex with men). Firstly, we give the global stability of disease-free equilibrium and the endemic equilibrium in terms of basic reproduction number R0 for deterministic model. And then the existence of global positive solutions and the existence of unique ergodic stationary distribution under R0S>1 for stochastic model are given. Further, the long-time stochastic dynamic of the model is investigated, including the criteria on the extinction and persistence in mean for the stochastic model. Finally, we give some numerical simulations to illustrate our theoretical results, and the sensitive analysis shows that ART (antiretroviral therapy) and PrEP (pre-exposure prophylaxis) treatments can effectively control the spread of AIDS among MSM population.

Electronic Medical Record Data Missingness and Interruption in Antiretroviral Therapy Among Adults and Children Living With HIV in Haiti: Retrospective Longitudinal Study.

Children (aged 0-14 years) living with HIV often experience lower rates of HIV diagnosis, treatment, and viral load suppression. In Haiti, only 63% of children living with HIV know their HIV status (compared to 85% overall), 63% are on treatment (compared to 85% overall), and 48% are virally suppressed (compared to 73% overall). Electronic medical records (EMRs) can improve HIV care and patient outcomes, but these benefits are largely dependent on providers having access to quality and nonmissing data. We sought to understand the associations between EMR data missingness and interruption in antiretroviral therapy treatment by age group (pediatric vs adult). We assessed associations between patient intake record data missingness and interruption in treatment (IIT) status at 6 and 12 months post antiretroviral therapy initiation using patient-level data drawn from iSanté, the most widely used EMR in Haiti. Missingness was assessed for tuberculosis diagnosis, World Health Organization HIV stage, and weight using a composite score indicator (ie, the number of indicators of interest missing). Risk ratios were estimated using marginal parameters from multilevel modified Poisson models with robust error variances and random intercepts for the facility to account for clustering. Data were drawn from 50 facilities and comprised 31,457 patient records from people living with HIV, of which 1306 (4.2%) were pediatric cases. Pediatric patients were more likely than adult patients to experience IIT (n=431, 33% vs n=7477, 23.4% at 6 months; P<.001). Additionally, pediatric patient records had higher data missingness, with 581 (44.5%) pediatric records missing at least 1 indicator of interest, compared to 7812 (25.9%) adult records (P<.001). Among pediatric patients, each additional indicator missing was associated with a 1.34 times greater likelihood of experiencing IIT at 6 months (95% CI 1.08-1.66; P=.008) and 1.24 times greater likelihood of experiencing IIT at 12 months (95% CI 1.05-1.46; P=.01). These relationships were not statistically significant for adult patients. Compared to pediatric patients with 0 missing indicators, pediatric patients with 1, 2, or 3 missing indicators were 1.59 (95% CI 1.26-2.01; P<.001), 1.74 (95% CI 1.02-2.97; P=.04), and 2.25 (95% CI 1.43-3.56; P=.001) times more likely to experience IIT at 6 months, respectively. Among adult patients, compared to patients with 0 indicators missing, having all 3 indicators missing was associated with being 1.32 times more likely to experience IIT at 6 months (95% CI 1.03-1.70; P=.03), while there was no association with IIT status for other levels of missingness. These findings suggest that both EMR data quality and quality of care are lower for children living with HIV in Haiti. This underscores the need for further research into the mechanisms by which EMR data quality impacts the quality of care and patient outcomes among this population. Efforts to improve both EMR data quality and quality of care should consider prioritizing pediatric patients.

Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Once a death sentence, HIV is now considered a manageable chronic disease due to the development of antiretroviral therapy (ART) regimens with minimal toxicity and a high barrier for genetic resistance. While highly effective in arresting AIDS progression and rendering the virus untransmissible in people living with HIV (PLWH) with undetectable viremia (U=U) [1, 2]), ART alone is incapable of eradicating the "reservoir" of resting, latently infected CD4+ T cells from which virus recrudesces upon treatment cessation. As of 2022 estimates, there are 39 million PLWH, of whom 86% are aware of their status and 76% are receiving ART [3]. As of 2017, ART-treated PLWH exhibit near normalized life expectancies without adjustment for socioeconomic differences [4]. Furthermore, there is a global deceleration in the rate of new infections [3] driven by expanded access to pre-exposure prophylaxis (PrEP), HIV testing in vulnerable populations, and by ART treatment [5]. Therefore, despite outstanding issues pertaining to cost and access in developing countries, there is strong enthusiasm that aggressive testing, treatment, and effective viral suppression may be able to halt the ongoing HIV epidemic (ie, UNAIDS' 95-95-95 targets) [6-8]; especially as evidenced by recent encouraging observations in Sydney [9]. Despite these promising efforts to limit further viral transmission, for PLWH, a "cure" remains elusive; whether it be to completely eradicate the viral reservoir (ie, cure) or to induce long-term viral remission in the absence of ART (ie, control; Figure 1). In a previous salon hosted by Pathogens and Immunity in 2016 [10], some researchers were optimistic that a cure was a feasible, scalable goal, albeit with no clear consensus on the best route. So, how are these cure strategies panning out? In this commentary, 8 years later, we will provide a brief overview on recent advances and failures towards identifying determinants of viral persistence and developing a scalable cure for HIV. Based on these observations, and as in the earlier salon, we have asked several prominent HIV cure researchers for their perspectives.

A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy

BackgroundConcomitant use of efavirenz-based antiretroviral therapy and a standard-dose etonogestrel contraceptive implant resulted in 82% lower etonogestrel exposure compared to women not receiving antiretroviral therapy. The clinical impact of this reduced exposure is supported by retrospective cohort evaluations which demonstrated higher rates of unintended pregnancies when contraceptive implants were combined with efavirenz. We hypothesized that placement of two etonogestrel implants in those taking efavirenz-based antiretroviral therapy could increase etonogestrel exposure and improve measures of contraceptive efficacy. ObjectivesThis study compared the rate of ovulation and etonogestrel pharmacokinetics in women on efavirenz-based antiretroviral therapy receiving two etonogestrel implants (136mg, DoublET group) versus one etonogestrel implant (68mg, Control group). Study DesignThis randomized, open-label study enrolled Ugandan women with regular menstrual periods who were receiving efavirenz-based antiretroviral therapy for treatment of HIV. Participants were randomized 1:1 to the DoublET or Control group, and the etonogestrel implant(s) were placed in the same arm at enrollment. All participants used a copper intrauterine device to prevent pregnancy. Ovulation was evaluated by weekly serum progesterone concentrations measured over 4 consecutive weeks at months 3 (weeks 9-12), 6 (weeks 21-24), and 12 (weeks 45-48). Progesterone concentrations >3ng/mL were interpreted as ovulation. The ovulation rate in each group was compared using Fisher’s exact test by month and generalized estimating equations over 48 weeks. Plasma was collected at day 3 and weeks 1, 4, 12, 24, 36 and 48 after implant placement, and analyzed by a validated LC-MS/MS method for etonogestrel. Etonogestrel concentrations were summarized as median (interquartile range, IQR) and compared between groups by geometric mean ratio (GMR) with 90% Confidence Interval (CI). ResultsAll participants (n=72) were cisgender Ugandan women, median age 31 (IQR 29, 36), and 36 participants were enrolled in each study group. Two participants in the Control group were discontinued; one at week 1 due to undetected pregnancy at entry and another at week 45 due to clinically significant depression. There were 47 ovulations over 104 person-months (45%) in 25 of 34 participants in the Control Group, and 2 ovulations over 108 person-months (2%) in 2 of 36 participants in the DoublET group [Month 3: 11 (31%) vs 0 (0%); Month 6: 17 (49%) vs 0 (0%); Month 12: 19 (56%) vs 2 (6%), respectively (all p<0.001)]. The odds of ovulation were reduced by 97.7% (95% CI: 90.1- 99.5) in the DoublET group over 48 weeks. At each time point, etonogestrel was more than two-fold higher in the DoublET group compared to controls (GMR 2.30-2.83), with the GMR of 2.83 (1.89, 3.35 90% CI) at week 48. There were no differences in the adverse events between groups and no participant discontinued due to adverse events. ConclusionOver 48 weeks of combined use, placing two etonogestrel implants suppressed ovulation and increased plasma etonogestrel exposure compared to one etonogestrel implant among women on efavirenz-based antiretroviral therapy. Doubling the dose of etonogestrel with efavirenz-based antiretroviral therapy could improve contraceptive effectiveness.

