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BACKGROUND: In Sierra Leone (SL), a low-income country in West Africa, dental care is very limited, largely private, and with services focused in the capital Freetown. There is no formal dental education. Ten dentists supported by a similar number of dental care professionals (DCPs) serve a population of over 7.5 million people. The objective of this research was to estimate needs-led requirements for dental care and human resources for oral health to inform capacity building, based on a national survey of oral health in SL. METHODS: A dedicated operational research (OR) decision tool was constructed in Microsoft Excel to support this project. First, total treatment needs were estimated from our national epidemiological survey data for three key ages (6, 12 and 15 years), collected using the 'International Caries Classification and Management System (ICCMS)' tool. Second, oral health needs were extrapolated to whole population levels for each year-group, based on census demographic data. Third, full time equivalent (FTE) workforce capacity needs were estimated for mid-level providers in the form of Dental Therapists (DTs) and non-dental personnel based on current oral disease management approaches and clinical timings for treatment procedures. Fourth, informed by an expert panel, three oral disease management scenarios were explored for the national population: (1) Conventional care (CC): comprising oral health promotion (including prevention), restorations and tooth extraction; (2) Surgical and Preventive care (S5&6P and S6P): comprising oral health promotion (inc. prevention) and tooth extraction (D5 and D6 together, & at D6 level only); and (3) Prevention only (P): consisting of oral health promotion (inc. prevention). Fifth, the findings were extrapolated to the whole population based on demography, assuming similar levels of treatment need. RESULTS: To meet the needs of a single year-group of childrens' needs, an average of 163 DTs (range: 133-188) would be required to deliver Conventional care (CC); 39 DTs (range: 30-45) to deliver basic Surgical and Preventive care (S6P); 54 DTs for more extended Surgical and Preventive care (S5&6P) (range 38-68); and 27 DTs (range: 25-32) to deliver Prevention only (P). When scaled up to the total population, an estimated 6,147 DTs (range: 5,565-6,870) would be required to deliver Conventional care (CC); 1,413 DTs (range: 1255-1438 DTs) to deliver basic Surgical and Preventive care (S6P); 2,000 DTs (range 1590-2236) for more extended Surgical and Preventive care (S5&6P) (range 1590-2236); and 1,028 DTs to deliver Prevention only (P) (range: 1016-1046). Furthermore, if oral health promotion activities, including individualised prevention, could be delivered by non-dental personnel, then the remaining surgical care could be delivered by 385 DTs (range: 251-488) for the S6P scenario which was deemed as the minimum basic baseline service involving extracting all teeth with extensive caries into dentine. More realistically, 972 DTs (range: 586-1179) would be needed for the S5&6P scenario in which all teeth with distinctive and extensive caries into dentine are extracted. CONCLUSION: The study demonstrates the huge dental workforce needs required to deliver even minimal oral health care to the Sierra Leone population. The gap between the current workforce and the oral health needs of the population is stark and requires urgent action. The study also demonstrates the potential for contemporary epidemiological tools to predict dental treatment needs and inform workforce capacity building in a low-income country, exploring a range of solutions involving mid-level providers and non-dental personnel.

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BACKGROUND: Hypertension is a stronger predictor of hemorrhagic than ischemic strokes in the general population. We aimed to identify whether hypertension or other risk factors, including HIV-related factors, differ in their associations with stroke subtypes in people living with HIV (PLWHIV). METHODS: HIV-1-positive individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed from the time of first blood pressure (BP) measurement after 1/1/1999 or study entry until the first of a validated stroke, 6 months after last follow-up or 1/2/2014. Stroke events were centrally validated using standardized criteria. Hypertension was defined as one systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Poisson and Cox proportional hazards regression models determined associations of established cerebro/cardiovascular disease and HIV-related risk factors with stroke and tested whether these differed by stroke subtype. FINDINGS: 590 strokes (83 hemorrhagic, 296 ischemic, 211 unknown) occurred over 339,979 person-years (PYRS) (incidence rate/1000 PYRS 1.74 [95% confidence interval (CI) 1.60-1.88]). Common predictors of both hemorrhagic and ischemic strokes were hypertension (relative hazard 3.55 [95% CI 2.29-5.50] and 2.24 [1.77-2.84] respectively) and older age (1.28 [1.17-1.39] and 1.19 [1.12-1.25]). Male gender (1.62 [1.14-2.31] and 0.60 [0.35-0.91]), previous cardiovascular events (4.03 [2.91-5.57] and 1.44 [0.66-3.16]) and smoking (1.90 [1.41-2.56] and 1.08 [0.68-1.71]) were stronger predictors of ischemic then hemorrhagic strokes, whereas hypertension, hepatitis C (1.32 [0.72-2.40] and 0.46 [0.30-0.70]) and estimated glomerular filtration rate < 60 mL/min/1.72 m3 (4.80 [2.47-9.36] and 1.04 [0.67-1.60]) were stronger predictors of hemorrhagic than ischemic strokes. A CD4 count < 200 cells/µL was associated with an increased risk of hemorrhagic stroke only. INTERPRETATION: Risk factors for stroke may differ by subtype in PLWHIV, emphasizing the importance of further research to increase the precision of stroke risk estimation.

