Association between HIV infection and hypertension: a global systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: Improved access to effective antiretroviral therapy has meant that people living with HIV (PLHIV) are surviving to older ages. However, PLHIV may be ageing differently to HIV-negative individuals, with dissimilar burdens of non-communicable diseases, such as hypertension. While some observational studies have reported a higher risk of prevalent hypertension among PLHIV compared to HIV-negative individuals, others have found a reduced burden. To clarify the relationship between HIV and hypertension, we identified observational studies and pooled their results to assess whether there is a difference in hypertension risk by HIV status. METHODS: We performed a global systematic review and meta-analysis of published cross-sectional studies that examined hypertension risk by HIV status among adults aged > 15 (PROSPERO: CRD42019151359). We searched MEDLINE, EMBASE, Global Health and Cochrane CENTRAL to August 23, 2020, and checked reference lists of included articles. Our main outcome was the risk ratio for prevalent hypertension in PLHIV compared to HIV-negative individuals. Summary estimates were pooled with a random effects model and meta-regression explored whether any difference was associated with study-level factors. RESULTS: Of 21,527 identified studies, 59 were eligible (11,101,581 participants). Crude global hypertension risk was lower among PLHIV than HIV-negative individuals (risk ratio 0.90, 95% CI 0.85-0.96), although heterogeneity between studies was high (I2 = 97%, p < 0.0001). The relationship varied by continent, with risk higher among PLHIV in North America (1.12, 1.02-1.23) and lower among PLHIV in Africa (0.75, 0.68-0.83) and Asia (0.77, 0.63-0.95). Meta-regression revealed strong evidence of a difference in risk ratios when comparing North American and European studies to African ones (North America 1.45, 1.21-1.74; Europe 1.20, 1.03-1.40). CONCLUSIONS: Our findings suggest that the relationship between HIV status and prevalent hypertension differs by region. The results highlight the need to tailor hypertension prevention and care to local contexts and underscore the importance of rapidly optimising integration of services for HIV and hypertension in the worst affected regions. The role of different risk factors for hypertension in driving context-specific trends remains unclear, so development of further cohorts of PLHIV and HIV-negative controls focused on this would also be valuable.

Pharmacokinetic parameters and weight change in HIV patients newly switched to dolutegravir-based regimens in SIMPL'HIV clinical trial.

This study aims to evaluate the association between dolutegravir (DTG) pharmacokinetic parameters and weight changes in treatment-experienced people with HIV (PWHIV) from the Simpl'HIV study newly switched to a dual DTG-based regimen. We used multivariable linear regressions to evaluate the association between DTG pharmacokinetic parameters at week 48 (derived using an established model) and weight change between week 0 and week 48. We adjusted our model for potential confounders including CD4 nadir, female sex, African origin, age, weight at week 0 and presence of a non-nucleoside reverse transcriptase inhibitor-based regimen before switch to DTG. The analysis included data from 39 PWHIV. An average significant weight gain of 2.4 kg was observed between baseline and week 48. DTG plasma exposure was not significantly associated with weight gain, even after adjusting for potential confounders (P = .9). We found no significant association between DTG pharmacokinetic parameters and weight gain amongst PWHIV newly switched to a DTG-based dual regimen.

Mapping the Current and Future Noncommunicable Disease Burden in Kenya by Human Immunodeficiency Virus Status: A Modeling Study.

BACKGROUND: The noncommunicable disease (NCD) burden in Kenya is not well characterized, despite estimates needed to identify future health priorities. We aimed to quantify current and future NCD burden in Kenya by human immunodeficiency virus (HIV) status. METHODS: Original systematic reviews and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection, and related precancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV disease and treatment, aforementioned NCDs, and cancers. The model was parameterized using systematic reviews and epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV status among adults. RESULTS: Systematic reviews identified prevalence/incidence data for each NCD except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in people living with HIV (PLWH) compared to persons not living with HIV (62% vs 51%), driven by their higher age profile and partly by HIV-related risk for NCDs. Hypertension and high total cholesterol are the main NCD drivers (adult prevalence of 20.5% [5.3 million] and 9.0% [2.3 million]), with CVD and cancers the main causes of death. The burden is projected to increase by 2035 (56% in persons not living with HIV; 71% in PLWH), with population growth doubling the number of people needing services (15.4 million to 28.1 million) by 2035. CONCLUSIONS: NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these among both the general and populations living with HIV; however, coverage remains low.