[Association between CD4+T lymphocyte and body composition with physical frailty among elderly HIV-infected patients in Chongqing City].

Objective: To identify the association between CD4+T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods: From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition. Results: The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×107 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [OR (95%CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [OR (95%CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group (Pinteraction<0.05). Conclusion: The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

Healthcare provisions associated with multiple HIV-related outcomes among adolescent girls and young women living with HIV in South Africa: a cross-sectional study.

Adolescent girls and young women (AGYW) living with HIV experience poor HIV outcomes and high rates of unintended pregnancy. Little is known about which healthcare provisions can optimize their HIV-related outcomes, particularly among AGYW mothers. Eligible 12- to 24-year-old AGYW living with HIV from 61 health facilities in a South African district completed a survey in 2018-2019 (90% recruited). Analysing surveys and medical records from n = 774 participants, we investigated associations of multiple HIV-related outcomes (past-week adherence, consistent clinic attendance, uninterrupted treatment, no tuberculosis [TB] and viral suppression) with seven healthcare provisions: no antiretroviral therapy (ART) stockouts, kind and respectful providers, support groups, short travel time, short waiting time, confidentiality, and safe and affordable facilities. Further, we compared HIV-related outcomes and healthcare provisions between mothers (n = 336) and nulliparous participants (n = 438). Analyses used multivariable regression models, accounting for multiple outcomes. HIV-related outcomes were poor, especially among mothers. In multivariable analyses, two healthcare provisions were "accelerators," associated with multiple improved outcomes, with similar results among mothers. Safe and affordable facilities, and kind and respectful staff were associated with higher predicted probabilities of HIV-related outcomes (p<0.001): past-week adherence (62% when neither accelerator was reported to 87% with both accelerators reported), clinic attendance (71%-89%), uninterrupted ART treatment (57%-85%), no TB symptoms (49%-70%) and viral suppression (60%-77%). Accessible and adolescent-responsive healthcare is critical to improving HIV-related outcomes, reducing morbidity, mortality and onward HIV transmission among AGYW. Combining these provisions can maximize benefits, especially for AGYW mothers.

Mental health burden among females living with HIV and AIDS in sub-Saharan Africa: A systematic review.

Mental health problems, particularly depression and anxiety, are common in women and young girls living with HIV/ AIDS particularly in low- and middle-income (LMICs) countries where women's vulnerability to psychiatric symptoms is heightened due to the prevalent intersectional stressors such as stigma and intimate partner violence. However, no synthesized evidence exists on the mental health burden of females living with HIV/AIDS (FLWHA) in Africa. This systematic review aimed to synthesize the current evidence on the mental health burden among FLWHA in sub-Saharan Africa. A systematic literature review of articles published from 2013-2023 was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Five electronic databases; PubMed, MEDLINE with full text, Scopus, Academic Search Complete, and Health Source: Nursing Academic Edition were searched for articles published in English. Nineteen articles (15 quantitative, 3 qualitative, and 1 case study) from over 7 African countries met the inclusion criteria. The majority of the studies' quality was determined to be moderate. The prevalence of depression ranged from 5.9 to 61% and anxiety from 28.9 to 61%. Mental health burden was a logical outcome of HIV diagnosis. Predictors of mental health outcomes in the context of HIV/AIDS were identified as intimate partner violence (IPV), stigma, childhood traumas, sexual abuse, poverty, unemployment, and social isolation. Social support and resilience were identified as protective factors against mental illness in FLWHA. Mental illness had a deleterious effect on viral suppression rates among FLWHA, resulting in delayed initiation of antiretroviral therapy treatment and increased mortality but had no impact on immune reconstitution in the face of ART adherence. Given the high prevalence rates of depression and anxiety and their relationship with HIV progression, it is crucial that mental health care services are integrated into routine HIV care.

Rapid initiation of antiretroviral therapy in Turkey: a modeling study.