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BACKGROUND: Antiretroviral (ART) drugs have been associated with higher triglycerides (TG), higher total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-C) levels. Associations between lipid levels with HIV viraemia and immunosuppression in the presence of ART remain unclear. METHODS: Participants from the D:A:D study with at least one TG/TC/HDL-C measurement were included. Linear mixed effect models were used to determine the association of ART, viral load (VL), nadir and current CD4+ T-cell count and previous AIDS diagnosis with lipids. RESULTS: Of 49,717 participants, 90%, 92% and 80% contributed at least one TG/TC/HDL-C measurement (median follow-up 6.8, 6.8 and 5.0 years, respectively). Predicted mean (95% CI) baseline levels for TG, TC and HDL-C (mmol/l), were 2.10 (2.05, 2.14), 4.94 (4.91, 4.98) and 1.08 (1.07, 1.10), respectively. Lopinavir was associated with the worst TG profile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar profile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG profile (-2.8%; -3.5%, -2.0%) compared with emtricitabine/tenofovir, whereas lamivudine/abacavir (+10.2%; +9.3%, +11.2%) and lamivudine/stavudine (+8.0%; +6.9%, +9.0%), were associated with the worst. Raltegravir was associated with lower TG (-5.2%; -6.4%, -3.9%), and nevirapine had a more favourable HDL-C profile (+11.3%; +10.8%, +11.7%) than efavirenz (+5.3%; 5.0%, 5.7%), compared to atazanavir. Higher VLs were associated with lower TG/TC/HDL-C, whereas higher CD4+ T-cell counts were associated with higher TG/TC/HDL-C. CONCLUSIONS: TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.

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BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. METHODS: Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. RESULTS: 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years' follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. CONCLUSIONS: Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals.

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OBJECTIVE: To consider associations between the latest/nadir CD4 cell count, and time spent with CD4 cell count less than 200 cells/µl (duration of immune depression), and myocardial infarction (MI), coronary heart disease (CHD), stroke, or cardiovascular disease (CVD) (CHD or stroke) in 33 301 HIV-positive individuals. DESIGN: Longitudinal cohort study. METHODS: Analyses were undertaken using Poisson regression. To investigate whether analyses of stroke were robust to the type of endpoint, we additionally included stroke-like events and rejected strokes into the stroke endpoint. RESULTS: Participants experienced 716 MI, 1056 CHD, 303 stroke, and 1284 CVD events. Whereas there was no evidence of a higher MI/CHD risk in those with lower latest/nadir CD4 cell counts after adjustment [current CD4 <100 cells/µl: relative rate (95% confidence interval) 0.96 (0.62-1.50) for MI, 0.89 (0.30-2.36) for CHD; nadir CD4 <100 cells/µl: 1.36 (0.57-3.23) for MI, 0.98 (0.45-2.16) for CHD], stroke and CVD rates were higher in those with a latest CD4 cell count less than 100 cells/µl [2.26 (1.29-3.94) and 1.14 (0.84-1.56), respectively]. All events occurred less frequently in those who had not experienced immune depression, although evidence for a linear association with duration of immune depression was weak. The association between stroke risk and the latest CD4 cell count strengthened as stroke-like and rejected strokes were included; conversely, associations with established stroke risk factors weakened. CONCLUSION: We do not find strong evidence that HIV-positive individuals with a low CD4 cell count are more likely to experience MI/CHD. Although strokes appear to occur more commonly at low CD4 cell counts, this may be partly explained by misclassification or other biases.

