Showing papers in "Journal of Acquired Immune Deficiency Syndromes in 2011"

Depression and HIV/AIDS treatment nonadherence: A review and meta-analysis

Abstract: We meta-analyzed the relationship between depression and HIV medication nonadherence to calculate the overall effect size and examine potential moderators. Overall, across 95 independent samples, depression was significantly (P < 0.0001) associated with nonadherence (r = 0.19; 95% confidence interval = 0.14 to 0.25). Studies evaluating medication adherence via interview found significantly larger effects than those using self-administered questionnaires. Studies measuring adherence along a continuum found significantly stronger effects than studies comparing dichotomies. Effect size was not significantly related to other aspects of adherence or depression measurement, assessment interval (ie, cross-sectional vs. longitudinal), sex, IV drug use, sexual orientation, or study location. The relationship between depression and HIV treatment nonadherence is consistent across samples and over time, is not limited to those with clinical depression, and is not inflated by self-report bias. Our results suggest that interventions aimed at reducing depressive symptom severity, even at subclinical levels, should be a behavioral research priority.

Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis.

Abstract: Objective To determine whether interferon-gamma release assays (IGRAs) improve the identification of HIV-infected individuals who could benefit from latent tuberculosis infection therapy. Design Systematic review and meta-analysis. Methods We searched multiple databases through May 2010 for studies evaluating the performance of the newest commercial IGRAs (QuantiFERON-TB Gold In-Tube [QFT-GIT] and T-SPOT.TB [TSPOT]) in HIV-infected individuals. We assessed the quality of all studies included in the review, summarized results in prespecified subgroups using forest plots, and where appropriate, calculated pooled estimates using random effects models. Results The search identified 37 studies that included 5736 HIV-infected individuals. In three longitudinal studies, the risk of active tuberculosis was higher in HIV-infected individuals with positive versus negative IGRA results. However, the risk difference was not statistically significant in the two studies that reported IGRA results according to manufacturer-recommended criteria. In persons with active tuberculosis (a surrogate reference standard for latent tuberculosis infection), pooled sensitivity estimates were heterogeneous but higher for TSPOT (72%; 95% confidence interval [CI], 62-81%) than for QFT-GIT (61%; 95% CI, 47-75%) in low-/middle-income countries. However, neither IGRA was consistently more sensitive than the tuberculin skin test in head-to-head comparisons. Although TSPOT appeared to be less affected by immunosuppression than QFT-GIT and the tuberculin skin test, overall, differences among the three tests were small or inconclusive. Conclusions Current evidence suggests that IGRAs perform similarly to the tuberculin skin test at identifying HIV-infected individuals with latent tuberculosis infection. Given that both tests have modest predictive value and suboptimal sensitivity, the decision to use either test should be based on country guidelines and resource and logistic considerations.

Male Antenatal Attendance and HIV Testing Are Associated with Decreased Infant HIV Infection and Increased HIV Free Survival

Abstract: Objective To investigate the relationship between male involvement in prevention of mother-to-child HIV transmission (PMTCT) services and infant HIV acquisition and mortality a prospective cohort study was undertaken between 1999 and 2005 in Nairobi, Kenya.

Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Québec's public health insurance database.

Abstract: Background: Morbidity associated with cardiovascular disease is increasing in the HIV-infected population. We aimed to study the impact of HIV and of antiretrovirals on acute myocardial infarction (AMI). Methods: We performed a cohort and a nested case-control study using the dataset of the Regie de l'Assurance Maladie du Quebec. HIV-positive patients were identified using ICD-9 diagnostic codes and matched to HIV-negative patients. Within the HIV-positive cohort, cases of AMI were identified and matched to HIV-positive patients without AMI. The coprimary outcomes were the risk of AMI associated with HIV exposure in the cohort study and that associated with exposure to antiretrovirals in the case-control study. Data were analysed using Poisson and conditional logistic regression. Results: About 7053 HIV-positive patients were matched to 27,681 HIV-negative patients. Incidence rates of AMI in the HIV+ cohort was 3.88 95% confidence interval (CI) (3.26 to 4.58) per 1000 patient-years, compared to 2.21 95% CI (1.93 to 2.52) per 1000 patient-years in the HIV cohort. The adjusted incidence ratio of AMI for HIV-infected patients was 2.11 95%CI (1.69 to 2.63). Among HIV+ patients, 125 AMI cases were matched with 1084 HIV+ patients. We found increased odds ratio (95% CI) of AMI associated with any exposure to abacavir 1.79 (1.16 to 2.76), P = 0.02, efavirenz 1.83 (1.21 to 2.76) P = 0.004, lopinavir 1.98 (1.24 to 3.16) P = 0.004, and ritonavir 2.29 (1.48 to 3.54) P < 0.001. Conclusions: HIV+ individuals were at higher risk of AMI than the general population, and several antiretrovirals were associated with an increased risk of AMI. Results should be interpreted with caution in absence of data on smoking and HIV clinical status.

