J Del Amo

Disease progression and survival in HIV-1-infected Africans in London

Objective:To examine differences in progression to AIDS and death between HIV-1-positive Africans (most infected in sub-Saharan Africa and therefore with non-B subtypes) and HIV-1-positive non-Africans in London. Design:Retrospective cohort study of 2048 HIV-1-positive individuals. Setting:HIV-1-infected individuals attending 11 of the largest HIV/AIDS units in London. Patients:Subjects were 1056 Africans and 992 non-Africans seen between 1982–1995. Results:There were no differences in crude survival from presentation to death between Africans and non-Africans (median 82 and 78 months, respectively; P = 0.22). Africans progressed more rapidly to AIDS [hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.02–1.45] but after adjustment for age, sex, Centers for Disease Control and Prevention category B symptoms and CD4+ lymphocyte count at presentation, year of HIV diagnosis and hospital attended, this difference was no longer significant (adjusted HR, 1.15; 95% CI, 0.93–1.43). Africans with AIDS had a reduced risk of death compared with non-Africans (HR, 0.78; 95% CI, 0.63–0.96) but not after adjustment for age, CD4+ lymphocyte count at AIDS, initial AIDS-defining conditions (ADC) and hospital attended (HR, 0.98; 95% CI, 0.76–1.27). Tuberculosis as the first ADC was associated with a 64% reduction in the risk of death. CD4+ lymphocyte decline was not significantly different between Africans and non-Africans (P = 0.18). Conclusions:Differences in progression to AIDS and death and CD4+ lymphocyte decline between HIV-1-infected Africans and non-Africans in London could not be attributed to ethnicity or different viral subtypes. Age and the clinical and immunological stage at presentation, or AIDS, were the major determinants of outcome. Compared with other diagnoses, tuberculosis as the initial ADC was associated with increased survival. Lack of access to health care and exposure to environmental pathogens are the most likely causes of reduced survival with AIDS in Africa, rather than inherently different rates of progression of immune deficiency due to racial differences or viral subtypes.

Disease progression and survival following specific AIDS-defining conditions: a retrospective cohort study of 2048 HIV-infected persons in London.

Objective: To assess the impact of specific AIDS‐defining conditions on survival in HIV‐infected persons, with emphasis on the effect of tuberculosis. Methods: A retrospective cohort analysis of HIV‐infected Africans and non‐Africans attending 11 specialist HIV/AIDS units in London enrolled for a comparison of the natural history of HIV/AIDS in different ethnic groups. Results: A total of 2048 patients were studied of whom 627 (31%) developed 1306 different AIDS indicator diseases. Pneumocystis carinii pneumonia accounted for 159 (25%) of initial AIDS episodes and tuberculosis for 103 (16%). In patients with HIV disease, tuberculosis had the lowest risk [relative risk (RR), 1.11; 95% confidence interval (CI), 0.75–1.63], and high‐grade lymphoma had the highest risk (RR, 20.56; 95% CI, 2.70–156.54) for death. For patients with a prior AIDS‐defining illness, the development of subsequent AIDS indicator diseases such as Pneumocystis carinii pneumonia (RR, 1.18; 95% CI, 0.77–1.83) and tuberculosis (RR, 1.36; 95% CI, 0.76–2.47) had the best survival, and non‐Hodgkins lymphoma had the worst survival (RR, 9.67; 95% CI, 1.26–74.33). Patients with tuberculosis had a lower incidence of subsequent AIDS‐defining conditions than persons with other initial AIDS diagnoses (rate ratio, 0.47; 95% CI, 0.37–0.59). Conclusions: Considerable variation exists in the relative risk of death following different AIDS‐defining conditions. The development of any subsequent AIDS‐defining condition is associated with an increased risk of death that differs between diseases, and this risk should be considered when evaluating the impact of specific conditions. Like other AIDS‐defining conditions, incident tuberculosis was associated with adverse outcome compared with the absence of an AIDS‐defining event, but we found no evidence of major acceleration of HIV disease attributable to tuberculosis.

