Barriers to health care services for migrants living with HIV in Spain.

Background: In Spain, migrants are disproportionately affected by HIV and experience high rates of late diagnosis. We investigated barriers to health care access among migrants living with HIV (MLWH) in Spain. Methods: Cross sectional electronic survey of 765 adult HIV-positive migrants recruited within 18 health care settings between July 2013 and July 2015. We collected epidemiological, demographic, behavioral and clinical data. We estimated the prevalence and risk factors of self-reported barriers to health care using multivariable logistic regression. Results: Of those surveyed, 672 (88%) had information on health care access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from Sub-Saharan Africa and 15% had an irregular immigration status. Men were more likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and lack of a health card (7%). Having an irregular immigration status was a risk factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2-7.2]) and women (OR: 10.5 [95%CI: 3.1-34.8]). Men who experienced racial stigma (OR: 3.1 [95%CI: 1.9-5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2-3.4]) were more likely to report barriers. Women who delayed treatment due to medication costs (6.3 [95%CI: 1.3-30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3-25.1]) were more likely to report barriers. Conclusion: Health care barriers were present in one in five5 MLWH, were more common in men and were associated to legal entitlement to access care, perceived stigma and financial constraints.

Time trends, characteristics, and evidence of scientific advances within the legal complaints for alleged sexual HIV transmission in Spain: 1996-2012.

This article quantifies and characterizes existing legal complaints for the sexual transmission of HIV in Spain, describes temporal trends and whether advance of scientific knowledge is reflected in charging decisions, judicial reasoning, and sentences. Sentences and writs dictated by Spanish penal and civil jurisdictions between 1981 and 2012 were obtained through legal databases systematic search. Sixteen sentences and 9 writs belonging to 19 cases were included; 17 judged by penal and two by civil jurisdictions. The first sentence was pronounced in 1996, 3 between 1999 and 2000, 4 between 2001 and 2005, and 18 between 2006 and 2012. In 10 (53%) cases there was effective HIV transmission, there was not in 6 (32%) and in 3 (15%) directionality could not be determined. Of the defendants, 15 (79%) were heterosexual males, 1 of which was an injecting drug user (IDU), 3 were men who have sex with men (MSM), and 1 was a heterosexual woman. In the 10 cases of HIV transmission, the mechanism was heterosexual sex and index cases were males in nine occasions. Disclosure of HIV status, use of condoms and its frequency, and its possible breaks were mentioned in only some sentences/judicial decisions and fewer mentioned the use of antiretroviral treatment. Very few cases referred to plasma viral load (VL), and there are incorrect statements regarding HIV transmissibility. Only one 2012 sentence mentioned VL levels, adherence to ART, CD4 lymphocyte levels, concomitant sexually transmitted infections, and references to pertinent literature. The number of judicial decisions in Spain is increasing and the profile of the plaintiffs, largely heterosexual women, does not reflect the groups most affected by the HIV epidemic, largely IDU and MSM. Most judgments and writs do not reflect HIV scientific and technical advances. It is of utmost importance that these complex processes incorporate the most up-to-date knowledge on the subject.

Decreasing prevalence of HCV coinfection in all risk groups for HIV infection between 2004 and 2011 in Spain.

While hepatitis C virus (HCV) infection seems to be expanding among HIV-infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV-infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1-27.5) in 2004-2005 to 8.2% (95% CI, 6.9-9.5) in 2010-2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0-8.9%; and heterosexual women, 14.5-4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4-76.4), birth decade 1961-1970 (OR, 2.1; 95% CI, 1.1-3.7) and low educational level (OR, 2.4; 95% CI, 1.6-3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.

Tuberculosis in a cohort of HIV-positive patients: epidemiology, clinical practice and treatment outcomes.

