Cohort Of HIV-infected Individuals Research Articles

Tuberculosis skin test, but not interferon-γ-releasing assays is affected by BCG vaccination in HIV patients

Of this study was to compare the results of tuberculin skin test (TST) with two interferon-γ releasing-assays (IGRA) in a cohort of HIV positive patients, to analyze impact of prior Bacille-Calmette-Guérin (BCG)-vaccination. Prospective cross sectional study, enrolling only asymptomatic adult HIV infected outpatients from a large German University hospital clinic. All participants were simultaneously tested for latent tuberculosis infection (LTBI) by QuantiFERON-TB Gold, T-SPOT.TB and TST. Only individuals with available definite results (positive/negative, indeterminates excluded) from all three test systems and recalling BCG-vaccination status by interview questionnaire were evaluated. From 286 study participants, 133 were evaluable; BCG-vaccination history was positive for 18 individuals, and negative for 115. The proportion of individuals with a positive TST was significantly higher for vaccinated (n=6, 33.3%) than for unvaccinated individuals (n=13, 11.3%, p=0.013). There were no significant differences in the proportion of patients with CDC stage C, origin from a TB endemic country or in the CD4 count between the two groups. TST but not IGRAs interfered significantly with prior BCG vaccination in a cohort of HIV infected individuals from a low prevalence TB country. Therefore IGRA should preferentially be used for LTBI-testing in BCG-vaccinated adult HIV-patients.

Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected individuals: a nested case-control study

BackgroundThe delay in initiating treatment for tuberculosis (TB) in HIV-infected individuals may lead to the development of a more severe form of the disease, with higher rates of morbidity, mortality and transmissibility. The aim of the present study was to estimate the time interval between the onset of symptoms and initiating treatment for TB in HIV-infected individuals, and to identify the factors associated to this delay.MethodsA nested case-control study was undertaken within a cohort of HIV-infected individuals, attended at two HIV referral centers, in the state of Pernambuco, Brazil. Delay in initiating treatment for TB was defined as the period of time, in days, which was greater than the median value between the onset of cough and initiating treatment for TB. The study analyzed biological, clinical, socioeconomic, and lifestyle factors as well as those related to HIV and TB infection, potentially associated to delay. The odds ratios were estimated with the respective confidence intervals and p-values.ResultsFrom a cohort of 2365 HIV-infected adults, 274 presented pulmonary TB and of these, 242 participated in the study. Patients were already attending 2 health services at the time they developed a cough (period range: 1 – 552 days), with a median value of 41 days. Factors associated to delay were: systemic symptoms asthenia, chest pain, use of illicit drugs and sputum smear-negative.ConclusionThe present study indirectly showed the difficulty of diagnosing TB in HIV-infected individuals and indicated the need for a better assessment of asthenia and chest pain as factors that may be present in co-infected patients. It is also necessary to discuss the role played by negative sputum smear results in diagnosing TB/HIV co-infection as well as the need to assess the best approach for drug users with TB/HIV.

Drug Resistance Pathways and Impact of Protease Mutation L10I/V in HIV-1 Non-B Subtypes