Cardiovascular Disease Prevention Policy in Human Immunodeficiency Virus: Recommendations From a Modeling Study.

Background: Cardiovascular disease (CVD) is expected to contribute a large noncommunicable disease burden among human immunodeficiency virus (HIV)-infected people. We quantify the impact of prevention interventions on annual CVD burden and costs among HIV-infected people in the Netherlands. Methods: We constructed an individual-based model of CVD in HIV-infected people using national ATHENA (AIDS Therapy Evaluation in The Netherlands) cohort data on 8791 patients on combination antiretroviral therapy (cART). The model follows patients as they age, develop CVD (by incorporating a CVD risk equation), and start cardiovascular medication. Four prevention interventions were evaluated: (1) increasing the rate of earlier HIV diagnosis and treatment; (2) avoiding use of cART with increased CVD risk; (3) smoking cessation; and (4) intensified monitoring and drug treatment of hypertension and dyslipidemia, quantifying annual number of averted CVDs and costs. Results: The model predicts that annual CVD incidence and costs will increase by 55% and 36% between 2015 and 2030. Traditional prevention interventions (ie, smoking cessation and intensified monitoring and treatment of hypertension and dyslipidemia) will avert the largest number of annual CVD cases (13.1% and 20.0%) compared with HIV-related interventions-that is, earlier HIV diagnosis and treatment and avoiding cART with increased CVD risk (0.8% and 3.7%, respectively)-as well as reduce cumulative CVD-related costs. Targeting high-risk patients could avert the majority of events and costs. Conclusions: Traditional CVD prevention interventions can maximize cardiovascular health and defray future costs, particularly if targeting high-risk patients. Quantifying additional public health benefits, beyond CVD, is likely to provide further evidence for policy development.

Associations between HIV status and self-reported hypertension in a high HIV prevalence sub-Saharan African population: a cross-sectional study.

OBJECTIVES: This study examined whether HIV status and antiretroviral therapy (ART) exposure were associated with self-reported hypertension in Zimbabwe. DESIGN: Study data were taken from a cross-sectional, general population survey, which included HIV testing (July 2018-December 2019). SETTING: The data were collected in Manicaland Province, Zimbabwe. PARTICIPANTS: 9780 people aged 15 years and above were included. OUTCOME MEASURE: Self-reported hypertension was the outcome measure. This was defined as reporting a previous diagnosis of hypertension by a doctor or nurse. After weighting of survey responses by age and sex using household census data, χ2 tests and logistic regression were used to explore whether HIV status and ART exposure were associated with self-reported hypertension. RESULTS: The weighted prevalence of self-reported hypertension was 13.6% (95% CI 12.9% to 14.2%) and the weighted prevalence of HIV was 11.1% (10.4% to 11.7%). In univariable analyses, there was no evidence of a difference in the weighted prevalence of self-reported hypertension between people living with HIV (PLHIV) and HIV-negative people (14.1%, 11.9% to 16.3% vs 13.3%, 12.6% to 14.0%; p=0.503) or between ART-exposed and ART-naive PLHIV (14.8%, 12.0% to 17.7% vs 12.8%, 9.1% to 16.4%,p=0.388). Adjusting for socio-demographic variables in logistic regression did not alter this finding (ORs:HIV status:0.88, 0.70 to 1.10, p=0.261; ART exposure:0.83, 0.53 to 1.30, p=0.411). CONCLUSIONS: Approximately one in seven PLHIV self-reported having hypertension, highlighting an important burden of disease. However, no associations were found between HIV status or ART exposure and self-reported hypertension, suggesting that it will be valuable to focus on managing other risk factors for hypertension in this population. These findings should be fully accounted for as Zimbabwe reorients its health system towards non-communicable disease control and management.