OBJECTIVE: To describe tuberculosis (TB) incidence, risk factors, clinical presentation, disease management and outcomes in human immunodeficiency virus (HIV) infected patients from the CoRIS cohort, Spain, 2004-2010. DESIGN: Open multicentre cohort of antiretroviral treatment (ART) naïve patients at entry. Incidence and risk factors were evaluated using multivariate Poisson regression. RESULTS: Among 6811 patients, 271 were eligible for the study and 198 for the estimation of the incidence rate; TB incidence ranged from 12.1 to 14.1/1000 person-years. TB was associated with low education level (rate ratio [RR] 2.65, 95%CI 1.73-4.07), being sub-Saharan African (RR 3.14, 95%CI 1.81-5.45), heterosexual (RR 2.01, 95%CI 1.22-3.29) or an injecting drug user (RR 2.11, 95%CI 1.20-3.69), not undergoing ART (RR 3.33, 95%CI 2.22-4.76), CD4 <200 cells/mm(3) (RR 5.20, 95%CI 3.25-8.33) and log-viral load of 4-5 (RR 5.44, 95%CI 3.28-9.02) or >5 (RR 13.10, 95%CI 8.27-20.76). Overall, 87% were new cases and 13% were previously treated cases; 175 (65%) were bacteriologically confirmed. Drug susceptibility testing was performed in 146 (83%) patients: resistance to first-line drugs was 11.1% in new and 36.4% in previously treated cases. Standard anti-tuberculosis treatment with four or three drugs was prescribed in respectively 55% and 36% of cases. Treatment default was 11%, and was higher among previously treated cases; 80% received ART during anti-tuberculosis treatment, 80% of new and 50% of previously treated cases were cured or completed treatment, and 18 (6.6%) died. CONCLUSION: TB incidence in HIV-infected patients remains high. Interventions should include early HIV diagnosis and access to ART, enhanced bacteriological confirmation, wider use of four-drug regimens and reduction in treatment default.

Compliance with national guidelines for HIV treatment and its association with mortality and treatment outcome: a study in a Spanish cohort.

OBJECTIVES: The aim of the study was to assess the adequacy of initial antiretroviral therapy (ART), in terms of its timing and the choice of regimens, according to the Spanish national treatment guidelines [Spanish AIDS Study Group-National Plan for AIDS (GeSIDA-PNS) Guidelines] for treatment-naïve HIV-infected patients. METHODS: A prospective cohort study of HIV-positive ART-naïve subjects attending 27 centres in Spain from 2004 to 2010 was carried out. Regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Delayed start of treatment was defined as starting treatment later than 12 months after the patient had fulfilled the treatment criteria. Multivariate logistic and Cox regression analyses were performed. RESULTS: A total of 6225 ART-naïve patients were included in the study. Of 4516 patients who started treatment, 91.5% started with a recommended or alternative treatment. The use of a nonrecommended treatment was associated with a CD4 count > 500 cells/µL [odds ratio (OR) 2.03; 95% confidence interval (CI) 1.14-3.59], hepatitis B (OR 2.23; 95% CI 1.50-3.33), treatment in a hospital with < 500 beds, and starting treatment in the years 2004-2006. Fourteen per cent of the patients had a delayed initiation of treatment. Delayed initiation of treatment was more likely in injecting drug users, patients with hepatitis C, patients with higher CD4 counts and during the years 2004-2006, and it was less likely in patients with viral loads > 5 log HIV-1 RNA copies/ml. The use of a nonrecommended regimen was significantly associated with mortality [hazard ratio (HR) 1.61; 95% CI 1.03-2.52; P = 0.035] and lack of virological response. CONCLUSIONS: Compliance with the recommendations of Spanish national guidelines was high with respect to the timing and choice of initial ART. The use of nonrecommended regimens was associated with a lack of virological response and higher mortality.

Inequalities in HIV disease management and progression in migrants from Latin America and sub-Saharan Africa living in Spain.

