Human Immunodeficiency Virus Progression Research Articles

Mathematical Modelling of HIV-HCV Coinfection Dynamics in Absence of Therapy.

Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals coinfected with HIV and latent HCV. Therefore, HIV and latently HCV-infected individuals need to seek early treatment so as to slow down the progression of HIV to AIDS and latent HCV to advanced HCV.

DNA methylation mediates the effect of cocaine use on HIV severity

BackgroundCocaine use accelerates human immunodeficiency virus (HIV) progression and worsens HIV outcomes. We assessed whether DNA methylation in blood mediates the association between cocaine use and HIV severity in a veteran population.MethodsWe analyzed 1435 HIV-positive participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS-BC). HIV severity was measured by the Veteran Aging Cohort Study (VACS) index. We assessed the effect of cocaine use on VACS index and mortality among the HIV-positive participants. We selected candidate mediators that were associated with both persistent cocaine use and VACS index by epigenome-wide association (EWA) scans at a liberal p value cutoff of 0.001. Mediation analysis of the candidate CpG sites between cocaine’s effect and the VACS index was conducted, and the joint mediation effect of multiple CpGs was estimated. A two-step epigenetic Mendelian randomization (MR) analysis was conducted as validation.ResultsMore frequent cocaine use was significantly associated with a higher VACS index (β = 1.00, p = 2.7E−04), and cocaine use increased the risk of 10-year mortality (hazard ratio = 1.10, p = 0.011) with adjustment for confounding factors. Fifteen candidate mediator CpGs were selected from the EWA scan. Twelve of these CpGs showed significant mediation effects, with each explaining 11.3–29.5% of the variation. The mediation effects for 3 of the 12 CpGs were validated by the two-step epigenetic MR analysis. The joint mediation effect of the 12 CpGs accounted for 47.2% of cocaine’s effect on HIV severity. Genes harboring these 12 CpGs are involved in the antiviral response (IFIT3, IFITM1, NLRC5, PLSCR1, PARP9) and HIV progression (CX3CR1, MX1).ConclusionsWe identified 12 DNA methylation CpG sites that appear to play a mediation role in the association between cocaine use and HIV severity.

Cost-effectiveness analysis of pre-exposure prophylaxis for the prevention of HIV in men who have sex with men in South Korea: a mathematical modelling study

In February 2018, the Ministry of Food and Drug Safety in Korea approved tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) co-formulate for use in pre-exposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) infection. This study aimed to estimate the cost-effectiveness of PrEP in men who have sex with men (MSM), a major risk group emerging in Korea. A dynamic compartmental model was developed for HIV transmission and progression in MSM aged 15–64 years. With a combined model including economic analysis, we estimated averted HIV infections, changes in HIV prevalence, discounted costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). PrEP was evaluated in both the general MSM and high-risk MSM populations and was assumed to reduce infection risk by 80%. Implementing PrEP in all MSM would avert 75.2% HIV infections and facilitate a gain of 37,372 QALYs at a cost of $274,822 per QALY gained over 20 years relative to the status quo. Initiating PrEP in high-risk MSM with an average of eight partners per year (around 20% of MSM) would improve the cost-effectiveness, averting 78.0% HIV infections and add 29,242 QALYs at a cost of $51,597 per QALY gained, which is within the willingness-to-pay threshold for Korea of $56,000/QALY gained. This result was highly sensitive to annual PrEP costs, quality-of-life for people who are on PrEP, and initial HIV prevalence. Initiating PrEP in a larger proportion of MSM in Korea would prevent more HIV infections, but at an increasing cost per QALY gained. Focusing PrEP on higher risk MSM and any reduction in PrEP cost would improve cost-effectiveness.

The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression.

