Ischemic Heart Disease in Chronic Hepatitis B: A Danish Nationwide Cohort Study.

Objective: Data on the risk of ischemic heart disease (IHD) in patients with chronic hepatitis B virus (CHB) are conflicting. Our objective was to address the rate of IHD in patients with CHB compared with individuals without CHB (control-persons) from the general population. Study Design and Setting: We conducted a cohort study of prospectively obtained data from Danish nationwide registries. We produced cumulative incidence curves and calculated the unadjusted incidence rate ratio (IRR) of IHD in persons with and without CHB. The adjusted association between having CHB and developing IHD was examined using a cause-specific Cox regression model. Results: In total, 6472 persons with CHB and 62,251 age- and sex-matched individuals from the general population were followed for 48,840 and 567,456 person-years, respectively, during which 103 (1,59%) with CHB and 1058 (1,70%) control-persons developed IHD. The crude IRR was 1.13 (95% CI: 0.91-1.39). CHB did not have a statistically significant effect on the rate of IHD after adjusting for several confounding factors (adjusted hazard ratio: 0.96, 95% CI: 0.76-1.21). Conclusion: In this nationwide cohort study, we did not find any difference between rate of IHD in persons with CHB in comparison with the general population.

Altered balance between collagen formation and degradation after successful direct-acting antiviral therapy of chronic hepatitis C.

The effect of direct-acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO-C3 and PRO-C4 reflect type III and IV collagen formation; C3M and C4M are degradation markers of type III and IV. We aimed to assess the markers' dynamics with DAA therapy in CHC patients. Plasma PRO-C3, PRO-C4, C3M and C4M were assessed before, during and up till one year after 12-24 weeks of DAA therapy in 77 CHC patients with advanced fibrosis (n = 14) or cirrhosis (n = 63). Liver stiffness was evaluated using transient elastography. PRO-C3, C3M and C4M levels decreased significantly (P < .00001) while PRO-C4 was unchanged (P = .20) during the study period. There was a steep decrease in the PRO-C3/C3M ratio during DAA therapy and follow-up (P < .02). The PRO-C4/C4M ratio was unchanged (P > .27). The dynamics of the collagen markers behaved similarly between patients with advanced fibrosis and cirrhosis. However, the cirrhosis patients had >20% higher levels of C3M, PRO-C4 and C4M at all time points (P < .05). The collagen markers correlated with liver stiffness at baseline and follow-up.Markers of type III and IV collagen formation and degradation decreased during and after successful DAA therapy in CHC patients with advanced liver disease, and associated with disease severity. These results indicate an altered balance between collagen formation and degradation after viral clearance suggesting favourable effects on liver fibrosis.

Early normalization of reduced urea synthesis capacity after direct-acting antiviral therapy in hepatitis C cirrhosis.

Laursen TL, Sandahl TD, Kazankov K, Eriksen PL, Kristensen LH, Holmboe CH, Laursen AL, Vilstrup H, Grønbæk H. Early normalization of reduced urea synthesis capacity after direct-acting antiviral therapy in hepatitis C cirrhosis. Am J Physiol Gastrointest Liver Physiol 319: G151-G156, 2020. First published June 29, 2020; doi:10.1152/ajpgi.00128.2020.-Effects of direct-acting antiviral (DAA) treatment of chronic hepatitis C (CHC) cirrhosis on metabolic liver function are unknown but important for prognosis. Ureagenesis is an essential metabolic liver function involved in whole body nitrogen homeostasis. We aimed to investigate the ureagenesis capacity before and immediately after DAA therapy and relate the findings to hepatic inflammation and structural changes. In an observational before-and-after intervention study, the ureagenesis capacity was quantified by functional hepatic nitrogen clearance (FHNC) in 9 CHC patients with cirrhosis and 10 healthy volunteers. Hepatic inflammation was evaluated by alanine aminotransferase (ALT) and the macrophage activation markers sCD163 and sMR. Structural changes were estimated as liver stiffness and by portal hypertension as the hepatic venous pressure gradient (HVPG). Before treatment, the FHNC in the patients was half of the controls [16.4 L/h (8.2-24.5) vs. 33.4 (29.2-37.6), P = 0.0004]; after successful DAA treatment, it normalized [28.4 (15.9-40.9), P = 0.008 vs. baseline]. DAA treatment normalized ALT (P < 0.0001) and decreased the elevated sCD163 from 5.6 mg/L (3.5-7.7) to 3.4 (2-0-4.8) (P < 0.001) and sMR from 0.35 mg/L (0.21-0.49) to 0.31 (0.17-0.45) (P < 0.01). Liver stiffness fell by 30% (P < 0.05) but remained over the cirrhosis threshold. HVPG was not affected (P = 0.59). DAA treatment restored the severely reduced ureagenesis capacity, along with amelioration of hepatic inflammation but without normalization of other cirrhosis characteristics. Our findings indicate that the anti-inflammatory effect of virus eradication independent of hepatic structural effects rapidly improves metabolic dysfunction. We suggest this effect to be an important early onset part of the expected clinical DAA treatment benefit.NEW & NOTEWORTHY Antiviral treatment of chronic hepatitis C restores the liver's reduced capacity to produce urea along with an improvement in liver inflammation without immediate effects on structural liver changes. The effect is suggested to be an important early onset part of the expected clinical treatment benefit.

