Manhattan Charurat

Cell-associated genital tract virus and vertical transmission of human immunodeficiency virus type 1 in antiretroviral-experienced women.

To determine the association between genital tract shedding of human immunodeficiency virus (HIV) type 1 and vertical transmission, a case-control substudy was conducted within the Women and Infants Transmission Study. Antenatal cervicovaginal lavage specimens were assessed for HIV-1 RNA in the supernatant and HIV-1 RNA and DNA in cell pellets. Multivariate analyses compared 26 women who transmitted HIV to their infants with 52 women who did not; 33% received combination antiretroviral therapy, and 65% received monotherapy. Adjusted odds ratios (ORs) for the presence (OR, 3.42; 95% confidence interval [CI], 0.76-15.4; P=.11) and titer (OR, 1.66; 95% CI, 0.93-2.99; P=.09) of HIV-1 DNA suggested that there is an independent association with vertical transmission. When analyses were restricted to vaginal and nonelective cesarean deliveries, each one-log increase in mean titer of HIV-1 DNA was associated with a significantly higher risk of transmission (OR, 2.28; 95% CI, 1.09-4.78; P=.03). The cell-associated genital tract compartment is important in the pathophysiology and prevention of vertical HIV-1 transmission.

Higher Incidence of Acute Kidney Injury With Intravenous Colistimethate Sodium Compared With Polymyxin B in Critically Ill Patients at a Tertiary Care Medical Center

Nephrotoxicity was assessed in 173 critically ill patients receiving intravenous colistin or polymyxin B; it occurred in 60.4% and 41.8%, respectively. Further investigation is necessary to elucidate the reason for the difference in nephrotoxicity observed between the groups and to assess the impact of severity of illness and dosing/administration.

Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

Epitopes located in and around the coreceptor binding site of HIV-1 envelope glycoprotein (gp120) exhibit enhanced exposure after attachment to the CD4 receptor and comprise some of the most conserved and functionally important residues on the viral envelope. Therefore, antibody responses to these epitopes [designated as CD4-induced (CD4i)] should be highly cross-reactive and potentially useful for HIV vaccine development. To address this question, rhesus macaques were vaccinated with subunit immunogens designed to raise humoral responses against CD4i epitopes and challenged rectally with SHIV162P3, which encodes a heterologous envelope versus the immunogen. We found that animals vaccinated with a rhesus full-length single-chain (rhFLSC) complex exhibited significantly accelerated clearance of plasma viremia and an absence of long-term tissue viremia compared with unvaccinated control animals. Such control of infection correlated with stronger responses to CD4i epitopes in the rhFLSC-vaccinated animals, compared with macaques immunized with gp120, cross-linked gp120–CD4 complexes, or soluble CD4 alone. These responses were strongly boosted in the rhFLSC-vaccinated animals by SHIV162P3 infection. The control of infection was not associated with anti-CD4 responses, overall anti-gp120-binding titers, or neutralizing activity measured in conventional assays. Vaccine-naive animals also developed anti-CD4i epitope responses after simian/ human immunodeficiency virus (SHIV) challenge, which appeared later than the overall anti-gp120 responses and in concert with the decline of viremia to a low set point. Collectively, these data suggest that antibodies to CD4i epitopes may play a role in controlling SHIV infection and provide insights for HIV vaccine development.

Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment

BACKGROUND Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified. METHODS Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures. RESULTS Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13). CONCLUSION Early HIV-1 infection increases a childs risk for poor neurodevelopmental functioning within the first 30 months of life.

Epidemiologic characteristics and natural history of HIV-1 natural viral suppressors.

Objective:The objective of this study was to detail the epidemiologic characteristics and natural history of HIV-1 natural viral suppressors (NVSs), a cohort of HIV-1-infected individuals who are able to suppress viral replication to undetectable levels in the absence of therapy. Design and Methods:HIV-1 patients who met the NVS criteria were enrolled into a prospective study. The incidence and prevalence of NVS were calculated by performing a chart review on all patients seen in 1 clinic in a 10-year period. Cumulative probability of progression-free survival was calculated by Kaplan-Meier product limit method. Results:Forty individuals enrolled in the study. The median year of diagnosis was 1994, and individuals demonstrated a median 6.7 years of HIV-1 viral suppression and CD4 count of 795 cells per microliter. NVS had an incidence of 1.1% [95% confidence interval (CI), 0.0 to 2.1] and prevalence of 1.5% (95% CI, 0.8 to 2.1). Only 1 patient (2.5%) has progressed. Within the first 10 years for follow-up having met the definition of NVS, 95.1% (95% CI 86.5% to 100%) of the NVS continued to control their viral loads to undetectable levels. Conclusions:The NVS cohort has demonstrated remarkable stability and a low rate of progression over many years. Detailed evaluations of viral-host immune regulatory factors associated with persistent HIV-1 natural viral suppression, and loss of such suppression, has the potential to provide important new insight in HIV pathogenesis and future immune regulatory targeted preventive and therapeutic research.