BackgroundHuman genetic variation—mostly in the human leukocyte antigen (HLA) and C–C chemokine receptor type 5 (CCR5) regions—explains 25% of the variability in progression of human immunodeficiency virus (HIV) infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of cytosine-guanine (CpG) islands might modulate progression of HIV infection.MethodsIn total, 85 samples were analyzed: 21 elite controllers (EC), 21 subjects with HIV before combination antiretroviral therapy (cART) (viremic, 93 325 human immunodeficiency virus type 1 [HIV-1] RNA copies/mL) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/mL), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485 577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, messenger RNA (mRNA) expression, and plasma protein levels in 5 individuals before and after initiation of cART.ResultsWe observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic versus HIVneg, 162 CpG sites (55 gene promoters) in viremic versus cART, 441 CpG sites (163 gene promoters) in viremic versus EC, but none in EC versus HIVneg. The TNF promoter region was hypermethylated in viremic versus HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg.ConclusionsOur study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART.

Impact of sickle cell disease on presentation and progression of paediatric HIV: a retrospective cohort study.

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. The study was a retrospective cohort study (study period 2004-2018). Cases of HIV+and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV+controls without SCD (HIV+/SCD-). Thirty-five HIV+/SCD+subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD+had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P=0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD+and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD+cohort (P=0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD+cohort showed a more rapid rise and higher total CD4 count (P=0.012, regression analysis). The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD+achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

Modelling immune deterioration, immune recovery and state-specific duration of HIV-infected women with viral load adjustment: using parametric multistate model

BackgroundCD4 cell and viral load count are highly correlated surrogate markers of human immunodeficiency virus (HIV) disease progression. In modelling the progression of HIV, previous studies mostly dealt with either CD4 cell counts or viral load alone. In this work, both biomarkers are in included one model, in order to study possible factors that affect the intensities of immune deterioration, immune recovery and state-specific duration of HIV-infected women.MethodsThe data is from an ongoing prospective cohort study conducted among antiretroviral treatment (ART) naïve HIV-infected women in the province of KwaZulu-Natal, South Africa. Participants were enrolled in the acute HIV infection phase, then followed-up during chronic infection up to ART initiation. Full-parametric and semi-parametric Markov models were applied. Furthermore, the effect of the inclusion and exclusion viral load in the model was assessed.ResultsInclusion of a viral load component improves the efficiency of the model. The analysis results showed that patients who reported a stable sexual partner, having a higher educational level, higher physical health score and having a high mononuclear component score are more likely to spend more time in a good HIV state (particularly normal disease state). Patients with TB co-infection, with anemia, having a high liver abnormality score and patients who reported many sexual partners, had a significant increase in the intensities of immunological deterioration transitions. On the other hand, having high weight, higher education level, higher quality of life score, having high RBC parameters, high granulocyte component scores and high mononuclear component scores, significantly increased the intensities of immunological recovery transitions.ConclusionInclusion of both CD4 cell count based disease progression states and viral load, in the time-homogeneous Markov model, assisted in modeling the complete disease progression of HIV/AIDS. Higher quality of life (QoL) domain scores, good clinical characteristics, stable sexual partner and higher educational level were found to be predictive factors for transition and length of stay in sequential adversity of HIV/AIDS.

Syphilis infection does not affect immunodeficiency progression in HIV-infected men who have sex with men in China.

Syphilis and human immunodeficiency virus (HIV) co-infection is expected to play a role in HIV-1-related immunodeficiency progression; however, studies involving syphilis/HIV co-infection have not been conclusive. We investigated the factors associated with co-infection of syphilis and HIV and to assess the effect of syphilis on HIV progression in the context of HIV-1 diversity in an observational cohort of 246 newly-diagnosed HIV-infected but antiretroviral therapy-naive men who have sex with men enrolled in Guangzhou, China between 2008 and 2012. CD4+ cell counts of all the participants were measured from the time of diagnosis until 2015 with an average of 32 ± 18 months. Logistic analysis indicated that patients with syphilis/HIV co-infection were more likely to be older with an adjusted odds ratio (AOR) of 2.48 (95% CI: 1.28–4.80) for those aged between 31 and 40 years and 3.20 (1.11–9.22) for those aged ≥40 years as compared to 16–30 year-olds. The AOR of patients infected with HIV-1 CRF07_BC as compared to CRF01_AE was 2.14 (95% CI: 1.01–4.53). Co-infection of syphilis and HIV was associated with lower baseline CD4+ cell count (0.45, 95% CI: 0.22–0.94), but was not associated with HIV disease progression (HR: 1.03; 95% CI, 0.86–1.23) based on Kaplan–Meier analysis. Our results provide new evidence about the interaction between syphilis and HIV and indicate differential rates of immunodeficiency progression as a function of HIV-1 genetic diversity.

