François Dabis

Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy

Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.

What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis

Using a simulation model, Andrea Ciaranello and colleagues find that the latest WHO PMTCT (prevention of mother to child transmission of HIV) guidelines plus better access to PMTCT programs, better retention of women in care, and better adherence to drugs are needed to eliminate pediatric HIV in Zimbabwe.

Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration

BackgroundIn March 2008, the D:A:D study published results demonstrating an increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We describe changes to the use of ABC since this date, and investigate changes to the association between ABC and MI with subsequent follow-up.MethodsA total of 49,717 D:A:D participants were followed from study entry until the first of an MI, death, 1 February 2013 or 6xa0months after last visit. Associations between a person’s 10-year cardiovascular disease (CVD) risk and the likelihood of initiating or discontinuing ABC were assessed using multivariable logistic/Poisson regression. Poisson regression was used to assess the association between current ABC use and MI risk, adjusting for potential confounders, and a test of interaction was performed to assess whether the association had changed in the post-March 2008 period.ResultsUse of ABC increased from 10xa0% of the cohort in 2000 to 20xa0% in 2008, before stabilising at 18–19xa0%. Increases in use pre-March 2008, and subsequent decreases, were greatest in those at moderate and high CVD risk. Post-March 2008, those on ABC at moderate/high CVD risk were more likely to discontinue ABC than those at low/unknown CVD risk, regardless of viral load (≤1,000 copies/ml: relative rate 1.49 [95xa0% confidence interval 1.34–1.65]; >1,000 copies/ml: 1.23 [1.02–1.48]); no such associations were seen pre-March 2008. There was some evidence that antiretroviral therapy (ART)-naïve persons at moderate/high CVD risk post-March 2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds ratio 0.74 [0.48–1.13]). By 1 February 2013, 941 MI events had occurred in 367,559 person-years. Current ABC use was associated with a 98xa0% increase in MI rate (RR 1.98 [1.72–2.29]) with no difference in the pre- (1.97 [1.68–2.33]) or post- (1.97 [1.43–2.72]) March 2008 periods (interaction Pu2009=u20090.74).ConclusionsDespite a reduction in the channelling of ABC for patients at higher CVD risk since 2008, we continue to observe an association between ABC use and MI risk. Whilst confounding cannot be fully ruled out, this further diminishes channelling bias as an explanation for our findings.

Evaluation of the impact of a breast cancer awareness program in rural Ghana: A cross‐sectional survey

Community awareness is crucial to early detection of breast cancer in low‐ and middle‐income countries. In Ghana 60% of the cases are detected at late stages. Breast Care International (BCI) is a Ghanaian non‐governmental organization dedicated to raising breast cancer awareness. A cross‐sectional survey was designed to assess the impact of BCI program on knowledge, attitudes and practices (KAP) toward breast cancer among women from rural communities of Ghana. A total of 232 women were interviewed in June 2011 in the Ashanti region; of these 131 participants were from a community that received the BCI program in August 2010 (intervention group) and 101 from another community that received the program post‐survey (referent group). Data analysis was performed using Epi‐Info version 3.5.3. Knowledge about breast cancer among participants who received the program was better than among those who did not. Only 53.5% of participants from the referent group knew that breast cancer usually appears as painless breast lump when compared to 82.3% from the intervention group. Participants who attended the program were significantly more likely to obtain higher knowledge scores (odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.14–3.86) and to state practicing breast self‐examination (OR = 12.29, 95% CI = 5.31–28.48). The BCI program improved KAP toward breast cancer. Further research is warranted to provide stronger evidence that the program improves breast cancer early detection.

Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study

Background HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d’Ivoire, Mali, and Senegal, in the West Africa region. Results Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3–51.7) and 42.4 years, IQR (37.0–47.3) for dually seropositive patients (pu200a=u200a0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm3, IQR (83–247) among HIV-2 infected patients and 146 cells/mm3, IQR (55–249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm3 after 24 months on ART for HIV-2 patients and 169 cells/mm3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7–4.3). Conclusions This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

HIV-induced immune deficiency is associated with a higher risk of hepatocarcinoma, ANRS CO3 Aquitaine Cohort, France, 1998–2008

