Showing papers in "AIDS in 2013"

Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population.

Abstract: Background: Due to the success of antiretroviral therapy (ART), it is relevant to ask whether death rates in optimally treated HIV are higher than the general population. The objective was to compare mortality rates in well controlled HIV-infected adults in the SMART and ESPRIT clinical trials with the general population. Methods: Non-IDUs aged 20-70 years from the continuous ART control arms of ESPRIT and SMART were included if the person had both low HIV plasma viral loads (≤400 copies/ml SMART, ≤500 copies/ml ESPRIT) and high CD4 T-cell counts (≥350 cells/ml) at any time in the past 6 months. Standardized mortality ratios (SMRs) were calculated by comparing death rates with the Human Mortality Database. Results: Three thousand, two hundred and eighty individuals [665 (20%) women], median age 43 years, contributed 12 357 person-years of follow-up. Sixty-two deaths occurred during follow up. Commonest cause of death was cardiovascular disease (CVD) or sudden death (19, 31%), followed by non-AIDS malignancy (12, 19%). Only two deaths (3%) were AIDS-related. Mortality rate was increased compared with the general population with a CD4 cell count between 350 and 499 cells/ml [SMR 1.77, 95% confidence interval (CI) 1.17-2.55]. No evidence for increased mortality was seen with CD4 cell counts greater than 500 cells/ml (SMR 1.00, 95% CI 0.69-1.40). Conclusion: In HIV-infected individuals on ART, with a recent undetectable viral load, who maintained or had recovery of CD4 cell counts to at least 500 cells/ml, we identified no evidence for a raised risk of death compared with the general population.

The increase in global HIV epidemics in MSM.

Abstract: Epidemics of HIV in MSM continue to expand in most low, middle, and upper income countries in 2013 and rates of new infection have been consistently high among young MSM. Current prevention and treatment strategies are insufficient for this next wave of HIV spread. We conducted a series of comprehensive reviews of HIV prevalence and incidence, risks for HIV, prevention and care, stigma and discrimination, and policy and advocacy options. The high per act transmission probability of receptive anal intercourse, sex role versatility among MSM, network level effects, and social and structural determinants play central roles in disproportionate disease burdens. HIV can be transmitted through large MSM networks at great speed. Molecular epidemiologic data show marked clustering of HIV in MSM networks, and high proportions of infections due to transmission from recent infections. Prevention strategies that lower biological risks, including those using antiretrovirals, offer promise for epidemic control, but are limited by structural factors including, discrimination, criminalization, and barriers to healthcare. Subepidemics, including among racial and ethnic minority MSM in the United States and UK, are particularly severe and will require culturally tailored efforts. For the promise of new and combined bio-behavioral interventions to be realized, clinically competent healthcare is necessary and community leadership, engagement, and empowerment are likely to be key. Addressing the expanding epidemics of HIV in MSM will require continued research, increased resources, political will, policy change, structural reform, community engagement, and strategic planning and programming, but it can and must be done.

Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection.

Abstract: Objective Here we evaluated whether neurocognitive disorders in HIV-infected individuals on effective antiretroviral therapy (ART) are associated with persistent monocyte activation as indexed by levels of soluble CD163 (sCD163), shed by monocyte/macrophages.

The burden of HIV: insights from the Global Burden of Disease Study 2010.

Abstract: Objectives: To evaluate the global and country-level burden of HIV/AIDS relative to 291 other causes of disease burden from 1980 to 2010 using the Global Burden of Disease Study 2010 (GBD 2010) as the vehicle for exploration.

Biobanking past, present and future: responsibilities and benefits.

Abstract: The review explores the field of biobanking as it has evolved from a simple collection of frozen specimens to the virtual biobank. Biorepository and biospecimen science has evolved in response to the changing landscape of external regulatory pressures, the advances made in the biological sciences, and the advent of the computer chip. Biospecimen banking is a growing enterprise crucial to health science research and other biological sciences. In this review we discuss the history of biobanking, highlight current and emerging issues, discuss demands and responses, and describe an example of a biobank, the University of California, San Francisco AIDS Specimen Bank that has functioned for 30 years.

An internationally generalizable risk index for mortality after one year of antiretroviral therapy.