[Elimination of hepatitis C virus in Denmark].

In Denmark, about 50% of patients with chronic hepatitis C virus (HCV) infection are undiagnosed. Since 2014, therapy containing direct-acting antivirals (DAA) has proven efficient and is available to all patients, who have a chronic HCV infection and a Danish personal identification number. The World Health Organization has a goal of elimination of viral hepatitis in 2030. Elimination of HCV in Denmark should focus on reducing HCV transmission, incidence and prevalence, combined with treatment with DAA of all infected patients. Micro-elimination strategies may play a major role, but a national strategy is lacking.

Time-dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct-acting antiviral therapy of chronic hepatitis C.

Sofosbuvir-based direct-acting antiviral (DAA) therapy generally cures chronic hepatitis C (CHC) infections, however, the effects on the underlying liver disease and the potential rate of recovery are unclear. We aimed to investigate the effects of DAA therapy on liver inflammation, fibrosis, metabolic function and cognitive function and the time course in CHC patients with advanced liver disease. Seventy-one CHC patients with advanced liver disease were studied before, during and one year after successful sofosbuvir-based DAA therapy. Liver inflammation was assessed by plasma sCD163 and sMR levels (ELISA), fibrosis by liver stiffness (transient elastography), function by galactose elimination capacity (GEC) and cognitive performance by continuous reaction time (CRT). During DAA therapy, we observed a rapid sCD163 decline from baseline to end of treatment (6.9 vs 3.8 mg/L, P < .0001), whereas the change in sMR was more subtle (0.37 vs 0.30 mg/L, P < .0001). Liver stiffness decreased by 20% at end of treatment (17.8 vs 14.3 kPa, P < .0001), together suggesting rapid resolution of liver inflammation. One year after treatment, liver stiffness decreased by an additional 15% (P < .0001), suggestive of fibrosis regression. The GEC improved at follow-up (all: 1.74 vs 1.98 mmol/min), mainly at 12 weeks post-treatment, both in patients with cirrhosis (n = 56) and those with advanced liver fibrosis (n = 15) (P < .001). The CRT improved at one-year follow-up (1.86 vs 2.09, P = .04). In conclusion, successful DAA therapy of CHC proves beneficial in advanced liver disease, with an initial rapid resolution of liver inflammation and a subsequent gradual but steady improvement in liver fibrosis, metabolic liver function and reaction time.

Hepatitis B and C in the adult population of Bissau, Guinea-Bissau: a cross-sectional survey.

OBJECTIVE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are prevalent in West Africa. To address the WHO 2030 goals of a 90% reduction in incidence and a 65% reduction in mortality for both infections, we assessed the prevalence of HBV and HCV from surveys in the general population. METHODS: Participants in this cross-sectional survey were included from randomly selected houses in a demographic surveillance site in Bissau, Guinea-Bissau. Participants were interviewed and had a blood sample drawn for viral analyses (HBsAg, anti-HBs, anti-HBc, anti-HCV and HCV RNA). Risk factors of HBV and HCV infection were determined by binomial regression adjusted for sex and age. RESULTS: A total of 2715 participants were included in this study. The overall HBsAg prevalence was 18.7% (95% CI: 17.3-20.2%). HBsAg was associated with male sex (adjusted risk ratio (aRR): 1.64), and prevalence decreased with age >34 years. HBV exposure was found in 91.9% of participants. Although 72.6% of individuals without sexual debut had been exposed to HBV, ever engaging in a sexual relationship was associated with higher risk of HBV exposure (aRR 1.18). The anti-HCV prevalence was 0.5% (95% CI: 0.3-0.9%), and 78.6% of those had detectable HCV RNA. Risk factors for anti-HCV sero-positivity were age above 55 (aRR 10.60), a history of blood transfusion (aRR 5.07) and being in a polygamous marriage (aRR 3.52). CONCLUSION: In Guinea-Bissau initiatives to implement treatment and widespread testing are needed to reach the WHO 2030 goals.

