Antiretroviral Drug Therapy Research Articles

Clinical Characteristics of Children with HIV Initiated on Antiretroviral Treatment at HIV Clinics in Bloemfontein, South Africa.

Background and Objective:Over the past 15 years, there have been three major updates to the South African national guidelines for the management of human immunodeficiency virus (HIV) in children. The purpose of this study is to describe the clinical characteristics of children who were initiated on antiretroviral therapy (ART) in Bloemfontein, South Africa, following these national treatment guidelines.Methods:Clinical information during initiation of ART in children aged 0-13 years was obtained from five HIV clinics in Bloemfontein from 2004 to 2019 as part of the establishment of an antiretroviral (ARV) pediatric registry at the University of the Free State. Data were analyzed for patient demographics, clinical presentation (World Health Organization (WHO) HIV-staging, growth rate and comorbid conditions), types of investigations done, and medicines prescribed.Results:The number of children initiated on ART increased from 168 in the period 2004-2009 to 349 (107.8%) in 2010-2014, and then dropped to 162 in the period 2015-2019. The increase in 2010-2014 was mainly in the <2 years age group by 54.8%, and in the 5 to 10 years age group by 344.4%. In the same period, the number of children with severe illness (WHO HIV-stage 4) decreased by 20.7%, while those with mild to moderate illness (WHO HIV-stage 2 and 3) increased by 17.3%. HIV infection was more severe in children under two years as more patients in this age group presented with WHO HIV-stages 3 and 4, severe underweight (below 3rd percentile), severely suppressed CD4 count (< 25%), and a high viral load (> 1000 copies/ml). There was increased use of ABC/3TC/LPVr in the < 3-year age group and ABC/3TC/EFV in the > 3-year age group. There was reduced use of the stavudine and other regimens.Conclusion and Global Health Implications:More children were started on ART and safer ARV drugs. Children under 2 years were the most debilitated by HIV, and there was an increase in HIV prevalence among children > 5 years. New strategies for the prevention and management of HIV among children in these two age groups are needed.

Cross-sectional study regarding pattern of adverse drug reactions in a tertiary care hospital, Kakinada, India

Introduction: Drugs are considered as double-edged weapons with the potential to cause benefit as well as harm. Recent studies reveal that adverse drug reactions (ADRs) imply a remarkable burden on the length of hospital stay, healthcare facilities, and sometimes they require additional investigations and drug therapies for the treatment of symptoms and diseases caused to the patient. So, further local studies are required to understand the scenario and to improve the safety of prescribing and monitoring drugs and improved patient adherence to medication. Objectives: To evaluate and assess the pattern of adverse drug reactions reported to the ADR Monitoring Centre, Rangaraya Medical College, Kakinada, India. Materials and Methods: The current study was a retrospective and an observational type of study carried out at the ADR Monitoring Centre of a tertiary care hospital. Total ADRs reported during the two years from June 2016 to June 2018 were included in the study. Each ADR was analyzed for demographic data, relationship to drugs as per causality assessment, and frequency of ADRs. Microsoft Excel 2019 and SPPS version 20 were used for data analysis. Results: The most common group of drugs showing ADRs were anti-retroviral therapy (ART) drugs, followed by anti-microbial agents. Most of the ADRs were probable and mild. Rash was the most frequently occurring ADR. Conclusion: The study of ADRs in a particular institute using demographic patterns will contribute to patient safety by sensitizing the clinicians in that particular institute.

