III. THE ROLE OF THE RESEARCH ETHICS COMMITTEES IN THE REGULATION OF PHARMA-SPONSORED STUDIES.

Participants of Pharma-sponsored research are exposed to risks, benefits, and uncertainties that do not occur in other forms of clinical studies. Ethics committees represent the subjects' first line of protection. This responsibility begins with the study review and ends after all study subjects finish the intervention. The objective of this paper is to review the most common controversial issues found in Pharma-sponsored studies. Potential solutions are proposed to prevent or resolve the polemical aspects. However, different challenges will be faced in the near future (e.g., when new therapies reach their late stage of development). All parties involved in research should work together to guarantee the protection of participants, the paramount principle on which clinical investigation is based. Pharma-sponsored research is a crucial driver to develop and implement innovative approaches to improve the informed consent process and the execution of the studies.

III. The role of the Research Ethics Committees in the regulation of Pharma-Sponsored studies

Participants of Pharma-sponsored research are exposed to risks, benefits, and uncertainties that do not occur in other forms of clinical studies. Ethics committees represent the subjects’ first line of protection. This responsibility begins with the study review and ends after all study subjects finish the intervention. The objective of this paper is to review the most common controversial issues found in Pharma-sponsored studies. Potential solutions are proposed to prevent or resolve the polemical aspects. However, different challenges will be faced in the near future (e.g., when new therapies reach their late stage of development). All parties involved in research should work together to guarantee the protection of participants, the paramount principle on which clinical investigation is based. Pharma-sponsored research is a crucial driver to develop and implement innovative approaches to improve the informed consent process and the execution of the studies.

Late Diagnosis Due to Missed Opportunities and Inadequate Screening Strategies in HIV Infected Mexican Women.

Late diagnosis of HIV remains a public health issue in Mexico. Most national programs target high-risk groups, not including women. More data on factors associated with late diagnosis and access to care in women are needed. In 2012-2013, Mexican women recently diagnosed with HIV were interviewed. Socio-cultural background, household-dynamics and clinical data were collected. Of 301 women, 49 % had <200 CD4 cells/mm3, 8 % were illiterate, 31 % had only primary school. Physical/sexual violence was reported by 47/30 %; 75 % acquired HIV from their stable partners. Prenatal HIV screening was not offered in 61 %; 40 % attended consultation for HIV-related symptoms without being tested for HIV. Seeking medical care ≥3 times before diagnosis was associated with baseline CD4 <200 cells/mm3 (adjusted OR 3.74, 95 % CI 1.88-7.45, p < 0.001). There were missed opportunities during prenatal screening and when symptomatic women seeked medical care. Primary care needs to be improved and new strategies implemented for early diagnosis in women.

A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts.

INTRODUCTION: Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. METHODS: Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2-7% of persons known to be living with HIV in these countries. RESULTS: Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm(3). Haiti, Mexico, and several states had >85% retention in care; lower (50-74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. CONCLUSIONS: These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.

[In-hospital mortality in HIV-infected patients: 10 years after the implementation of universal access to HAART in Mexico]. / Mortalidad hospitalaria en pacientes con infección por VIH: a diez años del acceso universal a TARAA en México.

OBJECTIVE: To establish the characteristics and causes of death of HIV patients who die while hospitalized. MATERIALS AND METHODS: We included HIV+ patients who died during hospitalization, in three hospitals in Mexico City between 2010 and 2013. Sociodemographic and clinical data were collected as well as causes of death. We identified preventable deaths (defined as deaths that occurred in patients with less than six months of HAART, or without HAART, with less than 350 CD4 at diagnosis and/or opportunistic events as the cause of hospitalization). RESULTS: 128 deaths were analyzed. The median of CD4 count was 47 cells/mm³; 18% of the patients ignored their HIV status at the time of hospitalization, 51% had less than six months of HAART, 40.5% had never received HAART before. The main causes of death were AIDS defining events, with 65.6%. We identified 70 preventable deaths (57%). CONCLUSIONS: Despite universal access to HAART, HIV patients in Mexico are still dying of AIDS defining illnesses, an indicator of late diagnosis. It is urgent to implement HIV testing programs to allow earlier diagnosis and make HAART benefit accessible to all.

Did Universal Access to ARVT in Mexico Impact Suboptimal Antiretroviral Prescriptions?

Background. Universal access to antiretroviral therapy (ARVT) started in Mexico in 2001; no evaluation of the features of ARVT prescriptions over time has been conducted. The aim of the study is to document trends in the quality of ARVT-prescription before and after universal access. Methods. We describe ARVT prescriptions before and after 2001 in three health facilities from the following subsystems: the Mexican Social Security (IMSS), the Ministry of Health (SSA), and National Institutes of Health (INS). Combinations of drugs and reasons for change were classified according to current Mexican guidelines and state-of-the-art therapy. Comparisons were made using χ (2) tests. Results. Before 2001, 29% of patients starting ARVT received HAART; after 2001 it increased to 90%. The proportion of adequate prescriptions decreased within the two periods of study in all facilities (P value < 0.01). The INS and SSA were more likely to be prescribed adequately (P value < 0.01) compared to IMSS. The distribution of reasons for change was not significantly different during this time for all facilities (P value > 0.05). Conclusions. Universal ARVT access in Mexico was associated with changes in ARVT-prescription patterns over time. Health providers' performance improved, but not homogeneously. Training of personnel and guidelines updating is essential to improve prescription.

