Higher HIV-1 RNA Levels Research Articles

HIV RNA/DNA Levels at Diagnosis Can Predict Immune Reconstitution: A Longitudinal Analysis.

HIV DNA mirrors the number of infected cells and the size of the HIV viral reservoir. The aim of this study was to evaluate the effect of pre-cART HIV DNA levels as a predictive marker of immune reconstitution and on the post-cART CD4 counts trends. HIV DNA was isolated from PBMCs and quantified by real-time PCR. Immune reconstitution was assessed up to four years. Piecewise-linear mixed models were used to describe CD4 count changes. 148 people living with HIV (PLWH) were included. The highest rate of immune reconstitution was observed during the first trimester. There was a trend showing that high HIV RNA level resulted in greater increase in CD4 count, especially during the first trimester of cART (difference above vs. below median 15.1 cells/μL/month; 95% CI -1.4-31.5; p = 0.073). Likewise, higher HIV DNA level would predict greater CD4 increases, especially after the first trimester (difference above vs. below median 1.2 cells/μL/month; 95% CI -0.1-2.6; p = 0.071). Higher DNA and RNA levels combined were significantly associated with greater CD4 increase past the first trimester (difference high/high vs. low/low 2.1 cells/μL/month; 95% CI 0.3-4.0; p = 0.024). In multivariable analysis, lower baseline CD4 counts predicted a greater CD4 rise. In successfully treated PLWH, pre-cART HIV DNA and HIV RNA levels are predictors of immune reconstitution.

The evaluation of risk factors related to reduced bone mineral density in young people living with HIV.

Low bone mineral density (BMD) is one of the comorbidities that develop in people living with HIV (PLWHIV). This study was conducted to review the frequency and risk factors of reduced BMD according to age in HIV-infected patients in Turkey. This retrospective cohort study included HIV-infected patients aged 18-50. Bone density was analysed using dual-energy X-ray absorptiometry (DXA) according to the Z-score in three different regions including the lumbar, total-hip and femoral-neck. The study included 224 PLWHIV with a mean age of 35.84-7.54, and 59.8% were ART naive. Of the patients, 40.6% had lower BMD than expected at least in one of the three examined regions including the lumbar, total hip and femoral neck. The low BMD ratios were found respectively as 11.6%, 11.6% and 28.6% in the femoral neck, total hip and lumbar regions. According to the logistic regression model, a high body mass index (p=0.003) and HIV-RNA level of ≥100.000IU/ml during the diagnosis in the ART-naive group (p=0.008) were associated with reduced bone demineralization. The low BMD frequency was high in the group that received ART for <24 months (p=0.001). Performing bone demineralization screening in the naive and young patient group, independently from ART status prior to making the diagnosis of HIV is important for organizing the bone health improvement methods.

Variation in Heart Failure Risk by HIV Severity and Sex in People With HIV Infection.

HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood. Integrated health care system. We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex. The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively). Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH.

Cytomegalovirus viremia and risk of disease progression and death in HIV-positive patients starting antiretroviral therapy.

The aim of this study was to assess the prevalence of cytomegalovirus (CMV) viremia in HIV-positive patients starting antiretroviral therapy (ART) and to evaluate its impact on clinical outcomes. A retrospective analysis of four clinical trials (INSIGHT FIRST, SMART, START, and ANRS REFLATE TB). Stored plasma samples from participants were used to measure CMV viremia at baseline prior to initiating ART and at visits through 1 year of follow-up after ART initiation. CMV viremia was measured centrally using a quantitative PCR assay. Within FIRST, associations of CMV viremia at baseline and through 8 months of ART were examined with a composite clinical outcome of AIDS, serious non-AIDS events, or death using Cox proportional hazards regression. Samples from a total of 3176 participants, 1169 from FIRST, 137 from ANRS REFLATE TB, 54 from SMART, and 1816 from START were available with baseline CMV viremia prevalence of 17, 26, 0, and 1%, respectively. Pooled across trials, baseline CMV viremia was associated with low CD4 + T-cell counts and high HIV RNA levels. In FIRST, CMV viremia was detected in only 5% of participants between baseline and month 8. After adjustment for CD4 + T-cell count and HIV RNA levels, hazard ratios for risk of clinical outcomes was 1.15 (0.86-1.54) and 2.58 (1.68-3.98) in FIRST participants with baseline and follow-up CMV viremia, respectively. Baseline CMV viremia in HIV-positive patients starting ART is associated with advanced infection and only persistent CMV viremia after ART initiation is associated with a higher risk of morbidity and mortality.