HIV treatment outcomes among HIV-infected, opioid-dependent patients receiving buprenorphine/naloxone treatment within HIV clinical care settings: results from a multisite study

Abstract: Background Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes.

Unnecessary Antiretroviral Treatment Switches and Accumulation of HIV Resistance Mutations; Two Arguments for Viral Load Monitoring in Africa

Abstract: Results: Of 250 patients with CIF switching to second-line ART, targeted VL was performed in 186. Unnecessary switch at reference HIV RNA ,1000 copies per milliliter occurred in 46.9% of CIF only patients versus 12.4% of patients with targeted VL (P , 0.001). NRTI cross-resistance was observed in 48.0% of 183 specimens available for genotypic analysis, comprising $2 TAMs (37.7%), K65R (7.1%), K70E (3.3%), or Q151M (3.3%). The presence of NRTI cross-resistance was associated with the duration of ART exposure and zidovudine use. Conclusions: Clinicoimmunological monitoring without viral load testing resulted in frequent unnecessary regimen switches. Prolonged treatment failure was indicated by extensive NRTI cross-resistance. Access to virological monitoring should be expanded to prevent inappropriate switches, enable early failure detection and preserve second-line treatment options in Africa.

Distribution of antiretroviral treatment through self-forming groups of patients in Tete province, Mozambique

Abstract: BACKGROUND As antiretroviral treatment cohorts continue to expand, ensuring patient retention over time is an increasingly important concern. This, together with capacity and human resource constraints, has led to the consideration of out-of-clinic models for the delivery of antiretroviral therapy (ART). In 2008, Medecins Sans Frontieres and the Provincial authorities launched a model of ART distribution and adherence monitoring by community groups in Tete Province, Mozambique. PROGRAMME APPROACH: Patients who were stable on ART for 6 months were informed about the community ART group model and invited to form groups. Group members had 4 key functions: facilitate monthly ART distribution to other group members in the community, provide adherence and social support, monitor outcomes, and ensure each group member undergoes a clinical consultation at least once every 6 months. Group members visit the health centre on a rotational basis, such that each group member has contact with the health service every 6 months. RESULTS Between February 2008 and May 2010, 1384 members were enrolled into 291 groups. Median follow-up time within a group was 12.9 months (IQR 8.5-14.1). During this time, 83 (6%) were transferred out, and of the 1301 patients still in community groups, 1269 (97.5%) were remaining in care, 30 (2%) had died, and 2 (0.2%) were lost to follow-up. DISCUSSION The Community ART Group model was initiated by patients to improve access, patient retention, and decongest health services. Early outcomes are highly satisfactory in terms of mortality and retention in care, lending support to such out-of-clinic approaches.

Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection.

Abstract: Author(s): Lyons, Jennifer L; Uno, Hajime; Ancuta, Petronela; Kamat, Anupa; Moore, David J; Singer, Elyse J; Morgello, Susan; Gabuzda, Dana | Abstract: ObjectiveMild forms of HIV-associated neurocognitive disorders (HAND) remain prevalent in the era of combination antiretroviral therapy (cART). Although elevated lipopolysaccharide (LPS) and immune activation are implicated in HAND pathogenesis, relationships of LPS and inflammatory markers to mild forms of HAND or impairment in specific cognitive domains are unknown. To examine these relationships, we compared plasma soluble CD14 (sCD14), CCL2, and LPS levels with neurocognitive test scores in a cART era cohort.MethodsWe analyzed plasma from HIV+ subjects (n = 97) with nadir CD4 counts l300 and high frequency of hepatitis C virus coinfection and illicit drug use for relationships between sCD14, CCL2, and LPS levels and neurocognitive test scores.ResultsPlasma sCD14 levels were higher in subjects with test scores indicating global impairment (P = 0.007), particularly in attention and learning domains (P = 0.015 and P = 0.03, respectively), regardless of HAND diagnosis. Plasma sCD14 levels correlated inversely with global, attention, and learning T scores (P = 0.036, 0.047, and 0.007, respectively) and yielded higher area under receiver operating characteristic values for predicting impaired scores than single-marker models based on plasma or cerebrospinal fluid viral load or CD4 count (area under receiver operating characteristic values = 0.71, 0.81, and 0.71, respectively) and in 4-marker models based on plasma sCD14 and 3 conventional markers compared with the 3-marker models.ConclusionsPlasma sCD14 is a biomarker associated with impaired neurocognitive testing in attention and learning domains in HIV-infected individuals with advanced disease, suggesting involvement of cortical and limbic pathways by inflammatory processes in the cART era. Plasma sCD14 is a potential biomarker to monitor HAND progression and therapeutic responses.