OBJECTIVES: The objective of the study was to analyse key HIV-related outcomes in migrants originating from Latin America and the Spanish-speaking Caribbean (LAC) or sub-Saharan Africa (SSA) living in Spain compared with native Spaniards (NSP). METHODS: The Cohort of the Spanish AIDS Research Network (CoRIS) is an open, prospective, multicentre cohort of antiretroviral-naïve patients representing 13 of the 17 Spanish regions. The study period was 2004-2010. Multivariate logistic or Fine and Gray regression models were fitted as appropriate to estimate the adjusted effect of region of origin on the different outcomes. RESULTS: Of the 6811 subjects in CoRIS, 6278 were NSP (74.2%), LAC (19.4%) or SSA (6.4%). For these patients, the follow-up time was 15870 person-years. Compared with NSP, SSA and LAC under 35 years of age had a higher risk of delayed diagnosis [odds ratio (OR) 2.0 (95% confidence interval (CI) 1.5-2.8) and OR 1.7 (95% CI 1.4-2.1), respectively], as did LAC aged 35-50 years [OR 1.3 (95% CI 1.0-1.6)]. There were no major differences in time to antiretroviral therapy (ART) requirement or initiation. SSA exhibited a poorer immunological and virological response [hazard ratio (HR) [corrected] 0.8 (95% CI 0.7-1.0) and HR [corrected] 0.7 (95% CI 0.6-0.9), respectively], while no difference was found for LAC. SSA and LAC showed an increased risk of AIDS for ages between 35 and 50 years [HR 2.0 (95% CI 1.1-3.7) and HR [corrected] 1.6 (95% CI 1.1-2.4), respectively], which was attributable to a higher incidence of tuberculosis. However, no statistically significant differences were observed in mortality. CONCLUSIONS: Migrants experience a disproportionate diagnostic delay, but no meaningful inequalities were identified regarding initiation of treatment after diagnosis. A poorer virological and immunological response was observed in SSA. Migrants had an increased risk of AIDS, which was mainly attributable to tuberculosis.

The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population.

OBJECTIVE: Methotrexate (MTX) is the first-choice drug for the treatment of rheumatoid arthritis (RA) patients. However, 30% of RA patients discontinue therapy within 1 year, usually because of adverse effects. Previous studies have reported conflicting results on the association of polymorphisms in the MTHFR gene with the toxicity of MTX in RA. The aim of this study was to assess the involvement of the C677T and A1298C polymorphisms in the MTHFR gene in the toxicity of MTX in a Spanish RA population. METHODS: The study included retrospectively 468 Spanish RA patients treated with MTX. Single nucleotide polymorphism (SNP) genotyping was performed using the oligonucleotide microarray technique. Allele and genotype association analyses with regard to MTX toxicity and a haplotype association test were also performed. RESULTS: Eighty-four out of the 468 patients (18%) had to discontinue therapy due to adverse effects or MTX toxicity. The C677T polymorphism (rs1801133) was associated with increased MTX toxicity [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.01-1.98, p = 0.0428], and the strongest association was shown in the recessive model (OR 1.95, 95% CI 1.08-3.53, p = 0.0246). The A1298C polymorphism (rs1801131) was not associated with increased MTX toxicity (OR 0.94, 95% CI 0.65-1.38, p = 0.761). A borderline significant risk haplotype was found: 677T-1298A (OR 1.40, 95% CI 1.00-1.96, p = 0.0518). CONCLUSION: These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population.

Higher incidence and persistence of high-risk human papillomavirus infection in female sex workers compared with women attending family planning.