Background: Molecular pathways to drug resistance have yet to be fully characterized in HIV-1 non-B subtypes. Furthermore, polymorphisms such as protease L10I/V are ubiquitous in non-B subtypes, but their biological implications are still unknown. We evaluated resistance pathways emerging at treatment failure in a cohort of HIV infected individuals in Mali, and characterized in vitro the role of L10I/V. Methods: Genotypic resistance testing was performed on plasma obtained from 132 HIV-infected individuals from Mali before and after 9 months of treatment using population sequencing. CRF02_AG chimeric viruses containing 10I/V mutants CRF02_AG were constructed using site directed mutagenesis and susceptibility to protease inhibitors (PI) as well as replicative capacity were determined in a PBMC culture assay. Results: At treatment initiation, 11/132 (8.3%; 95% CI 3.6-13.0%) patients harboured resistance mutations to NRTI (D67N, T69N, L210W, K219E and T215A) or NNRTI (K103N, V108I and V179E). Among these 11 patients, 5 with NNRTI mutations were in virological failure after 9 months of treatment. Six others with one Thymidine Analog Mutations (TAM) did not show complete resistance. Overall, 18/132 (14.0%; 95% CI 8.1-19.9%) patients failed at 9 months and resistance mutations to NRTI or NNRTI could be identified in 8 (6.10%; 95% CI 2.0-10.2%). NRTI mutation M184V was the most commonly observed, followed by NNRTI mutations Y181C and K103N. Polymorphisms in protease such as L10I/V were observed frequently. Their role was evaluated in vitro. CRF02_AGwt_10L showed a slight increase in IC50 for darunavir, lopinavir and nelfinavir compared to subtype BHXB2_10L with 1.2, 1.3 and 1.5 Fold-Changes (FC) respectively. Mutant’s viruses CRF02_AGL10I and CRF02_AGL10V showed a slight increase in IC50 for indinavir with 1.30 and 1.20 FC and a slight decrease in IC50 for lopinavir with 0.78 FC and 0.75 FC respectively compared to CRF02_AGwt_10L. We did not observe any difference in replicative capacity between CRF02_AGwt_10L and HXB2. However, compared to CRF02_AGwt_10L, mutants, viruses CRF02_AGL10I, and CRF02_AGL10V showed a significant reduction in replication capacity by 10% (p<0.03) and 12% (p<0.02) respectively. Conclusion: Primary resistance to NRTI and NNRTI impacts response to treatment. The presence of a single TAM mutation may have limited impact on first line treatment in CRF02_AG. A common polymorphism in non-B subtypes, L10V, may affect susceptibility of certain PIs. In the context of large-scale use of antiretroviral, monitoring the emergence of resistance in non-B subtypes is important to preserve treatment options.

Demographic Characteristics and Behavioral Risk Factors of HIV Infection and Association with Survival Among Individuals 50 Years or Older

To investigate the association of socio-behavioral characteristics and viro-immunological status with survival in a cohort of HIV-infected individuals by age in South Carolina (SC). Logistic regression was used to compare the characteristics of individuals' ≥50 years old to individuals 20-49 years old at HIV diagnosis who were reported to SC enhanced HIV/AIDS Reporting System (eHARS) from January 1998 to December 2009. Cox proportional hazards analysis was used to examine the time to death after HIV diagnosis over the study period. Of the 7531 participants, 1204 (16%) were ≥50 years old. Multivariable analyses suggested that individuals ≥50 years old were more likely to have simultaneous AIDS (aOR 1.80, 95% CI 1.54-2.10). For individuals ≥50 years old, the risk of death was more than three times when compared to the younger age group (HR: 3.46, 95% CI 2.27, 5.30). Routine HIV screening may decrease late-stage diagnosis and improved linkage to care may decrease mortality in older adults.

Increasing HIV infection among adults aged 50 years and over: a call for heightened awareness

The number of adults aged 50 years and over living with diagnosed HIV is on the increase. This increase is not only due to an aging cohort of HIV-infected individuals experiencing better survival rates as a result of effective antiretroviral therapy, but also as a result of greater numbers of diagnoses among this group, many of whom were infected when aged 50 years and older. Describing the unique challenges HIV presents to both older adults living with HIV and relevant health professionals, we raise the profile of HIV among persons aged 50 years and over, and highlight the importance for age-specific research activities in promoting earlier testing and treatment.

High prevalence of food insecurity among HIV-infected individuals receiving HAART in a resource-rich setting

This study aimed to assess the prevalence and correlates of food insecurity in a cohort of HIV-infected individuals on highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada. Adults receiving HAART voluntarily enrolled into the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) cohort. Individual food insecurity was measured using a modified version of the Radimer/Cornell Questionnaire. We performed bivariate analyses to determine differences between explanatory variables for individuals who were food secure and food insecure. We performed logistic regression to determine independent predictors of food insecurity. Of the 457 individuals enrolled in the LISA cohort, 324 (71.0%) were found to be food insecure. Multivariate analysis indicated that individuals who had an annual incomes less than $15,000 (odds ratio [OR] 3.15, 95% confidence interval [CI] 1.83, 5.44), used illicit drugs (OR 1.85, 95% CI 1.03, 3.33), smoked tobacco (OR 2.30, 95% CI 1.30, 4.07), had depressive symptoms (OR 2.34, 95% CI 1.38, 3.96), and were younger (OR 0.95, 95% CI, 0.92, 0.98) were more likely to be food insecure. Our results demonstrated a high (71%) prevalence of food insecurity among HIV-infected individuals receiving HAART in this resource-rich setting, and that food insecurity is associated with a compendium of environmental and behavioral factors. More research is needed to understand the biological and social pathways linking food insecurity to these variables in order to identify program strategies that can effectively improve food security among HIV-infected populations.

Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals

Chemokines influence HIV neuropathogenesis by affecting the HIV life cycle, trafficking of macrophages into the nervous system, glial activation, and neuronal signaling and repair processes; however, knowledge of their relationship to in vivo measures of cerebral injury is limited. The primary objective of this study was to determine the relationship between a panel of chemokines in cerebrospinal fluid (CSF) and cerebral metabolites measured by proton magnetic resonance spectroscopy (MRS) in a cohort of HIV-infected individuals. One hundred seventy-one stored CSF specimens were assayed from HIV-infected individuals who were enrolled in two ACTG studies that evaluated the relationship between neuropsychological performance and cerebral metabolites. Concentrations of six chemokines (fractalkine, IL-8, IP-10, MCP-1, MIP-1β, and SDF-1) were measured and compared with cerebral metabolites individually and as composite neuronal, basal ganglia, and inflammatory patterns. IP-10 and MCP-1 were the chemokines most strongly associated with individual cerebral metabolites. Specifically, (1) higher IP-10 levels correlated with lower N-acetyl aspartate (NAA)/creatine (Cr) ratios in the frontal white matter and higher MI/Cr ratios in all three brain regions considered and (2) higher MCP-1 levels correlated with lower NAA/Cr ratios in frontal white matter and the parietal cortex. IP-10, MCP-1, and IL-8 had the strongest associations with patterns of cerebral metabolites. In particular, higher levels of IP-10 correlated with lower neuronal pattern scores and higher basal ganglia and inflammatory pattern scores, the same pattern which has been associated with HIV-associated neurocognitive disorders (HAND). Subgroup analysis indicated that the effects of IP-10 and IL-8 were influenced by effective antiretroviral therapy and that memantine treatment may mitigate the neuronal effects of IP-10. This study supports the role of chemokines in HAND and the validity of MRS as an assessment tool. In particular, the findings identify relationships between the immune response—particularly an interferon-inducible chemokine, IP-10—and cerebral metabolites and suggest that antiretroviral therapy and memantine modify the impact of the immune response on neurons.

Depression is not an inevitable outcome of disclosure avoidance: HIV stigma and mental health in a cohort of HIV-infected individuals from Southern India

Previous research has shown that HIV stigma in India can be characterized by a framework dividing manifestations into enacted (discrimination), vicarious (hearing stories of discrimination), felt normative (perceptions of stigma's prevalence), and internalized stigma (personal endorsement of stigma beliefs). We examined whether this framework could explain associations among stigma, efforts to avoid HIV serostatus disclosure, and depression symptoms in a cohort of 198 HIV-infected individuals from Southern India who were followed up for one year as part of a study of antiretroviral adherence. Prior studies had suggested that disclosure avoidance was a primary outcome of stigma and that impaired well-being was a primary outcome of disclosure avoidance. Analyses from our longitudinal research revealed that the pattern of associations among stigma, disclosure avoidance, and depression symptoms remained consistent over time. Enacted and vicarious stigmas were correlated with felt normative stigma beliefs. In turn, felt normative stigma was correlated with disclosure avoidance. And, enacted stigma, internalized stigma, and disclosure avoidance were all associated with depression symptoms. However, even though the overall framework held together, internalized stigma and depression symptoms dropped significantly over time while other components remained unchanged. These findings suggest that, although HIV stigma may limit disclosure, it does not invariably lead to psychological maladjustment. Amidst ongoing perceptions and experiences of stigma, HIV-positive individuals can achieve significant improvements in their acceptance of the disease and in mental well-being.

Hepatitis B vaccination and risk of hepatitis B infection in HIV-infected individuals.