Nutritional Profile of Patients with Acquired Immunodefience Syndrome

Objective: To evaluate the nutritional status of patients living with the human immunodeficiency virus and making use of antiretroviral medication. Methods: This is an observational cross-sectional analytical study that was conducted from May to July 2018. The nutritional status was determined through the evaluation of anthropometric data. The anthropometric measurements collected were: body mass index, brachial circumference, triceps skin fold and waist circumference. Results: We evaluated 120 patients in regular use of antiretroviral therapy. According to the body mass index, most individuals (41.2%) presented eutrophy, followed by overweight (35.7%). Regarding waist circumference, about 30% of patients presented a much increased risk for cardiovascular diseases. It was also observed that 47.5% of the patients presented eutrophy through the arm circumference parameter. Regarding the anthropometric parameter, triceps skin fold, it was observed that 29.9% of the patients presented severe malnutrition, followed by obesity (24.2%). Conclusion: It is known that even individuals undergoing antiretroviral therapy, aiming at slowing the progression of the disease, may present a possible involuntary weight loss during treatment. When related, the parameters of arm circumference, triceps skin fold, and waist circumference characterize the clinical signs of lipodystrophic syndrome, defined as abnormal redistribution of body fat. It is concluded that constant nutritional monitoring of patients in regular use of antiretroviral therapy drugs is necessary in order to prevent possible complications in the nutritional status of patients living with the human immunodeficiency virus.

Enhancing current human immunodeficiency virus/hepatitis B and human immunodeficiency virus/hepatitis C virus co-infection management.

Enhancing current human immunodeficiency virus/hepatitis B and human immunodeficiency virus/hepatitis C virus co-infection management.

PIN39 Thirty Two YEARS of Antiretroviral Therapy (ART) for People Living with HIV in Spain: HAS IT Been an Efficient Intervention?

The aim of this study is to estimate the clinical and economic impact of ART in Spain over a 32-year period (1987-2018). A cost-benefit analysis was performed, using a second-order Monte Carlo simulation model, from a societal (base case) and National Health Service (NHS) perspective. New cases of HIV, AIDS and associated deaths in Spain were obtained from SINIVIH registry and UNAIDS. Local projections of new HIV cases, AIDS cases, and AIDS related deaths in a scenario without ART were estimated by triple exponential smoothing. HIV and AIDS cases averted and deaths prevented, were estimated. ART expenditure and the benefits of avoiding HIV infections and AIDS cases were obtained from National HIV plan assessment reports and Market Research data. The monetary value of a life was estimated as the local annual GDP per capita. The model’s assumptions and data were validated by a panel of 4 Spanish experts. The NHS invested 6,185 million euros on ART over 32 years. In that period, 323,651 AIDS deaths, 500,129 AIDS cases and 161,417 HIV cases were averted, with total savings of 41,997 million euros. The net benefit (net savings) associated with these results is estimated at 35,812 million euros (social perspective) and 1,032 million euros (NHS perspective). ART is a profitable investment as it would render benefit/cost ratios of 6.79 (95%CI 5.39-8.35) and 1.17 (95% CI: 1.16; 1.18) from a social and NHS perspective, respectively. Subanalysis of ART drugs marketed by Gilead Sciences (2002-2018), brought out a net benefit of 8,361 million euros, 23% of the total (benefit/cost ratio of 3.2 from a social perspective). The use of ART over 32 years in Spain has highly limited the amount of deaths from AIDS as well as new cases of both HIV and AIDS, while simultaneouly providing significant economic savings.

Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era.

Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era. Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time. Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens. There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Effectiveness of Medical Nutrition Therapy to Improve Dietary Habits for Promoting Bone Health in People Living with Chronic HIV

Introduction: Previous studies have established the risk of bone loss among people living with HIV affected by antiretroviral therapy drug side effects and inadequate nutrient intake. Until recently, there have been limits on using the medical nutrition therapy (MNT) to improve dietary habits for promoting bone health among people living with HIV. This was a randomized controlled trial study aimed to investigate the effectiveness of MNT in improving the bone health in people living with HIV by promoting dietary habits. Methods: PLHIV at Queen Savang Vadhana Memorial Hospital were randomly grouped (by quota sampling) into the MNT group (intervention group) and the control group. One hundred and thirty PLHIV were recruited to participate in this study by convenient sampling. Sixty-five participants of the MNT group made a total of 6 appointments (for 12 weeks) to meet registered dietitians for receiving MNT to improve dietary habits for improving bone health, while 65 participants in the control group received only routine care at the hospital service center. Results: In general, participants in the MNT group had significant increase in the amounts of calcium, vitamin D, potassium, and phosphorus intakes and length of exercise after the final week compared with before intervention. Also, they had significantly higher amount of nutrient intakes (calcium, vitamin D, potassium, and phosphorus) and length of exercise than the control group after finishing the final week of the experiment. Conclusion: In conclusion, MNT is effective for improving food habits and physical activity to promote bone health among people living with HIV.

