scholarly journals Better Virological Outcomes Among People Living With Human Immunodeficiency Virus (HIV) Initiating Early Antiretroviral Treatment (CD4 Counts ≥500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) Trial in South Africa

2019 ◽  
Vol 70 (3) ◽  
pp. 395-403 ◽  
Author(s):  
Geoffrey Fatti ◽  
Ashraf Grimwood ◽  
Jean B Nachega ◽  
Jenna A Nelson ◽  
Kelsea LaSorda ◽  
...  

Abstract Background There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. Methods This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. Results The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200–499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12–.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200–499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). Conclusions Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200–499 cells/µL. Clinical Trials Registration NCT01900977.

Author(s):  
Mariya V Sivay ◽  
Philip J Palumbo ◽  
Yinfeng Zhang ◽  
Vanessa Cummings ◽  
Xu Guo ◽  
...  

Abstract Background The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TWG) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075. Methods HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads >400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing. Results HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2–6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort. Conclusions This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TWG in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.


Intervirology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Mohammad Reza Jabbari ◽  
Hoorieh Soleimanjahi ◽  
Somayeh Shatizadeh Malekshahi ◽  
Mohammad Gholami ◽  
Leila Sadeghi ◽  
...  

<b><i>Objectives:</i></b> The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count &#x3c;100 cells/mm<sup>3</sup> and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. <b><i>Methods:</i></b> This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count &#x3c;100 cells/mm<sup>3</sup>, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). <b><i>Results:</i></b> Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (<i>p</i> value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (<i>p</i> &#x3c; 0.02). <b><i>Conclusions:</i></b> We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count &#x3c;100 mm<sup>3</sup>/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.


2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Rita O. Oladele ◽  
Alani S. Akanmu ◽  
Augustina O. Nwosu ◽  
Folasade T. Ogunsola ◽  
Malcolm D. Richardson ◽  
...  

Abstract Background.  Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods.  Sera were collected from 214 consenting HIV-infected participants with CD4+ counts &lt;250 cells/mm3, irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results.  Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4+ cell count was 160 cells/mm3 (interquartile range, 90–210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4+ cell counts &lt;100 cells/mm3, 4 of 80 (5.0%) in the 100–200 group, and 9 of 73 (12.3%) in 200–250 cells/mm3 group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts &lt;100 cells/mm3, which was unrelated to CrAg positivity (P = .018). Conclusions.  We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend CrAg screening for HIV-infected patients, even for patients on ART.


2020 ◽  
Vol 0 ◽  
pp. 1-8
Author(s):  
Tejas Kanthrao Mankeshwar ◽  
Ashok Kumar Sharma

Objectives: Abdominal pathologies are the second most common after pulmonary diseases in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients. Ultrasonography (USG) is a vital imaging technique for the evaluation of abdominal pathologies. This study was aimed at evaluating the abdominal pathologies using USG in HIV/AIDS and further analysis of its correlation with CD4 count. Material and Methods: The present study was carried out on 392 HIV-positive patients with abnormal abdominal sonographic findings. All data were analyzed by Chi-square test and one-way analysis of variance using SPSS 16.0 software. Results: Of these 392 patients, 66.3% were males, the mean age was 35.7 years, (range 7–64 years) and most of them were in 4th decade. On ultrasonographic evaluation, spleen was involved in 45.2% patients and liver as well as lymph nodes each was involved in 43.6% patients. Other cases displayed ascites and bowel thickening in 5.3% and 3.8% patients, respectively. Less involvement of kidney (2.3%), pancreas (1.5%), and biliary system (1.3%) was observed. In addition, pathologies such as hepatomegaly, splenomegaly, splenic microabscess, focal pancreatic lesion, mesenteric, and periportal lymphadenopathy showed significant correlation with CD4 counts. Lymphoma was found in 1% of patients, involving liver, pancreas, and retroperitoneal lymph nodes. Conclusion: Our study highlights the clinical utility of abdominal USG in HIV/AIDS patients. CD4 counts largely affect the differential diagnosis in HIV/AIDS patients. USG findings interpreted in the context of CD4 count may help in guiding the exact diagnosis.