HIV partner notification is effective and feasible in sub-Saharan Africa: opportunities for HIV treatment and prevention.

Abstract: BACKGROUND: Sexual partners of persons with newly diagnosed HIV infection require HIV counseling testing and if necessary evaluation for therapy. However many African countries do not have a standardized protocol for partner notification and the effectiveness of partner notification has not been evaluated in developing countries . METHODS: Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe Malawi were randomized to 1 of 3 methods of partner notification: passive referral contract referral or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group a health care provider notified partners directly. RESULTS: Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252. Among locatable partners 107 returned for HIV counseling and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners returned in the passive referral arm 45 of 88 (51%; 95% CI: 41% to 62%) in the contract referral arm and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider referral arm (P < 0.001). Among returning partners (n = 107) 67 (64%) of were HIV infected with 54 (81%) newly diagnosed. DISCUSSION: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible acceptable and effective among sexually transmitted infections clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.

Changes in inflammatory and coagulation biomarkers: A randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection

Abstract: Ojectives—Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naive to antiretroviral therapy (ART) or off ART (≥6 months) at study entry, risk of AIDS and serious non-AIDS events was increased for participants who deferred ART compared to those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Methods—Stored specimens for 254 participants (126 DC and 128 VS) who were naive to ART or off ART (≥6 months) were analyzed for interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) and D-dimer at baseline and months 2 and 6. Results—At month 6, 62% of VS group had HIV RNA <400copies/mL and median CD4 count was 190 cells/mm 3 higher than for the DC group (590 vs. 400 cells/mm 3 ). Compared with DC, the VS group had 32% (95%CI: 19 to 43%) lower D-dimer levels at month 6 (p<0.001); differences were not significant for hsCRP or IL-6 levels.

Transactional sex amongst AIDS-orphaned and AIDS-affected adolescents predicted by abuse and extreme poverty.

Abstract: This studys objectives were to (1) determine whether familial AIDS is associated with severe physical emotional and sexual abuse and with transactional sexual exploitation; and (2) explore whether relationships between familial AIDS and transactional sex are mediated by extreme poverty and abuse. The authors conducted a self-report study of adolescents in deprived South African communities. The sample included AIDS-orphaned (n = 236) other-orphaned (n = 231) and non-orphaned (n = 220) adolescents whose primary caregivers were sick from AIDS (n = 109) sick by other causes (n = 147) and healthy (n = 220). Abuse and transactional sex were measured with widely used and validated self-reporting measures. AIDS orphanhood and parental AIDS sickness predicted emotional and physical abuse and transactional sexual exploitation. Orphanhood or parental sickness by non-AIDS causes and having healthy caregivers did not predict any abuse outcomes. Adolescents affected by both AIDS orphanhood and sickness showed a three-fold likelihood of severe emotional and physical abuse and amongst girls a six-fold likelihood of transactional sexual exploitation compared with those in healthy families. Heightened risk of transactional sex amongst adolescents in AIDS-affected families was mediated by extreme poverty and abuse exposure. In combination the effects of familial AIDS food insecurity and exposure to abuse raised prevalence of transactional sex amongst girls from 1% to 57%.

Retention in HIV care for individuals not yet eligible for antiretroviral therapy: rural KwaZulu-Natal, South Africa

Abstract: Objectives To determine retention in HIV care for individuals not yet eligible for antiretroviral therapy (ART) and to explore factors associated with retention in a rural public health HIV programme.