Characteristics and outcomes of antiretroviral-treated HIV-HBV co-infected patients in Canada

BackgroundHepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients.MethodsA retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon’s Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI).ResultsHBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120–360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85–294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02).ConclusionThe prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.

Low seroprotection rate for meningococcus serogroupC in the adult HIV-1-infected population in Austria.

SummaryCurrent Advisory Committee on Immunization Practices (ACIP) guidelines recommend immunization of all human immunodeficiency virus (HIV)-infected patients against meningitis serotype ACWY due to recent outbreaks of meningitis C in homosexual men in the USA. Implementation of this recommendation in other countries, such as Austria is hindered by the scarce knowledge on the vaccine coverage. In this study the serostatus for meningococcus serogroup C was analyzed in 390 HIV-infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73% were on suppressive antiretroviral therapy, the mean CD4 cell count was 599 cells/μl and immunoglobulin G (IgG) seropositivity was 18% for meningococcus serogroup C. Migrants and patients who had acquired an infection via heterosexual intercourse had a higher chance for meningococcus serogroup C seropositivity. Importantly due to the well-preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. It is assumed that this measure would largely reduce the number of patients at risk for this vaccine-preventable disease.

Influence of the HIV GWG variant in the HIV infection progression in mono and HCV coinfected patients.

The HIV subtype B is the most frequent in Brazil. The HIV subtype B’ codes the amino acids glicine-tryptophan-glicine (GWG) instead of glicine-proline-glicine on the tip of gp120 V3 loop. This variant was associated to a slower HIV progression in mono-infected patients; however, there is no information in coinfected patients. This study evaluated the infection progression of HIV variant B’ on the hepatitis C virus presence. RNA isolated from plasma of the 601 infected patients were used to human immunodeficiency virus (HIV) subtyping and to classify the virus according their syncytium-inducing ability. The HIV infection progression was evaluated by clinical and laboratorial data. The results showed a significant association between HIV B’ variant and CD4 count and time of AIDS in HIV mono-infected patients. Notwithstanding the fact that we did not find a direct association between GWG variant and AIDS and in HIV coinfected patients no mitigating effect due to GWG presence was found. We did observe that the association between GWG variant and CD4 counts is lost in coinfected patients. This is first work showing influence of the HIV GWG variant in coinfected patients. Nevertheless, the presence of the GWG variant can indicate a better prognostic in the mono-infected patients.

Impact of Tobacco Smoke in HIV Progression: a Major Risk Factor for the Development of NeuroAIDS and Associated of CNS Disorders.

With the advent of highly active and combination antiretroviral therapy have substantially increased the life expectancy of patients infected with human immunodeficiency virus (HIV). However, this has brought into sharp contrast the incidence of several 'Non-acquired immunodeficiency syndrome (AIDS) diseases such as NeuroAIDS which identifies a group of neurological disorders caused primarily by HIV-mediated damage to the central and peripheral nervous systems. Given the patients depleted immune condition, the use and abuse of drug and addictive substances such as tobacco smoking can further deteriorates their overall health and accelerate the progression and severity of the disease. In this review we detail the pathogenesis, progression and characteristics of HIV and the impact of tobacco smoking as a risk factor for the progression of the disease to NeuroAIDS. This is a poorly understood aspect of HIV-related complications that needs to be addressed. Review of theoretical approaches and knowledge synthesis. Tobacco smoking is highly prevalent in HIV patients when compared to the general population. The oxidative damage and inflammatory stress caused by chronic smoking on the cerebrovascular system have been well established. Considering that HIV patients have an impaired immune system and smokers per se are more susceptible to viral and bacterial inflammatory neuropathologies than non-smokers, it is conceivable that tobacco smoking as a risk factor for the progression of HIV into NeuroAIDS and related neurological impairments. Tobacco smoke (TS) may bring about a synergistic effect in the context of persistent inflammatory state and cerebrovascular damage which facilitate HIV infection and progression to NeuroAIDS when compared to non-smokers.

