Start Of Highly Active Antiretroviral Therapy Research Articles

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China.

Objective CD4+ cell recovery is hampered in some human immunodeficiency virus (HIV)-infected patients, despite a successful highly active antiretroviral therapy (HAART) with suppressed viral replication. We investigated the factors that might have hindered the CD4+ cell recovery in these patients. Methods In this retrospective study, we collected the data of all immune nonresponders (INRs) in Wuhan, China, until the end of 2020. A linear model was constructed based on the data from 220 patients with baseline and follow-up records. The response variables in this study were the CD4+ cell count increase. The predictor variables considered in this study were those factors likely to affect the CD4+ cell recovery. Results Our findings revealed that the plasma HIV-1 viral load of all patients was suppressed and 87.3% patients' CD4+ cells was increased after more than one year of the HAART treatment. In addition, their last follow-up showed a significant reduction in complications. In our results, the body mass index (BMI), number of months since HIV diagnosis to HAART start, and nonuse of co-trimoxazole were negatively correlated with the increase in CD4+ cells (P < 0.05). However, there were positive associations between serum creatinine levels and CD4+ cell recovery (P < 0.05). Further stratified analyses indicated that the associations between HAART replacement or creatinine usage and CD4+ cell growth were only observed in those participants with a BMI <18.5 (P < 0.05). Conclusions An early initiation of HAART and co-trimoxazole preventive therapy (CPT) can promote immune reconstitution. BMI and serum creatinine can serve as monitoring indicators of immune reconstitution prognosis after the HAART.

Conserved broad HIV-1 Gag-specific responses associated with low viral load and high CD4+ T cell nadir and preserved HAART regimen.

Broad human immunodeficiency virus type 1 (HIV-1) Gag-specific cellular responses can control viremia and provide slow progression to Acquired immunodeficiency syndrome (AIDS). In this study, we evaluate multiple HIV-1 Gag-specific lymphoproliferative responses and find their connection with cluster of differentiation 4 (CD4)+ T cell count and viral load from chronically HIV-1-infected patients. We further search for the correlation between multiple Gag-specific lymphoproliferative responses and changes in highly active antiretroviral therapy (HAART) regimen. We found correlation between Gag-specific responses and higher CD4+ T cells nadir and low HIV-1 viral load. Additionally, we observed that HIV-1-infected subjects did not need to change HAART regimen, when multiple Gag responses are present. We concluded that the start of HAART when CD4+ T cell nadir is the highest as possible may promote Gag-specific cellular responses conservation. Multiple Gag responses must be important to suppress HIV-1 replication. Preserved Gag-specific responses reduce HIV-1 viral load and are associated with stability of HAART regimen. Keywords: HIV-1; Gag; lymphoproliferation; viral load; HAART.

1068PD - Non-Hodgkin lymphoma in HIV-positive patients treated with antiretroviral therapy and chemotherapy: A single institution retrospective study

BackgroundHIV+ pts have a 25-fold higher risk of developing NHL. Two independent prognostic factors influence incidence and prognosis: highly active antiretroviral therapy (HAART) and CD4+ lymphocyte count. Diagnosis of NHL can occur simultaneously (naive pts), or after diagnosis of HIV infection (experience-pts). MethodsSingle institution retrospective cohort study conducted in ASST FBF-Sacco Polo Luigi Sacco (Milan, Italy). Pts aged>=18 years, diagnosis of HIV infection and NHL, on HAART treated with first line R-CHOP-like chtp from Jan 2007 to Jan 2017. Chi-square, Fisher’s exact or Wilcoxon Rank-sum test, log-rank test or Cox regression model for OS, PFS and RR were used. ResultsWe enrolled 46 HIV+ pts: 11 naive-pts, 35 experience-pts (exp-pts). No difference in median age at diagnosis (49vs48ys p=0.40), sex (male 72.7vs85.7% p=0.37), histological types: DLBCL (2vs24), BL (3vs3), PEL (1vs0), PCNSL (1vs0), PBL (2vs2) low-grade NHL (2vs4) T-cell NHL(0 vs 2) (p=0.13). Naïve-pts higher stage (stage IV 90.9vs41.2% p=0.05). No difference in frequency of B symptoms (40vs41% p=0.99), bulky masses (18.2vs20.6% p=0.99), ≥2 extranodal sites (45.5vs40% p=0.61), CNS involvement (44.4vs38.2% p=0.99), AIDS-definig diseases (44.4vs28.6% p=0.43) HCV/HBV infection (p=0.08/0.99). Naive-pts aaIPI intermediate-high risk (90.0vs58.1% p=0.11). CD4+ count at NHL diagnosis(102vs222/mcl p=0.05). During R-CHOP-like chtp naïve-pts more infectious toxicity (50% vs 10.7% p=0.02). During a median (IQR 2-44) follow-up of 12 mts no difference in RR (CR 60% vs 62.5% p=0.85), median OS (67 mts vs 69.4 mts p=0.3) and PFS (p=0.8). ConclusionsThe compromised immune status in naïve-pts may explain their worst NHL conditions at diagnosis and toxicity during chtp. The immediate start of HAART in combination with chemotherapy probably reduce the impact of these factors in term of response to treatment and survival (RR, PFS and OS). CD4+ count together with HAART remain the independent prognostic factor with the greatest influence on OS [exp vs naïve-pts: OS HR 0.83 (95% CI); OS/CD4+ HR 1.80 (95% CI)]. Naive-pts should be treated with standard chtp regimens, without modification of dose or schedule. Legal entity responsible for the studyASST-FBF-SACCO. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Prevalence and Factors Associated With Herbal Medicine Use among HIV Positive Patients on Highly Active Antiretroviral Therapy in Selected Hospitals in Nairobi County