OBJECTIF: Le virus de l'hépatite B (VHB) et le virus de l'hépatite C (VHC) sont répandus en Afrique de l'Ouest. Pour atteindre les objectifs de 2030 de l'OMS d'une réduction de 90% de l'incidence et de 65% de la mortalité pour les deux infections, nous avons évalué la prévalence du VHB et du VHC à partir d'enquêtes dans la population générale. MÉTHODES: Les participants inclus dans cette enquête transversale provenaient de foyers sélectionnés au hasard dans un site de surveillance démographique à Bissau, en Guinée-Bissau. Les participants ont été interrogés et ont subi un prélèvement d'échantillon de sang pour des analyses virales (HBsAg, anti-HBs, anti-HBc, anti-HCV et ARN du HCV). Les facteurs de risque d'infection par le VHB et le VHC ont été déterminés par la régression binomiale ajustée en fonction du sexe et de l'âge. RÉSULTATS: 2.715 participants ont été inclus dans cette étude. La prévalence globale de l'HBsAg était de 18,7% (IC95%: 17,3-20,2%). L'HBsAg était associé au sexe masculin (rapport de risque ajusté (aRR): 1,64), et la prévalence diminuait avec l'âge >34 ans. Une exposition au VHB a été observée chez 91,9% des participants. Bien que 72,6% des personnes sans début d'activité sexuelle aient été exposées au VHB, le fait de s'engager dans des relations sexuelles était associé à un risque plus élevé d'exposition au VHB (aRR: 1,18). La prévalence d'anti-VHC était de 0,5% (IC95%: 0,3-0,9%) et 78,6% d'entre eux avaient de l'ARN du VHC détectable. Les facteurs de risque de séropositivité anti-VHC étaient l'âge de plus de 55 ans (aRR: 10,60), les antécédents de transfusion sanguine (aRR: 5,07) et le fait d'être dans un mariage polygame (aRR: 3,52). CONCLUSION: En Guinée-Bissau, des initiatives pour mettre en œuvre un traitement et des tests généralisés sont nécessaires pour atteindre les objectifs de l'OMS 2030.

Discriminatory rapid tests cause HIV-type misclassification-evaluation of three rapid tests using clinical samples from Guinea-Bissau.

BACKGROUND: Discrimination among HIV types is important because HIV-2 is naturally resistant to some of the first-line drugs used in the treatment of HIV-1. We evaluated three assays for HIV-type discriminatory capacity: SD Bioline HIV 1/2 3.0 (Bioline), First Response HIV 1-2-0 Card Test (First Response) and Genie III HIV-1/HIV-2 (Genie III). METHODS: Based on results from the Bioline assay, samples from 239 HIV-infected patients from the Bissau HIV cohort in Guinea-Bissau were retrospectively selected for evaluation. Genie III and First Response were scored by three independent readers and compared with a reference test (INNO-LIA HIV I/II Score) confirmed by HIV RNA as well as DNA detection. RESULTS: The best performing test was Genie III, with an average agreement with the reference test of 93.4%, followed by First Response (86.1%) and Bioline (72.4%). First Response and Bioline were scored with a false high number of HIV-1/2 dual infections. For both First Response and Genie III, there were discrepancies among independent readers, and some tests were scored as HIV non-reactive. CONCLUSIONS: Using these rapid tests with a suboptimal performance will presumably result in a high rate of false HIV-1/2 dual diagnoses, depriving patients of alternative treatment options in cases of treatment failure.

The Prevalence of Human Immunodeficiency Virus Coinfection Among Patients Newly Diagnosed With Chronic Hepatitis B or C in Denmark: A Nationwide Cohort Study.