To effectively control the HIV epidemic and meet global targets, policymakers recommend the rapid initiation of antiretroviral therapy (ART). Our study aims to investigate the effect of rapid ART programs on individuals diagnosed with HIV, considering varying coverage and initiation days after diagnosis, and compare it to standard-of-care ART treatment in Turkey. We used a dynamic compartmental model to simulate the dynamics of HIV infection in Turkey. Rapid treatment, defined as initiation of ART within 7 days of diagnosis, was contrasted with standard-of-care treatment, which starts within 30 days of diagnosis. This study considered three coverage levels (10%, 50%, and 90%) and two rapid periods (7 and 14 days after diagnosis), comparing them to standard-of-care treatment in evaluating the number of HIV infections between 2020 and 2030. Annual HIV incidence and prevalence for a 10-year period were obtained from model projections. In the absence of a rapid ART program, the model projected approximately 444,000 new HIV cases while the number of cases were reduced to 345,000 (22% reduction) with 90% of diagnosed cases included in the rapid ART program. Similarly, 10% and 50% rapid ART coverage has resulted in 3% and 13% reduction in HIV prevalence over a 10-year period. Rapid ART demonstrates the potential to mitigate the increasing HIV incidence in Turkey by reducing the number of infections. The benefit of the rapid ART program could be substantial when the coverage of the program reaches above a certain percentage of diagnosed population.

The changes in health service utilisation in Malawi during the COVID-19 pandemic.

The COVID-19 pandemic and the restriction policies implemented by the Government of Malawi may have disrupted routine health service utilisation. We aimed to find evidence for such disruptions and quantify any changes by service type and level of health care. We extracted nationwide routine health service usage data for 2015-2021 from the electronic health information management systems in Malawi. Two datasets were prepared: unadjusted and adjusted; for the latter, unreported monthly data entries for a facility were filled in through systematic rules based on reported mean values of that facility or facility type and considering both reporting rates and comparability with published data. Using statistical descriptive methods, we first described the patterns of service utilisation in pre-pandemic years (2015-2019). We then tested for evidence of departures from this routine pattern, i.e., service volume delivered being below recent average by more than two standard deviations was viewed as a substantial reduction, and calculated the cumulative net differences of service volume during the pandemic period (2020-2021), in aggregate and within each specific facility. Evidence of disruptions were found: from April 2020 to December 2021, services delivered of several types were reduced across primary and secondary levels of care-including inpatient care (-20.03% less total interactions in that period compared to the recent average), immunisation (-17.61%), malnutrition treatment (-34.5%), accidents and emergency services (-16.03%), HIV (human immunodeficiency viruses) tests (-27.34%), antiretroviral therapy (ART) initiations for adults (-33.52%), and ART treatment for paediatrics (-41.32%). Reductions of service volume were greatest in the first wave of the pandemic during April-August 2020, and whereas some service types rebounded quickly (e.g., outpatient visits from -17.7% to +3.23%), many others persisted at lower level through 2021 (e.g., under-five malnutrition treatment from -15.24% to -42.23%). The total reduced service volume between April 2020 and December 2021 was 8 066 956 (-10.23%), equating to 444 units per 1000 persons. We have found substantial evidence for reductions in health service delivered in Malawi during the COVID-19 pandemic which may have potential health consequences, the effect of which should inform how decisions are taken in the future to maximise the resilience of healthcare system during similar events.

Unveiling the Heart of the Matter: Echocardiographic Insights into Diastolic Function and Left Ventricular and Atrial Changes in HIV Patients with Controlled Viremia.

People living with human immunodeficiency virus (HIV) (PLWH) have increased risk of developing diastolic dysfunction (DD) and heart failure with preserved ejection fraction (EF). In this observational study, we evaluated DD and left ventricular hypertrophy (LVH) in PLWH receiving antiretroviral therapy (ART) with undetectable viremia. We conducted an observational study. All participants underwent transthoracic echocardiography to assess chamber size and systolic and diastolic function. Most patients showed concentric remodeling without LVH. All patients had normal left ventricle systolic function (EF median 61.3%, interquartile range: 57.8-66.2). None fulfilled the DD criteria, while two patients (6%) had undetermined diastolic function. Twenty percent (n = 7) of patients had an enlarged left atrium (left atrium volume index [LAVI] > 34 cm3/m2). These patients had a significantly lower CD4+ count (771.53 ± 252.81 vs. 446.00 ± 219.02, p = 0.01) and higher relative wall thickness (0.50 ± 0.05 vs. 0.44 ± 0.06, p = 0.03). Patients without immune restoration above 500 cells/μL had significantly higher LAVI (33.92 ± 6.63 vs. 24.91 ± 7.03, p = 0.01). One-fifth of patients had left atrial enlargement associated with worse immune restoration during ART treatment. The mechanism of left atrial enlargement and its association with cardiovascular risk require further investigations.