Changes in Programmatic Outcomes During 7 Years of Scale-up at a Community-Based Antiretroviral Treatment Service in South Africa

Abstract: OBJECTIVES: To assess sustainability of programmatic outcomes in a community-based antiretroviral therapy (ART) service in South Africa during 7 years of scale-up. METHODS: Prospective cohort of treatment-naive patients aged ≥ 15 years enrolled between 2002 and 2008. Data were analyzed by calendar period of ART initiation using time-to-event analysis and logistic regression. RESULTS: ART was initiated by 3162 patients (67% women; median age, 34 years) who were followed-up for a median of 2.4 years (interquartile range, 1.2-3.8). After 6 years, the cumulative probability of death and loss to follow-up (LTFU) was 37.4%. The probabilities of transfer-out to another ART service and of virological failure were 21.6% and 23.1%, respectively. Low mortality risk and excellent virological and immunological responses during the first year of ART were not associated with calendar period of ART initiation. In contrast, risk of LTFU and virological failure both increased between successive calendar periods in unadjusted and adjusted analyses. The number of patients per member of clinic staff increased markedly over time. CONCLUSIONS: Successful early outcomes (low mortality and good immunological and virological responses) were sustained between sequential calendar periods during 7 years of scale-up. In contrast, the increasing cumulative probabilities of LTFU or virological failure may reflect decreasing capacity to adequately support patients during long-term therapy as clinic caseload escalated.

Implementation science for the US President's Emergency Plan for AIDS Relief (PEPFAR).

Abstract: Working with implementing organizations and governments in over 32 countries, the US President’s Emergency Plan for AIDS Relief (PEPFAR) has contributed to the rapid acceleration of HIV treatment access, availability of care and support services, and HIV prevention interventions In the first phase of PEPFAR, these activities were appropriately carried out in an emergency fashion with the goal of using available interventions to reduce mortality and alleviate suffering from HIV disease as quickly and effectively as possible Many lessons have been learned through examination of programs, including simple evaluations and operations research Commensurate with the emergency response, however, state-of-the-art monitoring, evaluation, and research methodologies were not fully integrated or systematically performed In the second phase of PEPFAR, characterized by an increased emphasis on sustainability, programs must demonstrate value and impact to be prioritized within complex and resource-constrained environments In this context, there is a greater demand to causally attribute outcomes to programs Better attribution can be used to inform midcourse corrections in the scale-up of new interventions (eg, male circumcision) or to reevaluate investments in programs for which impact is less clear To meet these demands, PEPFAR is adopting an implementation science (IS) framework to improve the development and effectiveness of its programs at all levels IS is the study of methods to improve the uptake, implementation, and translation of research findings into routine and common practices (the ‘‘know-do’’ or ‘‘evidence to program’’ gap) For example, IS was used to evaluate the routine operational effectiveness of the South African National Prevention of Mother-to-Child Transmission Programme Investigators explored the survival of HIV-free infants across program sites and identified specific sources of variation such as health system factors (eg, limited antenatal visits and lack of syphilis screening) and individual behaviors (eg, breastfeeding practices) By framing the problem through IS, the study revealed opportunities for improving program performance that could be translated into immediate solutions (eg, improving quality of care, infant feeding counseling) In this way, IS proved to be a valuable tool that was used not only to improve program effectiveness, but also to explain what worked, why, and under what circumstances Although no less rigorous than biomedical research dictated by a static protocol with robust internal validity (ie, ‘‘proof-of-concept’’ research with a precisely defined and narrow objective), an IS approach represents a paradigmatic shift in emphasis to greater external validity The IS scope is also broader, seeking to improve program effectiveness and optimize efficiency, including the effective transfer of interventions from one setting to another The methods of IS facilitate making evidence-based choices between competing or combined interventions and improving the delivery of effective and costeffective programs

Clinical outcomes of adolescents and young adults in adult HIV care

Abstract: We sought to describe virologic and clinical retention outcomes among a group of HIV-infected adolescents and young adults (AYA) newly established in an adult HIV clinic compared with matched HIV-infected adults. AYA demonstrated lower rates of HIV-1 virologic suppression and higher rates of HIV-1 viral rebound and loss to follow-up compared with adults. African American AYA had the lowest rates of virologic suppression and the highest rates of viral rebound. Adult providers should consider HIV-infected AYA, particularly African American HIV-infected AYA, to potentially be at high risk for poor clinical outcomes in adult care.

High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques.

