Caroline Costello

HLA class I homozygosity accelerates disease progression in human immunodeficiency virus type 1 infection

Polymorphic products of HLA class I genes restrict cytotoxic T lymphocyte responses to the constantly evolving spectrum of HIV-1 antigens. Accordingly, homozygosity at class I loci can reduce the repertoire for such HLA-dependent interactions, leading to accelerated disease progression. To test this hypothesis we studied subjects from two distinct HIV/AIDS cohorts: 140 Dutch homosexual men and 202 Rwandan heterosexual women followed up to 13 years from HIV-1 seroconversion. We performed intermediate- and selective high-resolution molecular typing at HLA class I (A, B, and C) and high-resolution typing at HLA class II DRB1 and DQB1. Homozygosity at the HLA-A or -B locus or both was found at increasingly high frequency among individuals with successively more rapid progression to late-stage HIV-1-related conditions. In the combined cohorts (n = 342) the odds ratio (OR) due to HLA-A or -B antigen homozygosity in rapid versus slow progressors was 3.8 (p = 0.003); for Dutch men alone the OR was 3.5 (p = 0.102), and for Rwandan women the OR was 4.1 (p = 0.009). In contrast, homozygous genotypes at either HLA-C, DRB1, or DQB1 alone, or DRB1-DQB1 haplotypes, did not exert any deleterious effect on HIV-1 disease progression. These findings suggest strongly that diversity in addition to sequence specificity at HLA-A and -B loci can influence the rate of disease progression following HIV-1 infection.

Complications of interval laparoscopic tubal sterilization: findings from the United States collaborative review of sterilization☆

Objective To estimate the risk of intraoperative or postoperative complications for interval laparoscopic tubal sterilizations. Methods We used a prospective, multicenter cohort study of 9475 women who had interval laparoscopic tubal sterilization to calculate the rates of intraoperative or postoperative complications. The relative safety of various methods was assessed by calculating overall complication rates for each major method of tubal occlusion. Method-related complication rates also were calculated and included only complications attributable to a method of occlusion. We used logistic regression to identify independent predictors of one or more complications. Results When we used a more restrictive definition of unintended major surgery, the overall rate of complications went from 1.6 to 0.9 per 100 procedures. There was one life-threatening event and there were no deaths. Complications rates for each of the four major methods of tubal occlusion ranged from 1.17 to 1.95, with no significant differences between them. When complication rates were calculated, the spring clip method had the lowest method-related complication rate (0.47 per 100 procedures), although it was not significantly different from the others. In adjusted analysis, diabetes mellitus (adjusted odds ratio [OR] 4.5; 95% confidence interval [CI] 2.3, 8.8), general anesthesia (OR 3.2; CI 1.6, 6.6), previous abdominal or pelvic surgery (OR 2.0; CI 1.4, 2.9), and obesity (OR 1.7; CI 1.2, 2.6) were independent predictors of one or more complications. Conclusion Interval laparoscopic sterilization generally is a safe procedure; serious morbidity is rare.

A comparison of women's regret after vasectomy versus tubal sterilization.

OBJECTIVE To compare the 5‐year cumulative probability of regret and risk factors for regret among women whose husbands underwent vasectomy with women after tubal sterilization. METHODS A total of 525 women whose husbands underwent vasectomy were compared with 3672 women who underwent tubal sterilization in a prospective, multicenter, cohort study. RESULTS The cumulative probability of a woman expressing regret within 5 years after her husbands vasectomy was 6.1% (95% confidence interval [CI] 3.6, 8.6), which was similar to the 5‐year cumulative probability of regret among women after tubal sterilization (7.0%, 95% CI 5.8, 8.1). Women who reported substantial conflict with their husbands before vasectomy were more than 25 times more likely to request that their husband have a reversal than women who did not report such conflict (rate ratio 25.3, 95% CI 2.9, 217.2). Similarly, women who reported substantial conflict with their husbands or partners before tubal sterilization were more then three times as likely to regret their decision and more than five times as likely to request a reversal than women who did not report such conflict (rate ratio 3.1, 95% CI 1.4, 7.0, and rate ratio 5.4, 95% CI 1.6, 17.6, respectively). CONCLUSION Most women did not express regret after their husbands vasectomy and the probability of regret was similar to sterilized women. However, when there was substantial conflict between a woman and her husband before vasectomy or tubal sterilization, the probability of subsequent request for reversal was increased.