Clinical decision support systems to guide healthcare providers on HIV testing.

OBJECTIVE: To understand the impact of clinical decision support systems (CDSSs) on improving HIV testing and diagnosis. DESIGN: An original global systematic review (PROSPERO Number: CRD42020175576) of peer-reviewed articles reporting on electronic CDSSs that generate triggers encouraging healthcare providers to perform an HIV test. METHODS: Medline, Embase, Cochrane CENTRAL and CINAHL EBSCOhost were searched up to 17 November 2020 and reference lists of included articles were checked. Qualitative and quantitative syntheses (using meta-analyses) of identified studies were performed. RESULTS: The search identified 1424 records. Twenty-two articles met inclusion criteria (19 of 22 non-HIV endemic settings); 18 clinical and four laboratory-driven reminders. Reminders promoted 'universal' HIV testing for all patients without a known HIV infection and no recent documented HIV test, or 'targeted' HIV testing in patients with clinical risk-factors or specific diagnostic tests. CDSSs increased HIV testing in hospital and nonhospital setting, with the pooled risk-ratio amongst studies reporting comparable outcome measures in hospital settings (n = 3) of 2.57 [95% confidence interval (CI) 1.53-4.33, random-effect model] and in nonhospital settings (n = 4) of 2.13 (95% CI 1.78-4.14, random effect model). Results of the clinical impact of CDSSs on HIV diagnosis were mixed. CONCLUSION: CDSSs improve HIV testing and may, potentially, improve diagnosis. The data support the broader study of CDSSs in low- and high prevalent HIV settings to determine their precise impact on UNAIDS goals to reach universal HIV testing and treatment coverage.

Prophylaxis for COVID-19: a systematic review.

BACKGROUND: While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored. OBJECTIVES: To map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19. DATA SOURCES: PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: All studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations. INTERVENTIONS: PrEP and PEP candidate for COVID-19. METHODS: Systematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion. RESULTS: We identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements. CONCLUSIONS: The key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.

Network Analysis of Outpatients to Identify Predictive Symptoms and Combinations of Symptoms Associated With Positive/Negative SARS-CoV-2 Nasopharyngeal Swabs.

Background: Limited data exist on early predictive clinical symptoms or combinations of symptoms that could be included in the case definition of coronavirus disease 2019 (COVID-19), particularly for mild-to-moderate disease in an outpatient setting. Methods: A cohort study of individuals presenting with clinical symptoms to one of the largest dedicated networks of COVID-19 test centers in Geneva, Switzerland, between March 2 and April 23, 2020. Individuals completed a symptom questionnaire, received a nurse-led check-up, and nasopharyngeal swabs were obtained. An analysis of clinical features predicting the positivity and negativity of the SARS-CoV-2 RT-PCR test was performed to determine the relationship between symptoms and their combinations. Results: Of 3,248 patients included (mean age, 42.2 years; 1,504 [46.3%] male), 713 (22%) had a positive RT-PCR; 1,351 (41.6%) consulted within 3 days of symptom onset. The strongest predictor of a positive SARS-CoV-2 RT-PCR was anosmia, particularly in early disease, followed by fever, myalgia, and cough. Symptoms predictive of a negative test were breathing difficulties, abdominal symptoms, thoracic pain and runny nose. Three distinct networks of symptoms were identified, but did not occur together: respiratory symptoms; systemic symptoms related to fever; and other systemic symptoms related to anosmia. Conclusions: Symptoms and networks of symptoms associated with a positive/negative SARS-CoV-2 RT-PCR are emerging and may help to guide targeted testing. Identification of early COVID-19-related symptoms alone or in combination can contribute to establish a clinical case definition and provide a basis for clinicians and public health authorities to distinguish it from other respiratory viruses early in the course of the disease, particularly in the outpatient setting.

Novel outpatient management of mild to moderate COVID-19 spares hospital capacity and safeguards patient outcome: The Geneva PneumoCoV-Ambu study.