HIV-related oral lesions, demographic factors, clinical staging and anti-retroviral use.

BACKGROUND: The aim of the present study was to compare the prevalence of HIV-related oral lesions (HIV-OL) between two health centers for HIV in Mexico City and to analyze the factors that, in addition to combined antiretroviral therapy (CART) and low CD4(+), may be associated with possible differences in prevalence. METHODS: A cross-sectional observational study was performed between January 2000 and February 2003 at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), a specialized referral center for HIV/AIDS patients and the Clínica Especializada Condesa (CEC), a primary care center for HIV-infected individuals without social security insurance. A consecutive sample of HIV-infected individuals had an oral examination based on established clinical criteria. Demographic, clinical and laboratory data were obtained. Independent association of each factor with specific HIV-OL was assessed by logistic regression modeling. RESULTS: Eight hundred fifty individuals were examined (INCMNSZ: 479; CEC: 371). Hairy leukoplakia (HL), periodontal disease (PD) and Kaposi's sarcoma (KS) were independently associated with the study site [odds ratio (OR) = 1.7 (95% confidence interval (CI): 1.1-2.4), OR = 4.2 (95% CI: 1.3-13), OR = 10.1 (95% CI: 2.7-38.2), respectively], being more frequent in CEC patients. HL was independently associated with men having sex with men OR = 1.7 (95% CI: 1.1-2.8). All HIV-OL were independently associated with CD4(+) counts and, with the exception of PD and KS, with time under CART. CONCLUSIONS: The present comparative study showed that several factors were associated with a difference in prevalence of oral lesions found in two AIDS clinics located in Mexico City. Severe immune suppression, CART duration and the study site were associated with HIV-OL. Further investigation into factors such as socioeconomic determinants associated with HIV-OL is warranted.

[Effectiveness of preemptive therapy with ganciclovir in recipients of renal transplants at high risk (R-/D+) for the development of cytomegalovirus disease]. / Efectividad de la terapia anticipada con ganciclovir en receptores de trasplante renal de alto riesgo (R-/D+) para desarrollo de enfermedad por citomegalovirus.

Current management of renal transplant recipients who are CMV seronegative (R-) and receive an organ from a seropositive donor (D+) is controversial. These patients are at high risk for CMV disease and are usually treated with ganciclovir prophylaxis at variable dose and duration. An alternative to this approach is to administer ganciclovir only to those patients who are identified by virological markers to be at the highest risk to develop the disease (preemptive therapy). This prospective trial was conducted to asses the value of preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients on triple drug immunosuppression without antilymphocyte induction. Sixteen adults receiving their first kidney transplant were enrolled and followed with pp65 antigenemia assay performed biweekly for the first 16 postransplant weeks, and then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days) was administered as preemptive therapy upon detection of one or more antigen-positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those receiving preemptive therapy, pp65 antigenemia was also repeated after completion of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology (IgM) became positive in all patients after the first antigenemia result. The last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35 mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is effective in preventing CMV disease. By using this strategy, 9 of 16 patients were spared ganciclovir prophylaxis with no effect on rejection or CMV disease. The clinical benefit and cost/effectiveness of this strategy should be evaluated against universal prophylaxis in these high-risk patients.

Efectividad de la terapia anticipada con ganciclovir en receptores de trasplante renal de alto riesgo (R-/D+) para desarrollo de enfermedad por citomegalovirus / Effectiveness of preemptive therapy with ganciclovir in recipients of renal transplants at high risk (R-/D+) for the development of cytomegalovirus disease

Current management of renal transplant recipients who are CMV seronegative (R-) and receive an organ from a seropositive donor (D+) is controversial. These patients are at high risk for CMV disease and are usually treated with ganciclovir prophylaxis at variable dose and duration. An alternative to this approach is to administer ganciclovir only to those patients who are identified by virological markers to be at the highest risk to develop the disease (preemptive therapy). This prospective trial was conducted to asses the value of preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients on triple drug immunosuppression without antilymphocyte induction. Sixteen adults receiving their first kidney transplant were enrolled and followed with pp65 antigenemia assay performed biweekly for the first 16 postransplant weeks, and then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days) was administered as preemptive therapy upon detection of one or more antigen-positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those receiving preemptive therapy, pp65 antigenemia was also repeated after completion of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology (IgM) became positive in all patients after the first antigenemia result. The last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35 mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is effective in preventing CMV disease. By using this strategy, 9 of 16 patients were spared ganciclovir prophylaxis with no effect on rejection or CMV disease. The clinical benefit and cost/effectiveness of this strategy should be evaluated against universal prophylaxis in these high-risk patients.