Mother-to-child transmission of HIV-1: strong association with certain maternal HLA-B alleles independent of viral load implicates innate immune mechanisms.

The transmission of HIV-1 from mother to child during pregnancy is unlike other types of HIV-1 transmission because the child shares major histocompatibility complex (MHC) genes with the mother during a time while the mother is induced to tolerate the paternally derived fetal MHC molecules, in part through natural killer (NK) recognition of MHC polymorphisms. The relevance of these immune mechanisms to HIV-1 transmission was assessed by determining the HLA-B alleles of mother and infant. Almost half (48%) of mothers who transmitted with low viral loads had HLA-B*1302, B*3501, B*3503, B*4402, or B*5001 alleles, compared with 8% of nontransmitting mothers (P = 0.001). Conversely, 25% of mothers who did not transmit despite high viral loads had B*4901 and B*5301, vs. 5% of transmitting mothers (P = 0.003), a pattern of allelic involvement distinct from that influencing HIV-1 infection outcome. The infants HLA-B alleles did not appear associated with transmission risk. The HLA-B*4901 and B*5301 alleles that were protective in the mother both differed respectively from the otherwise identical susceptibility alleles, B*5001 and B*3501, by 5 amino acids encoding the ligand for the KIR3DL1 NK receptor. These results suggest that the probable molecular basis of the observed association involves definition of the maternal NK recognition repertoire by engagement of NK receptors with polymorphic ligands encoded by maternal HLA-B alleles, and that the placenta is the likely site of the effect that appears to protect against transmission of maternal HIV-1 through interrelating adaptive and innate immune recognition.

Screening for Hazardous Alcohol Use and Depressive Symptomatology Among HIV-Infected Patients in Nigeria: Prevalence, Predictors, and Association With Adherence:

Scores from the Alcohol Use Disorders Identification Test (AUDIT) and the Center for Epidemiological Studies Depression Scale (CES-D) administered to both antiretroviral therapy (ART)-experienced and -naive adults in HIV care in Nigeria were evaluated for association with participant characteristics and ART adherence measured by pharmacy records. Participants included 222 ART-experienced and 177 ART-naive adults, of whom 47 (12%) had AUDIT ≥8, 29 (7%) an AUDIT ≥10, 52 (13%) a CES-D ≥16, and 25 (6%) a CES-D ≥21. An elevated AUDIT score was more frequent among ART-naive and men, while disclosure of HIV status to others was associated with lower scores. An elevated CES-D score was more frequent among ART-naive and those with lower educational level, while disclosure of HIV status and choosing to be interviewed in English rather than Hausa was associated with lower scores. An elevated CES-D score was associated with poor adherence.

Reference Values of CD4 T Lymphocytes in Human Immunodeficiency Virus-Negative Adult Nigerians

ABSTRACT A cross-sectional study that involved secondary analysis of data collected from 681 pregnant women and 183 miners (94 men and 89 women; ratio of men to women, 1:0.95) in Jos, Nigeria, was carried out to determine the reference ranges for CD4+-cell counts in healthy HIV-negative adult Nigerians. The main results of interest were CD4+-cell counts and odds ratios (ORs) of low CD4+-cell counts, defined as below 350 cells per μl. CD4+-cell counts were similar in men and nonpregnant women, with a mean (standard deviation) of 828 (203) cells per μl, but pregnant women had a lower value of 771 (250) cells per μl. None of the factors assessed was related to the odds of having a low CD4+-cell count among men and nonpregnant women, but age, age of marriage, and alcohol usage were significant predictors in pregnant women. Compared to pregnant women less than 20 years old, older women had significantly lower odds of a low CD4+-cell count (ORs were 0.06 for women aged 20 to 29 years and 0.22 for those aged 30 to 39 years). When compared with those pregnant women who were married before 20 years of age, those who married at 20 to 29 years and 30 to 39 years had odds ratios of 6.41 and 9.40, respectively. Previous alcohol use was also associated with low CD4+-cell counts (OR, 5.15). The 95% confidence interval for CD4+-cell counts in healthy adult Nigerians is 547 to 1,327 cells per μl, and this is the first time this has been determined.

