Transmission Category Research Articles

Cancer Burden in the HIV-Infected Population in the United States

Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991-2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004-2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided. The US AIDS population expanded fourfold from 1991 to 2005 (96,179 to 413,080) largely because of an increase in the number of people aged 40 years or older. During 1991-2005, an estimated 79 656 cancers occurred in the AIDS population. From 1991-1995 to 2001-2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34,587 to 10,325 cancers; P(trend) < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10,059 cancers; P(trend) < .001). From 1991-1995 to 2001-2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers. Over a 15-year period (1991-2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies.

Sexual Transmission Risk Behavior of Adolescents With HIV Acquired Perinatally or Through Risky Behaviors

To describe the prevalence and predictors of the transmission-related behaviors of adolescents with HIV acquired perinatally (perinatal) or through risky behaviors (behavioral). HIV-positive adolescents (n = 166) aged 13-21, receiving care in 3 US cities, reported sexual behaviors, drug use, and psychosocial and demographic characteristics. HIV-related data were abstracted from medical records. Of 105 sexually experienced adolescents reporting risk history (42 perinatal, 63 behavioral), 49 had engaged in unprotected sex since learning their diagnosis (12 perinatal, 37 behavioral). Of sexually experienced girls, 19 had been pregnant (5 of 24 perinatal, 14 of 31 behavioral). Risk information was provided for 115 of 132 recent sex partners, 61 of whom had unprotected sex with study participants (10 with 8 perinatal participants; 51 with 33 behavioral participants). Recent unprotected sex was associated with sexual abuse during adolescence (adjusted odds ratio = 9.61, 95% CI: 1.07 to 86.12) and greater HIV knowledge (adjusted odds ratio = 1.29, 95% CI: 1.00 to 1.66) when transmission category, age, and sexual orientation were controlled. To limit HIV transmission and prevent unplanned pregnancies, developmentally appropriate risk-reduction interventions, and screening and treatment referral for sexual abuse, must be integrated into the care of both perinatally and behaviorally HIV-infected adolescents.

The age patterns of severe malaria syndromes in sub-Saharan Africa across a range of transmission intensities and seasonality settings

BackgroundA greater understanding of the relationship between transmission intensity, seasonality and the age-pattern of malaria is needed to guide appropriate targeting of malaria interventions in different epidemiological settings.MethodsA systematic literature review identified studies which reported the age of paediatric hospital admissions with cerebral malaria (CM), severe malarial anaemia (SMA), or respiratory distress (RD). Study sites were categorized into a 3 × 2 matrix of Plasmodium falciparum transmission intensity and seasonality. Probability distributions were fitted by maximum likelihood methods, and best fitting models were used to estimate median ages and to represent graphically the age-pattern of each outcome for each transmission category in the matrix.ResultsA shift in the burden of CM towards younger age groups was seen with increasing intensity of transmission, but this was not the case for SMA or RD. Sites with 'no marked seasonality' showed more evidence of skewed age-patterns compared to areas of 'marked seasonality' for all three severe malaria syndromes.ConclusionsAlthough the peak age of CM will increase as transmission intensity decreases in Africa, more than 75% of all paediatric hospital admissions of severe malaria are likely to remain in under five year olds in most epidemiological settings.

Poverty, Hunger, Education, and Residential Status Impact Survival in HIV

Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.

Late presenters to HIV care and treatment, identification of associated risk factors in HIV-1 infected Indian population

BackgroundTimely access to antiretroviral therapy is a key to controlling HIV infection. Late diagnosis and presentation to care diminish the benefits of antiretrovirals and increase risk of transmission. We aimed to identify late presenters in patients sent for first CD4 T cell count after HIV diagnosis, for therapy initiation evaluation. Further we aimed at identifying patient factors associated with higher risk of late presentation.MethodsRetrospective data collection and analysis was done for 3680 subjects visiting the laboratory for CD4 T cell counts between 2001 and 2007. We segregated the patients on basis of their CD4 T cell counts after first HIV diagnosis. Factors associated with risk of late presentation to CD4 T cell counts after HIV diagnosis were identified using univariate analysis, and the strength of association of individual factor was assessed by calculation of odds ratios.ResultsOf 3680 subjects, 2936 (83.37%) were defined as late presenters. Late testing varied among age groups, transmission categories, and gender. Males were twice as likely to present late as compared to females. We found significant positive association of heterosexual transmission route (p < 0.001), and older age groups of 45 years and above (p = 0.0004) to late presentation. Female sex, children below 14 years of age and sexual contact with HIV positive spouse were associated with significantly lower risks to presenting late. Intravenous drug users were also associated with lower risks of late presentation, in comparison to heterosexual transmission route.ConclusionsThe study identifies HIV infected population groups at a higher risk of late presentation to care and treatment. The risk factors identified to be associated with late presentation should be utilised in formulating targeted public health interventions in order to improve early HIV diagnosis.

