Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa.

BACKGROUND: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets. METHODS: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. RESULTS: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target. CONCLUSIONS: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic.

Validation of the D:A:D chronic kidney disease risk score in people living with HIV: the IeDEA West Africa Cohort Collaboration.

OBJECTIVES: A risk score for long-term prediction of chronic kidney disease (CKD) in people living with HIV (PLHIV) has been developed using data from the D:A:D cohort. We assessed the performance of the D:A:D risk score in a cohort of PLHIV in West Africa. METHODS: Data from PLHIV starting antiretroviral treatment in four clinics in Burkina Faso, Côte d'Ivoire and Togo participating in the IeDEA West Africa collaboration were analysed. CKD was defined as two consecutive estimated glomerular filtration rates (eGFRs) of ≤ 60 mL/min/1.73 m2 . The D:A:D score (short version) was calculated using age, gender, nadir CD4 and baseline eGFR and was categorized into low, medium, and high-risk groups. RESULTS: In 14 930 participants (70% female, median age = 38 years; median nadir CD4 count = 183 cells/µL) followed for a median duration of 5.7 years, 660 (4.4%) progressed to CKD, with an incidence [95% confidence interval (CI)] of 7.8 (7.2-8.4) per 1000 person-years (PY). CKD incidence rates were 2.4 (2.0-2.8), 8.1 (6.8-9.6) and, 30.9 (28.0-34.1) per 1000 PY in the low-, medium- and high-risk groups, respectively. In the high-risk group, 14.7% (95% CI: 13.3; 16.3) had progressed to CKD at 5 years. Discrimination was good [C-statistics = 0.81 (0.79-0.83)]. In all, 79.4% of people who progressed to CKD were classified in the medium- to high-risk group at baseline (sensitivity) and 66.5% of people classified in the low risk group at baseline did not progress to CKD (specificity). CONCLUSIONS: These findings confirm the validity of the D:A:D score in identifying individuals at risk of developing CKD who could benefit from enhanced kidney monitoring in West African HIV clinics.

Effects of Age, Level of Education and HIV Status on Cognitive Performance in West African Older Adults: The West Africa IeDEA Cohort Collaboration.

An in-depth understanding of the impact of aging, cognitive reserve, and HIV status on cognitive function is needed in older West African adults. Ninety-nine HIV-negative and 334 HIV-positive adults aged ≥ 50 years were enrolled in three clinics (Senegal and Côte d'Ivoire) participating in the IeDEA West Africa collaboration. All subjects underwent the Free and Cued Selective Reminding Test (FCSRT) and the Isaacs Set Test (IST). Age (both linear and quadratic), education level, and HIV status effects on Z-scores were assessed using multivariate linear regression models. Interactions between HIV status and age or educational level were tested. In the present cohort of older West African adults, the role of age and educational level on episodic memory and verbal fluency was observed without revealing an interaction between HIV status and age effect. As age had quadratic effects, older HIV-positive adults should not be considered as a unique group irrespective of their age. Low-educated HIV-positive patients had the lowest verbal fluency performance compared to others. Further studies are needed to duplicate these results. In clinical settings, screening and adapted programs focusing on improving cognition in those patients are needed.

Evolution of comorbidities in people living with HIV between 2004 and 2014: cross-sectional analyses from ANRS CO3 Aquitaine cohort.

BACKGROUND: The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. METHODS: The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. RESULTS: 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the "high" or "very high" risk groups of the disease risk scores for CKD, CVE and bone fracture score. CONCLUSIONS: Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.

