The role of herpes simplex virus type 2 and other genital infections in the acquisition of HIV-1 among high-risk women in northern Tanzania

BACKGROUND: We examined the role of herpes simplex virus type 2 (HSV-2) and other genital infections on human immunodeficiency virus type 1 (HIV-1) incidence in a cohort study conducted between 2002 and 2005 among female bar/hotel workers in Moshi, Tanzania. METHODS: At baseline and every 3 months thereafter, participants were interviewed, and blood and genital samples were collected. Predictors of HIV-1 incidence were evaluated using a Cox proportional hazards regression model. RESULTS: Of 845 women who were HIV-1 seronegative at baseline, 689 (81.5%) were monitored in the study for a total of 698.6 person-years at risk (PYARs). The overall HIV-1 incidence was 4.6/100 PYARs (95% confidence interval [CI], 3.0-6.2/100 PYARs), and condom use was very low. After adjustment for other risk factors, the risk of HIV-1 was increased among women with HSV-2 at baseline (hazard ratio [HR], 4.3 [95% CI, 1.5-12.4]) and in those who acquired HSV-2 during the study period (HR, 5.5 [95% CI, 1.2-25.4]). Other independent predictors of HIV-1 were baseline chlamydial infection (HR, 5.2), bacterial vaginosis (HR, 2.1), and the occurrence of genital ulcers (HR, 2.7). CONCLUSION: HSV-2 and other genital infections were the most important risk factors for HIV-1. Control of these infections could help to reduce HIV-1 incidence in this population.     

Identification of HLA class I-associated amino acid polymorphisms in the HIV-1C proteome

Human immunodeficiency virus type 1 (HIV-1) evasion of host cytotoxic T lymphocyte (CTL) targeting is linked to the expression of variant amino acid residues, or escape mutations, in positions that alter the normal processing, presentation, or recognition of targeted epitopes. The combined genetic variability of HIV and the class I human leukocyte antigen (HLA) loci makes it difficult to characterize CTL escape mutations on a population level. However, a role in CTL escape may be inferred by identifying HIV amino acid polymorphisms that are specifically associated with particular HLA class I alleles. We describe here the results of a comprehensive analysis of HIV-1 subtype C (HIV-1C) to identify HLA class I-associated amino acid polymorphisms. We identified 94 HLA-associated amino acid polymorphisms distributed across the 15 major viral proteins analyzed. HLA-B alleles were involved in more associations (50%) than alleles from either the HLA-A (27%) or HLA-C (24%) loci. HLA-associated polymorphisms were identified in 18 of 26 previously described HIV-1C CTL immunoreactive regions including 7 of the 8 classified as immunodominant. Comparison to known HIV-1 CTL epitopes revealed that 19 of the HLA-associated polymorphisms were located in CTL epitopes restricted by the associated HLA allele. These results suggest that HIV-1C retains the potential for CTL escape across the entire proteome including regions that are broadly targeted on a population scale. The impact of CTL escape on natural and vaccine-induced CTL immunity warrants the continued characterization of the role of such HLA-associated polymorphisms in this process.     

The reverse transcriptase 67N 70R 215Y genotype is the predominant TAM pathway associated with virologic failure among HIV type 1C-infected adults treated with ZDV/ddI-containing HAART in southern Africa

HIV-1C has become the dominant HIV-1 subtype in the global AIDS epidemic. Historically, the evolution of drug-resistant mutations was characterized primarily among antiretroviral (ARV)-treated HIV-1B infections. Whereas the non-B viruses are susceptible to the currently used ARVs, some differences between HIV-1 subtypes in response to ARV regimens have been reported. We analyzed the profile of ARV-associated mutations in HIV-1C infection treated with ZDV/ddI-containing regimens in an open-label, randomized 3 x 2 x 2 factorial study comparing ZDV/3TC vs. ZDV/ddI vs. d4T/3TC and EFV vs. NVP regimens in drug-naive adults in Botswana. The overall rate of virologic failure in the ZDV/ddI-containing arms was 14%. We addressed the development of NRTI-associated mutations in 23 virologically failed patients in the ZDV/ddI-containing arms. The 67N 70R 215Y genotype with wild-type amino acids at codon positions 41 and 210 was a dominant pattern of NRTI-associated mutations at the time of virologic failure. The mutation T215Y was the first step in the evolution of the 67N 70R 215Y genotype and was followed by mutations K70R and D67N. Representing a mixture of TAM-1 (41L/210W/215Y) and TAM-2 (67N/70R/215F /219Q) pathways, the 67N 70R 215Y genotype with wild-type amino acids at codon positions 41, 210, and 219 is a unique TAM pathway that is rarely seen in HIV-1B infection. Although limited by relatively small numbers, our data suggest that the 67N 70R 215Y genotype may be the HIV-1C-specific response to the first-line ZDV/ddI-containing regimen at the time of virologic failure. The presence of the 67N 70R 215Y genotype with wild-type amino acids at codon positions 41, 210, and 219 in HIV-1C infection suggests that the evolution of ARV-associated mutations and TAM pathways might be unique in non-B HIV-1 subtypes treated with particular ARV regimens.     