Anemia and thrombocytopenia in HIV-positive pregnant women

BACKGROUND: During pregnancy and childbirth, anemia and thrombocytopenia are twice as common among HIV-positive women as in the general population. It has not been yet clear to what extent HIV affects the incidence of cytopenias, therefore, the correlation between the incidence and the HIV RNA level and CD4 count in HIV-positive pregnant women, as well as the role of antiretroviral therapy, requires further study.&#x0D; AIM: The aim of this study was to assess the effect of the HIV RNA level and CD4 count on the frequency of anemia and thrombocytopenia in HIV-positive pregnant women.&#x0D; MATERIALS AND METHODS: In this study, we analyzed social and demographic features, epidemiological personal history data, the frequency of pregnancy and delivery complications, and the timing of the initiation of antiretroviral therapy in 303 HIV-positive pregnant women, as well as the data of screening for HIV infection of their children. The study included 27 mother-child pairs with perinatal HIV transmission and 276 mother-child pairs without mother-to-child transmission of HIV. All pregnant women were divided into groups depending on the CD4 count and HIV RNA level. A comparative analysis of anemia and thrombocytopenia frequencies was carried out in the study groups.&#x0D; RESULTS: A direct correlation was revealed between the frequency of anemia and thrombocytopenia in HIV-positive pregnant women and markers of HIV infection: severe immunodeficiency (CD4 200 cells/l, p 0.01) and high HIV RNA levels (more than 100,000 copies / ml, p 0.01) in peripheral blood.&#x0D; CONCLUSIONS: We confirmed the high frequency of cytopenias in HIV-positive pregnant women, which exceeds the general population level. In addition, we demonstrated the effectiveness of prescribing antiretroviral therapy among women of reproductive age who planned to become pregnant or did not exclude the possibility of pregnancy (who did not use the effective methods of contraception), as a means of anemia and thrombocytopenia prevention during pregnancy.

Viral resistance burden and APOBEC editing correlate with virological response in heavily treatment-experienced people living with multi-drug resistant HIV

BackgroundThe impact of drug resistance mutational load and APOBEC editing in heavily treatment-experienced (HTE) people living with multidrug-resistant HIV has not been investigated. Material and MethodsThis study explored the HIV-DNA and HIV-RNA mutational load of drug resistance and APOBEC-related mutations through next-generation sequencing (NGS, Illumina MiSeq) in 20 failing HTE participants enrolled in the PRESTIGIO registry. ResultsThe patients showed high levels of both HIV-DNA (4.5 [4.0–5.2] log10 copies/106 T-CD4+ cell) and HIV-RNA (4.5 [4.1–5.0] log10 copies/mL) with complex resistance patterns in both compartments. Among the 255 drug-resistant mutations found, 66.3% were concordantly detected in both HIV-DNA and HIV-RNA; 71.3% of mutations were already present in historical Sanger genotypes. At an intra-patient frequency > 5%, a considerable proportion of mutations detected through DNA-NGS were found in historical genotypes but not through RNA-NGS, and few patients had APOBEC-related mutations. Of 14 patients who switched therapy, the five who failed treatment had DNA resistance with higher intra-patient frequency and higher DNA/RNA mutational load in a context of tendentially less pronounced APOBEC editing compared with those who responded. ConclusionsUsing NGS in HIV-DNA and HIV-RNA together with APOBEC editing evaluation might help to identify HTE individuals with MDR who are more prone to experience virological failure.