BACKGROUND: There are no data on the incidence and persistence of high-risk human papillomavirus (HR-HPV) infections in female sex workers (FSWs). We aimed to describe and compare the rates of incidence and persistence of HR-HPV infections in FSWs and women from the general population (WGP) who attended healthcare facilities between May 2003 and December 2006 in Alicante, Spain. METHODS: Women with an established HR-HPV infection at study entry were evaluated for the analysis of HR-HPV persistence, and those testing negative for HR-HPV infection at entry were evaluated for the analysis of incidence. HR-HPV infection was determined by the Digene HC2 HR HPV DNA Test. RESULTS: A total of 736 women - 592 WGP and 144 FSWs - were followed for a median of 16.8 months. Global incidence and persistence rates were 3.98 per 100 woman-years (95% confidence interval (CI) 2.91-5.45) and 26.81 per 100 woman-years (95% CI 20.08-35.79), respectively. In the multivariate analysis, only commercial sex work was associated with a statistically significant higher incidence (relative risk (RR) 4.72, 95% CI 2.45-9.09) and persistence (RR 1.93, 95% CI 1.08-3.46) of HR-HPV infection. CONCLUSIONS: Our data show that FSWs have both a higher incidence and a higher persistence of HR-HPV than WGP and should be prioritized in HPV-related cancer screening programs.

Effectiveness of a PMTCT programme in rural Western Kenya.

We assess the coverage of a Prevention of Mother-to-child Transmission (PMTCT) programme in Busia (Kenya) from 1 January 2006 to 31 December 2008 and estimate the risk of transmission of HIV. We also estimate the odds of HIV transmission according to pharmacological intervention received. Programme coverage was estimated as the proportion of mother-baby pairs receiving any antiretroviral (ARV) regimen among all HIV-positive women attending services. We estimated the mother-to-child transmission (MTCT) rate and their 95% confidence interval (95%CI) using the direct method of calculation (intermediate estimate). A case-control study was established among all children born to HIV-positive mothers with information on outcome (HIV status of the babies) and exposure (data on pharmacological intervention). Cases were all HIV-positive children and controls were the HIV-negative ones. Exposure was defined as: (1) complete protocol: ARV prescribed according World Health Organisation recommendations; (2) partial protocol: does not meet criteria for complete protocol; and (3) no intervention: ARVs were not prescribed to both mother and child. Babies were tested using DNA Polymerase Chain Reaction at six weeks of life and six weeks after breastfeeding ceased. In the study period, 22,566 women accepted testing, 1668 were HIV positive (7.4%; 95%CI 7.05-7.73); 1036 (62%) registered in the programme and 632 were lost. Programme coverage was 40.4% (95%CI 37.9-42.7). Out of the 767 newborns, 28 (3.6%) died, 148 (19.3%) defaulted, 282 (36.7%) were administratively censored and 309 (40.2%) babies completed the follow-up as per protocol; 49 were HIV positive and MTCT risk was 15.86% (95%CI 11.6-20.1). The odds of having an HIV-positive baby was 4.6 times higher among pairs receiving a partial protocol compared to those receiving a complete protocol and 43 times higher among those receiving no intervention. Our data show a good level of enrolment but low global coverage rate. It demonstrates that ARV regimens can be implemented in low resource rural settings with marked decreases of MTCT. Increasing the coverage of PMTCT programmes remains the main challenge.

Incidence and risk factors for tuberculosis in HIV-positive subjects by HAART status.

OBJECTIVE: To estimate incidence rates and risk factors for tuberculosis (TB) in human immunodeficiency virus seroprevalent subjects. METHODS: Multicentre, hospital-based cohort study of patients presenting to 10 Spanish hospitals from 1 January 1997 to 31 December 2003. Poisson regression was used and highly active antiretroviral treatment (HAART) was modelled as a time-dependent covariate. RESULTS: A total of 4268 patients were followed for a median of 3.8 years; 221 TB cases were diagnosed over 16 464 person-years (py). TB rates were higher in HAART-naïve subjects (1.56 per 100 py, 95%CI 1.36-1.79) than those on HAART (0.5/100 py, 95%CI 0.31-0.80). Among HAART-naïves, TB risk factors were: being male, being an injecting drug user (IDU) (RR 2.01, 95%CI 1.28-3.16), having low CD4 counts (P < 0.001) and high viral loads (P < 0.001). HAART was protective (RR 0.26, 95%CI 0.16-0.40) and reductions in TB rates were observed in the last calendar period (RR 0.74, 95%CI 0.55-1.00). For patients on HAART, no differences were observed by category of transmission. Low CD4 counts at entry were associated with higher TB rates (P < 0.001). CONCLUSIONS: HAART was associated with lower TB rates, and TB risk factors differed according to whether or not patients had received HAART. To further reduce TB rates, additional strategies are needed, such as timely access and adherence to HAART, especially in IDUs.

