Clinical features of suspected Ebola cases referred to the Moyamba ETC, Sierra Leone: challenges in the later stages of the 2014 outbreak.

BACKGROUND: The last ebola virus disease (EVD) outbreak has been the most important since 1976. EVD cases decreased drastically in Sierra Leone at the beginning of 2015. We aim to determine the clinical findings and evolution of patients admitted to an Ebola treatment center (ETC) during the epidemic's late phase. METHODS: We analyze retrospectively data of patients admitted to the Moyamba ETC (December 2014-March 2015). Patients were classified in EVD or non-EVD patients according to the results of Ebola virus real-time reverse transcription polymerase chain reaction (ZAIRE-RT-PCR). RESULTS: Seventy-five patients were included, 41.3 % were positive for ZAIRE-RT-PCR. More women (68 % vs 28 %, p = 0.001) were EVD-positive. More EVD patients had previous contact with an Ebola patient (74.2 % vs 36.3 %, p < 0.001). At admission, EVD patients were more likely to have fatigue (96.7 %, p < 0.001), diarrhea (67.7 %, p = 0.002), and muscle pain (61.3 %, p = 0.009); but only objective fevers in 35.5 % of EVD patients. The most reliable criteria for diagnosis were: contact with an Ebola patient plus three WHO symptoms (LR + =3.7, 95 % CI = 1.9-7.3), and positive contact (LR + =2.3, 95 % CI = 1.15-4.20). Only 45.2 % of EVD patients developed fevers during stay, but 75 % developed gastrointestinal symptoms. Non-EVD patients had gastrointestinal problems (33 %), respiratory conditions (26.6 %), and others such as malaria, HIV or tuberculosis with a mortality rate of 11.4 %. vs 58 % in EVD group (p < 0.001). CONCLUSIONS: More non-EVD patients were admitted in the outbreak's late phases. The low percentage of initial fever highlights the need to emphasize the epidemiological information. EVD patients presented new symptoms getting worse and requiring closer follow-up. Diagnoses of non-EVD patients were diverse with a remarkable mortality, presenting a challenge for the health system.

Safe Reduction in CD4 Cell Count Monitoring in Stable, Virally Suppressed Patients With HIV Infection or HIV/Hepatitis C Virus Coinfection.

BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.

Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial.

BACKGROUND: Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir-ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed. METHODS: In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488. FINDINGS: Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047). INTERPRETATION: In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. FUNDING: Bristol Myers-Squibb and Fundación SEIMC-GESIDA.

Invasive pneumococcal disease in HIV-infected adults: clinical changes after the introduction of the pneumococcal conjugate vaccine in children.

BACKGROUND: Few data exist on the implications of widespread use of 7-valent pneumococcal conjugate vaccine in children in the invasive pneumococcal disease (IPD) in HIV-infected adults. We conducted a multicenter study to analyze differences in clinical presentation of IPD between HIV-infected and non-HIV-infected adults in the prevaccine and postvaccine era. METHODS: Study of all cases of IPD in HIV-infected adults diagnosed since 1996 to 2010. Episodes were classified into prevaccine (1996-2001), early postvaccine (2002-2004), and late postvaccine period (2005-2010). For each case, we identified an HIV-negative control patient with IPD matched by hospital, age, and vaccine period. RESULTS: Two hundred twenty-one episodes of IPD in HIV-infected patients were diagnosed. The incidence of IPD decreased from 7.81 to 3.69 episodes per 1000 patient-years (-53%; 95% confidence interval: -65% to -36%, P < 0.001) between prevaccine and late postvaccine period. There was an 81% (95% confidence interval: -88% to -69%, P < 0.001) decrease of IPD caused by vaccine serotypes. In late postvaccine period IPD in HIV-infected patients was associated to higher rates of respiratory failure (28.4% vs. 48.4%, P = 0.011), greater intensive care unit admission (8.2% vs. 21.7%, P = 0.02) and a higher need for mechanical ventilation (5.9% vs. 16.3%, P = 0.033). In the prevaccine period, non-HIV-infected patients had a more severe illness than in those with HIV infection; however, these differences disappeared in the late postvaccine period. CONCLUSIONS: In the late postvaccine era, the incidence of IPD in HIV-infected patients has decreased, however, clinical presentation seems to have changed to a more severe illness. The widespread use of highly active antiretroviral therapy, polyssacharide vaccine, and 7-valent pneumococcal conjugate vaccine has contributed to these changes.