To assess the association of hepatitis B virus (HBV) vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees. Observational cohort study. Participants enrolled from 1986 through 2004, unvaccinated and serologically negative for HBV infection at the time of HIV diagnosis, were followed longitudinally through 2007 for the occurrence of HBV infection. Risk factors for HBV infection were evaluated using time to event methods, including Kaplan-Meier survival curves and Cox proportional hazards models. During 11 632 person-years of follow-up, the rate of HBV infection was 2.01 (95% CI 1.75-2.27)/100 person-years. Receipt of at least one dose of vaccine was not associated with reduced risk of HBV (unadjusted hazard ratio 0.86, 95% CI 0.7-1.1; adjusted hazard ratio 1.08, 95% CI 0.8-1.4). Receipt of three or more doses of vaccine was also not associated with reduced risk (hazard ratio 0.96; 95% CI 0.56-1.64). Among 409 vaccinees with HBsAb less than 10 IU/l, 46 (11.2%) developed HBV infection compared with 11 of 217 (5.1%) vaccinees with HBsAb > or =10 IU/l (hazard ratio 0.51; 95% CI 0.3-1.0). In participants with initial HBsAb less than 10 IU/l, 16 of 46 (35%) infections were chronic, compared with none of 11 in those with initial HBsAb at least 10 IU/l (P = 0.02). Overall, HBV vaccination was not associated with reduced risk of HBV infection in our cohort of HIV-infected individuals. However, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infection risk, including chronic disease. Improvements in vaccine delivery and immunogenicity are needed to increase HBV vaccine effectiveness in HIV-infected patients.

Epidemiology of Hepatitis B virus infection in a US cohort of HIV-infected individuals during the past 20 years.

The epidemiologic trends of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV)-infected patients over the past 20 years are largely unknown. Prevalence and risk factors for HBV infection overall, at the time of HIV infection, and after HIV infection were examined in an ongoing observational HIV cohort study. Risk factors for HBV infection at the time of diagnosis of HIV infection were evaluated using logistic regression, and risk of incident HBV infection after diagnosis of HIV infection was evaluated using Cox proportional hazards models. Of the 2769 evaluable participants, 1078 (39%) had HBV infection, of whom 117 (11%) had chronic HBV infection. The yearly cross-sectional prevalence of HBV infection decreased from a peak of 49% in 1995 to 36% in 2008 (P < .001). The prevalence of HBV infection at the time of diagnosis of HIV infection decreased during 1989-2008 from 34% to 9% (P < .001). The incidence of HBV infection after diagnosis of HIV infection decreased from 4.0 cases per 100 person-years during the pre-highly active antiretroviral therapy (HAART) era to 1.1 cases per 100 person-years during the HAART era (P < .001); however, this incidence remained unchanged during 2000-2008 (P = .49), with >20% of HBV infections occurring after HIV infection being chronic. Decreased risk of HBV infection after diagnosis of HIV infection was associated with higher CD4 cell count and the use of HBV-active HAART. Receipt of 1 dose of HBV vaccine was not associated with reduced risk of HBV infection after diagnosis of HIV infection. Although the burden of HBV infection overall is slowly decreasing among HIV-infected individuals, the persistent rate of HBV infection after diagnosis of HIV infection raises concern that more-effective prevention strategies may be needed to significantly reduce the prevalence of HBV infection in this patient population.

Integrative Genomic Analysis of HIV-Specific CD8+ T Cells Reveals That PD-1 Inhibits T Cell Function by Upregulating the AP-1 Transcription Factor BATF.