Background: Traditional remedies have been used for many years in Africa to treat various ailments before the introduction of conventional medicines into the continent. Concurrent use of traditional herbal medicines (THM) with highly active antiretroviral therapy (HAART) is widespread among HIV infected patients. Studies done in different parts of the world show conflicting health outcomes among HIV positive patients using HAART and herbal medicine concurrently with some reporting better health outcomes while others report increased risk of adverse drug reactions. However, the extent of THM use is not known in most settings in Sub-Saharan Africa Kenya included. This study aimed to determine the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy (HAART) attending two comprehensive care centers in Nairobi County. Methods: A descriptive cross-sectional study was conducted at Kenyatta National Teaching and Referral Hospital and Mbagathi District Hospital. From the two centers a total of 370 participants were selected via systematic random sampling. The participants included were those aged 18 years and above, on HAART, and had consented to participate in the study. Data was collected using an interviewer-administered semi-structured questionnaire seeking information on herbal medicine use, socio-demographic and economic factors associated with herbal medicine use and the association between herbal medicine use and occurrence of adverse drug reactions. THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy (HAART) by the time of the study. Data was captured in excel sheet and exported to STATA for analysis. Results: The study established that the prevalence of herbal medicine use among HIV positive patients taking HAART was 15.5%. About 77.8% of the patients who had used herbal medicine had never disclosed to the doctor or any health care worker at the CCC about their herbal medicine use. Herbal medicine use led to decreased adherence to HAART. The longer the duration between HIV diagnosis and HAART start, the more likely a HIV positive patient was to use herbal medicine. Patients who use herbal medicine with HAART were more likely to experience adverse drug reactions. There were 59.7% participants who had good /fair adherence while 40.3% had poor adherence. Majority of those who had poor adherence had significantly higher proportion of side effects as compared to those had good/fair adherence. Conclusion: The prevalence of THM use among participants on HAART was high. This raises clinical and pharmacological concerns that need attention by the health care service providers. Keywords : Herbal Medicine, HIV, Antiretroviral Therapy DOI : 10.7176/JBAH/9-4-11

Trend of CD4+ Cell Counts at Diagnosis and Initiation of Highly Active Antiretroviral Therapy (HAART): Korea HIV/AIDS Cohort Study, 1992-2015.