Cholesterol efflux responds to viral load and CD4 counts in HIV+ patients and is dampened in HIV exposed

Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in human immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV patients at different stages of HIV disease progression. In this cross-sectional study, CE from ApoB-depleted plasma, lipids levels, viral load (VL), CD4+/CD8+ T-cells, high-sensitive C-reactive protein (hsCRP), and lipoprotein (a) were evaluated in untreated HIV-infected patients (UHIVs; n = 43), elite controllers (ECs; n = 8), HIV-exposed seronegative individuals (HESNs; n = 32), and healthy controls (HCs; n = 14). Among UHIVs, those with CD4+ <500 cells/mm3 presented the lowest significant CE, HDL cholesterol (HDL-C), and ApoAI levels. ECs showed similar HDL-C, ApoAI, and CE compared with HCs. Among UHIVs, CE positively correlated with CD4+ T-cell counts (Beta: 1.05; 95% CI: 1.02; 1.07), and for VL higher than 3.8 log, CE was inversely associated with VL (Beta: 0.70; 95% CI: 0.51; 0.95). Remarkably, HESNs presented higher CE (0.78 ± 0.14) than UHIVs (0.65 ± 0.17; P = 0.0005), but lower than HCs (0.90 ± 0.13; P = 0.009). hsCRP levels were highest in the UHIV group (0.45 ± 0.49). CE was sensitive to HIV disease progression. Low CE in HIV patients was associated with lower CD4+ T-cells and higher VL and hsCRP. CE was also lower in HESNs compared with HCs. Our results suggest that immune status secondary to HIV progression and exposure influence plasma HDL-CE capacity.

Missed Opportunities for HIV Screening Among a Cohort of Adolescents With Recently Diagnosed HIV Infection in a Large Pediatric Hospital Care Network

PurposeRoutine human immunodeficiency virus (HIV) screening reduces HIV progression and transmission. Our aims were to determine prevalence and factors associated with prior HIV screening among a cohort of youth living with HIV. MethodsRetrospective chart review of youth living with HIV aged 14–26 at an HIV clinic comparing characteristics between those with and without HIV screening within the year prior to diagnosis ResultsSubjects (n = 301) were male (85%), African-American (87%), and men who have sex with men (84%). Subjects seen 1 year prior to diagnosis (n = 58) contributed 179 visits for missed opportunities with 59% having a documented sexual history in the electronic health record and 48% tested for HIV. Subjects with symptoms suggesting acute HIV infection (51%) were more likely to be tested (p = .04). In the adjusted model, documentation of sexual history and demographic factors was not associated with prior testing. ConclusionWe identified high rates of missed opportunities for HIV testing and sexual history documentation in the year prior to diagnosis, underscoring the need for routine HIV screening in adolescents.

Looking for Novel Capsid Protein Multimerization Inhibitors of Feline Immunodeficiency Virus.

Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses. It causes acquired immunodeficiency syndrome (AIDS) in worldwide domestic and non-domestic cats and is a cause of an important veterinary issue. The genome organization of FIV and the clinical characteristics of the disease caused by FIV are similar to human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes, and macrophages, with a similar replication cycle in infected cells. Thus, the infection of cats with FIV is also a useful tool for the study and development of novel drugs and vaccines against HIV. Anti-retroviral drugs studied extensively with regards to HIV infection have targeted different steps of the virus replication cycle: (1) disruption of the interaction with host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus and cell membranes; (3) blocking of the reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and integration of viral DNA into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite the great success of anti-retroviral therapy in slowing HIV progression in humans, a similar therapy has not been thoroughly investigated for FIV infection in cats, mostly because of the little structural information available for FIV proteins. The FIV capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. During this step, the CA protein oligomerizes to form a protective coat that surrounds the viral genome. In this work, we perform a large-scale screening of four hundred molecules from our in-house library using an in vitro assembly assay of p24, combined with microscale thermophoresis, to estimate binding affinity. This screening led to the discovery of around four novel hits that inhibited capsid assembly in vitro. These may provide new antiviral drugs against FIV.