Abstract 916T cells responding to chronic infections such as HIV lose the ability to secrete cytokines or to proliferate, functions critical for control of viral replication, in a process termed exhaustion. However the molecular mechanisms of T cell exhaustion are not understood, and few therapeutic targets to reinvigorate exhausted T cells have been identified. We therefore conducted a comprehensive genomic analysis of HIV-specific CD8+ T cells to identify the mechanisms underlying defective function in T cell exhaustion. We used Affymetrix microarrays to study gene expression profiles from sorted Gag-specific tetramer+ CD8+ T cells in two cohorts of HIV-infected individuals that differed in their extent of T cell exhaustion: a) Progressors (n=24), who show chronic elevation of viral load and have defects in HIV-specific T cell cytokine secretion, proliferation and survival; and b) Controllers (n=18), who show spontaneous control of viral replication and have relatively good HIV-specific T cell function. Profiles of Gag-specific CD8+ T cells (median 21,500 cells/sample) from progressors showed marked alterations in gene expression compared with those from controllers (n=518 genes upregulated in progressors, moderated t-statistic >2.0). There was highly significant similarity at the whole-genome level between dysfunctional Gag-specific CD8+ T cells from progressors and exhausted CD8+ T cells in the mouse model of chronic LCMV infection (gene set enrichment analysis, P=4.8e−005), suggesting that T cell exhaustion is associated with an evolutionarily conserved program of gene expression. Next, we determined whether this exhausted signature was influenced by inhibitory signaling via the receptor PD-1, an inhibitory receptor known to be upregulated in expression on exhausted T cells. We developed an in vitro model of PD-1 signaling and identified a unique signature of genes upregulated by PD-1 ligation. The signature of PD-1 induced genes was highly significantly upregulated in profiles from Gag-specific CD8+ T cells in HIV progressors compared to controllers (P=5e−006), and in exhausted CD8+ T cells from the LCMV mouse model (P=2e−004). Thus the signature of T cell exhaustion in humans and mice is driven in part by the consequences of PD-1 signaling. Finally, we asked whether the genes upregulated by PD-1 in exhausted T cells directly inhibit T cell function. PD-1 ligation upregulated the transcription factor BATF in HIV-specific CD8+ T cells and in exhausted CD8+ T cells from the mouse model of LCMV infection. Enforced expression of BATF, an inhibitory member of the AP-1 family, in normal human T cells inhibited proliferation (P=0.02) and IL2 secretion (P=4.5e-05). Infection with LCMV in BATF transgenic mice resulted in marked acceleration of T cell exhaustion compared to wild-type animals, indicating that BATF represses T cell effector functions. Silencing of BATF using shRNA in primary human T cells showed that it was required for PD-1 mediated inhibition of T cell function. In summary, our results demonstrate that 1) PD-1 ligation induces a conserved transcriptional program in exhausted HIV-specific CD8+ T cells and in exhausted LCMV-specific CD8+ T cells in the mouse; 2) this transcriptional program includes the upregulation of genes such as BATF that directly inhibit T cell function. Our data suggest that BATF causes the functional defects seen in T cell exhaustion, and represents a new therapeutic target to rescue T cell function in HIV infection. Disclosures:No relevant conflicts of interest to declare.

Outbreak of Syphilis, but Not of Acute Hepatitis C, Among HIV-Infected Homosexual Men in Madrid

Background: Clustered cases of acute hepatitis C virus (HCV) infection, frequently accompanied by sexually transmitted diseases, have recently been reported among men who have sex with men (MSM) in several European cities. Method: We performed a retrospective record of cases of syphilis in a large cohort of HIV-infected individuals on regular follow-up in Madrid, Spain. HCV testing was carried out in all of them. Results: A total of 53 diagnosis of syphilis were made during the previous 4 years (2002 to 2005) in 729 HIV-infected MSM on regular follow-up. However, in only 2 of them (3.7%) asymptomatic HCV seroconversion occurred at the time of the syphilis episode. Both patients developed chronic hepatitis C. Conclusion: Acute HCV infection should periodically be ruled out in all HIV-infected MSM engaged in sexual risky behaviors presenting with syphilis.

Protective effect of acetyl- l-carnitine against oxidative stress induced by antiretroviral drugs

Both HIV infection per se and antiretroviral drugs might contribute to oxidative stress and mitochondrial dysfunctions. In this study we assess zidovudine, stavudine and didanosine on U937 and CEM cell lines. All these drugs induced apoptosis and increased intracellular hydrogen peroxide but not superoxide anions. The addition of acetyl- l-carnitine (ALC) was able to prevent the pro-oxidant effect of the drugs tested. Supplementation with ALC, deficient in certain cohorts of HIV-infected individuals, especially on high active antiretroviral therapy regimen, has been associated with favourable effects. These data suggest that one of these effects could be a direct anti-oxidant action.

