[Show abstract][Hide abstract] ABSTRACT: Despite advances in treatment of people living with HIV, morbidity and mortality remains unacceptably high in sub-Saharan Africa, largely due to parallel epidemics of poverty and food insecurity.
We conducted a pilot cluster randomized controlled trial (RCT) of a multisectoral agricultural and microfinance intervention (entitled Shamba Maisha) designed to improve food security, household wealth, HIV clinical outcomes and women's empowerment. The intervention was carried out at two HIV clinics in Kenya, one randomized to the intervention arm and one to the control arm. HIV-infected patients >18 years, on antiretroviral therapy, with moderate/severe food insecurity and/or body mass index (BMI) <18.5, and access to land and surface water were eligible for enrollment. The intervention included: 1) a microfinance loan (~$150) to purchase the farming commodities, 2) a micro-irrigation pump, seeds, and fertilizer, and 3) trainings in sustainable agricultural practices and financial literacy. Enrollment of 140 participants took four months, and the screening-to-enrollment ratio was similar between arms. We followed participants for 12 months and conducted structured questionnaires. We also conducted a process evaluation with participants and stakeholders 3-5 months after study start and at study end.
Baseline results revealed that participants at the two sites were similar in age, gender and marital status. A greater proportion of participants at the intervention site had a low BMI in comparison to participants at the control site (18% vs. 7%, p = 0.054). While median CD4 count was similar between arms, a greater proportion of participants enrolled at the intervention arm had a detectable HIV viral load compared with control participants (49% vs. 28%, respectively, p < 0.010). Process evaluation findings suggested that Shamba Maisha had high acceptability in recruitment, delivered strong agricultural and financial training, and led to labor saving due to use of the water pump. Implementation challenges included participant concerns about repaying loans, agricultural challenges due to weather patterns, and a challenging partnership with the microfinance institution. We expect the results from this pilot study to provide useful data on the impacts of livelihood interventions and will help in the design of a definitive cluster RCT.
This trial is registered at ClinicalTrials.gov, NCT01548599.
[Show abstract][Hide abstract] ABSTRACT: AimsWe examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes after HIV care entry overall and by several factors. We also compared using phosphatidylethanol (PEth, an alcohol biomarker) to augment self-report to using self-report alone.DesignProspective one-year observational cohort study with quarterly visits.SettingLarge rural HIV clinic in Mbarara, Uganda.Participants208 adults (89 women and 119 men) entering HIV care, reporting any prior year alcohol consumption.MeasurementsUnhealthy drinking was PEth + (≥50 ng/ml) or Alcohol Use Disorders Test – Consumption + (AUDIT-C+, over 3 months, women ≥3; men ≥4). We calculated adjusted odds ratios (AOR) for unhealthy drinking per month since baseline, and interactions of month since baseline with perceived health, number of HIV symptoms, anti-retroviral therapy (ART), gender, and self-reported prior unhealthy alcohol use.FindingsThe majority of participants (64%) were unhealthy drinkers (PEth + or AUDIT-C+) at baseline. There was no significant trend in unhealthy drinking overall (per-month AOR: 1.01; 95% CI: 0.94-1.07), while the per-month AORs were 0.91 (95% CI: 0.83-0.99) and 1.11 (95% CI: 1.01-1.22) when participants were not yet on ART and on ART, respectively (interaction p-value <0.01). In contrast, 44% were AUDIT-C+; the per-month AORs for being AUDIT-C+ were 0.89 (95% CI: 0.85-0.95) overall, and 0.84 (95% CI: 0.78-0.91) and 0.97 (95% CI: 0.89-1.05) when participants were not on and on ART, respectively.Conclusions
Unhealthy alcohol use among Ugandan adults entering HIV care declines prior to the start of anti-retroviral therapy but rebounds with time. Augmenting self-reported alcohol use with biomarkers increases the ability of current alcohol use measurements to detect unhealthy alcohol use. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Food insecurity and HIV/AIDS outcomes are inextricably linked in sub-Saharan Africa. We report on health and nutritional outcomes of a multisectoral agricultural intervention trial among HIV-infected adults in rural Kenya.
This is a pilot cluster randomized controlled trial.
The intervention included a human-powered water pump, a microfinance loan to purchase farm commodities, and education in sustainable farming practices and financial management. Two health facilities in Nyanza Region, Kenya were randomly assigned as intervention or control. HIV-infected adults 18 to 49 years' old who were on antiretroviral therapy and had access to surface water and land were enrolled beginning in April 2012 and followed quarterly for 1 year. Data were collected on nutritional parameters, CD4 T-lymphocyte counts, and HIV RNA. Differences in fixed-effects regression models were used to test whether patterns in health outcomes differed over time from baseline between the intervention and control arms.