Abstract: Objective: Despite the success of antiretroviral therapy (ART), excess mortality continues for those with HIV infection. A comprehensive approach to risk assessment, addressing multiorgan system injury on ART, is needed. We sought to develop and validate a practical and generalizable mortality risk index for HIV-infected individuals on ART. Design and methods: The Veterans Aging Cohort Study (VACS) was used to develop the VACS Index, based on age, CD4 cell count, HIV-1 RNA, hemoglobin, aspartate and alanine transaminase, platelets, creatinine and hepatitis C status, and a Restricted Index based on age, CD4 cell count and HIV-1 RNA with an outcome of death up to 6 years after ART initiation. Validation was in six independent cohorts participating in the ART Cohort Collaboration (ART-CC). Results: In both the development (4932 patients, 656 deaths) and validation cohorts (3146 patients, 86 deaths) the VACS Index had better discrimination than the Restricted Index (c-statistics 0.78 and 0.72 in VACS, 0.82 and 0.78 in ART-CC). The VACS Index also demonstrated better discrimination than the Restricted Index for HIV deaths and non-HIV deaths, in men and women, those younger and older than 50 years, with and without detectable HIV-1 RNA, and with or without HCV coinfection. Conclusions: Among HIV-infected patients treated with ART, the VACS Index more accurately discriminates mortality risk than traditional HIV markers and age alone. By accounting for multiorgan system injury, the VACS Index may prove a useful tool in clinical care and research. 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27:563–572

Intimate partner violence is associated with incident Hiv infection in women in Uganda

Abstract: OBJECTIVES: To quantify the association between intimate partner violence (IPV) and incident HIV infection in women in the Rakai Community Cohort Study between 2000 and 2009. DESIGN AND METHODS: Data were from the Rakai Community Cohort Study annual surveys between 2000 and 2009. Longitudinal data analysis was used to estimate the adjusted incidence rate ratio (IRR) of incident HIV associated with IPV in sexually active women aged 15-49 years, using a multivariable Poisson regression model with random effects. The population attributable fraction was calculated. Putative mediators were assessed using Baron and Kenny's criteria and the Sobel-Goodman test. RESULTS: Women who had ever experienced IPV had an adjusted IRR of incident HIV infection of 1.55 (95% CI 1.25-1.94, P = 0.000), compared with women who had never experienced IPV. Risk of HIV infection tended to be greater for longer duration of IPV exposure and for women exposed to more severe and more frequent IPV. The adjusted population attributable fraction of incident HIV attributable to IPV was 22.2% (95% CI 12.5-30.4). There was no evidence that either condom use or number of sex partners in the past year mediated the relationship between IPV and HIV. CONCLUSION: IPV is associated with incident HIV infection in a population-based cohort in Uganda, although the adjusted population attributable fraction is modest. The prevention of IPV should be a public health priority, and could contribute to HIV prevention. Language: en

The magnitude of loss to follow-up of HIV-exposed infants along the prevention of mother-to-child HIV transmission continuum of care: a systematic review and meta-analysis

Abstract: Introduction: Although prevention of mother-to-child HIV transmission (PMTCT) programs are widely implemented, many children do not benefit from them because of loss to follow-up (LTFU). We conducted a systematic review to determine the magnitude of infant/baby LTFU along the PMTCT cascade. Methods: Eligible publications reported infant LTFU outcomes from standard care PMTCT programs (not intervention studies) at any stage of the cascade. Literature searches were conducted in Medline, Embase, Web of Knowledge, CINAHL Plus, and Maternity and Infant Care. Extracted data included setting, methods of follow-up, PMTCT regimens, and proportion and timing of LTFU. For programs in sub-Saharan Africa, random-effects meta-analysis was done using Stata v10. Because of heterogeneity, predictive intervals (PrIs; approximate 95% confidence intervals of a future study based on extent of observed heterogeneity) were computed. Results: A total of 826 papers were identified; 25 publications were eligible. Studies were published from 2001 to 2012 and were mostly from sub-Saharan Africa (three were from India, one from UK and one from Ireland). There was extensive heterogeneity in findings. Eight studies reported on LTFU of pregnant HIV-positive women between antenatal care (ANC) registration and delivery, which ranged from 10.9 to 68.1%, pooled proportion 49.08% [95% confidence interval (CI) 39.6–60.9%], and PrI 22.0–100%. Fourteen studies reported LTFU of infants within 3 months of delivery, range 4.8–75%, pooled proportion 33.9% (27.6–41.5), and PrI 15.4–74.2. Children were also lost after HIV testing; this was reported in five studies, pooled estimate 45.5% (35.9–57.6), PrI 18.7–100%. Programs that actively tracked defaulters had better retention outcomes. Conclusion: There is unacceptable infant LTFU from PMTCT programs. Countries should incorporate defaulter-tracking as standard to improve retention.