Interactions between HIV and malaria in non-pregnant adults: evidence and implications

Interactions between HIV and malaria in non-pregnant adults: evidence and implications

Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment

To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV. In a prospectively followed cohort of HIV-infected individuals we examined the relationship between antemortem neuropsychological (NP) abilities and postmortem neuropathological data. Twenty-seven HIV-infected individuals with both neuropsychological and neuropathological data were identified. Laser confocal scanning microscopy was used to determine the degree of ND based on: (1) microtubule-associated protein (MAP2; reflecting neuronal cell bodies and dendrites) and (2) synaptophysin (SYN; a measure of presynaptic terminals). A regional combined score, based on the distribution of percentage neuropil occupied by MAP2 and SYN and emphasizing severity of ND, was created for each brain region: midfrontal cortex, hippocampus, and putamen. The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F(3,23) = 6.17; P < 0.01; R2 = 0.45). The correlations among regional ND measures demonstrated that ND is unevenly distributed across multiple brain regions. As the anatomic distribution and temporal progression of neuropathologic changes appears to differ across individuals, it is important to consider both cortical and subcortical brain regions in studies of neuropathogenesis and treatment of HIV-related brain disease. Furthermore, combining information from several markers of neural injury provided the strongest association with degree of neurocognitive impairment during life.

Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion

Although HAART has led to a reduction in overall mortality among HIV-infected individuals, its impact on death from specific causes is unknown. Twenty-two cohorts of HIV-infected individuals with known dates of seroconversion are pooled in the CASCADE collaboration. Causes of death (COD) were categorized into three AIDS-related and seven non-AIDS-related causes. The unknown causes were assigned a separate category. The cumulative incidence for each COD was calculated in the presence of the other competing COD, for the pre-HAART and HAART eras. A multivariate regression analyses for the cumulative rate of progression to the different COD was performed. A total of 1938 of 7680 HIV-seroconverters died. Pre-HAART, AIDS opportunistic infections (OI) was the most common COD, followed by unknown and HIV/AIDS-unspecified. In the HAART era, the cumulative incidence for all AIDS-related COD decreased, OI remaining the most important. Large reductions in death due to other infections and organ failure were seen. Cumulative death risk decreased in the HAART era for most causes. The effect of HAART was not the same for all risk groups. The cumulative risk of death from AIDS-related malignancies, OI and non-AIDS-related malignancies decreased significantly among homosexual men (MSM), whereas the risk of dying from (un)-intentional death increased significantly among injecting drug users (IDU). A non-significant increase in hepatitis/liver-related death was seen in MSM, IDU and haemophiliacs. Overall and cause specific mortality decreased following the introduction of HAART. OI remain the most common COD in the HAART era, suggesting that AIDS-related events will continue to be important in the future. Future trends in COD should be monitored using standardized guidelines.

The Effect on Treatment Comparisons of Different Measurement Frequencies in Human Immunodeficiency Virus Observational Databases

Data collected in a routine clinical setting are frequently used to compare antiretroviral treatments for human immunodeficiency virus (HIV). Differences in the frequency of measurement of HIV RNA levels and CD4-positive T-lymphocyte cell counts introduce a possible source of bias into estimates of the difference in effectiveness between treatments. The authors investigated the size of this bias when survival analysis methods are used to compare the initial efficacy of antiretroviral regimens. Data sets of clinical markers were simulated by use of differential equations that model the interaction between HIV and human T-cells. Cox proportional hazards and parametric models were fitted to the simulated data sets to evaluate the bias and coverage of 95% confidence intervals for the difference between regimens. The authors' results demonstrate that differences in the frequency of follow-up can substantially bias estimated treatment differences if methods do not correctly account for the intervals between measurements and if the statistical model chosen does not fit the data well. Analyses using methods applicable to interval-censored data reduce the bias. In the Athena cohort of HIV-infected individuals in the Netherlands from 1999 to 2003, there are differences in measurement frequency between current regimens that are of sufficient magnitude to conclude incorrectly that some regimens are more effective than others.