BACKGROUND: Early identification of patients with chronic viral hepatitis coinfected with human immunodeficiency virus (HIV) is essential for optimal care. The objectives of this study were to estimate the prevalence of HIV coinfection among patients newly diagnosed with chronic viral hepatitis, HIV testing prevalence, and identify factors associated with coinfection. METHODS: Patients with chronic viral hepatitis newly enrolled in The Danish Database for Hepatitis B and C between 2002 and 2015 were identified. The HIV coinfection prevalence was calculated, and risk factors associated with HIV coinfection were estimated by logistic regression. RESULTS: In total, 8490 patients were included: 3091 had chronic hepatitis B (CHB), 5305 had chronic hepatitis C (CHC), and 94 had CHB and CHC. The prevalence of HIV coinfection was 4.4% (95% confidence interval [CI], 4.0-4.9) and was higher among CHC and CHB-CHC patients than CHB patients with a prevalence of 5.3% (95% CI, 4.7-5.9), 6.4% (95% CI, 2.4-13.4), and 2.9 (95% CI, 2.3-3.5), respectively (P < .0001). The HIV testing prevalence increased from 65% to 88% between 2002 and 2014 concurrently with a decrease in the HIV coinfection prevalence from 7.8% (95% CI, 5.5-10.7) to 1.6% (95% CI, 0.7-3.2). Age 35-50 years, male sex, and sexual route of viral hepatitis transmission were associated with HIV coinfection with odds ratios of 4.42 (95% CI, 1.40-13.94), 2.21 (95% CI, 1.74-2.81), and 8.81 (95% CI, 6.30-12.33), respectively. CONCLUSIONS: The prevalence of HIV coinfection among patients with newly diagnosed chronic viral hepatitis decreased concurrently with an increase in HIV testing prevalence.

Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial.

BACKGROUND: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1-infected patients in Guinea-Bissau. METHODS: This open-label randomized, 2-arm superiority trial compared the use of 2 NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naive HIV-1-infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies per milliliter after 12 months of treatment. RESULTS: Between May 5, 2011, and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI [65/197 (33.0%)] and PI [68/203 (33.5%)] arms (P = 0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, P < 0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% confidence interval: 0.51 to 1.36) or frequency of clinical adverse events between treatment arms [NNRTI: 73/197 (37.1%); and PI: 69/203 (34.0%); P = 0.52]. CONCLUSIONS: In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.

Increased mortality among HIV infected patients with cryptococcal antigenemia in Guinea-Bissau.

Cryptococcal antigenemia may precede development of cryptococcal meningitis and death among patients with advanced HIV infection. Among 200 retrospectively and randomly selected ART-naïve patients with CD4 counts < 100 cells/µl from Guinea-Bissau, 20 (10%) had a positive cryptococcal antigen test. Self-reported headache and fever were predictors of a positive test, while cryptococcal antigenemia was a strong predictor of death within the first year of follow-up, MRR 2.22 (95% CI: 1.15-4.30). Screening for cryptococcal antigenemia should be implemented for patients with advanced HIV in Guinea-Bissau. Pre-emptive anti-fungal therapy should be initiated prior to ART-initiation if the screening is positive.

Detection of Pneumocystis jirovecii in oral wash from immunosuppressed patients as a diagnostic tool.

BACKGROUND: Diagnosis of Pneumocystis jirovecii (PJ) pneumonia ordinarily requires invasive procedures that could be avoided by PCR methodologies, if these could be designed with adequate cut-off values for confounding background carriage. METHODS: We designed a novel quantitative real-time PCR assay to detect the mitochondrial large subunit rRNA gene of PJ in oral washes. To benchmark levels of PJ carriage versus infection, we tested asymptomatic immunosuppressed patients including Danish (n = 88) and West African HIV-infected (n = 142) patients, renal transplant recipients (n = 51), rheumatologic patients (n = 102), patients with inflammatory bowel diseases (n = 98), and healthy blood donors (controls, n = 50). The fungal burden in patients with PJ pneumonia (PCP, n = 7) was also investigated. RESULTS: Danish HIV-infected patients (with viremia/low CD4) and recent transplant recipients were at most risk of being carriers (prevalence of 23% and 16.7% respectively), whereas PJ was rarely detected among rheumatologic patients, patients with inflammatory bowel diseases, and untreated West African HIV patients. PJ was not detected among healthy controls. The fungal burden in patients with PCP fell rapidly on treatment. CONCLUSIONS: The quantitative PCR method described could conceivably discriminate between carriage and disease, given suitable threshold values for the former, and predict treatment efficacy by measures of the fungal burden in daily oral washes.

Assessing factors for loss to follow-up of HIV infected patients in Guinea-Bissau.