Dramatic increase in HIV prevalence after scale-up of antiretroviral treatment.

Abstract: Objectives: To investigate HIV prevalence trends in a rural South African community after the scale-up of antiretroviral treatment (ART) in 2004. Methods: We estimated adult HIV prevalence (ages 15–49 years) using data from a large, longitudinal, population-based HIV surveillance in rural KwaZulu-Natal, South Africa, over the period from 2004 (the year when the public-sector ART scale-up started) to 2011. We control for selection effects due to surveillance nonparticipation using multiple imputation. We further linked the surveillance data to patient records from the local HIV treatment program to estimate ART coverage. Results: ART coverage of all HIV-infected people in this community increased from 0% in 2004 to 31% in 2011. Over the same observation period adult HIV prevalence increased steadily from 21 to 29%. The change in overall HIV prevalence is nearly completely explained by an increase of HIV-infected people receiving ART, and it is largely driven by increases in HIV prevalence in women and men older than 24 years. Conclusion: The observed dramatic increase in adult HIV prevalence can most likely be explained by increased survival of HIV-infected people due to ART. Future studies should decompose HIV prevalence trends into HIV incidence and HIV-specific mortality changes to further improve the causal attribution of prevalence increases to treatment success rather than prevention failure.

Evidence of an explosive epidemic of HIV infection in a cohort of men who have sex with men in Thailand.

Abstract: OBJECTIVE: To assess HIV-prevalence incidence and risk factors in a cohort of men who have sex with men (MSM) in Bangkok. DESIGN: : Cohort study with 4-monthly follow-up visits conducted between April 2006 and July 2012 at a dedicated study clinic in a central Bangkok hospital. Participants were 1744 homosexually active Thai men at least 18 years old and residents of Bangkok. METHODS: Men were tested for HIV-infection at every study visit and for sexually transmitted infections at baseline. Demographic and behavioural data were collected by audio-computer-assisted self-interview. Logistic regression analysis was used to evaluate risk factors for HIV-prevalence and Cox proportional hazard analysis to evaluate risk factors for HIV-incidence. RESULTS: Baseline HIV-prevalence was 21.3% (n = 372) and 60 months cumulative HIV-incidence was 23.9% (n = 222). Overall HIV-incidence density was 5.9 per 100 person-years. Multivariate risk factors for HIV-prevalence were older age secondary/vocational education (vs. university or higher) employed or unemployed (vs. studying) nitrate inhalation drug use for sexual pleasure receptive anal intercourse history of sexual coercion no prior HIV-testing and anti-HSV-1 and 2 and Treponema pallidum positivity at baseline. Multivariate risk factors for HIV-incidence were younger age living alone or with roommate (vs. with a partner or family) drug use for sexual pleasure inconsistent condom use receptive anal intercourse group sex and anti-HSV-1 and 2 and T. pallidum positivity at baseline. Having no anal intercourse partners was inversely associated with HIV-incidence. CONCLUSION: The high HIV prevalence and incidence in this cohort of Bangkok MSM documents an explosive epidemic. Additional preventive interventions for MSM are urgently needed.

Hepatitis C virus reinfection incidence and treatment outcome among HIV-positive MSM.

Abstract: OBJECTIVE: Liver disease secondary to hepatitis C virus (HCV) infection in the context of HIV infection is one of the leading non-AIDS causes of death. Sexual transmission of HCV infection among HIV-positive MSM appears to be leading to increased reports of acute HCV infection. Reinfection after successful treatment or spontaneous clearance is reported among HIV-positive MSM but the scale of reinfection is unknown. We calculate and compare HCV reinfection rates among HIV-positive MSM after spontaneous clearance and successful medical treatment of infection. DESIGN: Retrospective analysis of HIV-positive MSM with sexually acquired HCV who subsequently spontaneously cleared or underwent successful HCV treatment between 2004 and 2012. RESULTS: Among 191 individuals infected with HCV, 44 were reinfected over 562 person-years (py) of follow-up with an overall reinfection rate of 7.8/100 py [95% confidence interval (CI) 5.8-10.5]. Eight individuals were subsequently reinfected a second time at a rate of 15.5/100 py (95% CI 7.7-31.0). Combining all reinfections, 20% resulted in spontaneous clearance and treatment sustained viral response rates were 73% (16/22) for genotypes one and four and 100% (2/2) for genotypes two and three. Among 145 individuals with a documented primary infection, the reinfection rate was 8.0 per 100 py (95% CI 5.7-11.3) overall, 9.6/100 py (95% CI 6.6-14.1) among those successfully treated and 4.2/100 py (95% CI 1.7-10.0) among those who spontaneously cleared. The secondary reinfection rate was 23.2/100 py (95% CI 11.6-46.4). CONCLUSION: Despite efforts at reducing risk behaviour, HIV-positive MSM who clear HCV infection remain at high risk of reinfection. This emphasizes the need for increased sexual education, surveillance and preventive intervention work.

Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers.

Abstract: Objective: To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection. Design: A prospective cohort. Methods: HIV-infected patients on continuous antiretroviral therapy (ART) in the control arms of three randomized trials (N = 5023) were included in an analysis of predictors of cancer (any type, infection-related or infection-unrelated). Hazard ratios for IL-6, CRP and D-dimer levels (log-transformed) were calculated using Cox models stratified by trial and adjusted for demographics and CD4 cell counts and adjusted also for all biomarkers simultaneously. To assess the possibility that biomarker levels were elevated at entry due to undiagnosed cancer, analyses were repeated excluding early cancer events (i.e. diagnosed during first 2 years of follow-up). Results: During approximately 24 000 person-years of follow-up (PYFU), 172 patients developed cancer (70 infection-related; 102 infection-unrelated). The risk of developing cancer was associated with higher levels (per doubling) of IL-6 (hazard ratio 1.38, P<0.001), CRP (hazard ratio 1.16, P=0.001) and D-dimer (hazard ratio 1.17, P=0.03). However, only IL-6 (hazard ratio 1.29, P= 0.003) remained associated with cancer risk when all biomarkers were considered simultaneously. Results for infection-related and infection-unrelated cancers were similar to results for any cancer. Hazard ratios excluding 69 early cancer events were 1.31 (P= 0.007), 1.14 (P=0.02) and 1.07 (P = 0.49) for IL-6, CRP and D-dimer, respectively. Conclusion: Activated inflammation and coagulation pathways are associated with increased cancer risk during HIV infection. This association was stronger for IL-6 and persisted after excluding early cancer. Trials of interventions may be warranted to assess whether cancer risk can be reduced by lowering IL-6 levels in HIV-positive individuals.

HIV among MSM in a large middle-income country

Abstract: OBJECTIVE: To conduct the first national biological and behavioral surveillance survey for HIV among MSM in Brazil. DESIGN: A cross-sectional surveillance study utilizing Respondent Driven Sampling (RDS) in 10 cities following formative research. Planned sample: 350 MSM reporting sex with another man in the last 12 months at least 18 years of age and residing in the city of the study. METHODS: Conventional RDS recruitment. Results were calculated for each city using RDSAT 5.6. For the national estimate a new individual weight using a novel method was calculated. The 10 cities were aggregated treated as strata and analyzed using STATA11.0. Self-reported HIV status and logistic regression was used to impute missing values for serostatus an important issue for RDSAT. RESULTS: A total of 3859 MSM were interviewed. Sample was diverse most self-identified as mulatto or black were social class C or below and had relatively low levels of education. More than 80% reported more than one partner in the last 6 months. Only 49% had ever tested for HIV. HIV prevalence among MSM ranged from 5.2 to 23.7% in the 10 cities (3.7-16.5% without imputation) and was 14.2% for all cities combined with imputation. The overall prevalence was two and three times higher than that estimated for female sex workers and drug users respectively in Brazil. Half of those who tested HIV positive were not aware of their infection. CONCLUSION: The AIDS epidemic in Brazil is disproportionately concentrated among MSM as has been found in other countries. Renewed efforts to encourage testing prevention and treatment are required.

Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis.

Abstract: Since 2002, the WHO has recommended either nevirapine (NVP) or efavirenz (EFV) as part of first-line antiretroviral therapy These two drugs are known to have differing toxicity profiles, but the risk of these toxicities overall is not well established

Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial.