Risk factors for IRIS in HIV-associated Pneumocystis-pneumonia following ART initiation

HIV-infected patients with Pneumocystis-pneumonia (PCP) may develop paradoxical immune reconstitution inflammatory syndrome (IRIS), when combination antiretroviral therapy (cART) is started early during the course of PCP-treatment (PCPT). The aim of this study was to identify risk factors and predictors for PCP-IRIS and to improve individualized patient care. An ICD-10 code hospital database query identified all Frankfurt HIV Cohort patients being diagnosed with PCP from January 2010 - June 2016. Patient charts were evaluated retrospectively for demographic, clinical and therapeutic (cART/PCPT) characteristics and incidence of paradoxical IRIS according to French's case definitions. IRIS occurred in 12/97 patients that started cART while on PCPT (12.4%). They had a higher rate of re-hospitalization (41.7vs. 4.7%; odds ratio (OR) 14.46; p=0.009), intensive care treatment (66.7vs. 30.6%; OR=4.54; p=0.018), and longer median hospitalization (48 days vs. 23; p<0.001). A high HIV-RNA level (>6Log10/ml) before cART initiation was associated with IRIS development (41.6vs. 15.0%; OR 4.05; p=0.042). Serum immunoglobulin G-levels (IgG) [mg/dl] were lower (894.0vs. 1446.5; p=0.023). Higher hospitalization rate and morbidity parameters underscore the clinical importance of PCP-related paradoxical IRIS. A baseline viral load of >6Log10/ml and serum IgG may help to assess individual risks for PCP-IRIS.

Na\xefve CD4+ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study

BackgroundSome long-term non-progressors (LTNPs) have decreasing CD4+ T cell counts and progress to AIDS. Exploring which subsets of CD4+ T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis.MethodsTwenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4+ cell count dropped to < 400 cells/μL during follow-up or as non-decreased (non-DG) if their CD4+ cell count was ≥400 cells/μL. Laboratory and clinical assessments were conducted at 6 consecutive visits to identify DG characteristics.ResultsThe LTNPs were infected with HIV for 12 (IQR: 11.5–14) years, and 23 were classified as the B′ subtype. Six individuals lost LTNP status 14.5 (IQR: 12.5–17.5) years after infection (DG), and the CD4+ T cell count decreased to 237 (IQR: 213–320) cells/μL at the latest visit. The naïve CD4+ T cell count decrease was greater than that of memory CD4+ T cells [− 128 (IQR: − 196, − 107) vs − 64 (IQR: − 182, − 25) cells/μL)]. Nineteen individuals retained LTNP status (non-DG). At enrolment, the viral load (VL) level (p = 0.03) and CD8+CD38+ percentage (p = 0.03) were higher in DG than non-DG individuals. During follow-up, viral load and CD8+CD38+ percentage were significantly increased and negatively associated with CD4+ cell count [(r = − 0.529, p = 0.008), (r = − 0.476, p = 0.019), respectively]. However, the CD8+CD28+ percentage and B cell count dropped in DG and were positively correlated with CD4+ T cell count [(r = 0.448, p = 0.028), (r = 0.785, p < 0.001)].ConclusionImmunological progression was mainly characterized by the decrease of naïve CD4+ T cell in LTNPs infected with HIV by blood products and it may be associated with high HIV RNA levels.

Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015

People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

Very high baseline HIV viremia impairs efficacy of non-nucleoside reverse transcriptase inhibitor-based ART: a long-term observation in treatment-na\xefve patients

BackgroundIt is not completely clear whether a very high pre-therapy viral load (≥ 500 000 copies/ml) can impair the virological response. The aim of this study was to examine the influence of very high baseline HIV-RNA levels on long-term virological responses under one type of regimen.MethodsA retrospective study was performed based on data from two multicenter cohorts in China from January to November 2009, and from May 2013 to December 2015. Untreated HIV infected adults between 18 and 65 years old were recruited before receiving non-nucleoside reverse transcriptase inhibitor-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, good adherence, and were followed for at least 24 weeks. Virological suppression was defined as the first HIV-RNA < 50 copies/ml. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥ 200 copies/ml without virological suppression within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥ 50 copies/ml after virological suppression). Chi-square test, Kaplan–Meier analysis, Cox proportional hazards model and Logistic regression were used to compare virological response between each pretreated viral load stratum.ResultsA total of 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108–276) weeks. By week 48, rates of virological suppression in three groups (< 100 000, 100 000–500 000 and ≥ 500 000 copies/ml) were 94.1, 85.0, and 63.8%, respectively (P < 0.001). Very high baseline HIV viremia over 500 000 copies/ml were found to be associated with delayed virological suppression (≥ 500 000 vs < 100 000, adjusted relative hazard = 0.455, 95% CI: 0.32–0.65; P < 0.001) as well as incomplete viral suppression (≥ 500 000 vs < 100 000, adjusted odds ratio [aOR] = 6.084, 95% CI: 2.761–13.407; P < 0.001) and viral rebound (≥ 50 000 vs < 100 000, aOR = 3.671, 95% CI: 1.009–13.355, P = 0.048).ConclusionsVery high levels of pre-treatment HIV-RNA were related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with this clinical character.

Features of the course and therapy of HIV infection in children at different stages of the disease

Purpose of the study . Analysis of clinical and laboratory features of the course of HIV infection and antiviral therapy in children at different stages of the disease. Materials and methods. Under supervision in the department of motherhood and childhood there were 90 children with HIV infection, which were divided into 3 groups: 1st group – 35 people. with a diagnosis of HIV infection in the first 2 months of life, group 2 – 25 people. with a diagnosis at the age of 6-12 months and the 3rd group (30 people) with a diagnosis of HIV infection over the age of 2 years. Statistical processing of the research results was carried out using the software package Statistica for Windows (version 8.0). Research results. Early detection of HIV infection and the beginning of antiretroviral therapy (ARVT) led to the absence of clinical manifestations of the disease, low levels of HIV RNA in the blood and normal levels of CD4 lymphocytes, which persisted for 3 years of observation. The detection of HIV infection and the start of ART in the first 6–12 months of life of children was characterized by clinical symptoms up to CNS damage, high levels of HIV RNA in the blood, moderate decrease in CD4 lymphocytes, with normalization after 3–6 months of treatment and after 3 years of observation. Late diagnosis of HIV infection in children – over 2 years of age is characterized by severe forms of the disease with secondary manifestations – AIDS in 20,0% of cases, low rates of CD4 lymphocytes, damage to the central nervous system with the formation of spastic diplegia, and slow recovery of immunity. The use of the drug Viferon, rectal suppositories in the combined treatment of EBV-mononucleosis and a generalized form of CMV infection allows the early treatment of the main symptoms of herpes virus infections and normalization of laboratory parameters. Conclusion Our prospective study showed that mother-tochild transmission of HIV was realized due to the absence of the first stage of chemoprophylaxis (during pregnancy), and was also aggravated in 9 cases (10,0%) by breastfeeding. The severity of the clinical manifestations of HIV infection, the levels of CD4-lymphocytes and HIV RNA in the blood directly depend on the period of detection and the initiation of ART in children. The inclusion of human recombinant interferon alpha-2b with antioxidants (Viferon rectal suppositories) in the etiopathogenetic therapy of comorbid herpes virus diseases (EBV-mononucleosis, a generalized form of CMV infection) is effective and safe.