BackgroundCD4+ cell counts reflect immunologic status of human immunodeficiency virus (HIV) patients. Recommended CD4+ cell counts for the initiation of highly active antiretroviral therapy (HAART) has increased over the past several years in various HIV treatment guidelines. We investigated the trend of CD4+ cell counts at diagnosis and treatment start using data from the Korea HIV/acquired immune deficiency syndrome (AIDS) Cohort Study.Materials and MethodsThe Korea HIV/AIDS Cohort Study started in 2006 and enrolled HIV patients from 21 tertiary and secondary hospitals in South Korea. The data for CD4+ cell counts at diagnosis and HAART initiation from these HIV patients were analyzed by three-year time intervals and presented by number of CD4+ cells (≤100, 101-200, 201-350, 351-500 and >500 cells/mm3). The HIV-RNA titer at diagnosis and HAART initiation were presented by 3-year intervals by groups ≤50,000, 50,001-100,000, 100,001-200,000, 200,001-1,000,000, and >1,000,000 copies/mL.ResultsMedian values of CD4+ cell count and HIV-RNA titer at initial HIV diagnosis were 247 cells/mm3 and 394,955 copies/mL, respectively. At time of initiating HAART, median values of CD4+ cell count and HIV-RNA were 181 cells/mm3 and 83,500 copies/mL, respectively. Patients with low CD4+ cell count (CD4+ cell count ≤200 cells/mm3) at diagnosis (31-51%) and initiation of HAART accounted for the largest proportion (30-65%) over the three-year time intervals. This proportion increased until 2010-2012.ConclusionCD4+ cell count at initiation of HAART was found to be very low, and the increase in late initiation of HAART in recent years is of concern. We think that this increase is primarily due to an increasing proportion of late presenters. We recommend early detection of HIV patients and earlier start of HAART in order to treat and prevent spread of HIV infection.

Predictors of Sub-Optimal CD4 Recovery during the First Six Months of Anti-Retroviral Treatment (ART) in HIV Infected Children: A Retrospective Cross Sectional Study from Tikur Anbessa Tertiary Hospital, Addis Ababa, Ethiopia

Background: Highly active anti-retroviral therapy (HAART) has brought significant change in reducing morbidity and mortality among children living with HIV/AIDS. Decisions concerning initiation and/or shifting of antiretroviral therapy (ART) are guided by monitoring the laboratory parameters of plasma HIV RNA (viral load) and CD4+ T cell count in addition to the patient’s over all clinical response. The demonstrations of the prognostic value of the CD4 cell count was of major importance in the development of therapeutic strategies. Therefore, the objective of this study was to assess factors predicting suboptimal CD4 cell recovery during first six months of ART. Methods: The study is retrospective cross sectional study to assess factors predicting suboptimal CD4 cell recovery. Medical records of patients’ were retrieved and important variables are captured to standard questionnaire tool. T-test is used to assess changes in CD4 cell count after initiation of ART. Binary logistic and multiple regressions were used to assess factors predicting CD4 cell recovery. Results: Data of 360 children were analyzed. CD4 cell count at the start of HAART ranged from 3-2003 cell/mL with an interquartile range of 231-317 cell/mL. After 6 months of HAART, the CD4 cell count has increased ranging from 71-2300 cell/mL with inter quartile range of 458-612 cell/mL and mean CD4 cell count difference of 230, 95%CI (199.414-260.613); P<0.001. Advanced clinical stage of the disease, severe degree of immunosupression, presence of anemia, presence of chronic diarrhea at base line, poor weight gain during first six months of HAART adversely affect the trends of CD4 recovery. Conclusion: Our study demonstrated that advanced clinical stage of the disease, severe degree of immunosupression, presence of anemia at baseline and presence of chronic diarrhea, poor weight gain during first six months of HAART were factors adversely affect the trends of CD4 recovery.

The CD4 slope can be a predictor of immunologic recovery in advanced HIV patients: a case-control study.

Background/Aims:Advanced human immunodeficiency virus (HIV) infection, despite sustained viral suppression by highly active antiretroviral therapy (HAART), is a risk factor for poor immunologic recovery. However, some patients with advanced infection do show immunologic recovery. In this study, predictive factors of immunologic recovery were analyzed in advanced HIV patients showing sustained viral suppression.Methods:A case-control study was conducted in HIV-infected adult patients with HIV-1 RNA < 50 copies/mL maintained for 4 years or longer and who were receiving HAART. Advanced HIV infection was defined as a baseline CD4 T cell count < 200/mm3. Immunologic responders were defined as patients showing immunologic recovery (CD4 T cell counts ≥ 500/mm3 at 4 years with HAART). To analyze the CD4 T cell kinetics, the CD4 slope (monthly changes in the CD4 T cell count) was estimated for each patient using a linear regression between the CD4 T cell count and the time since HAART initiation.Results:Of 102 eligible patients, 73 had advanced HIV, and 33 (45.2%) showed immunologic recovery. The median CD4 slopes (cells/mm3 per month) during 0 to 6 and 0 to 12 months of HAART in the 73 advanced patients were significantly higher in responders than in non-responders (0 to 6 months, 38.6 vs. 22.8; 0 to 12 months, 24.5 vs. 13.5). Multivariate analyses showed opportunistic infections at the start of HAART (adjusted odds ratio [OR], 0.28) and a CD4 slope ≥ 20 during 0 to 12 months of HAART (adjusted OR, 10.10) were independently associated with immunologic recovery.Conclusions:The CD4 slope can be an early predictor of long-term immunologic recovery in advanced HIV patients.