Epigenetic alterations are associated with monocyte immune dysfunctions in HIV-1 infection

Monocytes are key cells in the immune dysregulation observed during human immunodeficiency virus (HIV) infection. The events that take place specifically in monocytes may contribute to the systemic immune dysfunction characterized by excessive immune activation in infected individuals, which directly correlates with pathogenesis and progression of the disease. Here, we investigated the immune dysfunction in monocytes from untreated and treated HIV + patients and associated these findings with epigenetic changes. Monocytes from HIV patients showed dysfunctional ability of phagocytosis and killing, and exhibited dysregulated cytokines and reactive oxygen species production after M. tuberculosis challenge in vitro. In addition, we showed that the expression of enzymes responsible for epigenetic changes was altered during HIV infection and was more prominent in patients that had high levels of soluble CD163 (sCD163), a newly identified plasmatic HIV progression biomarker. Among the enzymes, histone acetyltransferase 1 (HAT1) was the best epigenetic biomarker correlated with HIV - sCD163 high patients. In conclusion, we confirmed that HIV impairs effector functions of monocytes and these alterations are associated with epigenetic changes that once identified could be used as targets in therapies aiming the reduction of the systemic activation state found in HIV patients.

Consequence of HIV and HCV co-infection on host immune response, persistence and current treatment options.

Hepatitis C virus (HCV) is a common opportunistic pathogen especially among Human immunodeficiency virus (HIV) infected patients. Due to incongruous studies, the pathological effect of HCV on HIV induced disease are still not fully understood. While some studies have showed no effect of HCV on HIV infection, others reported a defined role of HCV in aggravating the rates of AIDS-related illnesses and mortality. The explanation of such variances may be due to the host immune response, viral genotypes, sub-type and quasi-species distribution. The factors that complicate the management of HIV/HCV patients are: (1) reduced HCV antibody production, (2) drug interactions, (3) liver disease and (4) different epidemiologic characteristics. However, it is abundantly clear that the morbidity and mortality caused by HCV have increased since the introduction of highly active antiretroviral therapy (HAART) against HIV. In this review, the consequence of HIV/HCV co-infection on host immune response, viral replication, disease progression, mortality and morbidity, viral load, persistence and current treatment options have been discussed. Based on the clinical studies, it is necessary to evaluate the effect of HCV therapy on HIV progression and to provide a fully active HCV treatment for patients receiving HIV treatment. In conclusion, it is recommended to provide fully active HAART therapy in combination with a known HCV therapy.

English

Patients with human immunodeficiency virus (HIV) infection exhibit a generalized, non-HIV-specific polyclonal B-cell activation resulting in hypergammaglobulinemia of all immunoglobulin isotypes as well as increased production of HIV-specific IgG and IgM. These immunoglobulins have the potential to be used as markers for monitoring the progression of HIV infection. With the inherent challenges of cost and convenience in the use of the conventional markers for HIV monitoring, that is, viral load and CD4+ count, there is the need to investigate the possible prognostic role of the above mentioned immunoglobulins in the management of HIV patients in Nigeria. The IgG, IgA and IgM profile as well as the CD4+ T cell count of forty HIV seropositive subjects was assayed before and after 3 months follow-up in a case series descriptive study. The Igs were measured using enzyme linked immunosorbent assay (ELISA), while CD4 count was done using flow cytometry. In the determination of concentration/value changes of parameters at baseline and follow up in HIV progression, only IgM, waist and hip circumference showed significant differences (p &lt; 0.05) within the period under study. While in the determination of the effect of therapy on the subjects, significant differences (p &lt; 0.05) were observed only in the values of CD4 count and BMI. While statistically significantly inverse relationship was observed between the CD4 counts and IgM concentrations, the values of IgG and IgA were inverse but not significant in relation to CD4 count. This study concluded that immunoglobulins (G, A and M) are not reliable in monitoring short term response to therapy unlike CD4 count although IgM has good diagnostic value like CD4 at baseline. Key words: HIV/AIDS, CD4+ count, viral load, antiretroviral, immunoglobulins.