Intestinal lymphangiectasia: an undescribed cause of malabsorption and incomplete immunological recovery in HIV-infected patients.

BACKGROUND: Although paradoxical virological and immunological response after HAART has been well studied, intestinal lymphangiectasia (IL) in HIV-1 infected patients has not previously described. METHODS: To describe HIV patients who developed IL. DESIGN: Clinical Case series. PATIENTS: 4 patients with HIV and IL diagnosis based on clinical, endoscopic and pathological findings. RESULTS: All four cases had prior mycobacterial infections with abdominal lymph node involvement and a very low CD4 cell count nadir. They developed intestinal lymphangiectasia despite appropriate virological suppression with HAART and repeatedly negative mycobacterial cultures. Two patients were clinically symptomatic with oedemas, ascites, diarrhoea, asthenia, weight loss; but the other two were diagnosed with malabsorption as a result of laboratory findings, with hypoproteinemia and hypoalbuminemia. Three of them were diagnosed by video capsule endoscopy. CONCLUSIONS: IL should be considered in HIV-1 infected patients who present with clinical or biochemical malabsorption parameters when there is no immunological recovery while on HAART.

[Role of fixed-dose combinations of antiretrovirals in HIV-1 therapy]. / El papel de las combinaciones de antirretrovirales a dosis fijas en el tratamiento de la infección por VIH-1.

The launch of generic forms of some of the drugs included in fixed-dose combinations of antiretrovirals (FDCA) raises the potential risk of breaking these combinations in order to allow the administration of the new cheaper generic drug. This could result in a step back in some major advances achieved in simplicity and treatment adherence, resulting in an increased risk of selective treatment withdrawal of some of the drugs administered separately. Due to the mechanism of action of the currently available antiretroviral treatment administration must be life-long in infected individuals, both children and adults. FDCA are a significant advance in antiretroviral treatment simplification, contributing to increase compliance of complex chronic therapies, thus increasing the patient's quality of life. They reduce the risk of treatment errors and can also reduce the possibility of unprescribed monotherapy with selective non-compliance. Hence, they contribute to reduce the risk of selection of HIV-1 clones with antiretroviral resistance, a situation that not only compromises future treatment options of the infected individual, but can also be transmitted and are a situation of Public Health concern. Excluding those cases that require a particular dose adjustment, FDCA are a preferred treatment option and their use must be strongly recommended in all scenarios where the components included in the combination are preferred drugs.

Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults.

This is a randomized trial to compare the immunoglobulin G response and the antibody avidity after two pneumococcal vaccinations, conjugated pneumococcal vaccine (CPV) and polysaccharide pneumococcal vaccine (PPV) 4 weeks after vs. PPV alone in 202 HIV-infected adults. There were no differences in the two strategies, either in the percentage of immunoglobulin G two-fold increase for the CPV included serotypes or immunoglobulin G two-fold increase, reaching the level of 1 microg/ml except for serotype 23F (26% responded after conjugated pneumococcal vaccine + PPV vs. 14% after PPV). No avidity increases were seen in any strategy.

Raltegravir, etravirine, and ritonavir-boosted darunavir: a safe and successful rescue regimen for multidrug-resistant HIV-1 infection.

BACKGROUND: Boosted darunavir (DRV/r) plus etravirine (ETR), in DUET trials, and raltegravir, in BENCHMRK trials, showed high rates of virologic response in patients with multidrug-resistant HIV-1 infection, particularly when associated with two more fully active antiretroviral drugs. No data from clinical trials, about this combination, are available. PATIENTS AND METHODS: Thirty-two consecutive heavily pretreated patients with multidrug-resistant HIV-1 infection who started a new salvage regimen with RAL (400 mg twice daily), ETR (200 mg twice daily), and DRV/r (600/100 mg twice daily) were studied. Clinical evaluation and immunologic, virologic, and biochemical parameters were collected at baseline and at Weeks 4, 12, and 24. RESULTS: Median baseline characteristics were age 44 years, 13 years on antiretroviral therapy, nine prior highly active antiretroviral therapy regimens, 261 CD4 cells/mL, and HIV-1 RNA 4.2 log10 copies/mL. Sixteen (50%) and 14 (44%) patients were enfuvirtide- and tipranavir-experienced, respectively. Three-class resistance mutations were present in all patients. Three patients (9%) had isolates with three ETR resistance mutations. All patients were DRV-naïve with a median of one DRV resistance mutation. At Weeks 4, 12, and 24, respectively, 63%, 81%, and 94% of patients achieved HIV1-RNA less than 50 copies/mL. Median CD4 cell count increased 30, 73, and 103 cells/mL at Weeks 4, 12, and 24, respectively. No patient had adverse events leading to discontinuation of the regimen. CONCLUSION: The combination of raltegravir, ETR, and DRV/r was a highly effective and well-tolerated antiretroviral salvage regimen in patients infected with multidrug-resistant HIV-1.

Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain).

OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.

Effectiveness of polysaccharide pneumococcal vaccine in HIV-infected patients: a case-control study.

BACKGROUND: Polysaccharide pneumococcal vaccine (PPV) is recommended among human immunodeficiency virus (HIV)-infected patients, although its effect in reducing the incidence of pneumonia or invasive pneumococcal disease is not well established. Our objective was to determine the effectiveness of 23-valent PPV in HIV-infected adults and the risk factors for pneumococcal pneumonia or invasive pneumococcal disease. METHODS: We performed a retrospective case-control study in 4 Spanish hospitals for the period from January 1995 through December 2005 using the HIV database from each hospital to identify case patients with Streptococcus pneumoniae disease and control subjects without a history of pneumococcal infection. RESULTS: A total of 184 case patients and 552 control subjects were identified. The factors associated with pneumococcal disease in bivariate analysis were active injection drug use (odds ratio [OR], 3.33; 95% confidence interval [CI], 2-5.55), alcoholism (OR, 3.03; 95% CI, 1.86-4.91), chronic obstructive pulmonary disease (OR, 2.58; 95% CI, 1.3-5.1), cirrhosis (OR, 6.05; 95% CI, 3.2-11.4), antiretroviral therapy (OR, 0.23; 95% CI, 0.16-0.32), trimethoprim-sulfamethoxazole prophylaxis (OR, 0.66; 95% CI, 0.45-0.97), viral load <5000 copies/mL (OR, 0.38; 95% CI, 0.26-0.54), and previous PPV (OR, 0.39; 95% CI, 0.24-0.65). Risk factors for pneumococcal disease in multivariate analysis were cirrhosis (OR, 5.64; 95% CI, 2.53-12.53), chronic obstructive pulmonary disease (OR, 2.90; 95% CI, 1.21-6.94), and alcoholism (OR, 2.15; 95% CI, 1.11-4.19), whereas protective factors were receipt of antiretroviral therapy (OR, 0.23; 95% CI, 0.14-0.36) and receipt of pneumococcal vaccine (OR, 0.44; 95% CI, 0.22-0.88), even in patients with CD4 lymphocyte counts <200 cells/microL. CONCLUSIONS: Antiretroviral therapy and PPV have a significant, independent protective effect against pneumococcal disease, regardless of CD4 lymphocyte count; thus, all patients with HIV infection should be vaccinated with PPV to prevent pneumococcal disease.

Genotypic and phenotypic resistance patterns at virological failure in a simplification trial with nevirapine, efavirenz or abacavir.

BACKGROUND: The NEFA Study was a randomized study comparing nevirapine (NVP), efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors. OBJECTIVE: To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms. METHODS: Patients with virological failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml, were analysed for phenotypic susceptibility and HIV-1 mutations. RESULTS: Of the 460 patients included in the study, 51 (11%) experienced virological failure after 24 months of follow-up while on assigned study medication. A higher proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12 (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms. In general, there was a good concordance among genotype and phenotype resistance testing, except for ABC, stavudine and didanosine, where phenotypic resistance testing added valuable information (fold change in the median inhibitory concentration). CONCLUSIONS: Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy. Phenotypic resistance testing may be helpful in interpreting unclear genotypic results.

[Recommendations from GESIDA/SEFH/PNS to improve adherence to antiviral treatment (2004)]. / Recomendaciones GESIDA/SEFH/PNS para mejorar la adherencia al tratamiento antirretroviral en el año 2004.

