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Background: Long-term maternal outcomes after postpartum antiretroviral therapy (ART) discontinuation are unknown., Methods: Retrospective review of pregnancies in HIV-infected women on treatment between 1997 and 2005. Women were grouped by postpartum ART use and followed until new opportunistic infection (OI), death or last clinic visit., Results: Of 172 pregnancies, postpartum ART discontinuation occurred in 123 (71.5%) women and was associated with greater parity, no partner during pregnancy, and no indication for OI prophylaxis or preconception ART in multivariate analysis (P < .05). Median follow-up was 32.5 months after delivery. There were 12 OIs and 2 deaths; 10 OIs and both deaths occurred in women who had discontinued ART., Conclusion: Postpartum ART discontinuation is common, especially among those with less advanced HIV disease, but may leave women at increased risk of long term adverse outcomes. This study highlights the need for larger longitudinal studies to determine appropriate recommendations for postpartum ART administration.

Background: Previous studies suggest that depot medroxyprogesterone acetate (DMPA) is associated with an increased risk of sexually transmitted infection (STI) acquisition. The primary aim of this study was to characterize the potential association between DMPA use and risk of STI acquisition among HIV-infected women., Study Design: This is a retrospective cohort study among HIV-infected women followed at a university clinic from 1997 to 2005. Medical records were reviewed for demographic data, HIV parameters, self-reported condom use, substance use, duration of follow-up and incident cases of gonorrhea, chlamydial infection and trichomoniasis., Results: Of 304 HIV-infected women identified, 82 received DMPA and 222 did not. Overall incidence rates of trichomoniasis, chlamydial infection and gonorrhea were 8.4, 4.0 and 3.1 cases per 100 person-years, respectively, with no significant differences between the women receiving or not receiving DMPA., Conclusions: In this HIV-infected cohort, STI rates were higher than the general population, yet DMPA use did not appear to enhance the risk of STI acquisition. This latter finding suggests that the concern for STI acquisition should not be a limiting factor in the use of DMPA in HIV-infected women. The implementation of additional secondary prevention strategies remains an important focus in the HIV epidemic.

Since the advent of highly active antiretroviral therapy, life expectancies for persons with HIV infection are similar to those for uninfected people. A growing proportion of HIV-infected individuals are now over the age of 50. We are also seeing an increase in the incidence of HIV infection in older adults. To meet the challenges of the ongoing HIV epidemic, prevention efforts should include a focus on older adults. Also, HIV care providers must address the many comorbidities that are common in the aging population. Additional research will clarify how the processes of aging and HIV infection overlap and interact. This review addresses many of these important considerations.

Background: The association of fat distribution with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations is not well-defined in HIV-infected individuals. Obesity is associated with hepatic steatosis, and ALT is a marker of steatosis in the general population., Methods: Cross-sectional analysis of 1119 HIV-infected and 284 control subjects. Hepatitis C virus (HCV) RNA testing determined HCV infection. Magnetic resonance imaging measured regional adipose tissue volume., Results: After adjustment for demographic and lifestyle factors, visceral adipose tissue (VAT) was positively associated with ALT in HIV/HCV-coinfected subjects (+9.8%, 95% confidence interval [CI]: 2.8 to 17.6), HIV-monoinfected subjects (+8.0%, 95% CI: 4.2 to 12.1), and controls (+5.9%, 95% CI: 2.0 to 10.1). In contrast, lower trunk subcutaneous adipose tissue (SAT) was negatively associated with ALT in HIV/HCV-coinfected subjects (-14.3%, 95% CI: -24.7 to -4.2) and HIV-monoinfected subjects (-11.9%, 95% CI: -18.4 to -5.3); there was a trend toward an association in controls (-7.1%, 95% CI: -22.7 to 5.9). Estimated associations between regional adipose tissue and AST were small and did not reach statistical significance., Conclusions: More VAT and less lower trunk SAT are associated with elevated ALT, which likely reflects the presence of steatosis. There was little association with AST. HCV infection and having more VAT or less lower trunk SAT are independently associated with elevated ALT in HIV infection. Study regarding the association between VAT, trunk SAT, HCV, and progression of steatosis and fibrosis is needed in HIV-infected individuals.