Determinants of Smoking Cessation Attempts Among HIV-Infected Patients: Results from a Hospital-Based Prospective Cohort

Non-acquired immune-deficiency syndrome (AIDS) defining malignancies (especially lung cancer) and bacterial infections as well as cardiovascular diseases now account for almost one third of deaths and morbid events in treated patients infected by the Human Immunodeficiency Virus (HIV). Tobacco smoking is a major modifiable risk factor of these emergent conditions and almost half of these patients are regular smokers in resource-rich countries. To estimate the effect of HIV infection characteristics on smoking cessation attempts among HIV-infected smokers. All smokers of the ANRS CO3 Aquitaine Cohort with at least two visits between 2000 and 2005 were included in this analysis. The probability of smoking cessation attempts was estimated using survival analyses for recurrent events (frailty model). Covariates were CD4 cell count, gender, age, HIV transmission categories, duration since HIV-diagnosis, AIDS stage, antiretroviral therapy, and cardiovascular history. Among 2223 smokers, 743 attempted to quit smoking at least once. The incidence of smoking cessation attempt was lower among patients infected through injection drug use (IDU) and was higher among patients aged 50 or older (HR=1.4), those with a known duration of HIV infection >15 years (HR=1.5), and those who had already tried to quit smoking once (HR=4.2) or more (HR=5.8). Traditional characteristics associated with smoking cessation attempts are the most important to explain smoking cessation attempts in HIV-infected patients. These results indicate that strategies successfully implemented in other populations should be reinforced to fit the needs of HIV-infected patients.

Bacterial Pneumonia among HIV-Infected Patients: Decreased Risk After Tobacco Smoking Cessation. ANRS CO3 Aquitaine Cohort, 2000–2007

BackgroundBacterial pneumonia is still a substantial cause of morbidity and mortality in HIV-infected patients in the era of combination Antiretroviral Therapy. The benefit of tobacco withdrawal on the risk of bacterial pneumonia has not been quantified in such populations, exposed to other important risk factors such as HIV-related immunodeficiency. Our objective was to estimate the effect of tobacco smoking withdrawal on the risk of bacterial pneumonia among HIV-infected individuals.Methodology/Principal FindingsPatients of the ANRS CO3 Aquitaine Cohort with ≥ two visits during 2000–2007 and without bacterial pneumonia at the first visit were included. Former smokers were patients who stopped smoking since ≥ one year. We used Cox proportional hazards models adjusted on CD4+ lymphocytes (CD4), gender, age, HIV transmission category, antiretroviral therapy, cotrimoxazole prophylaxis, statin treatment, viral load and previous AIDS diagnosis. 135 cases of bacterial pneumonia were reported in 3336 patients, yielding an incidence of 12 ‰ patient-years. The adjusted hazard of bacterial pneumonia was lower in former smokers (Hazard Ratio (HR): 0.48; P = 0.02) and never smokers (HR: 0.50; P = 0.01) compared to current smokers. It was higher in patients with <200 CD4 cells/µL and in those with 200 to 349 CD4 cells/µL (HR: 2.98 and 1.98, respectively; both P<0.01), but not in those with 350 to 499 CD4 cells/µL (HR: 0.93; P = 0.79), compared to those with ≥500 CD4 cells/µL. The interaction between CD4 cell count and tobacco smoking status was not statistically significant.Conclusions/SignificanceSmoking cessation dramatically reduces the risk of bacterial pneumonia, whatever the level of immunodeficiency. Smoking cessation interventions should become a key element of the clinical management of HIV-infected individuals.

