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Introduction South Africa is moving into a new era of HIV treatment with “treat all” policies where people may be on treatment for most of their lives. We need to understand treatment outcomes and facilitators of long‐term antiretroviral treatment (ART) adherence and retention‐in‐care in the South African context. In one of the first studies to investigate long‐term treatment outcomes in South Africa, we aimed to describe ten‐year patient outcomes at a large public‐sector HIV clinic in Johannesburg and explore patient experiences of the treatment programme over this time in order to ascertain factors that may aid or hinder long‐term adherence and retention. Methods We conducted a cohort analysis (n = 6644) and in‐depth interviews (n = 24) among HIV‐positive adults initiating first‐line ART between April 2004 and March 2007. Using clinical records, we ascertained twelve‐month and ten‐year all‐cause mortality and loss to follow‐up (LTF). Cox proportional hazards regression was used to identify baseline predictors of attrition (mortality and LTF (>3 months late for the last scheduled visit)) at twelve months and ten years. Twenty‐four patients were purposively selected and interviewed to explore treatment programme experiences over ten years on ART. Results Excluding transfers, 79.5% (95% confidence intervals (CI): 78.5 to 80.5) of the cohort were alive, in care at twelve months dropping to 35.1% (95% CI: 33.7 to 36.4) at ten years. Over 44% of deaths occurred within 12 months. Ten‐year all‐cause mortality increased, while LTF decreased slightly, with age. Year and age at ART initiation, sex, nationality, baseline CD4 count, anaemia, body mass index and initiating regimen were predictors of ten‐year attrition. Among patients interviewed, the pretreatment clinic environment, feelings of gratitude and good fortune, support networks, and self‐efficacy were facilitators of care; side effects, travel and worsening clinical conditions were barriers. Participants were generally optimistic about their futures and were committed to continued care. Conclusions This study demonstrates the complexities of long‐term chronic HIV treatment with declining all‐cause mortality and increasing LTF over ten years. Barriers to long‐term retention still present a significant challenge. As more people become eligible for ART in South Africa under “treatment for all,” new healthcare delivery challenges will arise; interventions are needed to ensure long‐term programme successes continue.

Background Antiretroviral therapy (ART) use by people living with HIV reduces HIV transmission, morbidity, mortality, and improves quality of life. Good ART adherence is required to achieve these benefits. We investigated how the environmental, social, economic and behavioural experiences of people living with HIV with poor viral suppression could explain their non-adherence to long term ART. Methods This qualitative cross-sectional study was conducted in Uganda between September 2015 and April 2016. Thirty individuals on ART for 5 years or more (10 on first line and 20 on second line), with poor viral suppression, were randomly selected from a cohort of people living with HIV on ART. In-depth interviews about ART; awareness, adherence counselling, obstacles to daily adherence and regimen switches were conducted. Emerging themes from the interviews transcripts and field notes were identified and thematic content analysis done. Participants’ consent, compensation, confidentiality and study ethical approvals were ensured. Results We found that poor adherence to long term ART was due to: travel for work or social activities, stigma, receiving little or no continuous ART adherence education, alcohol consumption and use of alternative ‘HIV cure’ medicines. Other reasons included; ART side effects, treatment fatigue, belief that long-term ART or God can ‘cure HIV’, and food security. Conclusions Achieving optimal ART benefits requires continuous provision of ART adherence education to individuals on long term ART. This helps them overcome the challenges related to living with HIV: worries of food insecurity, alcohol misuse, economic hardship, and beliefs in HIV cures and use of unproven alternative HIV treatments. People living with HIV who travel require adherence support and larger quantities of ART refills to cover their time away.

Background Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. Methods We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. Results A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4–37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167–379) cells/mm 3 and median follow-up duration was 7.6 (IQR 1.9–15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm 3 . The overall crude incidence of TB was 4.66 (95% CI 3.87–5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m 2 , and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). Conclusion Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored.

There is a growing number of perinatally HIV-1-infected children worldwide who must maintain life-long ART. In early life, HIV-1 infection is established in an immunologically inexperienced environment in which maternal ART and immune dynamics during pregnancy play a role in reservoir establishment. Children that initiated early antiretroviral therapy (ART) and maintained long-term suppression of viremia have smaller and less diverse HIV reservoirs than adults, although their proviral landscape during ART is reported to be similar to that of adults. The ability of these early infected cells to persist long-term through clonal expansion poses a major barrier to finding a cure. Furthermore, the effects of life-long HIV persistence and ART are yet to be understood, but growing evidence suggests that these individuals are at an increased risk for developing non-AIDS-related comorbidities, which underscores the need for an HIV cure.

Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techniques in blood and tissue of early-treated seroconverters, late-treated patients, ART-naïve seroconverters, and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced the total and integrated HIV-1 DNA levels compared with later treatment initiation, but not reaching the low levels found in LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (HIV-1 unspliced RNA) and enhanced immune preservation (CD4/CD8), reminiscent of LTNPs, were found in early compared to late-treated patients. This suggests that early treatment is associated with some immunovirological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure. Many people with HIV infections are able to live relatively normal lives thanks to major advances in drug therapies. A cure, however, remains elusive. One reason for this is that the virus can hide in certain types of human cells, where it is protected from the immune system and the effects of “antiretroviral” drugs. This creates reservoirs of virus particles in the body that can quickly multiply and spread if treatment stops. Some people who become infected with HIV are able to contain the virus without the help of drug treatments. These individuals – known as long-term non-progressors – do not become ill and only have low numbers of HIV particles in reservoirs. People who receive treatment early in the course of an HIV infection also have fewer viruses in reservoirs and are less likely to develop severe illness. Therefore, it might be possible to develop a “functional” cure that may not completely eliminate the virus from the body, but would prevent illness and allow the individuals to eventually stop taking antiretroviral drugs. Now, Malatinkova, De Spiegelaere et al. studied samples from 84 patients with HIV-1 to find how much effect an early start to treatment has on the amount of the virus in reservoirs. People who started treatment soon after infection had lower levels of HIV-1 in their blood than people who started treatment later (even after 10 years of treatment). However, patients that started treatment early had higher levels of HIV-1 in the blood than the patients who were long-term non-progressors. All the patients had similar levels of HIV-1 in tissue samples taken from the rectum, regardless of when they started treatment. The experiments suggest that HIV-1 reservoirs form very soon after infection. Malatinkova, De Spiegelaere et al. found that in addition to reducing reservoirs of HIV-1, an early start to drug treatment reduced the ability of the virus to make copies of its genetic code. People who started treatment earlier also had healthier immune cells. Together, the experiments support the benefits of starting drug treatments as soon as possible after a person is infected with HIV-1. It is important to further characterize thoroughly the viral reservoir in patients with limited HIV-1 reservoirs and to look for other immune factors involved in virus control, in the search for a functional cure of HIV.

The introduction of antiretroviral therapy (ART) significantly decreases the incidence of tuberculosis (TB) in people living with human immunodeficiency virus (PLWHIV). However, a considerable proportion is still co-infected with TB after ART initiation. Thus, this study aimed to assess the effect of long-term HAART on the incidence of TB among PLWHIV in Addis Ababa, Ethiopia. A matched nested case-control study was conducted among PLWHIV who were enrolled in ART clinics in Addis Ababa, Ethiopia from 2013 up to 2018. Cases were HIV-TB co-infected individuals who were taking antiretroviral treatment, while controls were PLWHIV without TB who were taking antiretroviral treatment. The cases and controls are matched exactly in age and sex. Data were entered in Epi Info version 7.1 and analyzed using SPSS version 20. Bi-variable and multivariable conditional logistic regression were employed along with 95% CI. A P-value <0.05 in the multivariable analysis was considered statistically significant. Fifty-seven cases were compared with 114 controls. Accordingly, previous TB history (X ; 13.790, < 0.001), baseline functional status (X ; 9.120, = 0.010), baseline WHO clinical stage (X ; 10.083, = 0.001), baseline hemoglobin value (X ; 6.985, = 0.008), baseline body mass index (X ; 3.873, = 0.049), isoniazid preventive treatment (X ; 8.047, = 0.005), baseline CD4 value (X ; 12.741, < 0.001) and length of stay on ART (X ; 53.359, < 0.001) were associated with developing TB. Length of stay on ART was found to be the statistically significant determinant of TB infection after ART initiation (aOR = 5.925, 95% CI = 2.649-13.250). Advanced clinical stages at the baseline, previous TB history, and not taking IPT were associated with TB infection. The long-term ART exposure significantly decreases tuberculosis incidence in PLWHIV. Thus, retaining PLWHIV on ART would be important to decrease the incidence of TB in this group of individuals.

We investigated the prevalence, predictors of and effect of Antiretroviral Therapy (ART) regimen on cardiometabolic risk among HIV-positive Ugandan adults at enrolment into a prospective cohort to study the Complications of Long-Term ART (CoLTART). We collected data on cardiometabolic risk factors including dyslipidemia, hypertension, hyperglycemia, obesity and calculated the mean atherogenic index for Plasma (AIP) and 10 year Framingham risk score (FHS). Exposures were: ART regimen, duration on ART, demographic, socio-economic, behavioral, and life-style factors including smoking, physical activity and diet (including fruit and vegetables consumption). We enrolled 1024 participants, 65% female, mean age was 44.8 years (SD 8.0) and median duration on ART was 9.4 years (IQR 6.1-9.8). The prevalence of abdominal obesity was 52.6%, BMI≥25 kg/m -26.1%, hypertension-22.6%, high AIP-31.3% and FHS above 10% was 16.6%. The prevalence of low High Density Lipoprotein (HDL) was 37.5%, high Total cholesterol (Tc)-30.2%, high Low Density Lipoprotein (LDL) -23.6%, high Triglycerides (TG)-21.2%, low physical activity-46.4% and alcohol consumption-26.4%. In multivariate linear regression analyses, increasing age was associated with higher mean Tc, HDL, LDL, FHS (P<0.001) and hyperglycemia (p<0.005). In multivariate logistic regression analyses, Protease Inhibitor (PI) containing regimens were significantly associated with higher risks of abnormal: Tc, LDL, TG, AIP, abdominal obesity, hypertension, low HDL and lower risk of a FHS >10% compared to the non PI regimen. ART increases cardiometabolic risk. Integration of routine assessment for cardiometabolic risk factors and preventive interventions into HIV care programs in resource-limited settings is recommended.