Risk Factors for Low CD4+ Count Recovery Despite Viral Suppression Among Participants Initiating Antiretroviral Treatment With CD4+ Counts > 500 Cells/mm3: Findings From the Strategic Timing of AntiRetroviral Therapy (START) Trial.

Low CD4 recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4 counts of >500 cells/mm. United States, Africa, Asia, Europe and Israel, Australia, Latin America. Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4 recovery was defined as a CD4 increase of <50 cells/mm from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression. Low CD4 recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4 cell counts (OR, 1.09 per 100 fewer cells/mm; P = 0.004), higher baseline CD8 cell counts (OR, 1.05 per 100 more cells/mm; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log10 decrease; P < 0.001) were associated with low CD4 recovery. D-dimer had a quadratic association with low CD4 recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, the odds of low CD4 recovery were elevated across the levels of screening CD4 count; but at higher HIV RNA levels, the odds of low CD4 recovery were higher among those with lower vs. higher screening CD4. Low CD4 recovery is frequent among participants starting ART at high CD4 counts. Risk factors include male sex, lower screening CD4 cell counts, higher CD8 cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4 recovery on clinical outcomes.

Hepatitis B virus coinfection is associated with high early mortality in HIV-infected Tanzanians on antiretroviral therapy

There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.

Comparison of Self-report to Biomarkers of Recent HIV Infection: Findings from the START Trial.

Identifying individuals with recent HIV infection is critical to research related to viral reservoirs, outbreak investigations and intervention applications. A multi-assay algorithm (MAA) for recency of infection was used in conjunction with self-reported date of infection and documented date of diagnosis to estimate the number of participants recently infected in the Strategic Timing of AntiRetroviral Treatment (START) trial. We tested samples for three groups of participants from START using a MAA: (1) 167 individuals who reported being infected≤6months before randomization; (2) 771 individuals who did not know their date of infection but were diagnosed within 6months before randomization; and (3) as controls for the MAA, 199 individuals diagnosed with HIV≥2years before randomization. Participants with low titer and avidity and a baseline viral load>400 copies/mL were classified as recently infected. A significantly higher percentage of participants who self-reported being infected≤6months were classified as recently infected compared to participants diagnosed≥2years (65% [109/167] vs. 2.5% [5/199], p<0.001). Among the 771 individuals who did not know their duration of infection at randomization, 206 (26.7%) were classified as recently infected. Among those diagnosed with HIV in the 6months prior to enrollment, the 373 participants who reported recent infection (n=167) or who had confirmed recent infection by the MAA (n=206) differed significantly on a number of baseline characteristics from those who had an unknown date of infection and were not confirmed by the MAA (n=565). Participants recently infected by self-report and/or MAA were younger, more likely to be Asian, less likely to be black, less likely to be heterosexual, more likely to be enrolled at sites in the U.S., Europe or Australia, and have higher HIV RNA levels. There was good agreement between self-report of recency of infection and the MAA. We estimate that 373 participants enrolled in START were infected within 6months of randomization. Compared to those not recently infected, these participants were younger, had higher HIV RNA levels and were more likely to come from high income countries and from populations such as MSM with more regular HIV testing.

Sensitivity of the STAT-VIEW rapid self-test and implications for use during acute HIV infection

ObjectivesHIV testing is an important step towards diminishing incident infections. Rapid self-tests whose use is becoming more common in France could help increase access to testing, yet could fail to...