“MSM” Encompasses Several Distinct Populations

The HIV transmission category “MSM” (men who have sex with men) now accounts for about half of reported incident HIV infections and two thirds of prevalent infections in the U.S. Research indicates, however, that this risk group actually includes several distinct populations who carry very different HIV risks. A total of 4319 U.S. men, ages 18 to 59, were interviewed about sexual behavior and tested …

Development of an HIV Clinical Cohort Database for Enhancing Epidemiologic Surveillance in Hong Kong

The Hong Kong HIV Cohort Database is an observational cohort including all patients enrolled in 2 HIV specialist clinical services in Hong Kong. Basic demographics, HIV transmission category, and the diagnoses of AIDS were captured using a standardized template. As of December 2006, 2132 HIV cases had been registered in the database, representing two thirds of all reports submitted to the government's surveillance system. Non-Chinese and young females≤24 years were less represented in the cohort. Description of cohort cases was, however, more complete in terms of transmission category and presentation with AIDS-defining illnesses. Overall, Pneumocystis jirovecci, tuberculosis, and systemic mycosis accounted for a majority of AIDS cases within 3 months of HIV diagnosis. There was a gradual rise of HIV positive men having sex with men in the cohort, notably after 2002, an observation also made in other Asian countries.

Access to Regular HIV Care and Disease Progression among Black African Immigrants

To describe the characteristics of human immunodeficiency virus (HIV)-infected black African immigrants living in King County, Washington, we evaluated delay in HIV diagnosis, access to HIV care, and risk of progression to AIDS or death. We compared differences in the risk of progression to AIDS or death between HIV-positive African-born black individuals and 2 groups of HIV-positive US-born individuals. There were significant differences across the groups in residence at time of HIV diagnosis, gender, HIV transmission category, and initial CD4 count. Black Africans were more likely to present with an AIDS diagnosis (45%), compared to both US-born nonblacks (25%) and US-born blacks (35%). No significant independent associations were observed in rates of HIV disease progression when black African immigrants were compared to their US-born counterparts. Once having initiated HIV care, African-born blacks accessed HIV care and progressed to AIDS at similar rates compared to US-born individuals. However, African-born blacks initiated care with more advanced HIV disease. Results underscore the need for health interventions promoting HIV testing among black African immigrants and reducing barriers to HIV testing.

Association of HIV transmission categories with sociodemographic, viroimmunological and clinical parameters of HIV-infected patients

To analyse sociodemographic, viroimmunological and clinical parameters in different HIV-transmission categories at baseline and during treatment, 3039 patients were followed up for 12 months after the initiation of a nelfinavir-based regimen. Multiple baseline parameters were significantly different in the diverse categories, including CD4 counts (P<0.0001) and viral load (P=0.02). There were differences in the groups regarding the CD4 response (P=0.01), but not the virological response (P=0.4), to therapy over time. Multivariate analyses revealed that transmission categories were significantly related to baseline CD4 counts (P=0.01), viral load at 12 months (P=0.0006), poorer adherence to therapy of injecting drug users (IDUs) vs. each of the other groups (P<0.001) and failure to complete the 12-month evaluation of IDU vs. heterosexual (P=0.003) and men who have sex with men (MSM) groups (P=0.02). We conclude that transmission categories had a significant influence on several baseline parameters and viroimmunological outcomes following highly active antiretroviral therapy (HAART), as well as on adherence to therapy and to medical appointments.

Impact of Highly Active Antiretroviral Therapy (HAART) on AIDS and Death in a Cohort of Vertically HIV Type 1-Infected Children: 1980–2006

We evaluated the population effectiveness of highly active antiretroviral therapy (HAART) on the risk of AIDS and death in a multicenter cohort of 346 HIV-1 vertically infected children born between 1980 and 2006 in the Comunidad Autónoma de Madrid (CAM), Spain. Risks of AIDS and death in patients with the same duration of HIV infection were compared in different calendar periods [CP1: 1980-1989, CP2: 1990-1993 (reference), CP3: 1994-1996, CP4: 1997-1998, CP5: 1999-2006] through cumulative incidence curves and Cox proportional hazards models, allowing for late entry, that included the calendar period as the time-dependent covariate and adjusting for gender and mother's transmission category. The median follow-up was 11.8 years [interquartile range (IQR), 6.3-15.9]. Median CD4+ T cell percentage increased up to 26.5 in CP5 (IQR, 19.5-36.7) while the viral load decreased (median log(10) copies/ml in CP5, 3.66; IQR, 3.07-4.22). Multivariate analysis showed significant reduction in the risk of death since 1997 onward [CP4: adjusted hazard ratios (AHR), 0.29; 95% confidence interval (CI), 0.12-0.69; CP5: AHR, 0.06; 95% CI, 0.03-0.15]. Reduction in progression to AIDS reached borderline significance in CP4 (AHR, 0.49; 95% CI, 0.23-1.05) and was more marked in the last period (CP5: AHR, 0.30; 95% CI, 0.16-0.59). The reductions in the incidence of AIDS and death observed since 1996 were largely attributable to HAART.