Prevention is an important aspect of HIV care in the era of highly active antiretroviral therapy. Vaccines provide an excellent opportunity to avert certain infectious diseases for which patients with HIV infection are at increased risk due to immunosuppression. However, the state of immunosuppression reduces the efficacy of vaccines and increases the risk associated with certain vaccines. The study of vaccine responses in patients with HIV infection has greatly advanced the understanding of the underlying immune deficits, particularly with regards to reduced CD4 cell number and function and the level of immune activation associated with chronic viremia. This research has also solidified the safety and utility of vaccines for this population. Continued research of vaccine responses will further our understanding of the immune system and optimize the utilization of routine immunizations.

Chronic hepatitis B virus infections are a major cause of morbidity and mortality in HIV co-infected patients. The standard of care for treating HCV co-infection has been guided by major clinical trials, but the treatment of HBV co-infection has not been as thoroughly studied and the standard of care remains largely untested. The single pill formulation of tenofovir with emtricitabine has become a standard treatment approach in HBV co-infected patients. WU114 was a phase 1 clinical trial that examined the safety and tolerability of sequential treatment of HBV with pegylated interferon-alpha2a plus delayed-initiation tenofovir in HIV co-infected individuals. We postulated that initial HBV viral load reduction with pegylated interferon prior to initiation of nucleoside/nucleotide therapy would increase seroconversion events and durability of HBV virologic suppression. No severe pegylated IFN-alpha2a drug toxicities were seen in either the monotherapy or delayed tenofovir arms. Sequential pegylated interferon and tenofovir-based therapy was tolerable and should be compared with dual nucleoside/nucleotide suppression to determine relative frequencies of seroconversion and durability of HBV suppression in co-infected patients.

Fc receptor-like proteins (FcRLs) are a growing family of molecules homologous to FcgammaRI. Whereas all 7 previously reported Fc receptor homologs are expressed by B cells, here we report a new receptor, FcRL6, that is expressed by cytolytic cells including natural killer (NK) cells and effector and effector-memory CD8(+) T cells. FcRL6 contains a novel cytoplasmic cysteine-rich motif and recruits SHP-2 through a phosphorylated ITIM, indicating a potential signaling function in effector lymphocytes. In vitro, FcRL6 does not greatly influence NK-cell or CD8(+) T-cell-mediated cytotoxicity and has minimal impact on cytokine secretion. However, FcRL6 expression among T lymphocytes is greatly expanded in human immunodeficiency virus type 1 (HIV-1)-infected individuals, and includes not only effector and effector-memory CD8(+) T cells but also populations of CD4(+) T cells. Expansion of FcRL6-positive lymphocytes is not related to viral load, but is indicative of the dysregulated expansion of terminally differentiated effector lymphocyte populations in response to chronic HIV-1 infection and may serve as an important marker for chronic immune activation and for tracking the generation of effector cells following immune stimulation.

Objective: Coinfection with hepatitis C virus (HCV) is reported to be associated with a higher prevalence of lipodystrophy than HIV infection alone. We examine the association between HCV and adipose tissue volume in HIV-infected men and women., Methods: Cross-sectional analysis of HIV-infected subjects from the study of Fat Redistribution and Metabolic Change in HIV Infection. MRI measured regional adipose tissue volume. Detectable HCV RNA defined HCV infection., Results: Twenty percent of 792 men and 26% of 329 women were HIV/HCV-coinfected. HIV/HCV-coinfected and HIV-monoinfected women had similar amounts of subcutaneous adipose tissue (SAT) in the leg, lower trunk, upper trunk, and arm and similar amounts of visceral adipose tissue (VAT). Similar findings were seen in men, except in the leg and VAT. After adjustment, HCV infection remained associated with more leg fat in men (12.2%, 95% confidence interval [CI]: 0.3 to 25.3; P = 0.043). Among those on stavudine, HIV-monoinfected men had less leg fat (-7% effect per year of stavudine use, 95% CI: -9 to -5; P < 0.001); a weaker association was seen in HIV/HCV-coinfected men (-2% effect, 95% CI: -7 to 3; P = 0.45). Indinavir was associated with less leg fat (-4% in HIV-monoinfected men, 95% CI: -6 to -1; P = 0.002; -5% in HIV/HCV-coinfected men, 95% CI: -11 to 2; P = 0.14)., Conclusions: Our findings suggest that HIV/HCV coinfection is not associated with less SAT in men and women. HCV infection seems to mitigate the loss of leg fat seen in HIV-infected men on stavudine.