Treatment initiation factors and cognitive outcome in youth with perinatally acquired HIV infection.

Although cognitive outcomes among perinatally infected youth have improved with highly active antiretroviral therapy (HAART), the impact of the age of initiation of treatment and the central nervous system (CNS) penetration effectiveness (CPE) of the regimen on cognitive outcomes is unknown. We aimed to describe the association between initiation age/regimen CPE score and cognitive outcomes in perinatally HIV-infected youth. Linear regression was used to retrospectively assess the association between full-scale IQ score (FSIQ) and age of initiation of HAART, regimen CPE, and the presence/absence of an AIDS diagnosis before initiation of HAART in an urban US cohort. A total of 88 of 181 subjects (48.6%) had an AIDS diagnosis. In 69, AIDS preceded the start of HAART. Mean FSIQ (mean age 155.4 months) was 86.3 [standard deviation (SD) 15.6]. Neither age of initiation of HAART (P = 0.45) nor regimen CPE score (P = 0.33) was associated with FSIQ. Mean FSIQ for patients with an AIDS diagnosis before HAART initiation [82 (SD 17.0)] was significantly lower than for patients initiating HAART before an AIDS diagnosis [90 (SD 13)] (P = 0.001). Of the 129 subjects without AIDS by age 5 years, 41 (31.8%) initiated HAART before age 5 years; four of 41 later developed AIDS, compared with 32 of 88 of those who did not initiate HAART before age 5 years. The relative risk of AIDS if HAART was initiated before age 5 years was 0.19 (95% confidence interval 0.05-0.60). Earlier age at HAART initiation and higher CPE score of a regimen did not improve cognitive outcomes. However, initiating HAART prior to AIDS protected against AIDS and was associated with a significantly higher FSIQ.

CMV retinitis in an HIV patient with clinical and immunological failure on HAART

Cytomegalovirus (CMV) retinitis is a complication of patients infected with human immunodeficiency virus (HIV) in advance stage when CD4 count is less than 50 cells/cumm. Before the introduction of highly active antiretroviral therapy (HAART), approximately 30% of patients with AIDS developed CMV retinitis, which declined in 75% of cases after the start of HAART. We report a case of CMV retinitis in an HIV-positive patient who developed it as a WHO clinical stage 4 condition representing clinical failure along with dramatic decrease in CD4 count due to immunological failure on failing first-line HAART.

A pilot study to evaluate the effect of HAART on gonadal dysfunction in male HIV patients

Background: Derangement of gonadal functions has been reported in association with HIV infection, but data from Indian population are not sufficient. Aims & Objective: To evaluate the effect of highly active antiretroviral therapy (HAART) on the gonadal dysfunction in male HIV patients. Materials and Methods: A total of 45 male HIV-positive patients were included and divided in two groups on the basis of CD4 cell count. Patients in groups A and B had CD4 count ≤200 and >200 cell/μL, respectively. Baseline hormone level was measured before the start of HAART, and the patients were followed up for 6 months and the hormone levels were measured again. Results: In group A (n = 29), six (20.69%) patients had testosterone level

Outcome of highly active antiretroviral therapy in HIV-infected Indian children.