Primary and secondary cases in Escherichia coliO157 outbreaks: a statistical analysis

BackgroundWithin outbreaks of Escherichia coli O157 (E. coli O157), at least 10–15% of cases are thought to have been acquired by secondary transmission. However, there has been little systematic quantification or characterisation of secondary outbreak cases worldwide. The aim of this study was to characterise secondary outbreak cases, estimate the overall proportion of outbreak cases that were the result of secondary transmission and to analyse the relationships between primary and secondary outbreak cases by mode of transmission, country and median age.MethodsPublished data was obtained from 90 confirmed Escherichia coli O157 outbreaks in Great Britain, Ireland, Scandinavia, Canada, the United States and Japan, and the outbreaks were described in terms of modes of primary and secondary transmission, country, case numbers and median case age. Outbreaks were tested for statistically significant differences in the number of ill, confirmed, primary and secondary cases (analysis of variance and Kruskal-Wallis) and in the rate of secondary cases between these variables (Generalised Linear Models).ResultsThe outbreaks had a median of 13.5 confirmed cases, and mean proportion of 0.195 secondary cases. There were statistically significant differences in the numbers of ill, confirmed, primary and secondary cases between modes of primary transmission (p < 0.021), and in primary and secondary cases between median age categories (p < 0.039) and modes of secondary transmission (p < 0.001).Secondary case rates differed statistically significantly between modes of secondary and primary transmission and median age categories (all p < 0.001), but not between countries (p = 0.23). Statistically significantly higher rates of secondary transmission were found in outbreaks with a median age <6 years and those with secondary transmission via person to person spread in nurseries. No statistically significant interactions were found between country, mode of transmission and age category.ConclusionOur analyses indicated that ~20% of E. coli O157 outbreak cases were the result of secondary spread, and that this spread is significantly influenced by age and modes of primary and secondary transmission, but not country. In particular, the results provide further data emphasising the importance of simple but effective preventive strategies, such as handwashing, that can reduce the risk of secondary spread, particularly amongst young children in nurseries.

Sexually acquired HIV infections in the United States due to acute-phase HIV transmission: an update