Association between exposure to antiretroviral drugs and the incidence of hypertension in HIV-positive persons: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

OBJECTIVES: Previous studies have suggested that hypertension in HIV-positive individuals is associated primarily with traditional risk factors such as older age, diabetes and dyslipidaemia. However, controversy remains as to whether exposure to antiretroviral (ARV) drugs poses additional risk, and we investigated this question in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort. METHODS: The incidence of hypertension [systolic blood pressure (BP) > 140 and/or diastolic BP > 90 mmHg and/or initiation of antihypertensive treatment] was determined overall and in strata defined by demographic, metabolic and HIV-related factors, including cumulative exposure to each individual ARV drug. Predictors of hypertension were identified using uni- and multivariable Poisson regression models. RESULTS: Of 33 278 included persons, 7636 (22.9%) developed hypertension over 223 149 person-years (PY) [incidence rate: 3.42 (95% confidence interval (CI) 3.35-3.50) per 100 PY]. In univariable analyses, cumulative exposure to most ARV drugs was associated with an increased risk of hypertension. After adjustment for demographic, metabolic and HIV-related factors, only associations for nevirapine [rate ratio 1.07 (95% CI: 1.04-1.13) per 5 years] and indinavir/ritonavir [rate ratio 1.12 (95% CI: 1.04-1.20) per 5 years] remained statistically significant, although effects were small. The strongest independent predictors of hypertension were male gender, older age, black African ethnicity, diabetes, dyslipidaemia, use of lipid-lowering drugs, high body mass index (BMI), renal impairment and a low CD4 count. CONCLUSIONS: We did not find evidence for any strong independent association between exposure to any of the individual ARV drugs and the risk of hypertension. Findings provide reassurance that screening policies and preventative measures for hypertension in HIV-positive persons should follow algorithms used for the general population.

Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus-co-infected patients (ANRS CO13-HEPAVIH).

Liver steatosis is common in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV-co-infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13-HEPAVIH is a French nationwide multicentre cohort of HIV-HCV-co-infected patients. Medical and socio-behavioural data from clinical follow-up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use ("never or sometimes"). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV-HCV-co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367.

Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15-29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. RESULTS: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. CONCLUSIONS: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

Barriers to antiretroviral treatment initiation in rural KwaZulu-Natal, South Africa.

OBJECTIVES: Although antiretroviral therapy (ART) has been freely available since 2004 in South Africa, not all those who are eligible initiate ART. We aimed to investigate individual and household characteristics as barriers to ART initiation in men and women in rural KwaZulu-Natal. METHODS: Adults ≥ 16 years old living within a sociodemographic surveillance area (DSA) who accessed the local HIV programme between 2007 and 2011 were included in the study. Individual and household factors associated with ART initiation within 3 months of becoming eligible for ART were investigated using multivariable logistic regression stratified by sex and after exclusion of individuals who died before initiating ART. RESULTS: Of the 797 men and 1598 women initially included, 8% and 5.5%, respectively, died before ART initiation and were excluded from further analysis. Of the remaining 733 men and 1510 women, 68.2% and 60.2%, respectively, initiated ART ≤ 3 months after becoming eligible (P = 0.34 after adjustment for CD4 cell count). In men, factors associated with a higher ART initiation rate were being a member of a household located < 2 km from the nearest HIV clinic and being resident in the DSA at the time of ART eligibility. In women, ART initiation was more likely in those who were not pregnant, in members of a household where at least one person was on ART and in those with a high wealth index. CONCLUSIONS: In this rural South African setting, barriers to ART initiation differed for men and women. Supportive individual- and household-level interventions should be developed to guarantee rapid ART initiation taking account gender specificities.

Comparison of transient elastography (FibroScan), FibroTest, APRI and two algorithms combining these non-invasive tests for liver fibrosis staging in HIV/HCV coinfected patients: ANRS CO13 HEPAVIH and FIBROSTIC collaboration.