Abstract: OBJECTIVE: To evaluate the effect of home visits by community health workers (CHWs) on maternal and infant well being from pregnancy through the first 6 months of life for women living with HIV (WLH) and all neighborhood mothers. DESIGN AND METHODS: In a cluster randomized controlled trial in Cape Town townships neighborhoods were randomized within matched pairs to either standard care comprehensive healthcare at clinics (n=12 neighborhoods; n=169 WLH; n=594 total mothers); or Philani Intervention Program home visits by CHWs in addition to standard care (PIP; n=12 neighborhoods; n=185 WLH; n=644 total mothers). Participants were assessed during pregnancy (2% refusal) and reassessed at 1 week (92%) and 6 months (88%) postbirth. We analyzed PIPs effect on 28 measures of maternal and infant well being among WLH and among all mothers using random effects regression models. For each group PIPs overall effectiveness was evaluated using a binomial test for correlated outcomes. RESULTS: Significant overall benefits were found in PIP compared to standard care among WLH and among all participants. Secondarily compared to standard care PIP WLH were more likely to complete tasks to prevent vertical transmission use one feeding method for 6 months avoid birth-related medical complications and have infants with healthy height-for-age measurements. Among all mothers compared to standard care PIP mothers were more likely to use condoms consistently breastfeed exclusively for 6 months and have infants with healthy height-for-age measurements. CONCLUSION: PIP is a model for countries facing significant reductions in HIV funding whose families face multiple health risks.

The new role of antiretrovirals in combination HIV prevention: a mathematical modelling analysis.

Abstract: BACKGROUND AND OBJECTIVES: : Antiretroviral drugs can reduce HIV acquisition among uninfected individuals (as pre-exposure prophylaxis: PrEP) and reduce onward transmission among infected individuals (as antiretroviral treatment: ART). We estimate the potential impact and cost-effectiveness of antiretroviral-based HIV prevention strategies. DESIGN AND METHODS: : We developed and analysed a mathematical model of a hyperendemic setting with relatively low levels of condom use. We estimated the prevention impact and cost of various PrEP interventions, assuming a fixed amount of spending on PrEP; investigated the optimal role of PrEP and earlier ART in terms of epidemiological impact and cost; and systematically explored the impact of earlier ART and PrEP, in combination with medical male circumcision services; on HIV transmission. RESULTS: : A PrEP intervention is unlikely to generate a large reduction in HIV incidence, unless the cost is substantially reduced. In terms of infections averted and quality adjusted life years gained, at a population-level maximal cost-effectiveness is achieved by providing ART to more infected individuals earlier rather than providing PrEP to uninfected individuals. However, early ART alone cannot reduce HIV incidence to very low levels and PrEP can be used cost-effectively in addition to earlier ART to reduce incidence further. If implemented in combination and at ambitious coverage levels, medical male circumcision, earlier ART and PrEP could produce dramatic declines in HIV incidence, but not stop transmission completely. CONCLUSION: : A combination prevention approach based on proven-efficacy interventions provides the best opportunity for achieving the much hoped for prevention advance and curbing the spread of HIV.

Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: a systematic review and meta-analysis.

Abstract: BACKGROUND HIV/AIDS has historically had a sex and gender-focused approach to prevention and care. Some evidence suggests that HIV-positive men have worse treatment outcomes than their women counterparts in Africa. METHODS We conducted a systematic review and meta-analysis of the effect of sex on the risk of death among participants enrolled in antiretroviral therapy (ART) programs in Africa since the rapid scale-up of ART. We included all cohort studies evaluating the effect of sex (male, female) on the risk of death among participants enrolled in regional and national ART programs in Africa. We identified these studies by searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird random-effects method to pool the proportions of men receiving ART and the hazard ratios for death by sex. RESULTS Twenty-three cohort studies, including 216 008 participants (79 892 men) contributed to our analysis. The pooled proportion of men receiving ART was 35% [95% confidence interval (CI): 33-38%]. The pooled hazard ratio estimate indicated a significant increase in the risk of death for men when compared to women [hazard ratio: 1.37 (95% CI: 1.28-1.47)]. This was consistent across sensitivity analyses. INTERPRETATION The proportion of men enrolled in ART programs in Africa is lower than women. Additionally, there is an increased risk of death for men enrolled in ART programs. Solutions that aid in reducing these sex inequities are needed.

Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study

Abstract: Objective: To evaluate the efficacy and safety/tolerability of dolutegravir (DTG, S/GSK1349572), a potent inhibitor of HIV integrase, through the full 96 weeks of the SPRING-1 study.

High HIV-1 incidence, correlates of HIV-1 acquisition, and high viral loads following seroconversion among MSM.