BackgroundWith the advent of highly active antiretroviral therapy (HAART), HIV infection has become a chronic condition in children with improved survival and quality of life. Reports on long term effectiveness of non-nucleoside reverse transcriptase inhibitor based HAART in HIV-infected children in developing countries are limited.MethodsA chart review was conducted and children who received at least six months of HAART between 2004–2011 at All India Institute of Medical Sciences (AIIMS), Delhi were included. The clinical, immunological and virological responses to HAART were documented. Factors predicting non-adherence and non-response to treatment were described.ResultsOne seventy five children (boys: 74.9%) were included in the study, with a median follow up of 43 (IQR:17, 68) months. The median age at diagnosis was 119 (IQR: 75, 156) months. The median CD4 count at start of HAART was 340 cells/μL (IQR: 185,704), which increased to 924 cells/μL (IQR:591,1278) at 48 months after HAART and plateaued at 749 (IQR: 542,1056) cells/ μL after 90 months of therapy. The weight for age (WAZ) and height for age (HAZ) z score both showed improvement with time after HAART initiation [baseline: WAZ −2.8 (IQR:-4,-1.6), HAZ −2.1 (IQR:-3.4,-0.69); at 42 months of therapy: WAZ −1.2 (IQR:-2.1, 0.01), HAZ −0.75(IQR:-1.6,-0.37)]. Adverse events were reported in 21 (12%) children. Non-adherence to therapy, treatment failure and death were noted in 35 (20%), 9 (5.1%) and 6 (3.4%) children respectively.ConclusionsOur experience shows that HAART in HIV-infected children is effective, safe and is associated with good immunological and virological response as well as improvement in growth parameters.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0701-2) contains supplementary material, which is available to authorized users.

HAART and liver: is it safe?

Liver disease caused by hepatitis C virus (HCV) is a major cause of morbidity in HIV patients. This study investigates the possibility that chronic HCV increases the risk of hepatotoxicity after highly active antiretroviral therapy (HAART) initiation. The data from 30 coinfected HIV/HCV and 35 HIV monoinfected patients between August 2008 and August 2010, since the start of HAART, were analyzed along with data from every three months, with clinical/laboratory evaluation until the end of twelve months. The aim of this study was to assess risk and incidence of hepatotoxicity in both groups. Before the introduction of HAART, coinfected patients had higher average levels of transaminases than did the monoinfected group (p < 0.001). After initiation of HAART, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in coinfected patients, regardless of type of HAART they received. Twenty-two (73%) of the coinfected patients had some degree of hepatotoxicity versus only seven (20%) of the monoinfected patients. No patient had severe hepatotoxicity. Risk of hepatotoxicity after HAART in a coinfected patient was 3.7 times higher than in a monoinfected patient (RR 3.7 [1.8-7.4], p < 0.001). This study demonstrates that coinfected patients are at an increased risk for developing hepatotoxicity, but the clinical and immunological benefits of HAART are higher than the risk of hepatotoxicity and rarely justify discontinuation of therapy.

Early Highly Active Antiretroviral Therapy Enhances B-cell Longevity

We have previously reported that an early initiation of highly active antiretroviral therapy (HAART) in HIV-1 vertically infected children enhanced the function of memory B-cells gained during childhood routine vaccinations. On the other hand, a significant waning of immunity was observed for patients with a late treatment. In this follow-up study, we report data from a sample of patients in our cohort including late-treated patients being revaccinated with routine childhood vaccines. The levels of serum antibodies and cellular immunity were measured by antigen-specific enzyme-linked immunosorbent assay and B-cell ELISpot. Moreover, flow cytometry on the frequencies of mature-activated (CD10-CD21-) and double-negative (CD27-IgD-) B-cells as hallmarks of immune activation and immune senescence, respectively, was performed for all patients. Reduced protective humoral immunity and cellular immunity to routine childhood vaccines was observed in late-treated patients. Moreover, we found that timing of HAART related with the frequencies of mature activated and double negative. Altogether the data presented in this follow-up study reenforce the importance for an early start of HAART in HIV-1 vertically infected individuals and suggest that timing of HAART is a fundamental factor to take into account for vaccination design in this population.

Survival of HIV patients with tuberculosis started on simultaneous or deferred HAART in the THRio cohort, Rio de Janeiro, Brazil

BackgroundThe timing of highly active antiretroviral therapy (HAART) after a tuberculosis diagnosis in HIV-infected patients can affect clinical outcomes and survival. We compared survival after tuberculosis diagnosis in HIV-infected adults who initiated HAART and tuberculosis therapy simultaneously to those who delayed the start of HAART for at least two months. MethodsThe THRio cohort includes 17,983 patients receiving HIV care in 29 public clinics in Rio de Janeiro, Brazil. HAART-naïve patients at the time of a new TB diagnosis between September 2003 and June 2008 were included. Survival was measured in days from diagnosis of TB. We compared survival among patients who initiated HAART within 60 days of TB treatment (simultaneous – ST) to those who started HAART >60 days of TB treatment or never started (deferred – DT). Kaplan–Meier plots and Cox proportional hazards regression analyses were conducted. ResultsOf 947 patients diagnosed with TB, 572 (60%) were HAART naïve at the time of TB diagnosis; 135 were excluded because of missing CD4 count results. Among the remaining 437 TB patients, 56 (13%) died during follow-up: 25 (10%) among ST patients and 31 (16%) in DT group (p=0.08). ST patients had lower median CD4 counts at TB diagnosis than DT patients (106 vs. 278, p<0.001). Cox proportional hazards utilizing propensity score analysis showed that DT patients were more likely to die (adjusted HR=1.89; 95% CI: 1.05–3.40; p=0.03). ConclusionHAART administered simultaneously with TB therapy was associated with improved survival after TB diagnosis. HAART should be given to patients with HIV-related TB as soon as clinically feasible.