Neuro-AIDS: Current Status and Challenges to Antiretroviral Drug Therapy (ART) for Its Treatment

Introduction:The infiltration of HIV into the brain alters the functions of the nervous system known as Neuro-AIDS. It leads to neuronal defects clinically manifested by motor and cognitive dysfunctions.Materials and Methods:Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy is used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which act as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders, including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination of antiretroviral therapy.Results and Conclusion:Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful in treating neuro-AIDS and related disorders effectively.

Managing HIV-associated inflammation and ageing in the era of modern ART.

This paper aims to address the concerns around ongoing immune activation, inflammation, and resistance in those ageing with HIV that represent current challenges for clinicians. Presentations at a symposium addressing issues of ageing with HIV infection were reviewed and synthesised. The changing natural history and demographics of human immunodeficiency virus (HIV)-infected individuals means new challenges in contemporary management. In the early years of the epidemic,management was focussed on acute, potentially life-threatening AIDS-related complications. From initial monotherapy with first-generation antiretroviral therapy (ART), the development of combination highly active ART (HAART) allowed HIV control but ART toxicities, treatment adherence and drug resistance emerged as major issues. Today, the availability of potent and tolerable ART has made viral suppression achievable in most people living with HIV (PLHIV), and clinicians are confronted with managing a chronic condition among an ageing population. The combination of diseases of ageing and the co-morbidities associated with HIV-infection, even when well controlled, results in a complex set of challenges for many older PLHIV. There is a growing appreciation that many non-AIDS-related co-morbidities are caused, at least in part, by persistent, low-grade immune activation, inflammation, and hypercoagulability, despite suppressive ART. In order to further improve HIV management, it is important to understand the enduring effects of chronically suppressed HIV infection, the potential contribution of these factors to the ageing process, the possibility of drug resistance, and the impact of different treatment strategies, including early ART initiation.

Incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy in public hospitals of Northern Ethiopia: Multicenter retrospective study.

BackgroundThis study aimed to determine the incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy (ART) in public hospitals of Northern Ethiopia.MethodsA retrospective study was conducted from September 1, 2007 to July 30, 2017 on 227 patients. The data were extracted using a retrieval checklist from the patient’s charts. The incidence rate of treatment failure was calculated using Kaplan–Meier methods and Cox proportional hazard model was used to assess factors associated with treatment failure.ResultThe study subjects were followed for a total observation of 788.58 person-years with a median follow-up period of 35 (IQR: 17–60) months after switching to second-line ART. About 57 (25.11%) patients developed treatment failure, out of which, 32 (56.14%) occurred during the first two years. The overall incidence of second-line treatment failure was 72.3 per 1000 person years (95%CI: 55.75–93.71) of observation. The Kaplan–Meier estimates of cumulative treatment failure after 1, 2, and around 10 years of follow-up were 12.31% (95%CI: 8.60–17.45%), 14.99% (95%CI: 10.82%-20.57%), and 48.67% (95%CI: 32.45–67.81%) respectively. Age >45 years AHR = 3.33, 95%CI = 1.33–8.31), WHO stage IV (AHR = 3.63, 95%CI = 1.72–7.67), CD4 count <100 cells/mm3 (AHR = 3.79, 95%CI = 1.61–8.91), TB co-morbidity (AHR = 3.39 95%CI = 1.91–6.01) and poor adherence level (AHR = 3.63, 95% CI = 1.89–6.96) at the start of second line ART were significantly associated with second-line ART failure.ConclusionIncidence of second-line ART treatment failure in the first 2 years of follow-up was high. The rate of second-line ART failure was higher in patients who started second-line ART with poor drug adherence, CD4 count <100 cells/mm3, TB co-morbidity, age >45 years, and being in WHO stage IV. Therefore, intensive counseling and adherence support should be given along with strong TB screening. Moreover, the government of Ethiopia should consider endorsing third-line ART drugs after careful cost–benefit analysis.