Abstract: BACKGROUND: HIV-1 incidence estimates and correlates of HIV-1 acquisition in African MSM are largely unknown. METHODS: Since 2005 HIV-1-uninfected men who reported sex with men and women (MSMW) or sex with men exclusively (MSME) were followed at scheduled visits for collection of behavioural and clinical examination data and plasma for HIV-1 testing. Urethral or rectal secretions were collected from symptomatic men to screen for gonorrhoea. Poisson regression methods were used to estimate adjusted incidence rate ratios to explore associations between risk factors and incident HIV-1 infection. Plasma viral loads (PVLs) were assessed over 2 years following seroconversion. RESULTS: Overall HIV-1 incidence in 449 men was 8.6 [95% confidence interval (CI) 6.7-11.0] per 100 person-years. Incidence was 5.8 (95% CI 4.2-7.9) per 100 person-years among MSMW and 35.2 (95% CI 23.8-52.1) per 100 person-years among MSME. Unprotected sex receptive anal intercourse exclusive sex with men group sex and gonorrhoea in the past 6 months were strongly associated with HIV-1 acquisition adjusted for confounders. PVL in seroconverters was more than 4 log10 copies/ml at 230 (73.4%) of 313 visits in MSMW and 153 (75.0%) of 204 visits in MSME. CONCLUSION: HIV-1 incidence is very high among MSM in coastal Kenya and many seroconverters maintain high PVL for up to 2 years after infection. Effective HIV-1 prevention interventions including treatment as prevention are urgently needed in this population.

Cognitive disorders in HIV-infected patients: are they HIV-related?

Abstract: Objectives: Large unselected studies on representative samples of HIV-infected patients with a whole battery of neuropsychological tests and cerebral MRI scan are required to assess the frequency of neurocognitive impairment (NCI), the determinants of mild neurocognitive disorders (MNDs), or HIV-associated dementia (HAD) and the relationship between NCI and MRI scan findings. Methods: Investigation of 400 consecutively enrolled HIV-1-infected adults from the ANRS CO3 Aquitaine Cohort, using standardized neurocognitive tests chosen to achieve consistency with Frascati’s criteria. Half of the patients had a cerebral MRI scan allowing gray and white matter volume measurement. Factors associated with NCI were studied by logistic regression models. Results: Median age of participants was 47 years, 79% were male and 89% received combination antiretroviral treatment (cART), of whom 93% had plasma HIV RNA below 500copies/ml. Median CD4 cell count was 515 cells/ml. Prevalence of NCI was 59%, including 21% of asymptomatic NCI, 31% of MND, and 7% of HAD. A low level of education, prior neurologic AIDS-defining disorders event, anxiety, depressive symptoms, and prior history of brain damage were independently associated with MND or HAD, but neither HIV nor cART-related variables. The presence of NCI was significantly associated with lower gray matter fraction. Interpretation: In this large unselected cohort, a high prevalence of symptomatic neurocognitive disorders was mainly related to its traditional determinants and associated with gray matter atrophy at early stages of the disease. 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27:391‐400

Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials.

Abstract: BACKGROUND In the week 48 primary analysis of ECHO and THRIVE, rilpivirine demonstrated noninferior efficacy and more favourable tolerability versus efavirenz in treatment-naive, HIV-1-infected adults. Pooled 96-week results are presented. METHODS Patients (N = 1368) received rilpivirine 25 mg once-daily (q.d.) or efavirenz 600 mg q.d., with two background nucleoside/nucleotide reverse transcriptase inhibitors, in two randomized, double-blind, double-dummy Phase III trials. RESULTS At week 96, response rate (% confirmed viral load <50 copies/ml; intent-to-treat, time-to-loss-of-virologic response) was 78% in both groups. Responses were similar for both treatments by background regimen, sex, race, and in patients with more than 95% adherence (M-MASRI) or baseline viral load 100,000 copies/ml or less. Responses were lower and virologic failure higher for rilpivirine versus efavirenz in patients with 95% or less adherence or baseline viral load more than 100,000 copies/ml. Beyond week 48, the incidence of virologic failure was comparable (3 versus 2%) between treatment groups, rilpivirine resistance-associated mutations were consistent with those observed in year 1, there were few adverse events in both groups and no new safety concerns. Over 96 weeks, discontinuations due to adverse events (4 versus 9%), treatment-related grade 2-4 adverse events (17 versus 33%), rash (4 versus 15%), dizziness (8 versus 27%) and abnormal dreams/nightmares (8 versus 13%), and grade 2-4 lipid abnormalities were lower with rilpivirine than efavirenz. Only 2 and 4% of patients in the rilpivirine and efavirenz treatment groups, respectively, reported at least possibly treatment-related grade 2-4 adverse events during the second year of treatment. CONCLUSIONS Rilpivirine 25 mg q.d. and efavirenz 600 mg q.d. had comparable responses at week 96. Rilpivirine had more virologic failures but improved tolerability versus efavirenz. The majority of virologic failures occurred in the first 48 weeks.