Since the early days of antiretroviral therapy, adherence has emerged as the milestone of success; in fact, it is the most potent predictor of effectiveness. The main factors related to adherence include the complexity of the therapeutic regimen, adverse effects, psychological problems, alcoholism and active addiction to drugs, lack of social and family support and the patient's beliefs and attitudes about the treatment. Adherence monitoring should be part of the HIV patient's regular care, and should be done with feasible, easily applied methods adapted to the different clinical settings. The minimally acceptable measures should include use of a validated questionnaire, together with data from the Pharmacy Department's drug dispensation registry. All patients that begin HAART or undergo a change of treatment should participate in a treatment education program imparted by health professionals with knowledge and experience in the management of patients with HIV infection. The health team (doctors, pharmacists and nursing professionals) should offer maximum availability to solve the doubts and problems that may occur during treatment. When sub-optimal adherence is detected, intervention strategies based on psychological therapy, educational efforts and personal advice should be attempted, in order to adapt the treatment scheme to the patient's habits and provide solutions to the problem of non-compliance. In certain situations, co-morbid conditions will also require attention. Treatment adherence, being a multidimensional problem, needs a multidisciplinary team approach. The choice of therapy, only one aspect of the multidimensional problem of adherence, must be a careful and individualized decision; however, simpler regimens with regard to the number of pills and daily dose are desirable.

Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection.

BACKGROUND: We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved. METHODS: We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter. RESULTS: At 12 months, the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups. CONCLUSIONS: When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.

[Adherence to antiretroviral therapy measured by pill count and drug serum concentrations. Variables associated with a bad adherence]. / Adherencia a los fármacos antirretrovirales medida por la concentración de fármacos y el recuento de comprimidos. Variables relacionadas con una mala adherencia.

BACKGROUND: We aimed at measuring the adherence to HAART by means of pill count and drug plasma levels. In addition, we aimed at determining variables associated with suboptimal adherence. PATIENTS AND METHOD: Prospective observational study of 202 consecutive patients with HIV infection who were receiving antiretroviral treatment, followed up during 9 months. At baseline and at the end of the study a structured questionnaire was administered and a review of medical charts was performed. The adherence was assessed by monthly pill count while drug plasma levels were measured every three months. We considered that a patient adherence was not fulfilled when the mean pill count was < 90% or when any plasma drug level was lower than that expected. RESULTS: Of 143 available patients, 41.2% were non-adherent. According to the univariate analysis, non-adherent patients were more likely to be younger, female, under a methadone maintenance scheme, under psychiatric treatment, to have depression (according to the Beck Depression Inventory), to have adverse antiretroviral effects and to have a previous history of voluntary withdrawal of the treatment. Men who had sex with other men were significantly more adherent. In the multivariate analysis, female sex [OR 2.6 (1.04-6.65)], to be under a methadone program [OR 9.43 (1.01-88)], to have adverse drug effects [OR 2.63 (1.09-6.33)] and to have a previous history of voluntary withdrawal [OR 2.63 (1.09-6.36)] were independent risk factors for non-adherence. CONCLUSIONS: Adherence to antiretroviral therapy was 58.8%, similar to that seen in other chronic diseases. To be under a methadone maintenance program and having an active drug addiction was related with non-adherence. Women with worst adherence levels had frequently psychiatric comorbidity and more adverse drug effects.

[Adherence to antiretroviral drug therapy. A systematic review]. / Estudios de adherencia a los fármacos antirretrovirales. Una revisión sistemática.

BACKGROUND: We performed a systematic review of the medical literature in order to determine the level of adherence to antiretroviral therapy and its relation with the social, demographic, and clinical characteristics of patients. METHOD: Systematic search of published primary studies in MEDLINE, EMBASE and IME and review of reports presented in main congresses related to infectious diseases and AIDS. Observational and intervention studies carried out in adult patients between 1990 and the first semester of 2001 were selected following descriptive and quality criteria. Both English language and Spanish language reports were analyzed. RESULTS: 30 studies fulfilled previously established requirements. Most studies show high adherence levels between 50% and 80% patients, with a range between 28% and 82%. In univariate or multivariate analyses, factors associated with worse adherence levels were as follows: females, younger people, low education level, low income, active drug consumption, lack of self-perception of the efficacy of antiretroviral agents, stress and lack of motivation, high number of tablets and complexity of administration guidelines. Most prospective studies show a good correlation between adherence and control of HIV infection determined by the measurement of the viral load. CONCLUSIONS: The number of primary studies with methodological quality is limited and future works must be performed under strict design conditions. Most studies show that a high proportion of patients, between 20% and 50%, do not have optimal levels of adherence. Patients with higher adherence levels exhibit greater clinical effectivity. Social, demographic, psychological and other factors related to the lack of adherence must be taken into account in order to improve the compliance in these patients.