Interviews for the assessment of long-term incapacity for work: a study on adherence to protocols and principles

Background  

Assessments for long-term incapacity for work are performed by Social Insurance Physicians (SIPs) who rely on interviews with claimants as an important part of the process. These interviews are susceptible to bias. In the Netherlands three protocols have been developed to conduct these interviews. These protocols are expert- and practice-based. We studied to what extent these protocols are adhered to by practitioners.     

Exposure to maternal depression and marital conflict: gender differences in children's later mental health symptoms

OBJECTIVE: To investigate effects of the timing of initial exposure to maternal depression and marital conflict on kindergarten children's mental health symptoms. METHOD: For 406 families (of 570 originally recruited), mothers reported on major depression and marital conflict on multiple occasions in the child's infancy and toddler/preschool periods. Mothers and teachers completed the MacArthur Health and Behavior Questionnaire when children were in kindergarten. RESULTS: Children evidenced co-occurring internalizing and externalizing symptoms, although the mix was more toward internalizing for girls and externalizing for boys. Symptoms were more severe among children exposed to either adversity, and these effects were additive. Boys exposed to maternal depression in infancy had a preponderance of internalizing behaviors, but if subsequently exposed to marital conflict, the mix toward externalizing behaviors increased to match levels of clinic-referred children. For girls, the preponderance of internalizing symptoms increased to match levels of clinic-referred children when initial exposure to marital conflict occurred in the toddler/preschool period. CONCLUSIONS: It is important to consider both adversities across developmental periods, to distinguish the symptom severity from directionality, and to consider child gender. Prevention and intervention efforts that consider these findings are warranted.     

Concurrent and Longitudinal Associations Between Diurnal Cortisol and Body Mass Index Across Adolescence

PurposeChildhood and adolescent obesity have reached epidemic levels; however, little is known about the psychobiological underpinnings of obesity in youth and whether these differ from the mechanisms identified in adults. The current study examines concurrent (i.e., measured at the same point in time) and longitudinal (i.e., using earlier cortisol measures to predict later body mass index [BMI]) associations between diurnal cortisol and BMI across adolescence.MethodsAdolescent diurnal cortisol was measured over 3 days at each 11, 13, and 15 years. Hierarchical linear modeling was used to extract average measures of predicted morning, afternoon, evening levels of cortisol and the diurnal slope at each assessment. Adolescent BMI (kg/m²) was measured at 11, 13, 15, and 18 years. Sex, family socioeconomic status, mother's BMI, pubertal status, and adolescent mental health were examined as possible confounding variables.ResultsLinear regressions revealed that blunted patterns of adolescent cortisol were associated with increased measures of BMI across adolescence both concurrently and longitudinally, particularly when examining measures of cortisol in early adolescence. Multinomial logistic regressions extended the linear regression findings beyond BMI scores to encompass categories of obesity.ConclusionsThe current study builds on previous research documenting diurnal cortisol–obesity findings in adults by demonstrating similar findings exist both concurrently and longitudinally in adolescents. Findings suggest the association between cortisol and BMI is developmentally influenced and that blunted diurnal cortisol patterns can be identified in overweight individuals at a younger age than previously thought.     

His Bundle Extrasystoles Revisited: The Great Electrocardiographic Masquerader

A 74‐year‐old man with past history of near syncope presented with frequent periods of second‐degree atrioventricular block (2° AVB). An electrophysiological study revealed prolonged atrial‐His and His‐ventricular (HV) intervals and frequent His bundle (H) extrasystoles. The latter manifested in the surface electrocardiogram as premature atrial, junctional, or ventricular beats, as well as 2° AVB that mimicked Wenckebach or Mobitz II block. Procainamide markedly suppressed H extrasystole. However, because of the presence of prolonged HV interval and history of presyncope, a permanent pacemaker was inserted. The case illustrates the varied manifestation of H extrasystole and presents guidelines for management. (PACE 2011; e56–e59)