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BACKGROUND: An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort study of HIV-positive individuals. METHODS: Using Poisson regression, we investigated associations between the latest ALT level and MI, coronary heart disease (CHD), and stroke, after adjusting for known confounders and cumulative/recent exposure to antiretroviral drugs. Analyses were also performed for the end points of all-cause/liver-related mortality and new-onset diabetes mellitus. RESULTS: By February 2011, participants had experienced 541 MIs, 804 CHD, and 258 stroke events. The MI rate decreased from 3.1/1000 person-years among those with ALT ≤18 U/L to 2.1/1000 person-years among those with ALT >60 U/L. After adjustment for confounders, each 2-fold increment in ALT was associated with a 19% drop in the MI rate {relative rate, 0.81 [95% confidence interval (CI): 0.74 to 0.89], P = 0.0001}. A weaker inverse association was seen for CHD with no indication of a linear association between ALT levels and stroke (P = 0.72). Adjusted relative rates were 0.88 (95% CI: 0.81 to 0.97) and 0.70 (95% CI: 0.54 to 0.92) in those who were hepatitis C virus negative and hepatitis C virus positive, respectively, and 0.72 (95% CI: 0.58 to 0.89) and 0.84 (0.77 to 0.93) in injection drug users and non-injection drug users, respectively. Liver-related mortality and diabetes both demonstrated a positive association with ALT levels, whereas all-cause mortality showed a U-shaped relationship. CONCLUSIONS: Higher ALT levels are associated with lower MI risk in HIV-positive individuals, but with higher risks of liver-related mortality and diabetes mellitus.

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BACKGROUND: Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown. METHODS: D:A:D study participants with an estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤ 70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤ 60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD]) or until the last eGFR measurement during follow-up. An eGFR was considered confirmed if it was detected at 2 consecutive measurements ≥ 3 months apart. Predictors and eGFR-related ARV discontinuations were identified using Poisson regression. RESULTS: Of 22 603 persons, 468 (2.1%) experienced a confirmed eGFR of ≤ 70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up [95% confidence interval {CI}, 4.35-5.22]) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up [95% CI, 1.10-1.56]) during a median follow-up duration of 4.5 years (interquartile range [IQR], 2.7-6.1 years). A current eGFR of 60-70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio [aIRR], 1.72 [95% CI, 1.38-2.14]) but not other ARVs compared with a current eGFR of ≥ 90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year [95% CI, 1.12-1.25]) and ritonavir-boosted atazanavir use (aIRR, 1.19/year [95% CI, 1.09-1.32]) were independent predictors of a confirmed eGFR of ≤ 70 but were not significant predictors of CKD whereas ritonavir-boosted lopinavir use was a significant predictor for both end points (aIRR, 1.11/year [95% CI, 1.05-1.17] and 1.22/year [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs. CONCLUSIONS: Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.

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OBJECTIVES: To explore the relationship between elevated triglyceride levels and the risk of myocardial infarction (MI) in HIV-positive persons after adjustment for total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and nonlipid risk factors. BACKGROUND: Although elevated triglyceride levels are commonly noted in HIV-positive individuals, it is unclear whether they represent an independent risk factor for MI. METHODS: The incidence of MI during follow-up was stratified according to the latest triglyceride level. Multivariable Poisson regression models were used to describe the independent association between the latest triglyceride level and MI risk after adjusting for TC and HDL-C, nonlipids cardiovascular disease (CVD) risk factors, HIV and treatment-related factors. RESULTS: The 33,308 persons included in the study from 1999 to 2008 experienced 580 MIs over 178,835 person-years. Unadjusted, the risk of MI increased by 67% [relative risk (RR) 1.67, 95% confidence interval 1.54-1.80] per doubling in triglyceride level. After adjustment for the latest TC and HDL-C level, the RR dropped to 1.33 (95% confidence interval 1.21-1.45); this effect was further attenuated by other CVD risk factors and the RR was reduced to 1.17 (95% confidence interval 1.06-1.29). In models that additionally adjusted for HIV and treatment factors, the risk was further diminished, although remained significant (RR 1.11, 95% confidence interval 1.01-1.23). CONCLUSION: Higher triglyceride levels were marginally independently associated with an increased risk of MI in HIV-positive persons, although the extent of reduction in RR after taking account of latest TC, latest HDL-C and other confounders suggests that any independent effect is small.

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