Effect of telephone calls and text message reminder interventions on the adherence to antiretroviral drugs among HIV/AIDS clients receiving care in Sokoto state, Nigeria

Background: Adherence to antiretroviral therapy (ART) has been proven to be a good predictor of clinical outcome among patients on ART. This study aimed to assess the effect of phone reminder interventions on the knowledge of Human immunodeficiency syndrome (HIV)/ Acquired immunodeficiency syndrome (AIDS), ART and adherence to ART drugs among non-adherent patients receiving care in Sokoto State.Methods: A quasi-experimental study was conducted among 196 non-adherent HIV patients between February and July 2017. The intervention group received monthly telephone calls and weekly text messages for twelve weeks while the control group received only standard of care. Self-report adherence, forgetfulness to take ART and knowledge of HIV/AIDS and ART were measured pre- and post- intervention. Data were processed and analysed using IBM Statistical package for social sciences (SPSS) version 22 computer statistical software package.Results: At baseline, although majority of participants in both groups had good knowledge of HIV/AIDS, ART drug adherence, they were both non-adherent to ART and it was mainly due to forgetfulness. At post intervention, respondents with good knowledge and adherent to ART were significantly higher in the intervention group. There was also a significantly lower proportion of forgetfulness among the intervention group compared with control group (c2=47.57, p&lt;0.001).Conclusion: The interventions were found to be effective. The Federal Ministry of Health (FMoH) with the support of implementing partners need to integrate these interventions into clinical setting as part of comprehensive care for HIV care and treatment to assist in improving their knowledge of HIV/AIDS, ART and adherence to ART.

Regional Brain Recovery from Acute Synaptic Injury in Simian Immunodeficiency Virus-Infected Rhesus Macaques Associates with Heme Oxygenase Isoform Expression.

Brain injury occurs within days in simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) infection, and some recovery may occur within weeks. Inflammation and oxidative stress associate with such injury, but what drives recovery is unknown. Chronic HIV infection associates with reduced brain frontal cortex expression of the antioxidant/anti-inflammatory enzyme heme oxygenase-1 (HO-1) and increased neuroinflammation in individuals with cognitive impairment. We hypothesized that acute regional brain injury and recovery associate with differences in regional brain HO-1 expression. Using SIV-infected rhesus macaques, we analyzed multiple brain regions through acute and chronic infection (90 days postinfection [dpi]) and quantified viral (SIV gag RNA), synaptic (PSD-95; synaptophysin), axonal (neurofilament/neurofilament light chain [NFL]), inflammatory, and antioxidant (enzymes, including heme oxygenase isoforms [HO-1, HO-2]) markers. PSD-95 was reduced in the brainstem, basal ganglia, neocortex, and cerebellum within 13 dpi, indicating acute synaptic injury throughout the brain. All areas except the brainstem recovered. Unchanged NFL was consistent with no acute axonal injury. SIV RNA expression was highest in the brainstem throughout infection, and it associated with neuroinflammation. Surprisingly, during the synaptic injury and recovery phases, HO-2, and not HO-1, progressively decreased in the brainstem. Thus, acute SIV synaptic injury occurs throughout the brain, with spontaneous recovery in regions other than the brainstem. Within the brainstem, the high SIV load and inflammation, along with reduction of HO-2, may impair recovery. In other brain regions, stable HO-2 expression, with or without increasing HO-1, may promote recovery. Our data support roles for heme oxygenase isoforms in modulating recovery from synaptic injury in SIV infection and suggest their therapeutic targeting for promoting neuronal recovery.IMPORTANCE Brain injury induced by acute simian (or human) immunodeficiency virus infection may persist or spontaneously resolve in different brain regions. Identifying the host factor(s) that promotes spontaneous recovery from such injury may reveal targets for therapeutic drug strategies for promoting recovery from acute neuronal injury. The gradual recovery from such injury observed in many, but not all, brain regions in the rhesus macaque model is consistent with the possible existence of a therapeutic window of opportunity for intervening to promote recovery, even in those regions not showing spontaneous recovery. In persons living with human immunodeficiency virus infection, such neuroprotective treatments could ultimately be considered as adjuncts to the initiation of antiretroviral drug therapy.