The effect of history of injection drug use and alcoholism on HIV disease progression

The effectiveness of highly active antiretroviral therapy (HAART) in preventing disease progression can be negatively influenced by the high prevalence of substance use among patients. Here, we quantify the effect of history of injection drug use and alcoholism on virologic and immunologic response to HAART. Clinical and survey data, collected at the start of HAART and at the interview date, were based on the study Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) in British Columbia, Canada. Substance use was a three-level categorical variable, combining information on history of alcohol dependence and of injection drug use, defined as: no history of alcohol and injection drug use; history of alcohol or injection drug use; and history of both alcohol and injection drug use. Virologic response (pVL) was defined by ≥2 log10 copy/mL drop in a viral load. Immunologic response was defined as an increase in CD4 cell count percent of ≥100%. We used cumulative logit modeling for ordinal responses to address our objective. Of the 537 HIV-infected patients, 112 (21%) were characterized as having a history of both alcohol and injection drug use, 173 (32%) were nonadherent (<95%), 196 (36%) had a CD4+/pVL+ (Best) response, 180 (34%) a CD4+/pVL− or a CD4− /pVL+ (Incomplete) response, and 161 (30%) a CD4− /pVL− (Worst) response. For individuals with history of both alcohol and injection drug use, the estimated probability of non-adherence was 0.61, and (0.15, 0.25, 0.60) of Best, Incomplete and Worse responses, respectively. Screening and detection of substance dependence will identify individuals at high-risk for nonadherence and ideally prevent their HIV disease from progressing to advanced stages where HIV disease can become difficult to manage.

Definition of Advanced Age in HIV Infection: Looking for an Age Cut-Off

The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged <25 years at start of HAART, those aged 50-54, 55-59, 60-64, 65-59, and 70 or older were 32% (aHR: 0.68, 95% CI: 0.52-0.87), 29% (aHR: 0.71, 95% CI: 0.53-0.96), 34% (aHR: 0.66, 95% CI: 0.46-0.95), 39% (aHR: 0.61, 95% CI: 0.37-1.00), and 43% (aHR: 0.57, 95% CI: 0.31-1.04) less likely to experience an IR. The VR was similar across all age groups. Finally, patients aged 50-59 showed a 3-fold increase (aHR: 3.58; 95% CI: 1.07-11.99) in their risk of death compared to those aged <30 years. In HIV infection, patients aged ≥50 years have a poorer immunological response to HAART and a poorer survival. This age could be used to define medically advanced age in HIV-infected people.

Association of Polymorphisms of the Mu Opioid Receptor Gene with the Severity of HIV Infection and Response to HIV Treatment

Mu opioid receptor (OPRM1) ligands may alter expression of chemokines and chemokine receptors involved in penetration of human immunodeficiency virus (HIV) type 1 into the cell. We suggest that OPRM1 variants may affect the pathophysiology of HIV infection. DNA samples from 1031 eligible African Americans, Hispanics, and whites from the Women's Interagency HIV Study (WIHS) who were alive as of April 2006 were analyzed. We performed regression analysis of association of 18 OPRM1 variants with a change of viral load and CD4 cell count during 2 periods: between admission to WIHS and the start of highly active antiretroviral therapy (HAART) (interval X) and between the start of HAART and the most recent WIHS visit (interval Y), and examined the association of these variants with HIV status. Regardless of genotype, a significant decrease in viral load during interval X was found for each ethnicity. Whites with allele G of the functional polymorphism 118A > G (reference sequence rs1799971) showed a smaller decrease in viral load; those bearing minor alleles IVS1 + 1050A, IVS1 + 14123A, and IVS2 + 31A showed a larger decrease in viral load over interval X (0.01 < P < .05). Hispanics with the same alleles showed a greater increase in CD4 cell count over interval Y (0.01 < P < .05). We found an association between OPRM1 variants and HIV status in African Americans and whites. OPRM1 polymorphisms may alter the severity of HIV infection before and after HAART.