We enrolled 72 and 68 participants in the intervention and control groups, respectively. At 12 months follow-up, we found a statistically significant increase in CD4 cell counts (165 cells/μl, P < 0.001) and proportion virologically suppressed in the intervention arm compared with the control arm (comparative improvement in proportion of 0.33 suppressed, odds ratio 7.6, 95% confidence interval: 2.2-26.8). Intervention participants experienced significant improvements in food security (3.6 scale points higher, P < 0.001) and frequency of food consumption (9.4 times per week greater frequency, P = 0.013) compared to controls.
Livelihood interventions may be a promising approach to tackle the intersecting problems of food insecurity, poverty and HIV/AIDS morbidity.
No preview · Article · Jul 2015 · AIDS (London, England)
[Show abstract][Hide abstract] ABSTRACT: Exposure to psychological stress and depression are associated with shorter white blood cell telomere length (TL) in adults, possibly via associated lifelong oxidative stressors. Exposure to maternal depression increases risk for future depression and behavior problems in children, and Latino youth are at high risk. Few studies have evaluated the role of exposure to maternal depression or child behavior in relation to TL in children. We assessed early-childhood exposures to maternal depression from birth to the age of 5 years and child behavior from ages 3-5 years in a cohort of Latino children in relation to child leukocyte TL at ages 4 and 5 years. Children who had oppositional defiant behavior at 3, 4 or 5 years had shorter TL than those without by ~450 base pairs (P<0.01). In multivariate analyses, independent predictors for shorter TL at 4 and 5 years of age included oppositional defiant disorder at 3, 4 or 5 years (β=-359.25, 95% CI -633.84 to 84.66; P=0.01), exposure to maternal clinical depression at 3 years of age (β=-363.99, 95% CI -651.24 to 764.74; P=0.01), shorter maternal TL (β=502.92, 95% CI 189.21-816.63) and younger paternal age at the child's birth (β=24.63, 95% CI 1.14-48.12). Thus, exposure to maternal clinical depression (versus depressive symptoms) in early childhood was associated with deleterious consequences on child cellular health as indicated by shorter TL at 4 and 5 years of age. Similarly, children with oppositional defiant behavior also had shorter TL, possibly related to early exposures to maternal clinical depression. Our study is the first to link maternal clinical depression and oppositional defiant behavior with shorter TL in the preschool years in a relatively homogenous population of low-income Latino children.
Preview · Article · Jun 2015 · Translational Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Objective To determine whether the Sjögren's syndrome B (SSB)-positive/Sjögren's syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS.
Methods Among registrants in the Sjögren's International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders.
Results Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria.
Conclusions The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.
Full-text · Article · Mar 2015 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Smoking as a risk factor for oral candidiasis in HIV-infected adults. Chattopadhyay A, Patton LL. J Oral Pathol Med 2013;42(4):302-08.
Caroline H. Shiboski, DDS, MPH, PhD, Stephen C. Shiboski, PhD PURPOSE/QUESTION: Is smoking an independent risk factor for OC among adults with HIV/AIDS, and does smoking modify the relationship between OC and other important risk factors like CD4 cell count?
This investigation was supported by USPHS Grant 5T32DE07191, P30-HD27360, and R29DE11369 from the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA TYPE OF STUDY/DESIGN: Cohort study
Level 2: Limited-quality, patient-oriented evidence
No preview · Article · Dec 2013 · The journal of evidence-based dental practice
[Show abstract][Hide abstract] ABSTRACT: Background Anal cancer is more common in women than in men, yet little is known about the natural history of HPV in women. The objective was to examine the natural history of anal HPV in heterosexual women and to examine risk factors associated with persistence. Methods: Young women participating in a HPV cohort study were seen at 4-month intervals for cervical and anal testing for HPV DNA. The distribution of time to clearance was estimated using the Kaplan-Meier approach, and risks for persistence assessed using Cox regression models. Results: Seventy-five women (mean age 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high risk (HR) HPV, 82.6% of low risk (LR) HPV and 76.2% of HPV16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV 16 (P=0.009) or any HR HPV (P=0.046) detection, weekly alcohol use (P=0.018), anal touching during sex (P=0.034), and ever having anal sex (P=0.06) were associated with HPV 16 persistence. Having a new sex partner (P<0.001) and condom use during vaginal sex (P=0.06) were associated with clearance. Similar associations were found for clearance all HR HPV infections. Only concomitant cervical HPV infection was associated with non-16 HR HPV persistence. Conclusions: The majority of anal HPV infections cleared within 3 years. HPV 16 infections were slower to clear than other HR HPV, consistent with its role in anal cancer. Sexual behaviour was associated with persistence, suggesting that education and behavioural interventions may decrease persistence and the risk of anal cancer.