Identification of acute human immunodeficiency virus (HIV) infection, the stage of disease during the first few months of infection in which HIV viral replication and shedding peak before HIV antibodies are detectable [1], is of public health importance because acutely infected persons are likely to be unaware of their status and more infectious and may continue to engage in high-risk behavior that furthers HIV transmission. Pinkerton [2] used a simple mathematical model to estimate the number and proportion of sexually acquired HIV infections in the United States that are due to acute-phase transmission and found that an estimated 2760 persons acquired HIV as a consequence of risky sexual activities with an acutely infected sex partner. This accounted for 8.6% of the approximately 32 000 (then estimated) sexually acquired HIV infections each year. Since Pinkerton's estimates were published, the Centers for Disease Control and Prevention (CDC) reported annual HIV incidence estimates in the United States that are about 40% higher than previously estimated, increasing from 40 000 to 56 300 [3]. CDC also updated estimates for prevalence [4] and the proportion of undiagnosed HIV infections [5]. These changes in HIV surveillance data create a need for updated transmission estimates. We used Pinkerton's [2] framework and updated the model to reflect recently published HIV surveillance data. We used the latest prevalence estimates for persons living with HIV/AIDS (PLWH) [4], undiagnosed PLWH [5], and HIV incidence estimates [3]. We assumed that other parameters remained the same (Table 1).Table 1: Comparison with Pinkerton's estimates.The proportion of incident infections due to sexual transmission from a HIV-positive partner in an acute-HIV infection phase (Ia) remains (from [2]) where μ12 is the transmission rate ratio for acutely infected vs. nonacutely infected serostatus-unaware PLWH. μ23 is the transmission rate ratio for the nonacutely infected serostatus-unaware vs. serostatus-aware PLWH. N1 is the number of acutely infected PLWH available on a particular day. N2 is the number of nonacutely infected serostatus-unaware PLWH. N3 is the number of nonacutely infected serostatus-aware PLWH. In addition to the 45 500 new infections transmitted sexually [3], we assumed that some of the incident infections reported under men who have sex with men (MSM)/injection drug users (IDU) transmission category were caused sexually. The sexual and IDU transmissions in the MSM/IDU group were assumed to be in the same proportion as the ratio of incidence of MSM-only and IDU-only transmission groups (28 700: 6600 = 4.34: 1). Based on this ratio, about 1700 of the 2100 new MSM/IDU infections each year can be considered as sexually transmitted. We estimate that about 5371 persons each year acquired HIV as a consequence of risky sexual activities with an acutely infected sex partner in the United States. This accounts for about 11.4% of the total annual incident sexual infections compared with 8.6% as estimated by Pinkerton. PLWH unaware of their infections are estimated to be the sources for about 53.2% of the new infections. The overall transmission rate per PLWH is estimated at 0.012% per day (0.009% per day estimated by Pinkerton). The transmission rate per PLWH in the acute phase is also higher at 0.195% per day (0.141% per day estimated by Pinkerton). Applying the latest incidence data and assigning a proportion of the MSM/IDU transmission category to the number of incident cases due to sexual transmission resulted in an increase in the proportion of sexual transmissions due to acute phase transmission in the United States over what Pinkerton previously estimated. As the increase in incidence (40%) was larger than that in prevalence (10%), daily and annual transmission rates for all PLWH categories, including acutely infected PLWH, increased as they were computed as a ratio of incident infections. Our findings are consistent with Pinkerton's in that the proportion of sexually acquired infections in the United States due to acute-phase transmission is much smaller than has been suggested [9,10]. Our updated analysis is also useful, as it provides updated annual and daily transmission rates for acutely and nonacutely infected PLWH. Additional research on the risk behavior of persons with acute HIV infection in the United States, particularly their risk behavior after notification of their HIV status, is needed to further refine these estimates. Our analysis is subject to the same limitations as Pinkerton's analysis, particularly uncertainty in key parameters used to derive the acute phase transmission rate ratio [6–8]; however, our analysis does use updated, and likely more reliable, incidence data than were used in the Pinkerton analysis. In addition, our analysis does not include sensitivity analysis. Acknowledgements V.S.P., A.B.H., P.G.F., and S.L.S. contributed equally to the conception and design of the paper. V.S.P. conducted the analysis and wrote the first draft. A.B., P.G.F., and S.L.S. helped revise the draft. All the authors were involved in the final approval of the manuscript.

Effectiveness of antiretroviral regimens containing abacavir with tenofovir in treatment-experienced patients: Predictors of virological response and drug resistance evolution in a multi-cohort study

In treatment-naïve patients, a combination antiretroviral therapy (cART) containing tenofovir (TDF) and abacavir (ABC) with lamivudine leads to unacceptably high virological failure rates with frequent selection of reverse transcriptase mutations M184V and K65R. We explored the efficacy of at least 16 weeks of ABC + TDF-containing cART regimens in 307 antiretroviral-experienced HIV-1-infected individuals included in observational databases. Virological failure was defined as an HIV RNA > 400 copies/ml after at least 16 weeks of treatment. Patients had received a median of three prior cART regimens. Of these, 76% concomitantly received a potent or high genetic barrier regimen (with at least one protease inhibitor [PI]) or non-nucleoside reverse transcriptase inhibitor or thymidine analogue) while a third non-thymidine nucleoside analogue was used in the remaining patients. The 1-year estimated probability of virological failure was 34% in 165 patients with HIV RNA > 400 copies/ ml at ABC + TDF regimen initiation. Independent predictors of virological failure were the absence of a potent or high genetic barrier cART, the higher number of cART regimens experienced, and the use of a new drug class. In the subset of 136 patients for whom there were genotypic resistance test results prior to ABC + TDF initiation, the virological failure (1-year estimated probability 46%) was independently predicted by the higher baseline viral load, the concomitant use of boosted PI, and the presence of reverse transcriptase mutation M41L. In 142 patients starting ABC + TDF therapy with HIV RNA pound < or =400 copies/ml, virological failure (1-year estimated probability 17%) was associated only with the transmission category. In a small subset of subjects for whom there were an available paired baseline and follow-up genotype (n = 28), the prevalence of most nucleoside analogue reverse transcriptase inhibitor resistance mutations decreased, suggesting a possible low adherence to treatment. No selection of K65R was detected. The virological response to ABC + TDF-containing regimens in this moderately-to-heavily treatment experienced cohort was good. Higher viral load and the presence of M41L at baseline were associated with worse virological responses, while the concomitant prescription of drugs enhancing the genetic barrier of the regimen conveyed a reduced risk of virological failure. The Appendix provides the names of other members of the MASTER cohort.