OBJECTIVES: Combining noninvasive tests increases diagnostic accuracy for staging liver fibrosis in hepatitis C virus (HCV)-infected patients, but this strategy remains to be validated in HIV/HCV coinfection. We compared the performances of transient elastography (TE), Fibrotest (FT), the aspartate aminotransferase-to-platelet ratio index (APRI) and two algorithms combining TE and FT (Castera) or APRI and FT (SAFE) in HIV/HCV coinfection. METHODS: One hundred and sixteen HIV/HCV-coinfected patients (64% male; median age 44 years) enrolled in two French multicentre studies (the HEPAVIH cohort and FIBROSTIC) for whom TE, FT and APRI data were available were included in the study. Diagnostic accuracies for significant fibrosis (METAVIR F ≥ 2) and cirrhosis (F4) were evaluated by measuring the area under the receiver-operating characteristic curve (AUROC) and calculating percentages of correctly classified (CC) patients, taking liver biopsy as a reference. RESULTS: For F ≥ 2, both TE and FT (AUROC = 0.87 and 0.85, respectively) had a better diagnostic performance than APRI (AUROC = 0.71; P < 0.005). Although the percentage of CC patients was significantly higher with Castera's algorithm than with SAFE (61.2% vs. 31.9%, respectively; P < 0.0001), this percentage was lower than that for TE (80.2%; P < 0.0001) or FT (73.3%; P < 0.0001) taken separately. For F4, TE (AUROC = 0.92) had a better performance than FT (AUROC = 0.78; P = 0.005) or APRI (AUROC = 0.73; P = 0.025). Although the percentage of CC patients was significantly higher with the SAFE algorithm than with Castera's (76.7% vs. 68.1%, respectively; P < 0.050), it was still lower than that for TE (85.3%; P < 0.033). CONCLUSIONS: In HIV/HCV-coinfected patients, TE and FT have a similar diagnostic accuracy for significant fibrosis, whereas for cirrhosis TE has the best accuracy. The use of the SAFE and Castera algorithms does not seem to improve diagnostic performance.

Increased risk of cardiovascular disease (CVD) with age in HIV-positive men: a comparison of the D:A:D CVD risk equation and general population CVD risk equations.

OBJECTIVES: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. RESULTS: A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.

Factors associated with guideline-based hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients: role of comorbidities and physicians' perceptions.

OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

[Enhanced prenatal HIV couple oriented counselling session and couple communication about HIV (ANRS 12127 Prenahtest Trial)]. / Intervention de conseil VIH prénatal orienté vers le couple et communication conjugale autour du VIH (Essai ANRS 12127 Prenahtest).

BACKGROUND: The Prenahtest study investigated the efficacy of a couple-oriented HIV counselling session (COC) in encouraging couple HIV counselling and testing, and improving intra-couple communication about sexual and reproductive health. We report here on the effect of COC on intra-couple communication about HIV. METHODS: Within this 4-country trial (India, Georgia, Dominican Republic and Cameroon), 484 to 491 pregnant women per site were recruited and individually randomized to receive either the COC intervention, enhanced counselling with role playing, or standard post-test HIV counselling. Women were interviewed at recruitment, before HIV testing (T0), and 2 to 8 weeks after post-test HIV counselling (T1). Four dichotomous variables documented intra-couple communication about HIV at T1: 1) discussion about HIV, 2) discussion about condom use, 3) suggesting HIV testing and 4) suggesting couple HIV counselling to the partner. An intra-couple HIV communication index was created: low degree of communication ("yes" response to zero or one of the four variables), intermediate degree of communication ("yes" to two or three variables) or high degree of communication ("yes" to the four variables). To estimate the impact of COC on the intra-couple HIV communication index, multivariable logistic regressions were conducted. RESULTS: One thousand six hundred and seven women were included in the analysis of whom 54 (3.4%) were HIV-infected (49 in Cameroon). In the four countries, the counselling group was associated with intra-couple HIV communication (P≤0.03): women allocated to the COC group were significantly more likely to report high or intermediate degrees of intra-couple communication about HIV (versus low degree of communication) than women allocated to standard counselling. CONCLUSION: COC improved short-term communication about HIV within couples in different sociocultural contexts, a positive finding for a couple approach to HIV prevention.

Evaluation of HIV protease inhibitor use and the risk of sudden death or nonhemorrhagic stroke.