Lack of decline in hepatitis C virus incidence among HIV-positive men who have sex with men during 1990–2014

Hepatitis C virus (HCV) incidence among HIV-positive men who have sex with men (MSM) has increased since 2000, although there are regional differences. We aimed to 1) estimate trends in HCV incidence among HIV-positive MSM, 2) assess the association between incidence and geographical region, age and HIV-related measurements and, 3) assess temporal changes from HIV seroconversion to HCV infection. Data was used from MSM with well-estimated dates of HIV seroconversion from the CASCADE Collaboration (1990-2014). Smoothly varying trends in HCV incidence over time were allowed, using restricted cubic splines. The association of calendar year, age, CD4 count (lagged), HIV RNA (lagged), geographical region and HIV infection stage (recent vs. chronic) with HCV incidence were assessed using Poisson regression. Of 5,941 MSM, 337 acquired HCV during follow-up. HCV incidence significantly increased from 0.7/1,000 person-years in 1990 to 18/1,000 person-years in 2014. Recent calendar years, younger age, recent HIV infection and higher HIV RNA levels were significantly associated with HCV incidence, while CD4 count was not. Trends differed by geographical region; while incidence appeared to have stabilized in Western Europe and remained stable in Southern Europe, it continued to increase in Northern Europe in recent years. Time from HIV to HCV infection significantly decreased over time (p<0.001). HCV has continued to spread among HIV-positive MSM in recent years, but trends differ by geographical region. Interventions to decrease the risk of HCV acquisition and increase early diagnosis are warranted. Hepatitis C virus infection continues to spread among HIV-positive men who have sex with men, especially among younger individuals. However, trends seem to differ by European region in recent years. Furthermore, men who have sex with men with a higher HIV RNA load were more likely to get infected with the hepatitis C virus. During recent HIV infection, MSM appear to be at higher risk of acquiring hepatitis C.

Invasive Pneumococcal Disease Among HIV-Infected and HIV-Uninfected Adults in a Large Integrated Healthcare System.

It is unclear whether HIV-infected individuals remain at higher risk of invasive pneumococcal disease (IPD) compared with HIV-uninfected individuals. We conducted a cohort study of HIV-infected and demographically matched HIV-uninfected adults within Kaiser Permanente Northern California during the period 1996-2011. We used Poisson models to obtain rate ratios (RRs) for incident IPD associated with HIV infection and other risk factors. Among 13,079 HIV-infected and 137,643 HIV-uninfected adults, the IPD rate per 100,000 person-years was 160 (n = 109 events) for HIV-infected and 8 (n = 75 events) for HIV-uninfected subjects, with an adjusted RR of 13.0 [95% confidence interval (CI): 9.1-18.7]. For HIV-infected individuals, IPD incidence per 100,000 person-years decreased by 71% during study follow-up, from 305 in 1996-1999 to 88 in 2010-2011 (p < 0.001), with an adjusted RR of 6.6 (95% CI: 2.7-16.1) compared with HIV-uninfected subjects in 2010-2011. Risk factors for IPD among HIV-infected individuals included black compared with white race/ethnicity, smoking, cancer, and higher HIV RNA levels. The 23-valent pneumococcal polysaccharide vaccination was not associated with a reduced risk of IPD in HIV-infected or HIV-uninfected individuals. Among HIV-infected IPD cases, the most common serotype was 19A (33%), and 59% of serotypes were covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Despite a dramatic decline in IPD incidence for HIV-infected adults since 1996, IPD rates were nearly sevenfold higher compared with HIV-uninfected adults in recent years, even after adjustment for risk factors. Timely antiretroviral therapy initiation, risk reduction strategies, and recent guidelines recommending PCV13 use may further reduce IPD incidence among HIV patients.

HIV-1 is undetectable in preejaculatory secretions from HIV-1-infected men on suppressive HAART.