Differences between women and men in serial HIV prevalence and incidence trends.

To measure trends in HIV incidence and serial prevalence by sex in a intravenous drug users (IDUs) and heterosexuals (HT) cohort recruited in a counselling centre in Valencia (1988-2005). Serial prevalence and incidence rates were calculated and modelled by logistic and Poisson regression respectively. 5948 IDUs and 13343 HT were recruited. Prevalence was higher among female IDUs (46% vs. 41%), and female HT (4.1% vs. 2%). For IDUs, an interaction (P = 0.005) between sex and calendar was detected. Age-adjusted prevalence showed faster yearly decline in men (OR = 0.87 95%CI: 0.85-0.88) than in women (OR = 0.91 95%CI: 0.88-0.93). Incidence was higher in female IDUs (9.79% p-y) than in men, (5.38% p-y) with an annual decrease for both of 11%. HIV incidence was higher in female HT (0.62% p-y) compared to men 0.23% p-y with a 21% yearly decline. Gender differences in HIV prevalence and incidence trends have been detected. Women showed an increased vulnerability to infection in a country whose HIV epidemic has been largely driven by IDUs.

Prevalence and determinants of high-risk human papillomavirus (HPV) infection and cervical cytological abnormalities in imprisoned women.

The aim of the study was to estimate the prevalence and risk factors associated with infection by high-risk human papillomavirus (HR-HPV) in cervix and squamous intra-epithelial lesions (SIL) in imprisoned women. This was done by a cross-sectional study of imprisoned women attending the gynaecological clinic in Foncalent prison in Alicante, Spain. The study period was from May 2003 to December 2005. HR-HPV infection was determined through Digene HPV Test, Hybrid Capture II (HC-II). HPV typing was determined by multiplex nested PCR assay combining degenerate E6/E7 consensus primers. Multiple logistic regression modelling was used for the analysis of associations between variables where some were considered possible confounders after checking for interactions. A total of 219 women were studied. HR-HPV prevalence was 27.4% and prevalence of SIL was 13.3%. HIV prevalence was 18%, higher in Spaniards than in migrant women (24.6% vs. 14.3%, P<0.05). In multivariate analyses, risk factors for HPV infection were younger age (P for trend=0.001) and tobacco use (OR 2.62, 95% CI 1.01-6.73). HPV infection (OR 4.8, 95% CI 1.7-13.8) and HIV infection were associated with SIL (OR 4.8, 95% CI 1.6-14.1). The commonest HPV types were HPV16 (29.4%), HPV18 (17.6%), HPV39 (17.6%) and HPV68 (17.6%). The prevalence of both HR-HPV infection and SIL in imprisoned women found in this study is high. Determinants for each of the outcomes studied were different. HPV infection is the most important determinant for SIL. A strong effect of HIV co-infection on the prevalence of SIL has been detected. Our findings reinforce the need to support gynaecological clinics in the prison setting.

Trends in HIV testing, serial HIV prevalence and HIV incidence among people attending a Center for AIDS Prevention from 1988 to 2003.