Hepatitis A virus (HAV) infection remains a health risk for human immunodeficiency virus (HIV)-infected persons. While the inactivated HAV vaccine affords protection to immunocompetent persons >95% of the time, rates of developing protective antibody (anti-HAV) in HIV+ persons are considerably lower. Although low CD4+ T-cell counts have previously been reported to be correlated with this poor response, the effect of HIV viraemia on HAV vaccine response has not previously been reported. The medical records of HIV-infected patients who had received at least one dose of HAV vaccine (Havrix, 1440 EIU) were reviewed for factors associated with the development of a protective anti-HAV response. Serological data with regard to anti-HAV status after vaccination were available in 238 patients with 133 individuals (49.6%) developing immunity after vaccination. In a logistic regression model, the only factors associated with a protective antibody response were an HIV plasma RNA level <1000 copies/mL at the time of vaccination (P = 0.011) and male gender (P = 0.016). Neither nadir CD4+ T cell count nor CD4+ T-cell count at time of vaccination were predictive of the development of anti-HAV. Suppression of HIV replication at time of vaccination is associated with a protective antibody response to HAV vaccination in HIV-infected adults. The low rate of response warrants further research in alternative strategies for HAV vaccination among HIV-infected persons.

Background: The association between the use of highly active antiretroviral therapy (HAART) and an increased risk of metabolic syndrome and cardiovascular disease remains unclear., Methods: We conducted a prospective, cross-sectional study of the risk factors associated with metabolic syndrome and cardiovascular disease among patients from an urban outpatient human immunodeficiency virus (HIV) clinic. Evaluation included laboratory data that were obtained after an overnight fast and a health survey that assessed traditional risk factors associated with cardiovascular disease, HIV-related factors, and comorbidities. Data collected were compared with data files from a cohort from the National Health and Nutrition Examination Survey (NHANES; 2001-2002) of persons who were seronegative for HIV infection who were matched for age, sex, race, and tobacco use., Results: Four hundred seventy-one HIV-infected subjects provided complete data. The overall prevalence of metabolic syndrome was similar between the group HIV-infected patients and the group of persons who were seronegative for HIV infection (25.5% vs. 26.5%, respectively), although the HIV-infected patients had a significantly smaller waist circumference, lower body mass index, lower high-density lipoprotein cholesterol levels, higher triglyceride levels, and lower glucose levels, compared with the subjects from the NHANES cohort. Framingham 10-year risk scores were also similar between the 2 groups. HIV-infected patients with metabolic syndrome were more likely to be diabetic, older, and white and have a high CD4 cell count and body mass index, compared with patients without metabolic syndrome (P<.05 for all). The type or duration of antiretroviral therapy was not an independent risk factor for metabolic syndrome., Conclusions: The prevalence of metabolic syndrome is high among HIV-infected persons, but not higher than the prevalence among HIV-uninfected persons. Traditional risk factors play a more significant role in the development of metabolic syndrome than do HIV treatment-associated factors.