Concerns have arisen about possible effects of protease inhibitors (PIs) on cardiac conductivity. We found no significant association between current or recent PI exposure and sudden death or nonhemorrhagic stroke (adjusted rate ratio, 1.22; 95% confidence interval, .95-1.57), whereas cumulative exposure to PIs was associated with an increased risk (adjusted rate ratio, 1.06 per year of exposure; 95% confidence interval, 1.01-1.11).

Cervical human papillomavirus and HIV infection in women of child-bearing age in Abidjan, Côte d'Ivoire, 2010.

BACKGROUND: We sought to document the association of Human immunodeficiency Virus (HIV) infection and immunodeficiency with oncogenic Human Papillomavirus (HPV) infection in women with no cervical neoplastic lesions identified through a cervical cancer screening programme in Côte d'Ivoire. METHODS: A consecutive sample of women stratified on their HIV status and attending the national blood donor clinic or the closest HIV clinic was recruited during a cervical cancer screening programme based on the visual inspection. Diagnosis of HPV infection and genotype identification were based on the Linear Array; HPV test. RESULTS: A total of 445 (254 HIV-positive and 191 HIV-negative) women were included. The prevalence of oncogenic HPV infection was 53.9% (95% confidence interval (CI) 47.9-59.9) in HIV-positive women and 33.7% (95% CI 27.1-40.3) in HIV-negative women (odds ratio (OR)=2.3 (95% CI 1.5-3.3)). In multivariate analysis, HIV-positive women with a CD4 count <200 cells mm(3) or between 200 and 499 cells mm(3) were more likely to harbour an oncogenic HPV compared with women with a CD4 count ≥500 cells mm(3) with OR of 2.8 (95% CI 1.1-8.1) and 1.7 (95% CI 1.0-2.9), respectively. CONCLUSION: A high prevalence of oncogenic HPV was found in women with no cervical neoplastic lesions, especially in HIV-positive women. Despite antiretroviral use, immunodeficiency was a main determinant of the presence of oncogenic HPV.

Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients.

The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV-coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV-coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non-nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1-3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1-3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2-3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0-2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0-1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV-coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.

Cerebral alterations in West African HIV and non-HIV adults aged ≥50: An MRI study.

OBJECTIVES: To cross-sectionally describe brain alterations in PLHIV aged above 50 years old, receiving antiretroviral treatment (ART) and living in Senegal compared to HIV-negative subjects. METHODS: Twenty PLHIV and 26 HIV-negative subjects with comparable socio-demographic and clinical characteristics underwent an MRI exam (3D-T1 and FLAIR sequences). Global atrophy and White Matter Hyperintensities (WMH) were evaluated. After assessing the feasibility and acceptability of MRI scans in this population, we described atrophy and WHM prevalence and associated factors using logistic regressions. RESULTS: Overall, 43.5% of the study sample were aged ≥60 years, 58.7% were women, and 28.3% had hypertension. The overall prevalence of atrophy and WMH was 19.6% [95% CI: 8.1-31.1] and 30.4% [95% CI: 17.1-43.7]. HIV status had no significant effect on atrophy or WMH. Unemployment and hypertension were significantly associated with atrophy, whereas women were less likely to present atrophy. Aged ≥60 years was the only factor associated with WMH. CONCLUSIONS: A high prevalence of atrophy and WMH was observed in West African adults aged over 50 years without a clear HIV impact. As brain MRI studies are critical to better understand cognitive and emotional outcomes, we encourage those studies in older PLHIV in West Africa.

Prevalence and factors associated with renal impairment in HIV-infected patients, ANRS C03 Aquitaine Cohort, France.