AIM: To analyse trends in HIV testing, serial HIV prevalence and HIV incidence among people who underwent voluntary testing in a Center for AIDS Prevention in Valencia, Spain. METHODS: Open cohort study including all subjects who went to the Center for AIDS Prevention from 1988 to 2003. Information on sociodemographic variables and HIV test results was collected. Serial prevalence and incidence rates were calculated, and joinpoint regression was used to identify changes in trends over time. RESULTS: 21,241 subjects were analysed; 67% men, 27% injecting drug users (IDUs), 43% heterosexuals and 13% men who have sex with men (MSM). From 1988 to 1990, IDUs accounted for 57% of clinic attenders, decreasing to 14% by 1997-2003, accompanied by an increase in heterosexuals. Overall, HIV prevalence for the whole period was 15%, dropping from 35% to <10% after 1999 and to 3% by 2003, when HIV prevalence was 26% in IDUs, 6% in MSM and 2% in heterosexuals. Total HIV incidence was 2.5%. From 1988 to 1990, HIV incidence ranged from 6% to 8%, and a gradual and progressive decline observed from 1990 onwards. From 1995 onwards, HIV incidence was <2%. The highest incidence rate is seen in IDUs, 7-12% in the first period and 4-5% at the end. Among MSM, a change in the decreasing trend is seen by 1998, and increases in incidence are detected by 2002-3. CONCLUSIONS: Serial HIV prevalence has markedly decreased from 1988 in all transmission categories, although it is still high. With regard to HIV incidence, the drop has been marked too, although a worrying increase, that requires further follow-up, has been detected in MSM in the past 2 years.

Higher prevalence of human papillomavirus infection in migrant women from Latin America in Spain.

OBJECTIVES: To estimate prevalence and determinants of high risk (HR) human papillomavirus (HPV) by country of origin in women attending a family planning centre (FPC) in Alicante, Spain. METHODS: Cross sectional study of all women attending a FPC from May 2003 to January 2004. An ad hoc questionnaire was designed and data were collected prospectively. HR HPV infection was determined through the Digene HPV test, Hybrid Capture II, and positive samples for PCR were directly sequenced. Data were analysed through multiple logistic regression. RESULTS: HR HPV prevalence in 1011 women was 10% (95% CI: 8.2 to 12). Compared to Spaniards (prevalence 8.2%) HR HPV prevalence in Colombians was 27.5% (OR: 4.24 95% CI: 2.03 to 8.86), 23.1% in Ecuadoreans (OR: 3.35 95% CI: 1.30 to 8.63), and 22.73% in women from other Latin American countries (OR: 3.29 95% CI: 1.17 to 9.19). Women with more than three lifetime sexual partners had an increased risk of HR HPV infection (OR 3.21 95% CI: 2.02 to 5.10). The higher risk of HR HPV infection was maintained in Latin American women in multivariate analyses that adjusted for age, number of lifetime sexual partners, and reason for consultation. The commonest HPV types in women with normal cervical smears were HPV-18 (20%), HPV-16 (14%) and HPV-33 (11%). CONCLUSIONS: Prevalence of HR HPV is more than three times higher in Latin Americans than in Spaniards. Latin American women's HPV prevalence resembles more that of their countries of origin. It is essential that health service providers identify these women as a priority group in current cervical screening programmes.

Oncogenic human papillomavirus (HPV) type distribution and HPV type 16 E6 variants in two Spanish population groups with different levels of HPV infection risk.

The aim of this study is to determine oncogenic human papillomavirus (HPV) types and HPV type 16 (HPV16) variant distribution in two Spanish population groups, commercial sex workers and imprisoned women (CSW/IPW) and the general population. A multicenter cross-sectional study of 1,889 women from five clinical settings in two Spanish cities was conducted from May to November 2004. Oncogenic HPV infection was tested by an Hybrid Capture II (HC2) test, and positive samples were genotyped by direct sequencing using three different primer sets in L1 (MY09/11 and GP5+/GP6+) and E6/E7. HPV16 variants were identified by sequencing the E6, E2, and L1 regions. Four hundred twenty-five samples were positive for the HC2 test, 31.5% from CSW/IPW and 10.7% from the general population. HPV16 was the most frequent type. Distinct profiles of oncogenic HPV type prevalence were observed across the two populations. In order of decreasing frequency, HPV types 16, 31, 58, 66, 56, and 18 were most frequent in CSW/IPW women, and types 16, 31, 52, 68, 51, and 53 were most frequent in the general population. We analyzed HPV16 intratype variants, and a large majority (78.7%) belonged to the European lineage. AA variants were detected in 16.0% of cases. African variants belonging to classes Af1 (4.0%) and Af2 (1.3%) were detected. Different HPV types and HPV16 intratype variants are involved in oncogenic HPV infections in our population. These results suggest that HPV type distribution differs in CSW/IPW women and in the general population, although further analysis is necessary.