Invasive pneumococcal disease in a cohort of HIV-infected adults: incidence and risk factors, 1990–2003

To investigate the association between the introduction of HAART and invasive pneumococcal disease (IPD) in HIV-infected patients. Incidence of IPD was determined from 1990 to 2003 in a cohort of HIV-infected individuals and a nested case-control study assessed risk factors of IPD. There were 72 cases over 19,020 person-years of follow-up (overall IPD rate, 379/100,000 person-years). In the calendar periods 1990-1995, 1995-1998, and 1998-2003, the IPD incidence per 100,000 person-years was 279 [95% confidence interval (CI), 150-519], 377 (95% CI, 227-625) and 410 (95% CI, 308-545), respectively (P = 0.516). CD4 cell count < 200 cells/microl [odds ratio (OR), 3.0; 95% CI, 1.2-7.6), HIV RNA > 50,000 copies/ml (OR, 2.8; 95% CI, 1.2-6.5), hepatitis C (OR, 4.9; 95% CI, 1.7-14.9), serum albumin (OR, 0.1; 95% CI, 0.04-0.5), injection drug use in women (OR, 3.8; 95% CI, 1.6-8.8), and education beyond high school (OR, 0.2; 95% CI, 0.05-0.8) were significantly associated with IPD in multivariate analysis. No treatment factor, including HAART (OR, 0.7; 95% CI, 0.3-1.5) and pneumococcal vaccination (OR, 0.9; 95% CI, 0.5-1.6), was associated with IPD. IPD incidence did not change significantly during the widespread dissemination of HAART in this cohort. IPD risk was associated with several sociodemographic and clinical factors.

Sexual Behaviors and Sexual Risk in a Prospective Cohort of HIV-Positive Men and Women in New York City, 1994–2002: Implications for Prevention

As an ever-increasing number of people infected with HIV are living longer, healthier lives, concerns about continued transmission are growing along with an awareness of the need to develop "prevention for positives." This study of HIV-positive adults in New York City is the first examination of patterns of sexual behavior in a large, representative cohort of HIV-infected individuals followed over an extended time period. A total of 968 HIV-positive adults were interviewed every 6-12 months between 1994 and 2002 and reported considerable variability in sexual behaviors over time. Many persons were not sexually active at all for months at a time; some continued to have multiple partners. Over one third of the cohort had one or more periods when they had engaged in unprotected sex with a partner who was HIV-negative or status unknown (unsafe sex) and one in five reported exchanging sex. Periods of unsafe sex alternated with periods of safer sex. Predictors of sexual risk varied by gender, and among men who had sex with men, and men sexually active with women only. Contextual factors such as partner relations, housing status, and receipt of HIV services were as important as individual attributes as predictors of unsafe sex and sex exchange. The variability observed in sexual risk behavior reported over time provides new insight into the importance of engaging persons living with HIV in ongoing prevention programs.

A Randomized Controlled Trial to Enhance Antiretroviral Therapy Adherence in Patients with a History of Alcohol Problems

To assess the effectiveness of an individualized multicomponent intervention to promote adherence to antiretroviral therapy (ART) in a cohort of HIV-infected individuals with a history of alcohol problems. We conducted a randomized controlled trial to compare the usual medical follow-up with an adherence intervention. The principal enrolment site was Boston Medical Center, a private, not-for-profit, academic medical institution. HIV-infected patients with a history of alcohol problems on ART. A total of 151 were enrolled and 141 (93%) were assessed at follow-up. A nurse, trained in motivational interviewing, completed the following over 3 months in four encounters: addressed alcohol problems; provided a watch with a programmable timer to facilitate pill taking; enhanced perception of treatment efficacy; and delivered individually tailored assistance to facilitate medication use. Prior 30-day adherence > or =95%, prior 3-day adherence of 100%, CD4 cell count, HIV RNA and alcohol consumption, each at both short- and long-term follow-up. At follow-up, no significant differences in medication adherence, CD4 cell count, HIV RNA or alcohol consumption were found (all P values >0.25). A multicomponent intervention to enhance adherence among HIV-infected individuals with a history of alcohol problems was not associated with changes in medication adherence, alcohol consumption or markers of HIV disease progression. The failure to change adherence in a group at high risk for poor adherence, despite utilizing an intensive individual-focused patient intervention, supports the idea of addressing medication adherence with supervised medication delivery or markedly simplified dosing regimens.