Broad Human Immunodeficiency Virus (HIV)–Specific T Cell Responses to Conserved HIV Proteins in HIV-Seronegative Women Highly Exposed to a Single HIV-Infected Partner

Eighteen highly exposed but persistently seronegative (HEPS) women (HW) and their human immunodeficiency virus (HIV) type 1-seropositive male partners were studied for HIV-specific T cells and other host factors. Circulating HIV-specific T cells were measured by interferon-gamma enzyme-linked immunospot assays, using recombinant vaccinia virus vectors expressing HIV proteins. Nine (50%) of the HW and all HIV-seropositive persons had HIV-specific T cell responses. Only 2 (22%) of the HEPS responders recognized Env, compared with 94% of HIV-seropositive persons. A high percentage (75%) of the HW with HIV-specific T cell responses reported recent HIV exposure. Remarkably, however, long-lived HIV-specific T cells were detected in 2 HW who had an extended period (>3.9 years) of no HIV exposure. These findings have important implications for HIV vaccine design.

Correlation between Circulating Stromal Cell-Derived Factor 1 Levels and CD4+ Cell Count in Human Immunodeficiency Virus Type 1-Infected Individuals

Stromal cell-derived factor 1 (SDF-1) is the natural ligand that recognizes CXCR4, which also serves as a coreceptor for some strains of HIV-1. In this study, we explored SDF-1 blood levels among HIV-1-infected individuals exhibiting a wide range of CD4+ cell counts. Plasma or serum concentrations of SDF-1 protein were measured by ELISA in samples from 31 HIV-1-seronegative individuals and 79 HIV-1-infected subjects. Although SDF-1 protein levels were stable for months among seronegative individuals (mean intrasubject variation, 17%), the absolute values varied widely (0.28 to 106.5 ng/ml; mean, 25.6 ng/ml). In HIV-1-infected subjects, there was a direct correlation between SDF-1 level and CD4+ cell count. Subjects with fewer than 50 CD4+ cells per cubic microliter of blood had significantly lower mean SDF-1 levels (+/-SD) than did either HIV-1-infected subjects with higher CD4+ cell counts or uninfected controls: CD4+ cell count <50, mean SDF-1 level of 10.7+/-33.7, 50 < CD4+ cell count <200, mean SDF-1 level of 12.9+/-19.0, 200 < CD4+ cell count <500, mean SDF-1 level of 19.3+/-36.8; CD4+ cell count >500, mean SDF-1 level of 18.5+/-25.2; uninfected control mean SDF-1 level, 25.6+/-34.7. No significant change in SDF-1 level was detected after administration of antiretroviral therapy in nine subjects with advanced disease (mean intrasubject variation, 43%). Analysis of SDF-1 mRNA expression in lymph nodes from HIV-1-infected subjects at different disease stages revealed that the medullary cords contained stromal cells that express SDF-1 mRNA. This preliminary analysis suggests a possible link between lower SDF-1 levels and disease progression.

The effect of interval tubal sterilization on sexual interest and pleasure

OBJECTIVE To determine if interval tubal sterilization leads to a change in female sexual interest or pleasure and to identify predictors of a positive or negative effect. METHODS Our study population comprised 4576 women enrolled in a prospective, multicenter cohort study between 1978 and 1983. Potential demographic, clinical, and surgical predictors of sexual outcome were tested for significant variation from the overall pattern of unchanged, increased, and decreased sexual interest and pleasure. RESULTS Over 80% of the 4576 study women reported no consistent change in either sexual interest (80.0%) or pleasure (81.7%) after interval tubal sterilization. Among women with consistent change, positive effects were reported ten and 15 times more often than negative effects for sexual interest and pleasure, respectively. All subgroups of women, except for those with poststerilization regret, were significantly (P < .05) more likely to experience increased rather than decreased interest or pleasure. Women with poststerilization regret were the subgroup most likely to have a negative effect; in multivariate analyses, poststerilization regret was the only factor to be a predictor for decreased interest (odds ratio 4.0) and decreased pleasure (odds ratio 5.1). Similarly, women reporting regret were significantly less likely to report increased interest or pleasure. Whether the regret or the decreased sexual interest or pleasure occurred first is unclear. CONCLUSION Interval tubal ligation is unlikely to result in changed sexual interest or pleasure. Among those with change, the majority experienced positive sexual effects.

Characteristics of HLA Class I and Class II Polymorphisms in Rwandan Women

Objective: To define HLA class I and class II polymorphisms in Rwandans. Methods: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. Results: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were ≥0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. Discussion: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.