Preejaculatory fluid, a viscous, lubricating secretion expressed by penile urethral glands during sexual excitement, may play a role in the sexual transmission of HIV-1. The urethra has been shown to be an important site of HIV infection in men and male macaques, and preejaculatory fluid and urethral swabs from HIV-1-infected men often contain HIV. Recent studies have shown that HAART reduces but does not eliminate seminal HIV shedding in infected men, and that the penile urethra remains a site of persistent simian immunodeficiency virus infection in HAART-treated macaques. The objective of this study was to determine whether HIV-infected men on stable HAART continue to shed HIV into preejaculatory secretions. Single-center prospective study. Sixty HIV-infected men on HAART were recruited to provide preejaculatory fluid, semen, and blood for HIV RNA quantification by reverse transcription-PCR. Eight men had detectable HIV in blood; of these four had HIV in semen (range: 40-96 000 copies/ml), and one had HIV in preejaculate (2400 copies/sample). Fifty-two men had undetectable HIV RNA in blood; of these 10 (19.2%) had HIV RNA in semen (range: 59-800 copies/ml) whereas none (0%) had HIV RNA in preejaculate (P = 0.004). This study documents for the first time high levels of HIV RNA in preejaculate fluid. However, none of the men on stable HAART with undetectable blood viral load had HIV RNA in preejaculate, even though many had detectable HIV in semen. The urethral glands do not appear to be a principal source of HIV in men on suppressive HAART.

Use of antimüllerian hormone to predict the menopausal transition in HIV-infected women

HIV infection has been associated with early menopausal onset, which may have adverse long-term health consequences. Antimüllerian hormone, a biomarker of ovarian reserve and gonadal aging, is reduced in HIV-infected women. We sought to assess the relationship of antimüllerian hormone to age of menopause onset in HIV-infected women. We used antimüllerian hormone levels measured in plasma in 2461 HIV-infected participants from the Women's Interagency HIV Study to model the age at final menstrual period. Multivariable normal mixture models for censored data were used to identify factors associated with age at final menstrual period. Higher antimüllerian hormone at age 40 years was associated with later age at final menstrual period, even after multivariable adjustment for smoking, CD4 cell count, plasma HIV RNA, hepatitis C infection, and history of clinical AIDS. Each doubling of antimüllerian hormone was associated with a 1.5-year increase in the age at final menstrual period. Median age at final menstrual period ranged from 45 years for those in the 10th percentile of antimüllerian hormone to 52 years for those in the 90th percentile. Other factors independently associated with earlier age at final menstrual period included smoking, hepatitis C infection, higher HIV RNA levels, and history of clinical AIDS. Antimüllerian hormone is highly predictive of age at final menstrual period in HIV-infected women. Measuring antimüllerian hormone in HIV-infected women may enable clinicians to predict risk of early menopause, and potentially implement individualized treatment plans to prevent menopause-related comorbidities and to aid in interpretation of symptoms.

Elevated alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus coinfection

BACKGROUNDMortality related to human immunodeficiency (HIV) has improved with the use of antiretroviral therapy; however, liver disease–related mortality remains a major concern for the HIV population. Elevation of alanine aminotransferase (ALT) has been noted in HIV-infected persons even without viral hepatitis infection.OBJECTIVEThe objective of this study was to determine the incidence and prevalence of chronic alanine ALT elevation among patients infected with HIV who are negative for hepatitis B or C infection.DESIGNRetrospective chart review.SETTINGSWe reviewed the medical records of all patients infected with HIV who had been treated from November 2002 to December 2010.PATIENTS AND METHODSPatients with an unknown or positive HBV or HCV infection status were excluded. We identified patient demographics, route of transmission, peak viral load, and nadir CD4 count.RESULTSWe followed 440 patients for up to 2265 person-years. A total of 123 patients developed chronically elevated ALT levels, with an incidence of 5.8 cases per 100 person-years. Chronically elevated ALT levels were associated with high HIV viral load, mean body mass index, and diabetes mellitus. We found exposure to lamivudine in 58% of the patients, efavirenz in 41%, and zidovudine in 38%. Abdominal ultrasounds revealed fatty liver in 20 of 39 (51%) of the patients.CONCLUSIONAmong patients without viral hepatitis coinfection, the prevalence and incidence of chronic elevated ALT levels were high and accompanied by high HIV RNA levels and increased BMI.LIMITATIONSThe limitations of this report are its retrospective nature and lack of a control group.