Rapid Clearance of Virus after Acute HIV-1 Infection: Correlates of Risk of AIDS

OBJECTIVE Our objective was to define early virologic and immunologic determinants of human immunodeficiency virus (HIV) type 1 disease progression among 22 case subjects with acute infection from the Trinidad Seroconvertor Cohort. METHODS A linear segmented regression model was fitted to sequential quantitative virus load measurements. Parameters of virus kinetics during different phases of primary infection were correlated with clinical and immunologic end points, by use of Kaplan-Meier estimates and Cox regression. RESULTS Ten individuals developed acquired immunodeficiency syndrome (AIDS)-defining events. In univariate analysis, progression to AIDS was associated with rate of initial HIV clearance (P=.002), virus load during set point (P=.008), and CD4(+) cell count during steady state (P=.04). In the multivariate analysis, a rapid rate of initial clearance was the sole independent predictor of subsequent progression to AIDS and was associated with a 92% reduction in the risk of AIDS. The rate of initial clearance is inversely correlated with the number of early symptoms (r=-0.66; P=.0008). However, symptoms did not predict subsequent risk of AIDS. CONCLUSION Among a subset of patients, rapid clearance of plasma HIV-1 after peak viremia is associated with lower viral set point, prolonged virus suppression before loss of virologic control, and decreased risk of AIDS. These findings are consistent with the hypothesis that effective immune responses during the earliest phase of infection are important determinants of the subsequent natural history.

The immediate effect of the Same-Sex Marriage Prohibition Act on stigma, discrimination, and engagement on HIV prevention and treatment services in men who have sex with men in Nigeria: analysis of prospective data from the TRUST cohort

BACKGROUND In January, 2014, the Same-Sex Marriage Prohibition Act was signed into law in Nigeria, further criminalising same-sex sexual relationships. We aimed to assess the immediate effect of this prohibition act on stigma, discrimination, and engagement in HIV prevention and treatment services in men who have sex with men (MSM) in Nigeria. METHODS The TRUST cohort study uses respondent-driven sampling to assess the feasibility and effectiveness of engagement of MSM in HIV prevention and treatment services at a clinical site located with a community-based organisation trusted by the MSM community. TRUST is a prospective implementation research cohort of MSM (≥16 years) in Abuja, Nigeria. We compared HIV clinical outcomes and stigma, including fear and avoidance of health care, across baseline and quarterly visits before and after implementation of the the Same-Sex Marriage Prohibition Act. Outcomes assessed were measures of stigma and discrimination, loss to follow-up, antiretroviral therapy status, and viral load. We compared outcomes before and after the legislation with χ2 statistics, and estimated incident stigma-related events and loss to follow-up with Poisson regression. FINDINGS Between March 19, 2013, and Aug 7, 2014, 707 MSM participated in baseline study procedures, contributing to 756 before legislation (prelaw) and 420 after legislation (postlaw) visits. Reported history of fear of seeking health care was significantly higher in postlaw visits than in prelaw visits (n=161 [38%] vs n=187 [25%]; p<0・0001), as was avoidance of health care (n=118 [28%] vs n=151 [20%]; p=0・001). In incidence analyses, of 192 MSM with follow-up data and no history of an event at baseline, reported fear of seeking health care was higher in the postlaw than the prelaw period (n=144; incidence rate ratio 2・57, 95% CI 1・29–5・10; p=0・007); loss to follow-up and incident healthcare avoidance were similar across periods. Of the 161 (89%) of 181 HIV-infected MSM with HIV viral loads available, those who had disclosed sexual behaviour with a health-care provider were more often virally suppressed at baseline than those with no previous disclosure (18 [29%] of 62 vs 13 [13%] of 99 men; p=0・013). INTERPRETATION These analyses represent individual-level, quantitative, real-time prospective data for the health-related effects resulting from the enactment of legislation further criminalising same-sex practices. The negative effects of HIV treatment and care in MSM reinforce the unintended consequences of such legislation on global goals of HIV eradication. Strategies to reach MSM less likely to engage in HIV testing and care in highly stigmatised environments are needed to reduce time to HIV diagnosis and treatment. FUNDING National Institutes of Health.