Decreased efficacy of sofosbuvir/velpatasvir in HIV patients coinfected with HCV genotype 3b

Aim: To retrospectively assess the efficacy and safety of sofosbuvir/velpatasvir for hepatitis C virus (HCV) genotype 3b in HIV-infected patients receiving antiretroviral therapy (ART) treatment of lamivudine/tenofovir disoproxil fumarate/efavirenz. Methods: The primary end point of HCV treatment was estimated by sustained virologic response 12 weeks after treatment (SVR12). Results: Sixteen subjects who were followed up for 48 weeks after treatment were included. The SVR12 and SVR48 were 87.5% (95% CI: 60.4–97.8%) and 81.3% (95% CI: 53.7–95.0%), respectively. One patient experienced persistent low-level viremia of HIV after 12 weeks of treatment. Conclusion: 12 weeks of sofosbuvir/velpatasvir is safe but has limited efficacy for HCV GT3b in HIV-infected patients receiving ART regimen including efavirenz, especially among patients with baseline HCV RNA≥6.0 log10 IU/ml.

PSYCHOSOCIAL CORRELATES OF PREVENTION, CARE, AND WELL-BEING AMONG OLDER WOMEN LIVING WITH HIV

Abstract There are over 4.2 million older adults (ages 50+ years) living with human immunodeficiency virus (HIV) globally. Older women continue to make up a significant proportion of this population. Advances in antiretroviral therapy treatments have allowed HIV+ individuals to live longer, healthier lives. However, compared to all persons living with HIV, women have lower viral suppression rates and are less likely to be retained in care. While older women living with HIV (WLWH) face unique challenges with HIV prevention and care, such as caregiving responsibilities, gender discrimination, and ageism, there is a dearth of research focusing on their experiences. As the population of older WLWH continues to increase, understanding barriers and facilitators to HIV prevention and care among this population is a public health priority. This symposium will provide insight into psychosocial factors that influence HIV prevention, care, and well-being among older WLWH. Our first presentation highlights a qualitative study identifying sources of strength and concerns about aging with HIV among older women. Our second presentation examines social support networks and interpersonal strain in relation to loneliness among older WLWH. Our third presentation highlights the impact of patient-provider communication regarding HIV/AIDs on sexual health communication between older WLWH and their partners. Our fourth presentation examines mental health vulnerabilities and strengths of older WLWH during the humanitarian crisis in Ukraine. Discussant Dr. Anna Rubtsova will contextualize these findings and offer suggestions for future research to enhance well-being of older women across the continuum of HIV prevention and care.

Adolescent’s and youth’s adherence to antiretroviral therapy for better treatment outcome and its determinants: multi-center study in public health facilities

BackgroundLow-adherence to Anti-retroviral therapy (ART) negatively affects the clinical, immunological, and virologic outcomes of patients. Adherence is the most important factor in determining Antiretroviral Therapy (ART) treatment success and long-term viral suppression which ultimately reduces morbidity and mortality. Thus, this study aimed to identify factors affecting adherence to antiretroviral therapy among adolescents and youth living with HIV.MethodsFacility-based cross-sectional study was conducted from March 21 to April 30, 2020 among 316 respondents in selected five high-loaded hospitals with adolescent and youth clients using systematic random sampling technique. Patients’ adherence was assessed when they had reportedly taken 95% or higher of their prescribed antiretroviral drugs in the five days before the interview. Data were collected, entered into EPI Data and exported to SPSS for analysis. Binary logistic regression was used to see the association between dependent and independent variables.ResultsIn this study, 316 respondents participated in the study, with a 99.7% response rate. The mean age of respondents were 17.94 years and majority of them (58.5%) were females. The overall ART adherence among adolescents and youths was found to be 70.6%. Being female (AOR = 0.323, 95% CI, 0.164–0.637), presence of opportunistic infection (AOR = 0.483, 95% CI, 0.249–0.936), taking additional medication beside ART (AOR = 0.436, 95% CI, 0.206–0.922) and availability of youth friendly services within the facility (AOR = 2.206, 95% CI, 1.031–4.721) were found to be predictors.ConclusionThe adherence rate in this study was low which is below the recommended adherence level. Being female, taking additional medication beside ART and presence of opportunistic infection were determinants of adherence. As a result, significant work must be done on opportunistic infection prevention through health education and promotion for screening and risk reduction. Similarly, adolescents and youths service integration with the ART Clinic is strongly advised.