Abstract: Fluctuations in susceptibility to HIV or SHIV during the menstrual cycle are currently not fully documented. To address this, the time point of infection was determined in 19 adult female pigtail macaques vaginally challenged during their undisturbed menstrual cycles with repeated, low-dose SHIV(SF162P3) exposures. Eighteen macaques (95%) first displayed viremia in the follicular phase, as compared with 1 macaque (5%) in the luteal phase (P < 0.0001). Due to a viral eclipse phase, we estimated a window of most frequent virus transmission between days 24 and 31 of the menstrual cycle, in the late luteal phase. Thus, susceptibility to vaginal SHIV infection is significantly elevated in the second half of the menstrual cycle when progesterone levels are high and when local immunity may be low. Such susceptibility windows have been postulated before but not definitively documented. Our data support the findings of higher susceptibility to HIV in women during progesterone-dominated periods including pregnancy and contraceptive use.

Psychiatric risk factors for HIV disease progression: the role of inconsistent patterns of antiretroviral therapy utilization.

Abstract: Background In the era of anti-retroviral therapy (ART), depression and substance use predict hastened HIV disease progression but the underlying biological or behavioral mechanisms that explain these effects are not fully understood.

Who gets tested for HIV in a South African urban township? Implications for test and treat and gender-based prevention interventions.

Abstract: Background With increasing calls for linking HIV-infected individuals to treatment and care via expanded testing, we examined sociodemographic and behavioral characteristics associated with HIV testing among men and women in Soweto, South Africa. Methods We conducted a cross-sectional household survey involving 1539 men and 1877 women as part of the community-randomized prevention trial Project ACCEPT/HPTN043 between July 2007 to October 2007. Multivariable logistic regression models, stratified by sex, assessed factors associated with HIV testing and then repeated testing. Results Most women (64.8%) and 28.9% of men reported ever having been tested for HIV, among whom 57.9% reported repeated HIV testing. In multivariable analyses, youth and students had a lower odds of HIV testing. Men and women who had conversations about HIV/AIDS with increasing frequency and who had heard about antiretroviral therapy were more likely to report HIV testing, and repeated testing. Men who had ≥ 12 years of education and who were of high socioeconomic status, and women who were married, who were of low socioeconomic status, and who had children under their care had a higher odds of HIV testing. Women, older individuals, those with higher levels of education, married individuals, and those with children under their care had a higher odds of reporting repeated HIV testing. Uptake of HIV testing was not associated with condom use, having multiple sex partners, and HIV-related stigma. Conclusions Given the low uptake of HIV testing among men and youth, further targeted interventions could facilitate a test and treat strategy among urban South Africans.

Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration.

Abstract: Background: With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa. Methods: Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (2 consecutive unsuppressed viral loads with the second being >1000 copies/mL, after ≥24 weeks of therapy) and switch to second-line. Cox-proportional hazards models stratified by program were used to determine predictors of these outcomes. Results: The 3-year probability of virologic failure among 5485 children was 19.3% (95% confidence interval: 17.6 to 21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared with efavirenz) and exposure to prevention of mother to child transmission regimens were independently associated with failure [adjusted hazard ratios (95% confidence interval): 1.77 (1.11 to 2.83), 2.39 (1.57 to 3.64) and 1.40 (1.02 to 1.92), respectively]. Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (interquartile range) months between failure and switch was 5.7 (2.9-11.0). Conclusions: Triple ART based on nevirapine or ritonavir as a single protease inhibitor seems to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.

Providing immediate CD4 count results at HIV testing improves ART initiation.

Abstract: BACKGROUND: In South Africa CD4 count results are typically available within a week of testing. However 35%-55% of newly diagnosed HIV-positive patients do not return for their CD4 results and therefore do not access further care. We evaluated the impact of a CD4 count result and patient written information provided immediately after diagnosis on retention in care. METHODS: HIV-infected subjects were randomized to 3 arms; receipt of a CD4 result at time of HIV diagnosis receipt of written information and standard of care (CD4 collection after 1 week) or standard of care alone. The outcome of interest was enrollment for further care within 1 month for pre-antiretroviral therapy (ART) care or within 3 months for ART initiation. Secondary outcome was time taken from diagnosis to each stage of care pathway. Independent predictors of retention were assessed with multivariate analysis. RESULTS: Three hundred forty-four patients recruited of which 64.5% were females with a median age of 30 years (interquartile range: 27-35). Subjects were similar in age gender CD4 count education and employment status. Providing CD4 results at HIV diagnosis increases the likelihood of reporting for ART initiation (risk ratio = 2.1; 95% confidence interval = 1.39 to 3.17) compared with standard of care. Written information only reduced the time to presentation for pre-ART care although increasing age was associated with retention. There was 49% attrition in the standard of care arms. CONCLUSIONS: Receipt of a CD4 count at the time of HIV testing increases ART initiation rates. Point-of-care diagnostics can be used to improve retention but losses to pre-ART care remain high.

Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation.

Abstract: Background The relationship between gut microbial community composition at the higher-taxonomic order level and local and systemic immunologic abnormalities in HIV disease may provide insight into how bacterial translocation impacts HIV disease. Methods Antiretroviral-naive patients with HIV underwent upper endoscopy before and 9 months after starting antiretroviral treatment. Duodenal tissue was paraffin-embedded for immunohistochemical analysis and digested for fluorescence activated cell sorting for T-cell subsets and immune activation (CD38+/HLA-DR+) enumeration. Stool samples were provided from patients and control subjects for comparison. Metagenomic microbial DNA was extracted from feces for optimized 16S ribosomal RNA gene (rDNA) real-time quantitative polymerase chain reaction assays designed to quantify panbacterial loads and the relative abundances of proinflammatory Enterobacteriales order and the dominant Bacteroidales and Clostridiales orders. Results Samples from 10 HIV subjects before initiating and from six subjects receiving antiretroviral treatment were available for analysis. There was a trend for a greater proportion of Enterobacteriales in HIV-positive subjects compared with control subjects (P = 0.099). There were significant negative correlations between total bacterial load and duodenal CD4 and CD8 T-cell activation levels (r = -0.74, P = 0.004 and r = -0.67, P = 0.013, respectively). The proportions of Enterobacteriales and Bacteroidales were significantly correlated with duodenal CD4 T-cell depletion and peripheral CD8 T-cell activation, respectively. Conclusions These data represent the first report of quantitative molecular and cellular correlations between total/universal and order-level gut bacterial populations and gastrointestinal-associated lymphoid tissue levels of immune activation in HIV-infected subjects. The correlations between lower overall 16S rDNA levels and tissue immune activation suggest that the gut microbiome may contribute to immune activation and influence HIV progression.

Antiretroviral drugs in the cupboard are not enough: the impact of health systems' performance on mother-to-child transmission of HIV.

Abstract: OBJECTIVE: To model the effect of health systems performance on rates of mother-to-child HIV transmission. METHODS: We modeled the effect of variation in performance of the multiple steps of different prevention of mother-to-child transmission (PMTCT) protocols using hypothetical and reported data. SETTING: Data from a PMTCT program in a large province in South Africa was used to compare model predictions with reported outcomes for mother-to-child HIV transmission. MAIN OUTCOME MEASURE: Perinatal HIV transmission was predicted for infants of 6 weeks of age. RESULTS: HIV-infected pregnant women who fulfill eligibility criteria are initiated on lifelong antiretroviral treatment whereas noneligible HIV-infected women and their infants receive single-dose nevirapine in a health system functioning at reported performance levels and the overall vertical transmission rate would be 19.5%. Adding azidothymidine for women not eligible for lifelong treatment would further decrease the overall transmission rates only marginally to 17%. If the same steps were accomplished at 95% reliability then the overall transmission rates would be 9.4% and 4.1% respectively. CONCLUSIONS: Introduction of more effective combination antiretroviral interventions will yield only marginal reductions in childhood HIV infections and mortality unless health systems achieve high levels of performance at each step of the PMTCT pathway. Investment in and support for the mechanisms of delivering and sustaining PMTCT interventions at scale are required if gains in maternal and child survival are to be realized in countries highly affected by HIV.

Neurocognitive impact of substance use in HIV infection

Abstract: BACKGROUND—To determine how serious a confound substance use (SU) might be in studies on HIV-associated neurocognitive disorder (HAND) we examined the relationship of SU history to neurocognitive impairment (NCI) in participants enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study. METHODS—After excluding cases with behavioral evidence of acute intoxication and histories of factors that independently could account for NCI (e.g., stroke), baseline demographic, medical, SU, and neurocognitive data were analyzed from 399 participants. Potential SU risk for NCI was determined by the following criteria: lifetime SU DSM-IV diagnosis, self-report of marked lifetime SU, or positive urine toxicology (UTOX). Participants were divided into three groups: no SU (N = 134), Non-syndromic SU (N = 131), syndromic SU (N = 134) and matched on literacy level, nadir CD4, and depressive symptoms. RESULTS—While approximately 50% of the participants were diagnosed with HAND, a MANCOVA of neurocogntive summary scores, covarying for UTOX, revealed no significant effect of SU status. Correlational analyses indicated weak associations between lifetime heroin dosage and poor recall and working memory, as well as between cannabis and cocaine use and better verbal fluency.

Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.

Abstract: Background:In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure.Methods:We conducted a cross-sectional survey to investigate the aetiology of virologic failu

Analysis of data collected by RDS among sex workers in 10 Brazilian cities, 2009: estimation of the prevalence of HIV, variance, and design effect.

Abstract: Background: Respondent-driven sampling (RDS) is a chain- referral method that is being widely used to recruit most at-risk populations. Because the method is respondent driven, observations are dependent. However, few publications have focused on methodological challenges in the analysis of data collected by RDS. Methods: In this article, we propose a method for estimating the vari- ance of the HIV prevalence rate, based on the Markov transition prob- abilities and within recruitment cluster variation. The method was applied to a female commercial sex workers study carried out in 10 Brazilian cities in 2008. Both the inverse of network size and the size of the city were considered in the estimation of overall sampling weights. The study included a behavior questionnaire and rapid tests for HIV and syphilis. Results: About 2523 interviews were conducted successfully, excluding the seeds. Results show a positive homophily between recruits for those HIV+; HIV- recruiters selected HIV+ recruits 4% of the time; HIV+ recruiters selected other HIV+ recruits 19.6% of the time, about 5 times higher. The prevalence rate was estimated at 4.8% (95% confidence interval: 3.4 to 6.1), and a design effect of 2.63. Conclusions: Using statistical methods for complex sample designs, it was possible to estimate HIV prevalence, standard error, and the design effect analytically. Additionally, the proposed analysis lends itself to logistic regression, permitting multivariate models. The stratification in cities has proved suitable for reducing the effect of design and can be adopted in other RDS studies, provided the weights of the strata are known.

Predictors of successful early infant diagnosis of HIV in a rural district hospital in Zambézia, Mozambique

Abstract: BACKGROUND: A key challenge inhibiting the timely initiation of pediatric antiretroviral treatment is the loss to follow-up of mothers and their infants between the time of mothers HIV diagnoses in pregnancy and return after delivery for early infant diagnosis of HIV. We sought to identify barriers to follow-up of HIV-exposed infants in rural Zambezia Province Mozambique. METHODS: We determined follow-up rates for early infant diagnosis and age at first test in a retrospective cohort of 443 HIV-infected mothers and their infants. Multivariable logistic regression models were used to identify factors associated with successful follow-up. RESULTS: Of the 443 mother-infant pairs 217 (49%) mothers enrolled in the adult HIV care clinic and only 110 (25%) infants were brought for early infant diagnosis. The predictors of follow-up for early infant diagnosis were larger household size (odds ratio [OR] 1.29; 95% confidence interval [CI] 1.09-1.53) independent maternal source of income (OR 10.8; 95% CI 3.42-34.0) greater distance from the hospital (OR 2.14; 95% CI 1.01-4.51) and maternal receipt of antiretroviral therapy (OR 3.15; 95% CI 1.02-9.73). The median age at first test among 105 infants was 5 months (interquartile range 2-7); 16% of the tested infants were infected. CONCLUSIONS: Three of four HIV-infected women in rural Mozambique did not bring their children for early infant HIV diagnosis. Maternal receipt of antiretroviral therapy has favorable implications for maternal health that will increase the likelihood of early infant diagnosis. We are working with local health authorities to improve the linkage of HIV-infected women to HIV care to maximize early infant diagnosis and care.

Men who have sex with men have a 140-fold higher risk for newly diagnosed HIV and syphilis compared with heterosexual men in New York City.

Abstract: Objectives To describe the population of men who have sex with men (MSM) in New York City, compare their demographics, risk behaviors, and new HIV and primary and secondary (PS 95% CI: 4.5 to 5.6) differed by both age and race/ethnicity (2.3% among non-Hispanic black men; 7.4% among non-Hispanic white men). Compared with MSW, MSM differed significantly on all demographics and reported a higher prevalence of condom use at last sex (62.9% vs. 38.3%) and of past-year HIV testing (53.6% vs. 27.2%) but also more past-year sex partners. MSM HIV and P&S syphilis rates were 2526.9/100,000 and 707.0/100,000, each of which was over 140 times MSW rates. Rates were highest among young and black MSM. Over 4 years, HIV rates more than doubled and P&S syphilis rates increased 6-fold among 18-year-old to 29-year-old MSM. Conclusions The substantial population of MSM in New York City is at high risk for acquisition of sexually transmitted infections given high rates of newly diagnosed infections and ongoing risk behaviors. Intensified and innovative efforts to implement and evaluate prevention programs are required.