PURPOSE: The objective of this study was to ascertain vital status of patients considered lost to follow-up at an HIV clinic in Guinea-Bissau, and describe reasons for loss to follow-up (LTFU). METHODS: This study was a cross-sectional sample of a prospective cohort, carried out between May 15, 2013, and January 31, 2014. Patients lost to follow-up, who lived within the area of the Bandim Health Project, a demographic surveillance site (DSS), were eligible for inclusion. Active follow-up was attempted by telephone and tracing by a field assistant. Semi-structured interviews were done face to face or by phone by a field assistant and patients were asked why they had not shown up for the scheduled appointment. Patients were included by date of HIV testing and risk factors for LTFU were assessed using Cox proportional hazard model. RESULTS: Among 561 patients (69.5 % HIV-1, 18.0 % HIV-2 and 12.6 % HIV-1/2) living within the DSS, 292 patients had been lost to follow-up and were, therefore, eligible for active follow-up. Vital status was ascertained in 65.9 % of eligible patients and 42.7 % were alive, while 23.2 % had died. Information on reasons for LTFU existed for 103 patients. Major reasons were moving (29.1 %), travelling (17.5 %), and transferring to other clinics (11.7 %). CONCLUSION: A large proportion of the patients at the clinic were lost to follow-up. The main reason for this was found to be the geographic mobility of the population in Guinea-Bissau.

Clinical presentation and opportunistic infections in HIV-1, HIV-2 and HIV-1/2 dual seropositive patients in Guinea-Bissau.

BACKGROUND: Better understanding of HIV-2 infection is likely to affect the patient care in areas where HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. METHODS: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Simão Mendes in Guinea-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. RESULTS: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive patients were younger than HIV-2 and HIV-1/2 seropositive patients, but no difference in sex was observed. Patients with HIV-1 and HIV-1/2 had a lower baseline CD4 cell count than HIV-2 seropositive patients (median CD4 cell count 185, 198 and 404 cells/µl, respectively (p value 0.001 and 0.05). HIV-1 seropositive patients had a lower BMI and a higher prevalence of weight loss, skin rash and productive cough than HIV-2 seropositive patients (p value 0.03, 0.002, 0.03 and 0.04). Only four cases (2%) of pulmonary tuberculosis (TB) were diagnosed. One patient (1/96, 1%) was tested positive for cryptococcal antigen. CONCLUSION: HIV-1 and HIV-1/2 seropositive patients have lower CD4 cell counts than HIV-2 seropositive patients when diagnosed with HIV with only minor clinical and demographic differences among groups. Few patients were diagnosed with TB and cryptococcal disease was not found to be a major opportunistic infection among newly diagnosed HIV patients.

Diabetes mellitus and impaired fasting glucose in ART-naïve patients with HIV-1, HIV-2 and HIV-1/2 dual infection in Guinea-Bissau: a cross-sectional study.

BACKGROUND: The prevalence of diabetes mellitus (DM) is expected to increase in sub-Saharan Africa. Patients with HIV are at particular risk. We investigated the DM burden among antiretroviral therapy (ART)-naïve patients with HIV in Guinea-Bissau. METHODS: Patients were consecutively included. Demographic and lifestyle data were collected and one fasting blood glucose (FBG) measurement was used to diagnose DM (FBG≥7.0 mmol/L) and impaired fasting glucose (IFG) (FBG≥6.1 and <7.0 mmol/L). RESULTS: By June 2015, 953 newly diagnosed ART-naïve patients with HIV had been included in the study of whom 893 (93.7%) were fasting at the time of inclusion. Median age among the fasting patients was 37 years (IQR 30-46 years) and 562 (62.9%) were women. The prevalence of DM was 5.8% (52/893) while 5.6% (50/893) had IFG. DM was associated with family history of DM (OR 3.92, 95% CI 1.78 to 8.63), being 41-50 years (OR 2.98, 95% CI 1.18 to 7.49) or older than 50 years (OR 3.14, 95% CI 1.09 to 9.07) and Fula ethnicity (OR 2.72, 95% CI 1.12 to 6.62). CONCLUSIONS: DM prevalence was higher among younger patients compared with the background population in Bissau. Traditional risk factors for DM such as advancing age and a family history of DM apply also for ART-naïve patients with HIV.

Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

OBJECTIVES: Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients. METHODS: This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models. RESULTS: A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/µl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39). CONCLUSION: Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women.

High prevalence and excess mortality of late presenters among HIV-1, HIV-2 and HIV-1/2 dually infected patients in Guinea-Bissau - a cohort study from West Africa.