BACKGROUND: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes coronavirus disease (COVID-19), is creating an unprecedented burden on health care systems across the world due to its high rate of pneumonia-related hospitalizations. This study presents recommendations for the outpatient management of moderate SARS-CoV-2 pneumonia implemented at the Geneva University Hospital, Switzerland, from April 4 to June 30, 2020 and evaluated the impact of these recommendations on patient safety, patient satisfaction, and overall hospital capacity. METHODS: Recommendations for the outpatient management of moderate pneumonia implemented in the Geneva University Hospital (PneumoCoV-Ambu) between April 4 and June 30, 2020, were evaluated prospectively. The primary endpoint was hospitalization. Secondary endpoints were: severity of COVID-19 disease based on a 7-points ordinal scale assessed at 1 and 2 months following SARS-CoV-2 infection; patient satisfaction using a satisfaction survey and the analysis of number of beds and costs potentially averted. RESULTS: A total of 36 patients with COVID-19-related pneumonia were followed between April 4 and May 5, 2020. Five patients (14%) were hospitalized and none died over a median of 30 days follow-up. The majority of patients (n = 31; 86%) were satisfied with the ambulatory care they received. These novel recommendations for outpatient management resulted in sparing an estimated potential 124 hospital bed-nights and CHF 6'826 per capita averted hospitalization costs over the three months period. CONCLUSIONS: Recommendations developed for the outpatient management of COVID-19-related pneumonia were able to spare hospital capacity without increasing adverse patient outcomes. Widely implementing such recommendations is crucial in preserving hospital capacity during this pandemic.

Post-exposure Lopinavir-Ritonavir Prophylaxis versus Surveillance for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial.

BACKGROUND: Since the beginning of the COVID-19 pandemic, no direct antiviral treatment is effective as post-exposure prophylaxis (PEP). Lopinavir/ritonavir (LPV/r) was repurposed as a potential PEP agent against COVID-19. METHODS: We conducted a pragmatic open-label, parallel, cluster-randomised superiority trial in four sites in Switzerland and Brazil between March 2020 to March 2021. Clusters were randomised to receive LPV/r PEP (400/100 mg) twice daily for 5 days or no PEP (surveillance). Exposure to SARS-CoV-2 was defined as a close contact of >15 minutes in <2 metres distance or having shared a closed space for ≥2 hours with a person with confirmed SARS-CoV-2 infection. The primary outcome is the occurrence of COVID-19 defined by a SARS-CoV-2 infection (positive oropharyngeal SARS-CoV-2 PCR and/or a seroconversion) and ≥1 compatible symptom within 21 days post-enrolment. ClinicalTrials.gov (Identifier: NCT04364022); Swiss National Clinical Trial Portal: SNCTP 000003732. FINDINGS: Of 318 participants, 157 (49.4%) were women; median age was 39 (interquartile range, 28-50) years. A total of 209 (179 clusters) participants were randomised to LPV/r PEP and 109 (95 clusters) to surveillance. Baseline characteristics were similar, with the exception of baseline SARS-CoV-2 PCR positivity, which was 3-fold more frequent in the LPV/r arm (34/209 [16.3%] vs 6/109 [5.5%], respectively). During 21-day follow-up, 48/318 (15.1%) participants developed COVID-19: 35/209 (16.7%) in the LPV/r group and 13/109 (11.9%) in the surveillance group (unadjusted hazard ratio 1.44; 95% CI, 0.76-2.73). In the primary endpoint analysis, which was adjuted for baseline imbalance, the hazard ratio for developing COVID-19 in the LPV/r group vs surveillance was 0.60 (95% CI, 0.29-1.26; p =0.18). INTERPRETATION: The role of LPV/r as PEP for COVID-19 remains unanswered. Although LPV/r over 5 days did not significantly reduce the incidence of COVID-19 in exposed individuals, we observed a change in the directionality of the effect in favour of LPV/r after adjusting for baseline imbalance. LPV/r for this indication merits further testing against SARS-CoV-2 in clinical trials. FUNDING: Swiss National Science Foundation (project no.: 33IC30_166819) and the Private Foundation of Geneva University Hospitals (Edmond Rothschild (Suisse) SA, Union Bancaire Privée and the Fondation pour la recherche et le traitement médical).