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

Risk of cancer in patients with HIV disease

The aim of this study was to compare cancer incidence in a cohort of HIV-infected patients with the incidence rates in the population of South East England. Data collected for a retrospective cohort study of 2048 HIV-infected patients were analysed to examine the incidence of cancer. Cases of cancer occurring in South East England from 1985-1995 were obtained from the Thames Cancer Registry. Standardized incidence ratios were calculated by comparison of the observed number of cases for each cancer type in HIV-infected non-Africans with the numbers expected, calculated from the age and sex specific registration rates for the South East England population using person-years of observation. The crude incidence rates of cancer were calculated for HIV-infected Africans. The incidence of non-AIDS defining cancers such as Hodgkins disease (standardized incidence ratio 22; 95% CI: 3-80) and anal cancer (standardized incidence ratio 125; 95% CI: 3-697) were significantly increased for non-African males with HIV disease. Anal cancer was also significantly increased for non-African females (standardized incidence ratio 1667; 95% CI: 43-9287). Kaposis sarcoma (KS) was the commonest cancer among HIV-infected Africans and males had an incidence which was nearly 3 times that of females. There is evidence to suggest that the risks for other non-AIDS defining cancers were significantly increased in persons with HIV disease which may have implications for HIV/AIDS surveillance.

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.

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

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.

Effect of ignoring the time of HIV seroconversion in estimating changes in survival over calendar time in observational studies: results from CASCADE

ObjectiveTo compare estimates of changes in HIV survival over time derived from seroconverter and prevalent cohorts. Design and methodsUsing pooled data from 19 seroconverter cohorts (CASCADE), the relative risk of death from HIV seroconversion by calendar time at risk from 1 January 1991 was examined. The analyses were repeated, ignoring knowledge of the time of seroconversion, but adjusting for the CD4 cell count at the time the participant came under observation, thus mimicking a prevalent cohort. Estimates from the ‘prevalent’ cohort approach were compared with those obtained from the seroconverter cohort. ResultsOf 5428 subjects at risk on 1 January 1991 or later, 1312 (24.2%) had died. In the analysis based on time from seroconversion, estimates of the effect of calendar year showed marked reductions in mortality in 1997–1999 only, with no evidence of a linear trend over the period 1991–1996 (P-trend = 0.85). Using the prevalent cohort approach a decrease in the relative risk of death was observed from 1991 to 1998–1999, with a statistically significant trend of a decrease in risk from 1991 to 1996 (P-trend = 0.002). Similar findings were observed when the analyses was repeated taking the start date of the cohort as 1 January 1988. ConclusionLack of knowledge of HIV infection duration may lead to biased and exaggerated estimates of survival improvements over time. The adjustment for duration of infection in prevalent HIV cohorts through laboratory markers may compensate inadequately for this.

Calendar Time Trends in the Incidence and Prevalence of Triple-Class Virologic Failure in Antiretroviral Drug-Experienced People With HIV in Europe

Background: Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF over calendar time have not been fully characterised in recent years. Methods: Calendar time trends in the incidence and prevalence of TCVF from 2000 to 2009 were assessed in patients who started ART from January 1, 1998, and were followed within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Results: Of 91,764 patients followed for a median (interquartile range) of 4.1 (2.0–7.1) years, 2722 (3.0%) developed TCVF. The incidence of TCVF increased from 3.9 per 1000 person-years of follow-up [95% confidence interval (CI): 3.7 to 4.1] in 2000 to 8.8 per 1000 person-years of follow-up (95% CI: 8.5 to 9.0) in 2005, but then declined to 5.8 per 1000 person-years of follow-up (95% CI: 5.6 to 6.1) by 2009. The prevalence of TCVF was 0.3% (95% CI: 0.27% to 0.42%) at December 31, 2000, and then increased to 2.4% (95% CI: 2.24% to 2.50%) by the end of 2005. However, since 2005, TCVF prevalence seems to have stabilized and has remained below 3%. Conclusions: The prevalence of TCVF in people who started ART after 1998 has stabilized since around 2005, which most likely results from the decline in incidence of TCVF from this date. The introduction of improved regimens and better overall HIV care is likely to have contributed to these trends. Despite this progress, calendar trends should continue to be monitored in the long term.

AIDS defining conditions in Africans resident in the United Kingdom

A retrospective study of 55 HIV-1 seropositive African patients living in the UK, seen between January 1986 and November 1993, showed a total of 26 (47%) patients with AIDS. Thirty-one (56%) had symptomatic HIV disease at the time of presentation of whom 19 (34.5%) had an AIDS defining condition. Tuberculosis was the most common AIDS defining illness, accounting for 27% of all initial AIDS diagnoses, followed by Pneumocystis carinii pneumonia and oesophageal candidiasis in 19% each and chronic mucocutaneous genital herpes in 15%. The mean CD4 count at the time of the first AIDS defining event was 91 multiply 10/mm3 (range 4-320 10/ mm3). The profile of AIDS defining illnesses was different to published data of homosexual men and injecting drug users in the UK. This has practical implications when considering differential diagnoses and screening as well as prophylaxis for opportunistic infections in this group of patients.

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.