The rapidly expanding CRF01_AE epidemic in China is driven by multiple lineages of HIV-1 viruses introduced in the 1990s.

Abstract: Objectives: We sought to comprehensively analyze the origin, transmission patterns and sub-epidemic clusters of the HIV-1 CRF01_AE strains in China.

The CD4/CD8 ratio as a marker T-cell activation, senescence and activation/exhaustion in treated HIV-infected children and young adults.

Abstract: We explored the associations of the CD4/CD8 ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4+ and CD8+ T-cells, and a skewed T-cell phenotype from naive toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 ratio may identify patients with higher immunoactivation despite ART.

Incident fractures in HIV-infected individuals: a systematic review and meta-analysis.

Abstract: Objective(s): Some but not all studies indicate that individuals with HIV infection are at an increased risk of fracture. We systematically reviewed the literature to investigate whether incidence of fracture (both overall and fragility) differs between individuals with and without HIV. Design: A systematic review and meta-analysis. Methods: Medline, Scopus and the Cochrane Library databases for all studies ever published up to 28 September 2012 and electronically available conference abstracts from CROI, ASBMR, IAS and AIDS were searched. All studies reporting incidence of all fracture and fragility fracture in HIV-infected adults were included. A random effects model was used to calculate pooled estimates of incidence rate ratios (IRRs) for studies that presented data for HIV-infected and controls. For all studies, incidence rates of fracture and predictors of fracture among HIV-infected individuals were summarized. Results: Thirteen eligible studies were analysed, of which seven included controls. Nine studies reported all incident fractures and 10 presented incident fragility fractures. The pooled IRR was 1.58 [95% confidence interval (CI) 1.25-2.00] for all fracture and 1.35 (95% CI 1.10-1.65) for fragility fracture. Smoking, white race and older age were consistent predictors for fragility fractures. Conclusion: Our results indicate that HIV infection is associated with a modest increase in incident fracture. Future research should focus on clarifying risk factors, designing appropriate interventions and the long-term implications of this increased risk for an ageing HIV-infected population. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study.

Abstract: Results: The median ages of the HIV-infected and HIV-seronegative participants were 39 and 40 years, respectively. Among HIV-infected participants, 87.1% were receiving antiretroviral therapy (ART), their median CD4 þ cell count was 468 cells/ml and 84.3% had undetectable viral load. Both biomarkers were validated against chronological age in HIV-seronegative individuals. Telomere length was significantly shorter in HIVinfected individuals than in HIV-seronegative individuals (mean relative T/S ratio � SE:0.91 � 0.007 vs. 1.07 � 0.008, P < 0.0001). CD2NKA expression was higher in HIV-infected participants than in HIV-seronegative individuals (mean expression: 0.45 � 0.02 vs. 0.36 � 0.03, P ¼ 0.003). Socioeconomic factors were not associated with biological ageing in HIV-infected participants. However, in participants on ART with undetectable viral load, biomarker levels indicated greater biological ageing in those with lower current CD4 þ cell counts. Conclusion: Telomere length and CDKN2A expression were both consistent with increased biological ageing in HIV-infected individuals. Prospective studies of the impact of HIV on biological ageing in sub-Saharan Africa are warranted.

Efficacy of preexposure prophylaxis for HIV-1 prevention among high-risk heterosexuals: subgroup analyses from a randomized trial.

Abstract: BACKGROUND: Daily oral antiretroviral preexposure prophylaxis (PrEP) is a promising strategy for prevention of HIV-1 acquisition. Three clinical trials demonstrated PrEP efficacy; however two PrEP trials among women did not find protection against HIV-1. One hypothesis proposed for these divergent results is that PrEP efficacy may be reduced in populations with higher HIV-1 incidence. METHODS: Using data from the Partners PrEP Study a randomized placebo-controlled trial of daily oral tenofovir (TDF) and emtricitabine/tenofovir (FTC/TDF) PrEP among heterosexual HIV-1 serodiscordant couples from Kenya and Uganda we assessed PrEP efficacy among subgroups at higher risk for HIV-1 acquisition including subgroups of women with high HIV-1 incidence. RESULTS: The overall placebo arm HIV-1 incidence was 2.0 per 100 person-years. Among higher risk subgroups placebo arm HIV-1 incidence ranged from 3.9 to 6.6 per 100 person-years. In all subgroups PrEP was protective against HIV-1 acquisition with efficacy point estimates ranging from 64 to 84%. Among subgroups of women with placebo-arm HIV-1 incidence more than 5.0 efficacy estimates ranged from 64 to 84%. Monthly visit attendance for PrEP refills and tenofovir detection in plasma were high. CONCLUSION: Among higher-risk subgroups in the Partners PrEP Study including groups solely of higher-risk women both TDF alone and combined FTC/TDF PrEP had consistently high efficacy for HIV-1 protection. PrEP when used with high adherence is a highly effective prevention strategy for higher risk heterosexuals. Prioritizing PrEP for persons at high risk of HIV-1 will maximize its prevention impact.