The impact of scaling up cervical cancer screening and treatment services among women living with HIV in Kenya: a modelling study.

Introduction: We aimed to quantify health outcomes and programmatic implications of scaling up cervical cancer (CC) screening and treatment options for women living with HIV in care aged 18-65 in Kenya. Methods: Mathematical model comparing from 2020 to 2040: (1) visual inspection with acetic acid (VIA) and cryotherapy (Cryo); (2) VIA and Cryo or loop excision electrical procedure (LEEP), as indicated; (3) human papillomavirus (HPV)-DNA testing and Cryo or LEEP; and (4) enhanced screening technologies (either same-day HPV-DNA testing or digitally enhanced VIA) and Cryo or LEEP. Outcomes measured were annual number of CC cases, deaths, screening and treatment interventions, and engaged in care (numbers screened, treated and cured) and five yearly age-standardised incidence. Results: All options will reduce CC cases and deaths compared with no scale-up. Options 1-3 will perform similarly, averting approximately 28 000 (33%) CC cases and 7700 (27%) deaths. That is, VIA screening would yield minimal losses to follow-up (LTFU). Conversely, LTFU associated with HPV-DNA testing will yield a lower care engagement, despite better diagnostic performance. In contrast, option 4 would maximise health outcomes, averting 43 200 (50%) CC cases and 11 800 (40%) deaths, given greater care engagement. Yearly rescreening with either option will impose a substantial burden on the health system, which could be reduced by spacing out frequency to three yearly without undermining health gains. Conclusions: Beyond the specific choice of technologies to scale up, efficiently using available options will drive programmatic success. Addressing practical constraints around diagnostics' performance and LTFU will be key to effectively avert CC cases and deaths.

Recommendations for the use of mathematical modelling to support decision-making on integration of non-communicable diseases into HIV care.

INTRODUCTION: Integrating services for non-communicable diseases (NCDs) into existing primary care platforms such as HIV programmes has been recommended as a way of strengthening health systems, reducing redundancies and leveraging existing systems to rapidly scale-up underdeveloped programmes. Mathematical modelling provides a powerful tool to address questions around priorities, optimization and implementation of such programmes. In this study, we examine the case for NCD-HIV integration, use Kenya as a case-study to highlight how modelling has supported wider policy formulation and decision-making in healthcare and to collate stakeholders' recommendations on use of models for NCD-HIV integration decision-making. DISCUSSION: Across Africa, NCDs are increasingly posing challenges for health systems, which historically focused on the care of acute and infectious conditions. Pilot programmes using integrated care services have generated advantages for both provider and user, been cost-effective, practical and achieve rapid coverage scale-up. The shared chronic nature of NCDs and HIV means that many operational approaches and infrastructure developed for HIV programmes apply to NCDs, suggesting this to be a cost-effective and sustainable policy option for countries with large HIV programmes and small, un-resourced NCD programmes. However, the vertical nature of current disease programmes, policy financing and operations operate as barriers to NCD-HIV integration. Modelling has successfully been used to inform health decision-making across a number of disease areas and in a number of ways. Examples from Kenya include (i) estimating current and future disease burden to set priorities for public health interventions, (ii) forecasting the requisite investments by government, (iii) comparing the impact of different integration approaches, (iv) performing cost-benefit analysis for integration and (v) evaluating health system capacity needs. CONCLUSIONS: Modelling can and should play an integral part in the decision-making processes for health in general and NCD-HIV integration specifically. It is especially useful where little data is available. The successful use of modelling to inform decision-making will depend on several factors including policy makers' comfort with and understanding of models and their uncertainties, modellers understanding of national priorities, funding opportunities and building local modelling capacity to ensure sustainability.

Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial.

INTRODUCTION: Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2. METHODS AND ANALYSIS: COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732). REGISTERED REPORT IDENTIFIER: CCER 2020-0864.

The growing burden of noncommunicable disease among persons living with HIV in Zimbabwe.