BACKGROUND & AIMSnHIV and viral hepatitis co-infected patients are at high risk for hepatocarcinoma. The contribution of immunodeficiency is not well documented. We aimed at estimating the relationship between the occurrence of hepatocarcinoma and both types of measures of immunodeficiency, current and cumulative (time below a given threshold), to assess their independent effects.nnnMETHODSnHIV-infected adults included in the ANRS CO3 Aquitaine Cohort with no history of cancer, ≥ 3 months of follow-up between 1998 and 2008, ≥ 1 CD4+ cell count (CD4+), and documented hepatitis virus status were eligible. Extended Cox proportional hazards models with delayed entry were used to estimate the risk of hepatocarcinoma. Exposure to a CD4+ < 350 or <500 cells/mm(3) (current and cumulative duration) was time-updated. Hepatitis B or C virus co-infection and gender were fixed-effect variables.nnnRESULTSnSixteen cases of hepatocarcinoma were diagnosed among the 2864 eligible patients, the incidence rate was 0.78 case/1000 person-years (95% Confidence Interval [CI]: 0.40-1.16). Current CD4+ < 350 or < 500 was independently associated with a higher risk of hepatocarcinoma (Hazard Ratio [HR]: 5.0, CI 1.5-16.8, p = 0.009 and HR = 10.3, CI 1.3-82.8, p = 0.029, respectively). The occurrence of hepatocarcinoma was independent of the cumulative exposure to a CD4+ < 350 or < 500 (p = 0.38 or p = 0.80, respectively).nnnCONCLUSIONSnPresenting with CD4+ < 500 was associated with a higher risk of hepatocarcinoma, whereas the cumulative duration with immunodeficiency was not. These results suggest that moving CD4+ count above 500 following antiretroviral therapy initiation is associated with a decreased risk of hepatocarcinoma, regardless of the duration of HIV-induced immunodeficiency.

Hepatitis C virus RNA quantitation in a nationwide French cohort of patients co-infected with HIV and HCV: should the same test be applied to all samples?

In the ANRS CO13 HEPAVIH Cohort, HCV RNA measurement was performed with one of the two available real-time PCR assays [Roche Cobas AmpliPrep-Cobas TaqMan HCV (CAP-CTM) and the Abbott Real-Time HCV (ART)], according to the assay used in each center. To comply with the recommendations for using the same assay in multicenter clinical trials, all the 204 samples analyzed with ART were retested retrospectively by CAP-CTM. The aim of this study was to assess the usefulness of this strategy in real-life situations. A significant and positive correlation was observed between HCV RNA levels measured in the same samples with ART and CAP-CTM with all the genotypes tested. However, in 33 of the 204 (16%) clinical samples, the individual difference between HCV RNA levels measured by both assays was above ±0.5 log(10)IU/ml. Such viral load variations above 0.5 log(10) should be considered as significant. HCV RNA levels estimated by CAP-CTM for genotype 4 were significantly lower than those for genotypes 1, 2, and 3 (P<0.0001). This study shows that using the same assay in multicenter trials and cohorts is still relevant due to inter-assay differences observed in HCV plasma load measurements.

Evaluation of the impact of a breast cancer awareness program in rural Ghana

Community awareness is crucial to early detection of breast cancer in low‐ and middle‐income countries. In Ghana 60% of the cases are detected at late stages. Breast Care International (BCI) is a Ghanaian non‐governmental organization dedicated to raising breast cancer awareness. A cross‐sectional survey was designed to assess the impact of BCI program on knowledge, attitudes and practices (KAP) toward breast cancer among women from rural communities of Ghana. A total of 232 women were interviewed in June 2011 in the Ashanti region; of these 131 participants were from a community that received the BCI program in August 2010 (intervention group) and 101 from another community that received the program post‐survey (referent group). Data analysis was performed using Epi‐Info version 3.5.3. Knowledge about breast cancer among participants who received the program was better than among those who did not. Only 53.5% of participants from the referent group knew that breast cancer usually appears as painless breast lump when compared to 82.3% from the intervention group. Participants who attended the program were significantly more likely to obtain higher knowledge scores (odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.14–3.86) and to state practicing breast self‐examination (OR = 12.29, 95% CI = 5.31–28.48). The BCI program improved KAP toward breast cancer. Further research is warranted to provide stronger evidence that the program improves breast cancer early detection.