[Show abstract][Hide abstract] ABSTRACT: Background. The purpose of this study was to examine the rate of and risks for cervical HPV16 redetection in women with documented or suspected HPV16 infection.Methods. A convenience sample of women aged 13-21 years were seen at 4-month intervals for HPV DNA testing and cytology. Sera was obtained at baseline and annually.Results. 1,543 women entered the study. Of the 295 women with detection of HPV16 DNA and subsequent clearance, 18.1% had HPV16 redetected by 8.5 years-88% cleared this 2(nd) detection by 3 years. Of the 247 women who had antibodies to HPV16 and were HPV16 DNA negative at baseline, 15.3% had HPV16 redetected by year 5. Risks for redetection included douching, current use of medroxyprogesterone, reporting >1 sex partner or having a new sex partner and having a sexually transmitted infection. Development of CIN 2/3 was rare in women with redetection except for those with a prevalent HPV16.Conclusions. Reappearance of HPV16 DNA was observed in 18% of women. Most are associated with sexual exposure and appear benign. Interpretation of the studies is more complex in women with prevalent infections since it appears that this small subset reflects women with persistence already present at entry.
Preview · Article · Apr 2013 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
Because many human papillomavirus (HPV) infections are transient, rates of transmission may be miscalculated if the interval between testing spans several months. We examined rates of concordance and transmission in heterosexual couples over short intervals.
Twenty-five adult couples were enrolled and sampled for HPV DNA from the genitals, hand, and mouth 5 times over a 6-week period, including 24 hours after sexual intercourse and after 48 hours of abstinence. Concordance and transmission patterns were described.
Concordance between the couple's genital sites ranged from 64% to 95% for at least 1 HPV type. The highest rates of concordance were observed 24 hours after sexual intercourse. A similar peak in concordance was not seen between genital and nongenital anatomic sites. Transmission rates for female genital to male genital ranged from 26.8 to 187.5 per 100 person-months and for male genital to female genital from 14.5 to 100 per 100 person-months.
High rates of concordance shortly after intercourse suggest that some DNA detections in the genital area are contaminants from a partner and not established HPV infections. Female-to-male transmission appeared more common than male-to-female transmission.
No preview · Article · Jan 2013 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
Bacterial vaginosis (BV) has been linked to female HIV acquisition and transmission. We investigated the effect of providing a latex diaphragm with Replens and condoms compared to condom only on BV prevalence among participants enrolled in an HIV prevention trial.
We enrolled HIV-seronegative women and obtained a vaginal swab for diagnosis of BV using Nugent's criteria; women with BV (score 7-10) were compared to those with intermediate (score 4-6) and normal flora (score 0-3). During quarterly follow-up visits over 12-24 months a vaginal Gram stain was obtained. The primary outcome was serial point prevalence of BV during followup.
528 participants were enrolled; 213 (40%) had BV at enrollment. Overall, BV prevalence declined after enrollment in women with BV at baseline (OR = 0.4, 95% CI 0.29-.56) but did not differ by intervention group. In the intention-to-treat analysis BV prevalence did not differ between the intervention and control groups for women who had BV (OR = 1.01, 95% CI 0.52-1.94) or for those who did not have BV (OR = 1.21, 95% CI 0.65-2.27) at enrollment. Only 2.1% of participants were treated for symptomatic BV and few women (5-16%) were reported using anything else but water to cleanse the vagina over the course of the trial.
Provision of the diaphragm, Replens, and condoms did not change the risk of BV in comparison to the provision of condoms alone.
Full-text · Article · Oct 2012 · Infectious Diseases in Obstetrics and Gynecology
[Show abstract][Hide abstract] ABSTRACT: We investigated human cytomegalovirus pathogenesis by comparing infection with the low-passage, endotheliotropic strain VR1814 and the attenuated laboratory strain AD169 in human placental villi as explants in vitro and xenografts transplanted into kidney capsules of SCID mice (ie, mice with severe combined immunodeficiency). In this in vivo human placentation model, human cytotrophoblasts invade the renal parenchyma, remodel resident arteries, and induce a robust lymphangiogenic response. VR1814 replicated in villous and cell column cytotrophoblasts and reduced formation of anchoring villi in vitro. In xenografts, infected cytotrophoblasts had a severely diminished capacity to invade and remodel resident arteries. Infiltrating lymphatic endothelial cells proliferated, aggregated, and failed to form lymphatic vessels. In contrast, AD169 grew poorly in cytotrophoblasts in explants, and anchoring villi formed normally in vitro. Likewise, viral replication was impaired in xenografts, and cytotrophoblasts retained invasive capacity, but some partially remodeled blood vessels incorporated lymphatic endothelial cells and were permeable to blood. The expression of both vascular endothelial growth factor (VEGF)-C and basic fibroblast growth factor increased in VR1814-infected explants, whereas VEGF-A and soluble VEGF receptor-3 increased in those infected with AD169. Our results suggest that viral replication and paracrine factors could undermine vascular remodeling and cytotrophoblast-induced lymphangiogenesis, contributing to bleeding, hypoxia, and edema in pregnancies complicated by congenital human cytomegalovirus infection.