OBJECTIVES: We aim to characterize the future noncommunicable disease (NCD) burden in Zimbabwe to identify future health system priorities. METHODS: We developed an individual-based multidisease model for Zimbabwe, simulating births, deaths, infection with HIV and progression and key NCD [asthma, chronic kidney disease (CKD), depression, diabetes, hypertension, stroke, breast, cervical, colorectal, liver, oesophageal, prostate and all other cancers]. The model was parameterized using national and regional surveillance and epidemiological data. Demographic and NCD burden projections were generated for 2015 to 2035. RESULTS: The model predicts that mean age of PLHIV will increase from 31 to 45 years between 2015 and 2035 (compared with 20-26 in uninfected individuals). Consequently, the proportion suffering from at least one key NCD in 2035 will increase by 26% in PLHIV and 6% in uninfected. Adult PLHIV will be twice as likely to suffer from at least one key NCD in 2035 compared with uninfected adults; with 15.2% of all key NCDs diagnosed in adult PLHIV, whereas contributing only 5% of the Zimbabwean population. The most prevalent NCDs will be hypertension, CKD, depression and cancers. This demographic and disease shift in PLHIV is mainly because of reductions in incidence and the success of ART scale-up leading to longer life expectancy, and to a lesser extent, the cumulative exposure to HIV and ART. CONCLUSION: NCD services will need to be expanded in Zimbabwe. They will need to be integrated into HIV care programmes, although the growing NCD burden amongst uninfected individuals presenting opportunities for additional services developed within HIV care to benefit HIV-negative persons.

Projections of non-communicable disease and health care costs among HIV-positive persons in Italy and the U.S.A.: A modelling study.

BACKGROUND: Country-specific forecasts of the growing non-communicable disease (NCD) burden in ageing HIV-positive patients will be key to guide future HIV policies. We provided the first national forecasts for Italy and the Unites States of America (USA) and quantified direct cost of caring for these increasingly complex patients. METHODS AND SETTING: We adapted an individual-based model of ageing HIV-positive patients to Italy and the USA, which followed patients on HIV-treatment as they aged and developed NCDs (chronic kidney disease, diabetes, dyslipidaemia, hypertension, non-AIDS malignancies, myocardial infarctions and strokes). The models were parameterised using data on 7,469 HIV-positive patients from the Italian Cohort Naïve to Antiretrovirals Foundation Study and 3,748 commercially-insured patients in the USA and extrapolated to national level using national surveillance data. RESULTS: The model predicted that mean age of HIV-positive patients will increase from 46 to 59 in Italy and from 49 to 58 in the USA in 2015-2035. The proportion of patients in Italy and the USA diagnosed with ≥1 NCD is estimated to increase from 64% and 71% in 2015 to 89% and 89% by 2035, respectively, driven by moderate cardiovascular disease (CVD) (hypertension and dyslipidaemia), diabetes and malignancies in both countries. NCD treatment costs as a proportion of total direct HIV costs will increase from 11% to 23% in Italy and from 40% to 56% in the USA in 2015-2035. CONCLUSIONS: HIV patient profile in Italy and the USA is shifting to older patients diagnosed with multiple co-morbidity. This will increase NCD treatment costs and require multi-disciplinary patient management.

HIV and ageing: improving quantity and quality of life.

PURPOSE OF REVIEW: Evidence-based strategies are needed to address the growing complexity of care of those ageing with HIV so that as life expectancy is extended, quality of life is also enhanced. RECENT FINDINGS: Modifiable contributing factors to the quantity and quality of life in adults ageing with HIV include: burden of harmful health behaviours, injury from HIV infection, HIV treatment toxicity and general burden of age-associated comorbidities. In turn, these factors contribute to geriatric syndromes including multimorbidity and polypharmacy, physiologic frailty, falls and fragility fractures and cognitive dysfunction, which further compromise the quality of life long before they lead to mortality. SUMMARY: Viral suppression of HIV with combination antiviral therapy has led to increasing longevity but has not enabled a complete return to health among ageing HIV-infected individuals (HIV+). As adults age with HIV, the role of HIV itself and associated inflammation, effects of exposure to antiretroviral agents, the high prevalence of modifiable risk factors for age-associated conditions (e.g. smoking), and the effects of other viral coinfections are all influencing the health trajectory of persons ageing with HIV. We must move from the simplistic notion of HIV becoming a 'chronic controllable illness' to understanding the continually evolving 'treated' history of HIV infection with the burden of age-associated conditions and geriatric syndromes in the context of an altered and ageing immune system.