2004 ◽  
Vol 83 (8) ◽  
pp. 639-643 ◽  
Author(s):  
M. Gandhi ◽  
D.M. Koelle ◽  
N. Ameli ◽  
P. Bacchetti ◽  
J.S. Greenspan ◽  
...  

Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi’s sarcoma (KS), which occurs in epidemic form in human immunodeficiency virus(HIV)-infected individuals. Saliva is the only mucosal fluid in which infectious HHV-8 has been identified, although factors associated with HHV-8 salivary shedding remain unclear. Our study performed PCR analysis for HHV-8 DNA in saliva (and other body fluids) in 66 HIV- and HHV-8-co-infected women without KS so that we could examine predictors for HHV-8 DNA detection. CD4 count was the most significant predictor of HHV-8 salivary shedding, with increased prevalence of HHV-8 salivary DNA at higher CD4 counts. The odds of salivary HHV8 shedding at CD4 counts > = 350 cells/μL was 63 times the odds of shedding at CD4 < 350 (95%CI, 1.3–3078), with an increase in effect size when the analysis was restricted to those with a CD4 nadir > 200. Analysis of these data suggests an increased potential for HHV-8 transmission early in HIV infection, with implications for HHV-8 prevention.


Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1351-1357
Author(s):  
J Hassett ◽  
GF Gjerset ◽  
JW Mosley ◽  
MA Fletcher ◽  
E Donegan ◽  
...  

Patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1) infection have lower CD4+ counts and CD4+/CD8+ ratios than controls. This is usually interpreted as a therapy-induced immunodeficiency. Our data re-examine the effect of therapy on peripheral blood mononuclear cell immunophenotypic subpopulations in all congenital clotting disorders. Since late 1985 we have prospectively observed HIV-1 uninfected persons with all types and severity of disorder. Controls were household members without clotting disorders or HIV-1 infection. Analyses of immunophenotype and treatment included a longitudinal random effects model. Compared with controls, age-adjusted CD4+ counts were significantly lower in treated patients (P < .0001) and in patients with all types of clotting disorders who were seldom or never treated (P = .0005). Significantly lower values among both treated and untreated clotting disorder subjects (P < .05) were likewise found for total lymphocytes, several other T-cell subsets, and the CD4+/CD8+ ratio. For most indexes, including the CD4+ count and CD4+/CD8+ ratio, the type of clotting deficiency was not a significant variable. Comparing persons who had no or minimal therapy with those having the most showed increases in CD8+ (P = .0017) and CD20+ CD21- counts (P = .0255), and a lower CD20+ CD21+/CD20+ ratio (P = .0106) in the latter. Controls and persons with clotting disorders differ in CD4+ count. Among those with clotting factor disorders, there is no difference attributable to type of clotting disorder or factor therapy. Large amounts of treatment increased CD8+ and CD20+ CD21- counts, but were not associated with a change in CD4+ count.


Author(s):  
Marie C D Stoner ◽  
Daniel Westreich ◽  
Jennifer Ahern ◽  
Jessie Edwards ◽  
F Xavier Gómez-Olivé ◽  
...  

Abstract Background Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV. Methods We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors. Results Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, –1.4%; 95% confidence interval [CI], –2.7% to –.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by –1.3% (95% CI, –2.6% to –.2%). Conclusions To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence.


Author(s):  
Mark W Tenforde ◽  
Thandi Milton ◽  
Ikanyeng Rulaganyang ◽  
Charles Muthoga ◽  
Leabaneng Tawe ◽  
...  

Abstract Increasing the CD4-count threshold for cryptococcal antigen (CrAg) screening from ≤100 to ≤200 cells/µL resulted in a 3-fold increase in numbers screened. CrAg-prevalence was 3.5% at CD4 101–200 and 6.2% ≤100 cells/µL. Six-month mortality was 21.4% (9/42) in CrAg-positive CD4 ≤100 cells/µL and 3.2% (1/31) in CrAg-positive CD4 101–200 cells/µL.


Author(s):  
Yinfeng Zhang ◽  
Chris Wymant ◽  
Oliver Laeyendecker ◽  
M Kathryn Grabowski ◽  
Matthew Hall ◽  
...  

Abstract Background Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Methods Complete next-generation sequencing (NGS) data were obtained for 105 unique index–partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). Results Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. Conclusions We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.


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