High HIV incidence and prevalence and associated factors among young MSM, 2008.

Abstract: Objective To estimate HIV prevalence, annual HIV incidence density, and factors associated with HIV infection among young MSM in the United States. Design The 2008 National HIV Behavioral Surveillance System (NHBS), a cross-sectional survey conducted in 21 US cities. Methods NHBS respondents included in the analysis were MSM aged 18-24 with a valid HIV test who reported at least one male sex partner in the past year. We calculated HIV prevalence and estimated annual incidence density (number of HIV infections/total number of person-years at risk). Generalized estimating equations were used to determine factors associated with testing positive for HIV. Results Of 1889 young MSM, 198 (10%) had a positive HIV test; of these, 136 (69%) did not report previously testing HIV positive when interviewed. Estimated annual HIV incidence density was 2.9%; incidence was highest for blacks. Among young MSM who did not report being HIV infected, factors associated with testing HIV positive included black race; less than high school education; using both alcohol and drugs before or during last sex; having an HIV test more than 12 months ago; and reporting a visit to a medical provider in the past year. Conclusion HIV prevalence and estimated incidence density for young MSM were high. Individual risk behaviors did not fully explain HIV risk, emphasizing the need to address sociodemographic and structural-level factors in public health interventions targeted toward young MSM.

The contribution of HIV to pregnancy-related mortality: a systematic review and meta-analysis.

Abstract: Results: 23 studies were included (17 from sub-Saharan Africa). Meta-analysis of the risk ratios (RR) indicated that HIV-infected women had eight times the risk of a pregnancy-related death compared with HIV-uninfected women (pooled RR: 7.74, 95% CI 5.37–11.16). The excess mortality attributable to HIV among HIV-infected pregnant and postpartum women was 994 per 100,000 pregnant women. We predict that 12% of all deaths during pregnancy and up to one year postpartum are attributable to HIV/AIDS in regions with a prevalence of HIV among pregnant women of 2%. This figure rises to 50% in regions with a prevalence of 15%. Conclusion: The substantial excess of pregnancy-related mortality associated with HIV highlights the importance of integrating HIV and reproductive health services in areas of high HIV prevalence and pregnancy-related mortality. 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27:000–000

Gut Lactobacillales are associated with higher CD4 and less microbial translocation during HIV infection.

Abstract: Objective Early HIV infection is characterized by a dramatic depletion of CD4 T cells in the gastrointestinal tract and translocation of bacterial products from the gut into the blood. In this study, we evaluated if gut bacterial profiles were associated with immune status before and after starting antiretroviral therapy (ART). Design We evaluated the gut microbiota of men recently infected with HIV (n = 13) who were participating in a randomized, double-blind controlled trial of combination ART and maraviroc versus placebo and who were followed for 48 weeks. Methods To evaluate the gut microbiota of participants, we pyrosequenced the bacterial populations from anal swabs collected before and longitudinally after the initiation of ART. Associations of the gut flora with clinical variables (lymphocyte profiles and viral loads), activation and proliferation markers in peripheral blood mononuclear cells and gut biopsies (measured by flow cytometry) and markers of microbial translocation (lipopolysaccharide and soluble CD14) were performed by regression analyses using R statistical software. Results Using pyrosequencing, we identified that higher proportions of Lactobacillales in the distal gut of recently HIV-infected individuals were associated with lower markers of microbial translocation, higher CD4% and lower viral loads before ART was started. Similarly, during ART, higher proportions of gut Lactobacillales were associated with higher CD4%, less microbial translocation, less systemic immune activation, less gut T lymphocyte proliferation, and higher CD4% in the gut. Conclusion Shaping the gut microbiome, especially proportions of Lactobacillales, could help to preserve immune function during HIV infection.