Future challenges for clinical care of an ageing population infected with HIV: a modelling study.

BACKGROUND: The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. METHODS: We constructed an individual-based model of the ageing HIV-infected population, which followed patients on HIV treatment as they age, develop NCDs-including cardiovascular disease (hypertension, hypercholesterolaemia, myocardial infarctions, and strokes), diabetes, chronic kidney disease, osteoporosis, and non-AIDS malignancies-and start co-medication for these diseases. The model was parameterised by use of data for 10 278 patients from the national Dutch ATHENA cohort between 1996 and 2010. We made projections up to 2030. FINDINGS: Our model suggests that the median age of HIV-infected patients on combination antiretroviral therapy (ART) will increase from 43·9 years in 2010 to 56·6 in 2030, with the proportion of HIV-infected patients aged 50 years or older increasing from 28% in 2010 to 73% in 2030. In 2030, we predict that 84% of HIV-infected patients will have at least one NCD, up from 29% in 2010, with 28% of HIV-infected patients in 2030 having three or more NCDs. 54% of HIV-infected patients will be prescribed co-medications in 2030, compared with 13% in 2010, with 20% taking three or more co-medications. Most of this change will be driven by increasing prevalence of cardiovascular disease and associated drugs. Because of contraindications and drug-drug interactions, in 2030, 40% of patients could have complications with the currently recommended first-line HIV regimens. INTERPRETATION: The profile of patients in the Netherlands infected with HIV is changing, with increasing numbers of older patients with multiple morbidities. These changes mean that, in the near future, HIV care will increasingly need to draw on a wide range of medical disciplines, in addition to evidence-based screening and monitoring protocols to ensure continued high-quality care. These findings are based on a large dataset of HIV-infected patients in the Netherlands, but we believe that the overall patterns will be repeated elsewhere in Europe and North America. The implications of such a trend for care of HIV-infected patients in high-burden countries in Africa could present a particular challenge. FUNDING: Medical Research Council, Bill & Melinda Gates Foundation, Rush Foundation, and Netherlands Ministry of Health, Welfare and Sport.

Changes in first-line cART regimens and short-term clinical outcome between 1996 and 2010 in The Netherlands.

OBJECTIVES: Document progress in HIV-treatment in The Netherlands since 1996 by reviewing changing patterns of cART use and relating those to trends in patients' short-term clinical outcomes between 1996 and 2010. DESIGN AND METHODS: 1996-2010 data from 10,278 patients in the Dutch ATHENA national observational cohort were analysed. The annual number of patients starting a type of regimen was quantified. Trends in the following outcomes were described: i) recovery of 150 CD4 cells/mm(3) within 12 months of starting cART; ii) achieving viral load (VL) suppression ≤1,000 copies/ml within 12 months of starting cART; iii) switching from first-line to second-line regimen within three years of starting treatment; and iv) all-cause mortality rate per 100 person-years within three years of starting treatment. RESULTS: Between 1996 and 2010, first-line regimens changed from lamivudine/zidovudine-based or lamivudine/stavudine-based regimens with unboosted-PIs to tenofovir with either emtricitabine or lamivudine with NNRTIs. Mortality rates did not change significantly over time. VL suppression and CD4 recovery improved over time, and the incidence of switching due to virological failure and toxicity more than halved between 1996 and 2010. These effects appear to be related to the use of new regimens rather than improvements in clinical care. CONCLUSION: The use of first-line cART in the Netherlands closely follows changes in guidelines, to the benefit of patients. While there was no significant improvement in mortality, newer drugs with better tolerability and simpler dosing resulted in improved immunological and virological recovery and reduced incidences of switching due to toxicity and virological failure.