Background: Chronic seronegative hepatitis C virus (HCV) infection is defined as being HCV antibody (anti-HCV) negative, but HCV RNA positivity occurs in individuals infected with human immunodeficiency virus (HIV). However, associated factors are not well established because of the small number of reported cases., Methods: Multivariate logistic regression analysis of HIV-infected subjects from 4 cohorts (Tien et al., 2006; Bonacini et al., 2001; George et al., 2002; and Hall et al., 2004) determined factors associated with HCV RNA positivity in anti-HCV-negative subjects. HCV enzyme immunoassay 2.0 was used to determine anti-HCV status., Results: Among 1174 anti-HCV-negative, HIV-infected subjects, the prevalence of seronegative HCV infection was 3.2% (95% confidence interval [CI], 2.2%-4.3%). History of injection drug use (IDU; OR, 5.8; 95% CI, 2.7-12.8), higher alanine aminotransferase (ALT) level (OR, 2.0 per doubling; 95% CI, 1.3-3.2), and CD4 cell count <200 cells/ micro L (OR, 2.3; 95% CI, 1.1-4.8) were associated with HCV RNA positivity in anti-HCV-negative subjects. Among those with a history of IDU who had either a CD4 cell count <200 cells/ micro L or an ALT level greater than the upper limit of normal, the prevalence of seronegative HCV infection was 24% (95% CI, 13%-39%)., Conclusions: Detectable HCV RNA in the context of a negative HCV enzyme immunoassay 2.0 result in HIV-infected patients is low, but higher than the reported prevalence in HIV-uninfected patients. Our findings suggest that HCV RNA testing should be performed in anti-HCV-negative, HIV-infected patients, especially those with a history of IDU and either a CD4 cell count <200 cells/ micro L or an abnormal ALT level.

A total of 192 HIV-1-infected antiretroviral-naive individuals had genotyping performed in our midwest university clinic between 2003 and 2005. The overall prevalence of resistance with either a reverse transcriptase or major protease mutation was 18%. There did not seem to be a significant difference in primary resistance patterns between different modes of HIV transmission (heterosexual versus men who have sex with men), gender or between white and African-American individuals.

Background: Intermittent episodes of detectable human immunodeficiency virus (HIV) viremia (hereafter referred to as "blips") are generally not predictive of subsequent virologic failure. Limited data are available for patients treated with nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based regimens., Methods: A retrospective cohort study evaluated patients receiving highly active antiretroviral therapy who were followed for > or =12 months, achieved an HIV RNA load of <50 copies/mL, and underwent evaluation every 2-3 months. A blip was defined as 1 HIV RNA load measurement of 50-1000 copies/mL that was preceded and followed by another HIV RNA load measurement of <50 copies/mL. The frequency and predictors of blips and virologic failure were studied., Results: There were 244 patients in the NNRTI group and 136 patients in the protease inhibitor (PI) group. Baseline characteristics between the 2 groups were similar. A total of 34% of patients in the NNRTI group and 33% in the PI group experienced viral blips (P=.855), with corresponding incidences of 19.2 and 19.7 blips, respectively, per 100 person-years. Median time to blips was 50.0 months after initiation of therapy in the NNRTI group (95% confidence interval [CI], 44.8-55.3 months) and 43.6 months in the PI group (95% CI, 33.7-53.6 months; P=.632, by the log-rank test). By Cox proportional hazards model analysis, only a history of antiretroviral therapy use (hazard ratio [HR], 2.01; P<.001) and a CD4 cell count of <200 cells/ mu L (HR, 1.70; P=.021) increased the risk for having a blip. During a median follow-up period of 23.5 months, 7.8% of patients in the NNRTI group and 8.1% in the PI group experienced virologic failure (P=.917). Cox proportional hazards model analysis showed that only a baseline CD4 cell count of <200 cells/ mu L predicted virologic failure (HR, 2.74; P=.032)., Conclusions: There is no difference in the frequency or prognostic significance of viral blips between patients receiving NNRTI-based therapy and patients receiving PI-based therapy. Our results suggest that viral blips occur at a similar rate among patients receiving NNRTI-based regimens and patients receiving PI-based regimens and that they are not predictive of virologic failure.

Human immunodeficiency virus (HIV)-infected patients respond poorly to hepatitis B vaccination. Records of 194 HIV-infected patients were reviewed for factors associated with successful hepatitis B vaccination. Thirty-four patients (17.5%) developed a protective antibody response. In a logistic regression model, only a plasma HIV RNA level of <400 copies/mL at the time of vaccination was associated with a protective antibody response (P=.003).