Full-text · Article · Sep 2012 · American Journal Of Pathology
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:: Human papillomavirus (HPV), one of the commonest sexually transmitted infections, may be a cofactor in HIV acquisition. We systematically reviewed the evidence for an association of HPV infection with HIV acquisition in women, heterosexual men and men who have sex with men (MSM). DESIGN:: Systematic review and meta-analysis. METHODS:: Studies meeting inclusion criteria in Pubmed, Embase and conference abstracts up to 29/07/2011 were identified. Random effects meta-analyses were performed to calculate summary hazard ratios (HR). Publication bias and statistical heterogeneity were evaluated and population attributable fractions (PAFs) calculated. RESULTS:: Eight papers were included, with previously unpublished data from five authors. Seven studies found an association between prevalent HPV and HIV acquisition. Risk of HIV acquisition in women doubled with prevalent HPV infection with any genotype (HR = 2.06 (95%CI = 1.44-2.94), I = 0%), although adjustment for confounders was often inadequate. The effect was similar for high-risk (HR = 1.99 (95%CI = 1.54-2.56), I = 8.4%) and low-risk (HR = 2.01 (95%CI = 1.27-3.20), I = 0%) HPV genotypes with weak evidence of publication bias (P = 0.06). Two studies in men were identified: both showed an association between HPV infection and HIV acquisition. Unpublished data from one of two studies in women indicated an association between genotypes targeted by HPV vaccines and HIV acquisition. PAFs for HIV attributable to infection with any HPV genotype ranged between 21% and 37%. CONCLUSION:: If further studies validate the association between HPV infection and HIV acquisition, HPV vaccines may reduce HIV incidence in high HPV prevalence populations, in addition to preventing cervical cancer. HIV surveillance studies during implementation of HPV vaccine programmes are warranted.
Full-text · Article · Aug 2012 · AIDS (London, England)
[Show abstract][Hide abstract] ABSTRACT: Vulnerability of younger women to human papillomavirus 16 (HPV16) infection has been attributed to the predominance of ectocervical columnar epithelia in this age group. However, squamous metaplastic tissue may be more influential. We examined the extent of ectopy and metaplastic activity as risks for HPV16 acquisition in a prospective cohort.
Participants were HPV16 negative at the first two visits. Follow-up occurred every 4 months. Ectopy was quantitatively measured on colpophotographs. We calculated metaplastic rate as the difference in ectopy between visits. Cox proportional hazards models were constructed, adjusting for several covariates.
Analyses included 198 women (mean baseline age 17 years) for 1734 visits. Mean follow-up was 4.4 years. Incident HPV16 was detected in 36 (18%) women. Metaplastic rate between the two visits before HPV16 detection was significantly associated with incident infection (hazard ratio [HR], 1.17; confidence interval [CI], 1.02-1.33; P = .02). However, ectopy was not significant, whether measured before or concurrent to HPV16 detection (HR range, 0.99-1.00; CI range, .97-1.02; P range, .47-.65).
Dynamic metaplasia rather than the sheer extent of ectopy appears to increase risk for incident HPV16 in healthy young women. This in vivo observation is consistent with the HPV life cycle, during which host cell replication and differentiation supports viral replication.
Preview · Article · Jun 2012 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: To study the prevalence of extraglandular manifestations in primary Sjögren's syndrome (SS) among participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry.
A total of 1,927 participants in the SICCA registry were studied, including 886 participants who met the 2002 American-European Consensus Group (AECG) criteria for primary SS, 830 "intermediate" cases who had some objective findings of primary SS but did not meet AECG criteria, and 211 control individuals. We studied the prevalence of immunologic and hematologic laboratory abnormalities, specific rheumatologic examination findings, and physician-confirmed thyroid, liver, and kidney disease, as well as lymphoma among SICCA participants.
Laboratory abnormalities, including hematologic abnormalities, hypergammaglobulinemia, and hypocomplementemia, frequently occurred among primary SS cases and were more common among the intermediate cases than among control participants. Cutaneous vasculitis and lymphadenopathy were also more common among primary SS cases. In contrast, the frequency of physician-confirmed diagnoses of thyroid, liver, and kidney disease and lymphoma was low and only primary biliary cirrhosis was associated with primary SS case status. Rheumatologic and neurologic symptoms were common among all SICCA participants, regardless of case status.
Data from the international SICCA registry support the systemic nature of primary SS, manifested primarily in terms of specific immunologic and hematologic abnormalities. The occurrence of other systemic disorders among this cohort is relatively uncommon. Previously reported associations may be more specific to select patient subgroups, such as those referred for evaluation of certain neurologic, rheumatologic, or other systemic manifestations.