Determinants of response to first HAART regimen in antiretroviral-naïve patients with an estimated time since HIV seroconversion.

OBJECTIVE: To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV-1 seroconversion. DESIGN: Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout. RESULTS: In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log(10) HIV-1 RNA copies/mL at 1.5 months, P=0.03) and poorer long-term immunological response (522 vs 631 cells/microL at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/microL, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/microL at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long-term virological response (0.67 log(10) copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion. CONCLUSION: Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow-up carried out in high-risk subgroups such as IDUs who have poorer responses.

Influence of age and geographical origin in the prevalence of high risk human papillomavirus in migrant female sex workers in Spain.

OBJECTIVES: To estimate the prevalence and risk factors of high risk human papillomavirus (HPV) infection in migrant female sex workers (FSW) according to age and geographical origin. METHODS: Cross sectional study of migrant FSW attending a sexually transmitted infection (STI) clinic in Madrid during 2002. Information on sociodemographic characteristics, reproductive and sexual health, smoking, time in commercial sex work, history of STIs, HIV, hepatitis B, hepatitis C, syphilis, and genitourinary infections was collected. High risk HPV Infection was determined through the Digene HPV Test, Hybrid Capture II. Data were analysed through multiple logistic regression. RESULTS: 734 women were studied. Overall HPV prevalence was 39%; 61% in eastern Europeans, 42% in Ecuadorians, 39% in Colombians, 29% in sub-Saharan Africans, and 24% in Caribbeans (p = 0.057). HPV prevalence showed a decreasing trend by age; 49% under 20 years, 35% in 21-25 years,14% over 36 years% (p<0.005). In multivariate analyses, area of origin (p = 0.07), hormonal contraception in women not using condoms (OR 19.45 95% CI: 2.45 to 154.27), smoking, age, and an interaction between these last two variables (p = 0.039) had statistically significant associations with HPV prevalence. STI prevalence was 11% and was not related to age or geographical origin. CONCLUSIONS: High risk HPV prevalence in migrant FSW is elevated and related to age, area of origin, and use of oral contraceptives in women not using condoms. These data support the role of acquired immunity in the epidemiology of HPV infection and identifies migrant FSW as a priority group for sexual health promotion.

[Imputation of the date of HIV seroconversion in cohorts of haemophiliacs]. / Imputación del instante de seroconversión al VIH en cohortes de hemofílicos.

OBJECTIVES: To describe the methods used to impute HIV seroconversion date in the haemophiliac cohorts from GEMES project and to validate its use. METHOD: 632 haemophiliacs coming from three hemophilia units identified as HIV+ and 1.092 individuals coming from 5 project GEMES cohorts with a seroconversion window (time among test HIV and HIV+) less than 3 years where mid point (PM) was assumed as seroconversion date. For both groups, seroconversion date was imputed after estimating the probability distribution of seroconversion by means of the EM algorithm. Two imputation methods are used: one obtained from the expected value and the other from the geometric mean of 5 random samples. from the estimated distribution. Imputations have been validated in the non haemophiliacs cohorts comparing with the PM seroconversion date. Also AIDS free time and survival from the different seroconversion imputed dates were compared. RESULTS: Median seroconversion date is located in May of 1993 for the non haemophiliacs and in 1982 for the haemophiliacs. Not big differences are observed among the imputed seroconversion dates and the mid-point seroconversion date in the non-haemophiliac cohorts. Similar results are found for the haemophiliac cohorts. Also no differences are observed in the estimated AIDS-free time for both groups of cohorts. CONCLUSIONS: Geometric mean imputation from several random samples provides a good estimate of the HIV seroconversion date that can be used to estimate AIDS-free time and survival in haemophiliac cohorts where seroconversion date is ignored.