OBJECTIVES: The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors. METHODS: A cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (<15). Logistic regression models were used to investigate factors associated with RI. RESULTS: The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/microL and HIV plasma viral load (VL) was<50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6-4.3)], age >50 years (OR=9.8: 7.4-13.0) and 40-50 years (OR=1.9: 1.5-2.4), body mass index (BMI) <22 kg/m(2) (OR=3.3: 2.7-4.3) and tenofovir exposure (OR=1.4: 1.0-1.9 for <1 year and OR=1.5: 1.2-2.0 for >1 year). Advanced RI (CC <60 mL/min) was associated with age >50 years (OR=5.6: 2.9-10.9) and 40-50 years (OR=2.2: 1.1-1.4), BMI <22 kg/m(2) (OR=1.5: 1.0-2.4), hypertension (OR=2.5: 1.4-2.5) and indinavir (IDV) exposure >1 year (OR=2.3: 1.5-3.6). CONCLUSION: This survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.

Role of treatment for depressive symptoms in relieving the impact of fatigue in HIV-HCV co-infected patients: ANRS Co13 Hepavih, France, 2006-2008.

Fatigue is a major component of quality of life (QOL) and is associated with depression in HIV-HCV co-infected individuals. We investigated whether treating depressive symptoms (DS) could mitigate the impact of fatigue on daily functioning in co-infected patients, even those at an advanced stage of disease. The analysis was conducted on enrollment data of 328 HIV-HCV co-infected patients recruited in the French nationwide ANRS CO 13 HEPAVIH cohort. Data collection was based on medical records and self-administered questionnaires which included items on socio-behavioural data, the fatigue impact scale (FIS) in three domains (cognitive, physical and social functioning), depressive symptoms (CES-D classification) and use of treatments for depressive symptoms (TDS). After multiple adjustment for gender and unemployment, CD4 cell count <200 per mm(3) was associated with a negative impact of fatigue on the physical functioning dimension (P = 0.002). A higher number of symptoms causing discomfort significantly predicted a higher impact of fatigue on all three dimensions (P < 0.001). This was also true for patients with DS receiving TDS when compared with those with no DS but receiving TDS. A significant decreasing linear trend (P < 0.001) of the impact of fatigue was found across the categories 'DS/TDS', 'DS/no TDS', 'no DS/TDS' and 'no DS/no TDS'. Despite limitations related to the cross-sectional nature of this study, our results suggest that routine screening and treatment for DS can reduce the impact of fatigue on the daily functioning of HIV-HCV co-infected patients and relieve the burden of their dual infection.

Scaling up antiretroviral therapy for HIV-infected children in Côte d'Ivoire: determinants of survival and loss to programme.

OBJECTIVE: To investigate deaths and losses to follow-up in a programme designed to scale up antiretroviral therapy (ART) for HIV-infected children in Côte d'Ivoire. METHODS: Between 2004 and 2007, HIV-exposed children at 19 centres were offered free HIV serum tests (polymerase chain reaction tests in those aged < 18 months) and ART. Computerized monitoring was used to determine: (i) the number of confirmed HIV infections, (ii) losses to the programme (i.e. death or loss to follow-up) before ART, (iii) mortality and loss-to-programme rates during 12 months of ART, and (iv) determinants of mortality and losses to the programme. FINDINGS: The analysis included 3876 ART-naïve children. Of the 1766 with HIV-1 infections (17% aged < 18 months), 124 (7.0%) died, 52 (2.9%) left the programme, 354 (20%) were lost to follow-up before ART, 259 (15%) remained in care without ART, and 977 (55%) started ART (median age: 63 months). The overall mortality rate during ART was significantly higher in the first 3 months than in months 4-12: 32.8 and 6.9 per 100 child-years of follow-up, respectively. Loss-to-programme rates were roughly double mortality rates and followed the same trend with duration of ART. Independent predictors of 12-month mortality on ART were pre-ART weight-for-age z-score < -2, percentage of CD4+ T lymphocytes < 10, World Health Organization HIV/AIDS clinical stage 3 or 4, and blood haemoglobin < 8 g/dl. CONCLUSION: The large-scale programme to scale up paediatric ART in Côte d'Ivoire was effective. However, ART was often given too late, and early mortality and losses to programme before and just after ART initiation were major problems.