HIV-1 Sanctuary Sites-the Role of Membrane-Associated Drug Transporters and Drug Metabolic Enzymes.

Despite significant advances in the treatment of human immunodeficiency virus-1 (HIV) infection with highly active antiretroviral drug therapy, the persistence of the virus in cellular and anatomic reservoirs is a major obstacle preventing total HIV eradication. Viral persistence could result from a variety of contributing factors including, but not limited to, non-adherence to treatment and adverse drug reactions, latently infected cells carrying replication-competent virus, drug-drug interactions, and inadequate antiretroviral drug (ARV) concentrations reached in several anatomic sites such as the brain, testis, and gut-associated lymphoid tissues. The distribution of ARVs at specific sites of infection is primarily dependent on drug physicochemical properties and drug plasma protein binding, as well as drug efflux, influx, and metabolic processes. A thorough understanding of the functional roles of drug transporters and metabolic enzymes in the disposition of ARVs in immune cell types and tissues that are characterized as HIV reservoirs and sanctuaries is critical to overcome the challenge of suboptimal drug distribution at sites of persistent HIV infection. This review summarizes the current knowledge related to the expression and function of drug transporters and metabolic enzymes in HIV cellular and anatomic reservoirs, and their potential contribution to drug-drug interactions and insufficient drug concentration at these sites.

Emerging Trends in the Long-Acting Antiretroviral Therapy: Current Status and Therapeutic Challenges.

Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of people living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and lymph nodes leads to the build-up of viral reservoirs in these sites. To combat some of these challenges and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the arsenal, in the fight against HIV. Few long-acting preparations have been approved, and several others are in various clinical and preclinical stages of development. However, long-acting formulations also have their share of clinical issues like limited drug distribution, long term adverse drug reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological premises are being tested to mitigate some of these problems. One such promising approach involves nanotechnological methods, which are being used to develop ultra-long acting formulations and drug delivery systems, targeting tissues with residual HIV concentration. Long-Acting Slow Effective Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug modifications to design preparations with tailor-made favorable pharmacokinetics and wider drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards eliminating the disease.

Assessing the costs and efficiency of HIV testing and treatment services in rural Malawi: implications for future \u201ctest and start\u201d strategies

BackgroundReaching the 90–90-90 targets requires efficient resource use to deliver HIV testing and treatment services. We investigated the costs and efficiency of HIV services in relation to HIV testing yield in rural Karonga District, Malawi.MethodsCosts of HIV services were measured over 12 months to September 2017 in five health facilities, drawing on recognised health costing principles. Financial and economic costs were collected in Malawi Kwacha and United States Dollars (US$). Costs were calculated using a provider perspective to estimate average annual costs (2017 US$) per HIV testing episode, per HIV-positive case diagnosed, and per patient-year on antiretroviral therapy (ART), by facility. Costs were assessed in relation to scale of operation and facility-level annual HIV positivity rate. A one-way sensitivity analysis was undertaken to understand how staffing levels and the HIV positivity rate affected HIV testing costs.ResultsHIV testing episodes per day and per full-time equivalent HIV health worker averaged 3.3 (range 2.0 to 5.7). The HIV positivity rate averaged 2.4% (range 1.9 to 3.7%). The average cost per testing episode was US$2.85 (range US$1.95 to US$8.55), and the average cost per HIV diagnosis was US$116.35 (range US$77.42 to US$234.11), with the highest costs found in facilities with the lowest daily number of tests and lowest HIV yield respectively. The mean facility-level cost per patient-year on ART was approximately US$100 (range US$90.67 to US$115.42). ART drugs were the largest cost component averaging 71% (range 55 to 76%). The cost per patient-year of viral load tests averaged US$4.50 (range US$0.52 to US$7.00) with cost variation reflecting differences in the tests to ART patient ratio across facilities.ConclusionGreater efficiencies in HIV service delivery are possible in Karonga through increasing daily testing episodes among existing health workers or allocating health workers to tasks in addition to testing. Costs per diagnosis will increase as yields decline, and therefore, encouraging targeted testing strategies that increase yield will be more efficient. Given the contribution of drug costs to per patient-year treatment costs, it is critical to preserve the life-span of first-line ART regimens, underlining the need for continuing adherence support and regular viral load monitoring.