Cardiovascular disease is a major driver of morbidity and mortality in adults living with HIV. The drivers of cardiovascular disease in children living with perinatally acquired HIV (PHIV) with sustained HIV viral suppression are unclear. We explored the contribution of HIV-specific risk factors to arterial stiffness independently of traditional risk factors (metabolic syndrome [MetS]) in prepubertal children with PHIV with sustained viral suppression in a low-income country in Africa. For this cross-sectional analysis, arterial stiffness was assessed by pulse wave velocity -score (PWVz), measured using a Vicorder device. Metabolic syndrome components were measured. We retrospectively collected the antiretroviral therapy (ART) exposures, HIV stage, CD4 count and HIV viral load. A multivariate linear regression model was constructed for MetS components, retaining age and gender as obligatory variables. We then added HIV-related metrics to assess whether these had an independent or additive effect. We studied 77 virally suppressed children with PHIV without evidence of cardiovascular disease (from medical history and physical examination). In the initial model, the PWVz was independently associated with each MetS component. The PWVz was higher in participants with proportionally greater visceral fat (waist/height ratio), elevated lipids (triglyceride/high-density lipoprotein ratio) and insulin resistance (log homeostatic model assessment [HOMA]). The addition of age at ART initiation increased the model value from 0.36 to 0.43. In the resulting model, younger age at ART initiation was independently associated with a better PWVz ( < 0.001). Earlier ART initiation was independently associated with lower large artery stiffness. This effect was independent of the effect of elevated lipids, visceral fat and insulin resistance.

[Rolf Potts] evidently has spent years living what he preaches. And what he preaches is abstaining from the consumer culture by not acquiring lots of stuff, \"making work serve your interests\" (one of which presumably is to travel a lot), and keeping an open mind to whatever you find out there. He's even open to the reality that most of us can't wander forever and will choose to return to our settled lives, so he defines vagabonding as \"taking an extended time-out from your normal life - six weeks, four months, two years - to travel the world on your own terms.\" Yet his argument is rather thin - or maybe just, well, simple - and he ends up making the same points over and over, in his own words and those of others, to stretch it out to book length. Even so - and despite flurries of \"pop-out quotes\" that annoyingly interrupt the flow of the text and the addition of \"vagabonding voices\" and \"profiles\" at the end of each chapter - this is a rather slim paperback volume. Potts's argument could be made more powerfully and persuasively in a trimmed-down, less repetitious magazine article (which it evidently originally was). Either that or he might have forgone the endless philosophizing and gotten a lot more detailed about how you get from here to there, what there is to do, where to stay, etc.

The arts (e.g., music and painting) have received considerable theoretical and observational support as a cognitive stimulation technique for persons living with dementia (PLWD). However, particularly for visual arts, limited empirical support exists. Therefore, the purpose of this study was to pilot a free-form arts program for PLWD in the context of a cognitive stimulation paradigm and measure subsequent engagement, communication, cognitive-linguistic function, and quality of life. Three PLWD (one each in mild-to-moderate, moderate, and moderate-to-severe stages) were referred for study participation by a local long-term care facility. A single subject across subjects, ABA reversal design was used to assess intervention effects over a period of 8 weeks, in comparison to an active control condition (cooking activity). Cognitive-linguistic function and quality of life were assessed using standardized measures at baseline and follow-up. Engagement and communication were probed regularly across each study phase. Significant changes were seen in participants' engagement and communication during painting sessions compared to the control activity. A nonsignificant positive trend was noted for self-rated quality of life from baseline to follow-up. Pre-post testing revealed nominal change in cognitive-linguistic functions. An arts program led to significant increases in constructive engagement and communication and a trend toward increased self-rated quality of life for the three PLWD. The fact that these changes were not sustained outside intervention sessions (i.e., pre-post testing) is consistent with the need for a larger paradigm shift in which rehabilitation specialists-including speech-language pathologists-better integrate creative, meaningful activities into the everyday lives of PLWD to maximize ongoing engagement, communication, and quality of life.