No Role of Herpes Simplex Virus Type 2 (HSV-2) Infection on HIV Progression in Naïve HIV Patients

Background:Herpes simplex virus type 2 (HSV-2) is a common infection in human immunodeficiency virus (HIV) patients and may accelerate HIV progression by rising HIV viral load and decreasing CD4 count. However, the available data regarding the influence of HSV-2 seropositivity on HIV progression in HIV individuals are inconclusive. Therefore, we aimed to determine HSV-2 seroprevalence in naïve HIV patients and normal controls and also investigate the relation of HIV viral load and CD4 count with HSV-2 seropositivity. Subsequently, we investigated the association of HSV-2 serostatus with changing in CD4 count and HIV viral load in our subjects, after one year follow-up.Methods:In this study, 116 naïve HIV patients and 85 healthy controls from Tehran, Iran were enrolled. HSV-2 IgG antibody was detected by ELISA. CD4 count was determined by flowcytometry, and serum HIV RNA copy numbers were determined using real-time PCR.Results:The prevalence of HSV-2 IgG was 18.1% in naïve HIV patients and 0% in the control group (P = 0.000). HSV-2 seroconversion was observed in 2.43% of HIV patients after one year. There was no significant difference regarding HSV-2 serostatus with CD4 count and HIV RNA viral load in our study cohort at baseline and after one year.Conclusion:Our results revealed that the prevalence and incidence of HSV-2 infection are low in our HIV cases, and it is negligible in the control group. However, it seems that HIV/HSV2 co-infection has no role on HIV infection acceleration.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

We assessed non‐liver‐related non–acquired immunodeficiency syndrome (AIDS)‐related (NLR‐NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)–coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR‐NAR events considering death as the competing risk. The NLR‐NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR‐NAR cancer, bone events, and non‐AIDS‐related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T‐cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti‐HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5‐year follow‐up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35‐0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17‐1.09; P = 0.075). Conclusion: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver‐related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344–356).

HIV Progression Depends on Codon and Amino Acid Usage Profile of Envelope Protein and Associated Host-Genetic Influence.

Acquired immune deficiency syndrome (AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV). Two types of HIV have been characterized: HIV-1 and HIV-2. The present study investigated whether evolutionary selection pressure differs between rapid progressor (RP), slow progressor (SP), and long-term non-progressor (LTNP) of HIV-I infected individuals. An unexpected association between the evolutionary rate of substitution in envelope (env) gene and disease progression is observed. Our present study suggests that env genes of LTNP are subject to unusually strong functional constraint with respect to RP. We also observed that the three categories of env genes i.e., RP, SP, and LTNP, had their own characteristic pattern of amino acid usage and SP and LTNP sequences shared similar patterns of amino acid usage different from RP sequences and evolutionary rate significantly influenced the amino acid usage pattern of the three different types of env gene sequences. It was also noted that the evolutionary rate for the glycosylation sites of LTNP and SP sequences were even significantly less than the RP sequences. Comparative analysis on the influence of human host on the three categories of env genes are well correlated with the rates of disease progression suggesting the adaptive strategies of the viruses for successful residence and infection. Host associated selective constraints appeared most relaxed on the RP sequences and strongest in LTNP sequences. The present study clearly portrays how evolutionary selection pressure differs between three categories of env genes i.e., RP, SP, and LTNP. The env genes, coding for the env glycoproteins, experience severe selection constraints from the host due to their constant exposure to the host immune system. In this perspective it might be suggested that env gene evolution occurs mainly by negative selection with the occurrence of mutation that might not reach fixation in the viral population. This work also confers a deeper insight into the crucial effects of host factors that govern the overall progression of HIV infection.