Prevalence of diabetes mellitus and hypertension in people living with human immunodeficiency virus on antiretroviral therapy in Gweru district, Zimbabwe.

BackgroundWhile antiretroviral therapy (ART) has markedly increased survival in people living with human immunodeficiency virus (PLHIV), emerging trends of co-existence of non-communicable diseases (NCDs) and HIV could negate the gains already achieved in controlling HIV.AimThe study aimed to determine the prevalence of hypertension and diabetes mellitus in PLHIV on ART in Gweru district.SettingSix high-volume ART sites in Gweru district under Midlands province in Zimbabwe.MethodsThis was a cross-sectional study. Screening and data collection occurred over a 3-month cycle when all patients were expected to have visited the ART sites for their monthly ART drug supply. The process also allowed the identification of health system challenges regarding data management for HIV-NCD comorbidity. Poisson regression analysis was used to calculate NCD prevalence ratio (PR) in PLHIV.ResultsNearly 18 000 PLHIV registered for ART were identified. Hypertension (19.5%) and diabetes mellitus (8.4%) were the most common NCDs identified with a high proportion of those who did not know their diagnosis (over 50%). The prevalence of hypertension and/or diabetes mellitus among women was 74.9% compared to 25.1% in men (PR 3.22; 95% CI: 3.07–5.51, p = 0.0000). Other factors associated with increased prevalence of hypertension and/or diabetes mellitus were age group of ≥ 60 years (PR 2.5; 95% CI: 1.42–3.22, p = 0.00023), and duration of ≥ 5 years on ART (PR 6.4; 95% CI: 4.70–8.01, p = 0.0011). Separate data collection for NCDs and HIV was a key challenge affecting quantification of magnitude of HIV-NCDs comorbidity and subsequently management of NCDs in PLHIV.ConclusionsIndications of increasing prevalence of NCDs in PLHIV call for integrated electronic data management for HIV, TB and NCDs. This will allow active NCD case finding, and eventually improve prevalence data and treatment for HIV-NCD comorbidity. Future studies should focus on the health experiences and access to treatment in PLHIV diagnosed with NCDs; and to establish the accurate manner in which HIV status, ART and NCDs might be associated, through conducting a case control or cohort study.

The predictors of pain extent in people living with HIV.

To investigate the prevalence of widespread pain among people with HIV (PWH) and describe associations with antiretroviral therapy (ART) and markers of HIV disease stage. Cross-sectional analysis of cohort study in the United Kingdom and Ireland. Pain information was collected during the baseline visit (conducted from 2013 to 2015) through a self-completed manikin identifying pain at 15 sites from five body regions. Pain was classified as widespread if reported at at least four regions and at least seven sites, or regional otherwise. Chi-squared tests, Kruskal-Wallis tests and ordinal logistic regression were used to consider associations between pain extent and sociodemographic and HIV-related factors. Among the 1207 participants (614 PWH ≥ 50 years, 330 PWH < 50 years, 263 HIV-negative controls ≥50 years), pain was most commonly reported at the upper (left: 28.9%, right: 28.0%) and lower (left: 25.7%; right: 24.5%) leg, upper (18.6%) and lower (29.7%) back and shoulders (left: 16.0%; right: 16.8%). Widespread pain was more commonly reported in PWH than in HIV-negative controls (PWH ≥ 50 years: 18.7%; PWH < 50 years: 12.7%; HIV-negative ≥50 years: 9.5%) with regional pain reported in 47.6, 44.8 and 49.8%, respectively (global P = 0.001). In multivariable analyses, pain extent was greater in those with lower educational attainment, those exposed to more ART drugs, and those with a higher current CD4 cell count but longer exposure to immunosuppression. Widespread pain is commonly reported in PWH and is associated with longer duration of exposure to HIV, immunosuppression and ART. Our findings call for greater awareness, and interventions to support the management, of pain in PWH.

Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models

SummaryBackgroundThe COVID-19 pandemic could lead to disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimated that more than two-thirds of the approximately 38 million people living with HIV resided in 2018. We aimed to predict the potential effects of such disruptions on HIV-related deaths and new infections in sub-Saharan Africa.MethodsIn this modelling study, we used five well described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, an Imperial College London model, and Epidemiological MODeling software [EMOD]) to estimate the effect of various potential disruptions to HIV prevention, testing, and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months over 1 year from April 1, 2020. We considered scenarios in which disruptions affected 20%, 50%, and 100% of the population.FindingsA 6-month interruption of supply of antiretroviral therapy (ART) drugs across 50% of the population of people living with HIV who are on treatment would be expected to lead to a 1·63 times (median across models; range 1·39–1·87) increase in HIV-related deaths over a 1-year period compared with no disruption. In sub-Saharan Africa, this increase amounts to a median excess of HIV deaths, across all model estimates, of 296 000 (range 229 023–420 000) if such a high level of disruption occurred. Interruption of ART would increase mother-to-child transmission of HIV by approximately 1·6 times. Although an interruption in the supply of ART drugs would have the largest impact of any potential disruptions, effects of poorer clinical care due to overstretched health facilities, interruptions of supply of other drugs such as co-trimoxazole, and suspension of HIV testing would all have a substantial effect on population-level mortality (up to a 1·06 times increase in HIV-related deaths over a 1-year period due to disruptions affecting 50% of the population compared with no disruption). Interruption to condom supplies and peer education would make populations more susceptible to increases in HIV incidence, although physical distancing measures could lead to reductions in risky sexual behaviour (up to 1·19 times increase in new HIV infections over a 1-year period if 50% of people are affected).InterpretationDuring the COVID-19 pandemic, the primary priority for governments, donors, suppliers, and communities should focus on maintaining uninterrupted supply of ART drugs for people with HIV to avoid additional HIV-related deaths. The provision of other HIV prevention measures is also important to prevent any increase in HIV incidence.FundingBill & Melinda Gates Foundation.

Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis

HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Antiretroviral drug concentrations in brain tissue of adult decedents.

Determine concentrations of antiretroviral therapy (ART) drugs in the human brain. Cohort study of persons with HIV who consented to antemortem assessment and postmortem autopsy. Eleven persons with HIV who were taking ART at the time of death and had detectable concentrations of at least one ART drug in intracardiac aspirate at autopsy were evaluated. Autopsies were performed within 24 h of death and brain tissue was stored at -80 °C. Concentrations of 11 ART drugs were measured in three brain regions (globus pallidus, cortical gray matter, white matter) by HPLC tandem mass spectrometry with a lower limit of quantification of 25 ng/ml. Participants were mostly men (82%) with a mean age of 40.4 years. Drug concentrations in brain tissue were highly variable and exceeded published concentrations in cerebrospinal fluid for several drugs, including for tenofovir, efavirenz, and lopinavir. Drug concentrations correlated most strongly between cortical gray matter and globus pallidus (rho = 0.70) but less well between globus pallidus and white matter (rho = 0.43). Combining all drugs and brain regions (n = 89), higher drug concentrations in brain were associated with longer estimated duration of HIV infection (P = 0.015), lower HIV RNA in plasma (P = 0.0001), lower nadir CD4 T-cell count (P = 0.053), and worse neurocognitive performance (P = 0.017). This is the first analysis of ART drug concentrations in human brain tissue. Concentrations of several drugs in this analysis were similar to published concentrations in cerebrospinal fluid but others exceeded published concentrations. The association between higher drug concentrations in the brain and worse neurocognitive performance may indicate ART neurotoxicity.