Survival of blood donors and their spouses with HIV-1 subtype E (CRF01 A_E) infection in northern Thailand, 1992-2007

Objectives:To evaluate the survival patterns among adults in Thailand 8–14 years after HIV-1 subtype E (CRF01 A_E) infection. Design:Follow-up for the current vital status of adults who were estimated to have had incident HIV-1 subtype E infection 8–14 years previously. Methods:Data on the survival of a population of HIV-1-infected male blood donors and their seropositive wives was obtained during March–April 2007. These subjects were identified from a subpopulation of 150 individuals whose seroconversion interval was estimated to be less than 2 years and who were enrolled in 1992–1997. National registration, vital records, and death certificates, as appropriate, were obtained and Kaplan–Meier survival curves were constructed for the entire population, for males and females, and for individuals above and equal to or below the median age at infection. Results:The vital status was obtained for 138 of 150 subjects (92%). The overall median survival was 8.2 [95% confidence interval (CI) 7.1–9.4] years. The median survival did not differ significantly between men and women or in those above or below the median age. Conclusion:The median survival of 8.2 years in this population of young adults in Thailand was significantly less than that reported among persons of similar age in high-income countries or in eastern or southern Africa. The survival among individuals in Thailand infected with HIV-1 subtype E appears to be similar to that reported among individuals in Africa infected with HIV-1 subtype D.

Seroprevalence of Human Herpesvirus 8 Infection in Northern Thailand

BACKGROUND Human herpesvirus 8 (HHV-8) is associated with Kaposi sarcoma (KS) in patients with acquired immunodeficiency syndrome (AIDS) and KS, classical KS, or endemic KS. Because human immunodeficiency virus (HIV) infections and HIV/AIDS are common in Thailand but KS is very rare (only 0.2% of reported patients with AIDS in Thailand had KS), we determined the HHV-8 seroprevalence among populations who were HIV positive or at risk of HIV infection. METHODS A total of 992 persons from 2 populations underwent testing for lytic antibodies to HHV-8 using an immunofluorescence assay involving a BCBL-1 cell line at serum dilutions of 1 : 50 and 1 : 100. Serum specimens with positive results were titered to end points. Subjects included approximately 400 married couples in which the husband was HIV positive and the wife was HIV positive (200 couples) or HIV negative (200 couples). In addition, 200 HIV-negative men from a sexually transmitted diseases (STD) clinic were studied. RESULTS The antibody prevalence was 24.2% in the total population. The prevalence was higher among HIV-negative men (13.0%) but was similar among HIV-positive women (27.9%) and HIV-negative women (23.8%). The HHV-8 seroprevalence among wives whose husbands were HIV-1 positive did not differ according to their husbands HHV-8 status. There was no association between HHV-8 seroprevalence and reported sexual behavior or STD history. CONCLUSION Despite the rarity of KS among patients with AIDS in Thailand, HHV-8 infections are common and do not appear to be frequently transmitted sexually in these populations.

Lymphocyte homeostasis in HIV-infected northern Thais

Cross-sectional laboratory data were used to model the patterns of total lymphocyte count and lymphocyte subpopulation counts among persons with chronic HIV-1 subtype E (CRF01_AE) infection during the 6.5 years preceding death. The data cover 331 HIV-infected decedents from a heterosexual HIV transmission study of 590 northern Thai couples enrolled in 1992-1998. From blood collected at enrollment, the lymphocyte phenotypes (CD3, CD8, CD4, natural killer, and B cells) were stained using two-color monoclonal antibody combinations and quantified by flow cytometry. Piecewise linear splines modeled the associations between lymphocyte levels and time before death. Mean CD3, CD8, and B cell levels showed no temporal associations from 6.5 to 2 years before death, but each declined significantly during the 2 years before death. CD3 levels declined 31.0% [95% confidence interval (-40.3%, -19.8%)] and CD8 levels declined 24.6% (-35.4%, -13.5%) annually in the 2 years prior to death. In contrast, CD4 and NK cell levels declined little from 6.5 to 4.5 years before death but declined significantly over the 4.5 years prior to death. CD4 levels declined 22.1% (-29.2%, -12.0%) annually from 4.5 to 2 years prior to death and 63.7% (-72.3%, -53.6%) annually over the remaining 2 years. Similar lymphocyte patterns have been reported in U. S. and European populations with HIV-1 subtype B infection.