Experience of Pain among Women with Advanced HIV Disease

We evaluated pain frequency and severity in 339 women enrolled in the Women's Interagency HIV Study (WIHS). Among these, 63% were 39 years of age or younger, 17% were white, 54% African American, and 29% Hispanic; 32% did not complete high school; 58% had a CD4 less than 200; 65% had clinical AIDS; 60% were on highly active antiretroviral therapy (HAART); and 32% had a viral load of 50,000 or more. Data were collected between 1996 and 1998. Within the past 6 months 190 (56%) women experienced pain 6 or more days and 168 (50%) women indicated pain severity scores of 4 or 5 (5-point scale). Pain frequency and pain severity were not associated with age, education, ethnicity, current therapy, or location of the WIHS site. Pain frequency and severity were related to lower CD4 count, higher depression, with a history and longer duration of smoking and use of marijuana. Severity was associated with a history of crack/cocaine or heroin use or with injection drug use as the transmission category. In the multivariate models, pain severity was related to CD4 count and depression and to current tobacco use but not to crack, cocaine, heroin, or marijuana use. Pain frequency was related to depression and to former tobacco, crack, cocaine, heroin, or marijuana use but not to current use. The long-term effects of tobacco use may be to increase pain experience but women may also smoke tobacco or use other substances to give mild pain relief. Pain is frequent and often severe among women with HIV requiring medical management.

CD4 Responses in the Setting or Suboptimal Virological Responses to Antiretroviral Therapy: Features, Outcomes, and Associated Factors

The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.

Risk of death among Italian AIDS cases with AIDS-defining cancers in the post-HAART era

This study intended to quantify the impact of AIDS-defining cancers on the risk of death in the post-HAART era. With this aim in mind, data regarding all Italian AIDS cases reported to the National AIDS Registry were analyzed. Between 1999 and 2005, a total of 12,433 individuals were diagnosed with AIDS in Italy. Specifically excluded from this analysis were people with AIDS who were: 1) not-Italian citizen (n = 1918); 2) resident in Italian areas where individual information on death was not available (n = 108); 3) resident in unknown areas (n = 119); 4) pediatric or vertical transmission cases (n = 50); 5) diagnosed solely at autopsy (n = 576). The presence of AIDS-defining cancers (i.e., Kaposi's sarcoma-KS, non-Hodgkin lymphoma-NHL, and invasive cervical cancer-ICC) at AIDS diagnosis is routinely ascertained at the National AIDS Registry, together with some other information, including age, sex, date of AIDS diagnosis, HIV transmission category, CD4+ cells count. Information on vital status of AIDS cases, as of December 2006, was assessed through a semi-automated linkage procedure, ensuring confidentiality of individual data, with the national death certificates database. Survival function was estimated by the Kaplan-Meier method; Cox regression model was used to estimate death hazard ratios (HR), and corresponding 95% confidence intervals (CI), associated to the presence of AIDS-defining cancers at diagnosis, adjusted for age at AIDS diagnosis, sex, HIV transmission category, and CD4+ cells count at diagnosis. Of the 9,662 AIDS cases included in the present study, 478 had KS, 429 immunoblastic NHL, 158 Burkitt's lymphoma, 69 ICC, and 58 NHL of the central nervous system (CNS). As of December 2006, 3,096 deaths were registered: of these deaths, 505 occurred among cases with AIDS-defining cancers. The proportion of AIDS cases still alive 5 years after AIDS diagnosis was 66.6 percent. The shortest survival period was seen among individuals diagnosed with CNS NHL (median survival = 4 months), followed by those with immunoblastic NHL or Burkitt's lymphoma (median survival = 16 and 38 months, respectively), whereas the longest ones were recorded among cases with ICC or KS (median not reached). In comparison with AIDS cases without AIDS-defining cancers, those with a CNS NHL had a 4.7-fold higher risk of death (95% CI: 3.5–6.4), those with immunoblastic NHL or Burkitt's lymphoma had more than twice the risk (HR = 2.6, 95% CI: 2.2–2.9; and HR = 2.3, 95% CI: 1.8–2.8, respectively), and, among women, those with ICC had a 1.8-fold elevated risk (95% CI: 1.2–2.7). Conversely, among individuals with KS (HR = 0.7, 95% CI: 0.6–0.9) the risk of death was lower than that of cases without AIDS-defining cancers. In conclusion, this exhaustive survival analysis of Italian AIDS cases in the post-HAART era highlighted the persisting lethality of NHL and the long survival of cases with KS and ICC.