Progression of HIV infection and mortality by hepatitis C infection in patients with haemophilia over 20 years.

Hepatitis C virus (HCV) infection is an important cause of mortality in human immune deficiency virus (HIV)-positive haemophiliacs. This study describes progression to AIDS, death from HCV end-stage liver disease (ESLD) and all-cause mortality over 20 years. All HIV-positive haemophiliacs in La Paz University Hospital were included in this cohort. HIV seroconversion was estimated using mathematical techniques for interval-censored data from 1979 to 1985. Poisson regression was used to estimate rates of AIDS, death from ESLD and all causes in different periods: before 1988, 1988-89, 1990-91, 1992-93, 1994-95, 1996-97 and 1998-2001 using competing risk models. Among 383 cohort members, global AIDS incidence was 9.7 per 100 person-years, peaking in 1992-93 and dropping by 87% in 1998-2001 compared with before 1988 [incidence rate ratio (IRR) 0.13; 95% CI: 0.03-0.53]. Overall mortality was 7.5 per 100 person-years, was highest from 1992 to 1997, and fell by 66% in 1998-2001 compared with before 1988 (IRR 0.34; 95% CI: 0.14-0.81). Eighteen (5%) persons died of ESLD which represented 19% of deaths before 1988, 4% during 1988-89, 1990-91 and 1992-93, 2% in 1994-95, 10% in 1996-97 and 33% in 1998-2001. Overall death rate from ESLD was 0.5 cases per 100 person-years with no statistically significant trend observed over time. Important reductions in HIV disease progression to AIDS and death have been observed from 1998 to 2001, and can be attributed to highly active antiretroviral therapy. Although no increase in the rate of HCV-related deaths can be demonstrated, HCV accounts for an increasing proportion of deaths in the recent years.

Factors influencing HIV progression in a seroconverter cohort in Madrid from 1985 to 1999.

OBJECTIVE: To study HIV progression from seroconversion over a 15 year period and measure the population effectiveness of highly active antiretroviral therapy (HAART). METHODS: A cohort study of people with well documented dates of seroconversion. Cumulative risk of AIDS and death were calculated by extended Kaplan-Meier allowing for late entry. Cox proportional hazards models were used to study variables associated with HIV progression. To assess the impact of HAART, calendar time was divided in three periods; before 1992, 1992-6, and 1997-9. RESULTS: From January 1985 to May 2000, 226 seroconverters were identified. The median seroconversion interval was 11 months, median seroconversion date was March 1993. 202 (89%) were men, 76% of whom were homo/bisexual. A 66% reduction in progression to AIDS was observed in 1997-9 compared to 1992-96 (HR 0.34 95% CI: 0.16 to 0.70). People with primary education appeared to have faster progression to AIDS compared to those with university studies (HR 2.69 95%CI: 1.17 to 6.16). An 82% reduction in mortality from HIV seroconversion was observed in 1997-9 (HR 0.18 95% CI: 0.05 to 0.68) compared to 1992-6. Progression to death for people with primary education was twice as fast as for those with university education (p 0.0007). People without confirmation of an HIV negative test had faster progression (HR 4.47 95% CI: 1.18 to 16.92). CONCLUSIONS: The reduction in progression to AIDS and death from seroconversion from 1992-6 to 1997-9 in Madrid is likely to be attributable to HAART. HIV progression was faster in subjects with primary education; better educational level may be associated with better adherence to medication.