Efficacy of behavioral interventions to increase condom use and reduce sexually transmitted infections: a meta-analysis, 1991 to 2010.

Abstract: Objective In the absence of an effective HIV vaccine, safer sexual practices are necessary to avert new infections. Therefore, we examined the efficacy of behavioral interventions to increase condom use and reduce sexually transmitted infections (STIs), including HIV. Design Studies that examined a behavioral intervention focusing on reducing sexual risk, used a randomized controlled trial or a quasi-experimental design with a comparison condition, and provided needed information to calculate effect sizes for condom use and any type of STI, including HIV. Methods Studies were retrieved from electronic databases (eg, PubMed, PsycINFO) and reference sections of relevant papers. Forty-two studies with 67 separate interventions (N = 40,665; M age = 26 years; 68% women; 59% Black) were included. Independent raters coded participant characteristics, design and methodological features, and intervention content. Weighted mean effect sizes, using both fixed-effects and random-effects models, were calculated. Potential moderators of intervention efficacy were assessed. Results Compared with controls, intervention participants increased their condom use [d+ = 0.17, 95% confidence interval (CI) = 0.04, 0.29; k = 67], had fewer incident STIs (d+ = 0.16, 95% CI = 0.04, 0.29; k = 62), including HIV (d+ = 0.46, 95% CI = 0.13, 0.79; k = 13). Sample (eg, ethnicity) and intervention features (eg, skills training) moderated the efficacy of the intervention. Conclusions Behavioral interventions reduce sexual risk behavior and avert STIs and HIV. Translation and widespread dissemination of effective behavioral interventions are needed.

Activation of NK cells by ADCC antibodies and HIV disease progression

Abstract: Antibody-dependent cellular cytotoxicity (ADCC) is of considerable interest as an immune response that may facilitate control of HIV infection. We studied ADCC responses prospectively in a cohort of 79 HIV+ subjects followed for a mean of 2.3 years without antiretroviral therapy. We used a novel assay of the ability of ADCC to activate NK cells, either from the same HIV+ subject or a healthy blood donor. We found ADCC responses to either gp140 Env protein or HIV peptide pools were common in HIV+ subjects when NK cells from the HIV+ subject were used, but did not correlate with markers of HIV disease progression. In contrast, ADCC responses to whole gp140 Env protein were strongly associated with a slower decline in CD4 T cell loss when healthy donor NK cells were used as effectors. Our data had implications for induction of the most effective ADCC responses by HIV vaccines.

Inadequate coordination of maternal and infant HIV services detrimentally affects early infant diagnosis outcomes in Lilongwe, Malawi.

Abstract: OBJECTIVE To assess the continuity of care and outcome of pediatric HIV prevention, testing, and treatment services, focusing on early infant diagnosis with DNA polymerase chain reaction (PCR). DESIGN A retrospective observational cohort. METHODS Maternal HIV antibody, infant HIV DNA PCR test results, and outcome data from HIV-infected infants from the prevention of mother-to-child transmission, early infant diagnosis, and pediatric HIV treatment programs operating in Lilongwe, Malawi, between 2004 and 2008 were collected, merged, and analyzed. RESULTS Of the 14,669 pregnant women who tested HIV antibody positive, 7875 infants (53.7%) received HIV DNA PCR testing. One thousand eighty-four infants (13.8%) were HIV infected. Three hundred twenty (29.5%) children enrolled into pediatric HIV care, with 202 (63.1%) at the Baylor Center of Excellence. Among these, antiretroviral therapy was initiated on 110 infants (54.5%) whose median age was 9.1 months (interquartile range, 5.4-13.8) and a median of 2.5 months (interquartile range, 1.4-5.2) after HIV clinic registration. Sixty-nine HIV-infected infants (34.2%) died or were lost by December 2008. Initiation of antiretroviral therapy increased the likelihood of survival 7-fold (odds ratio, 7.1; 95% confidence interval, 3.68 to 13.70). CONCLUSIONS Separate programs for maternal and infant HIV prevention and care services demonstrated high attrition rates of HIV-exposed and HIV-infected infants, elevated levels of mother-to-child transmission, late infant diagnosis, delayed pediatric antiretroviral therapy initiation, and high HIV-infected infant mortality. Antiretroviral therapy increased HIV-infected infant survival, emphasizing the urgent need for improved service coordination and strategies that increase access to infant HIV diagnosis, improve patient retention, and reduce antiretroviral therapy initiation delays.