Infección por virus de la inmunodeficiencia humana en inmigrantes en España: características epidemiológicas y presentación clínica en la cohorte CoRIS, 2004–2006

A growing number of immigrants are using the public health services for HIV in Spain. We describe the sociodemographic, epidemiological, and clinical characteristics of a cohort of naïve HIV-infected subjects (CoRIS cohort) according to their place of origin. CoRIS is an open, hospital-based cohort of naïve, HIV-infected persons attended in 19 hospitals from 9 of the 19 autonomous regions in Spain. We describe the characteristics of the cohort members by place of origin, and compare them with the Spanish cases identified from January 2004 to October 2006, using the chi-square and Fisher exact tests. Of 2507 patients, 76.3% were men and median age was 36 years. By origin, 71.5% were Spanish, 16.0% Latin Americans (LA), 5.8% sub-Saharan Africans (SSA), 3.7% Western Europeans (WE), 1.7% Eastern Europeans (EE) and 1.4% North Africans (NA). Compared to Spaniards, there were significant differences by origin in sex, age, and transmission category. Median CD4 count at cohort entry was 352 cell/microL, with no differences according to origin. Median viral load was 48 962 copies/mL and was significantly lower for SSA. Over 11.4 months of follow-up, 57.9% initiated HAART with no differences by origin. Hepatitis C prevalence was 29.9% in Spaniards, 7.3% in Latin Americans, 11.7% in SSA, and 45.7% in EE (P<0.05). Overall, 13.4% were Mantoux-positive (28.6% in SSA and 30.8% in NA). Tuberculosis was more common among cases from EE (9.5%) and SSA (8.3%) compared to Spaniards (4.8%) (P<0.05). Almost one third of naïve HIV-infected patients in CoRIS are foreign-born. Their sociodemographic, epidemiological and clinical characteristics reflect the epidemic in their places of origin. However, their immunological status at cohort entry and initiation of HAART is no different from that of Spaniards.

The influence of the patients’ educational levels on socioeconomic, clinical, immunological and virological endpoints

To analyse the influence of educational levels on diverse baseline and follow-up characteristics and outcomes of HIV-infected patients, we sequentially evaluated 1352 individuals with known educational levels, who initiated a nelfinavir-based regimen. Higher educational degrees were associated with better baseline clinical (P=0.03) and immunological (P=0.003) conditions, not related to transmission categories, which were also observed during follow-up (P=0.003). However, these differences were only found in antiretroviral-experienced patients (P=0.002), while naïve patients had very similar values (P=0.8). Overall, there were different CD4 responses (P=0.06), but not viral load responses (P=0.6), to antiretroviral therapy according to the educational level, but these differences were more marked in the last six months of follow-up (P=0.008). Patients with higher educational degrees had higher rates of adherence to medical appointments both before (P=0.0003) and during the study period (P=0.01), as well as to antiretroviral therapy in univariate (P=0.003) and multivariate analyses (P=0.007). Similarly, baseline CD4 counts proved to be independently associated with education after adjustment for other variables (P=0.0006). The educational groups also differed in diverse socioeconomic parameters and certain beliefs about HIV infection (P<0.0001 for each). We conclude that the patient's educational level influences clinical and immunological outcomes of HIV infection. This impact is probably mediated through differences in the long-term effects of treatment, as a result of adherence to antiretroviral therapy and to medical indications. The evaluation of social aspects such as the patient's education should be incorporated into routine clinical practice to improve the results of treatment.