Predictors associated with CD4 cell count changes over time among HIV-infected children on anti-retroviral therapy follow-up in Mekelle General Hospital, Northern Ethiopia, 2019: a retrospective longitudinal study

IntroductionAIDS continues to be a serious global public health issue. It targets CD4 cells and immunological cells, which are in charge of the body's resistance against pathogenic pathogens. In situations with limited resources, CD4 cell measurement is essential for assessing treatment responses and clinical judgments in HIV-infected children receiving Anti-Retroviral Therapy (ART). The volatility of CD4 cells during ART follow-up is still largely uncharacterized, and there are few new datasets on CD4 cell changes over time. Therefore, the purpose of this analysis was to identify the factors that were predictive of CD4 cell count changes over time in children who started ART at Mekelle General Hospital in northern Ethiopia.MethodsA retrospective follow-up study was done. 437 patients in Mekelle general hospital, northern Ethiopia, from 2014–2016 were involved. All patients who have started anti-retrieval treatment (ART) and measured their CD4 cell count at least twice, including the baseline and those who initiated ART treatment, were included in the study population. An exploratory data analysis and linear mixed model analysis were used to explore the predictors of CD4 cell count change in patients and consider variability within and between patients.ResultsThis study found the correlation variation explained in cells accounted for between patients was 61.3%, and the remaining 38.7% variation existed within. This indicates that there is a substantial change in random slope and intercept between and within patients. WHO clinical stage IV (β = -1.30, 95% CI: -2.37, -0.23), co-infection HIV/TB (β = -1.78, 95% CI: -2.58, -0.98), children aged 2–5 (β = -0.43; 95% CI: -0.82, -0.04), and 6–14 years (β = -1.02; 95% CI: -1.47, -0.56), non-opportunistic infection (β = 1.33, 95% CI: 0.51, 2.14), and bedridden functional status (β = -1.74, 95% CI: -2.81, -0.68) were predictors of cell changes over time.ConclusionsThis study found that patients receiving ART experienced a significant change in CD4 cells over time. Because 61.3% of the variation in CD4 cells explained between patients and the remaining 38.7% within patients, such nested data structures are often strong correlation evidence. Co-infection of HIV/TB, functional status, age category of children, WHO clinical stage, and opportunistic infections are potential predictors of CD4 cells count change.Hence, special guidance and attention is also required, especially for those patients who have an opportunistic infections, higher WHO clinical stages, co-infections with HIV and TB, and bedridden functional status.

Backward bifurcation on HIV/AIDS SEI 1 I 2 TAR model with multiple interactions between sub-populations

The HIV/AIDS model was dynamically analyzed in this study. The model has seven compartments: the uneducated, the educated, the HIV-positive who take antiretroviral therapy (ART), the HIV-positive who do not take ART, people receiving ART treatment, people with AIDS who do not receive any treatment (full-blown AIDS), and the recovered. This model takes into account the analysis of the multiple interactions between the uneducated and the educated subpopulations, the HIV-positive who take and who do not take ART. The free-disease and endemic equilibrium points, as well as the basic reproduction number ( R 0 ) as a limit condition for infection-free and endemic occurrence, were produced by a mathematical analysis. The center-manifold hypothesis was used to prove that a backward bifurcation exists. The free-disease and endemic equilibrium points coexist when R 0 < 1 . This means that HIV/AIDS is still spreading. A basic reproduction number below one is insufficient to constitute a free-disease condition. In order to determine essential parameters that significantly contribute to HIV/AIDS transmission, we computed sensitivity index values using a sensitivity analysis. The HIV/AIDS model and bifurcation parameter both identified the rate of HIV transmission from uneducated individuals to HIV-positive individuals who do not receive ART as the most crucial parameter. A numerical simulation supports the dynamical analysis.