INTRODUCTION: HIV infected individuals with late presentation (LP) and advanced disease (AD) have been associated with higher mortality, higher cost of medical management, impaired CD4 cell count increment and potentially ongoing risk of HIV transmission. Here we describe the proportion of patients with LP and AD at an HIV clinic in Guinea-Bissau, identify risk factors and evaluate the outcome of these patients. METHODS: We included all patients >15 years diagnosed with HIV-1 and/or HIV-2 at the outpatient HIV clinic at Hospital National Simão Mendes, during June 2005 - December 2013 in a retrospective cohort study. Patients were followed until December 2014. LP and AD was defined as a baseline CD4 cell count of 200-349 cells/µL and <200 cells/µL, respectively. RESULTS: A total of 3,720/5,562 (65.7%) patients had a CD4 cell count measured within the first 90 days of HIV diagnosis. Forty-eight percent had AD and 23% had LP. Risk factors for presentation with AD were male sex, age >30 years, Fula and Mandinga ethnicity. HIV-2 and HIV-1/2 dually infected patients had lower risk of AD compared with HIV-1 infected patients. Although antiretroviral therapy (ART) was initiated for 64.4% of patients, those with AD progression had a 3.82 times higher mortality compared to patients with non-LP. CONCLUSION: The majority of HIV infected patients presented late. Most of the late-presenters had advanced disease and patients with advanced disease had a very high mortality. Initiatives to enroll patients in care at an earlier point are needed and should focus on risk groups.

Lack of awareness of treatment failure among HIV-1-infected patients in Guinea-Bissau - a retrospective cohort study.

INTRODUCTION: With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau. METHODS: In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up. RESULTS: We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9-107.8), 7.6 (95% CI: 1.6-35.5) and 3.1 (95% CI: 1.5-6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7-11.8). CONCLUSIONS: We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.

High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau.

BACKGROUND: With the widespread use of antiretroviral treatment (ART) in Africa, the risk of drug resistance has increased. The aim of this study was to evaluate levels of HIV-1 resistance among patients with HIV-1 and HIV-1/2 dual infections, treated with ART, at a large HIV clinic in Guinea-Bissau. FINDINGS: Patients were selected from the Bissau HIV cohort. All patients had HIV-1 or HIV-1/2 dual infection, a CD4 cell count performed before and 3-12 months after starting ART, and a corresponding available plasma sample. We measured viral load in patients with HIV-1 (n = 63) and HIV-1/2 dual (n = 16) infections a median of 184 days after starting ART (IQR: 126-235 days). In patients with virological failure (defined as viral load >1000 copies/ml) and with sufficient plasma available, we performed an HIV-1 genotypic resistance test. Thirty-six patients (46%) had virological failure. The CD4 cell count did not predict treatment failure. Of the 36 patients with virological failure, we performed a resistance test in 15 patients (42%), and nine patients (9/15; 60%) had resistance mutations. The most common mutation was K103N, which confers high-level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). No major mutations against protease inhibitors (PI) were found. CONCLUSIONS: Our results showed that patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau had a high rate of virological failure and rapid development of NNRTI resistance. It remains to be determined whether a more robust, PI-based treatment regimen might benefit this population more than NNRTIs.

Cohort Profile: The Bissau HIV Cohort-a cohort of HIV-1, HIV-2 and co-infected patients.

The West African country Guinea-Bissau is home to the world's highest prevalence of HIV-2, and its HIV-1 prevalence is rising. Other chronic viral infections like human T-lymphotropic virus type 1 (HTLV-1) and hepatitis B virus are common as well. The Bissau HIV Cohort was started in 2007 to gain new insights into the overall effect of introducing antiretroviral treatment in a treatment-naïve population with concomitant infection with three retroviruses (HIV-1, HIV-2 and HTLV-1) and tuberculosis. The cohort includes patients from the HIV clinic at Hospital Nacional Simão Mendes, the main hospital in Bissau, the capital of the country. From July 2007 to June 2013, 3762 HIV-infected patients (69% HIV-1, 18% HIV-2, 11% HIV-1/2 and 2% HIV type unknown) were included in the world's largest single-centre HIV-2 cohort. Demographic and clinical data are collected at baseline and every 6 months, together with CD4 cell count and routine biochemistry analyses. Plasma and cells are stored in a biobank in Denmark. The Bissau HIV Cohort is administered by the Bissau HIV Cohort study group. Potential collaborators are invited to contact the chair of the cohort study group, Christian Wejse, e-mail: [wejse@dadlnet.dk].