Elevated CD8 Counts During HAART Are Associated With HIV Virologic Treatment Failure

To evaluate whether elevated CD8 counts are associated with increased risk of virologic treatment failure in HIV-infected individuals. Retrospective cohort study. US Military HIV Natural History Study participants who initiated highly active antiretroviral therapy (HAART) in 1996-2008 had 6- and 12-month post-HAART HIV RNA <400 copies per milliliter, ≥ 2 subsequent HIV viral loads and a baseline CD8 count were eligible (n = 817). Baseline was 12 months after the start of HAART, virologic failure (VF) was defined as confirmed HIV RNA ≥ 400 copies per milliliter, and CD8 counts ≥ 1200 cells per cubic millimeter were considered elevated. Cox models were used to examine the effect of baseline and time-updated CD8 counts on VF. There were 216 failures for a rate of 5.6 per 100 person-years [95% confidence interval (CI): 4.9 to 6.4]. Among those initiating HAART in 2000-2008, the participants with elevated baseline CD8 counts had significantly greater risk of VF compared with those with baseline CD8 counts ≤ 600 cells per cubic millimeter [hazard ratio (HR) = 2.68, 95% CI: 1.13 to 6.35]. The participants with elevated CD8 counts at >20% of previous 6-month follow-up visits had a greater risk of failure at the current visit than those who did not (HR = 1.53, 95% CI: 1.14 to 2.06). Those with CD8 counts that increased after the start of HAART had a greater risk of failure than those with CD8 counts that decreased or remained the same (HR = 1.59, 95% CI: 1.19 to 2.13). Initial or serial elevated CD8 counts while on HAART or an increase in CD8 counts from HAART initiation may be early warnings for future treatment failure.

Impact of Non-HIV and HIV Risk Factors on Survival in HIV-Infected Patients on HAART: A Population-Based Nationwide Cohort Study

BackgroundWe determined the impact of three factors on mortality in HIV-infected patients who had been on highly active antiretroviral therapy (HAART) for at least one year: (1) insufficient response to (HAART) and presence of AIDS-defining diseases, (2) comorbidity, and (3) drug and alcohol abuse and compared the mortality to that of the general population.Methodology/Principal FindingsIn a Danish nationwide, population-based cohort study, we used population based registries to identify (1) all Danish HIV-infected patients who started HAART in the period 1 January 1998–1 July 2009, and (2) a comparison cohort of individuals matched on date of birth and gender (N = 2,267 and 9,068, respectively). Study inclusion began 1 year after start of HAART. Patients were categorised hierarchically in four groups according to the three risk factors, which were identified before study inclusion. The main outcome measure was probability of survival from age 25 to 65 years. The probability of survival from age 25 to age 65 was substantially lower in HIV patients [0.48 (95% confidence interval (CI) 0.42–0.55)] compared to the comparison cohort [0.88 (0.86 to 0.90)]. However, in HIV patients with no risk factors (N = 871) the probability of survival was equivalent to that of the general population [0.86 (95% CI 0.77–0.92)]. In contrast, the probability of survival was 0.58 in patients with HIV risk factors (N = 704), 0.30 in patients with comorbidities (N = 479), and 0.03 in patients with drug or alcohol abuse (N = 313).ConclusionsThe increased risk of death in HIV-infected individuals is mainly attributable to risk factors that can be identified prior to or in the initial period of antiretroviral treatment. Mortality in patients without risk factors on a successful HAART is almost identical to that of the non–HIV-infected population.

Association between use of HMG CoA reductase inhibitors and mortality in HIV-infected patients.

IntroductionHIV infection is a disease associated with chronic inflammation and immune activation. Antiretroviral therapy reduces inflammation, but not to levels in comparable HIV-negative individuals. The HMG-coenzyme A reductase inhibitors (statins) inhibit several pro-inflammatory processes and suppress immune activation, and are a logical therapy to assess for a possible salutary effect on HIV disease progression and outcomes.MethodsEligible patients were patients enrolled in the Johns Hopkins HIV Clinical Cohort who achieved virologic suppression within 180 days of starting a new highly active antiretroviral therapy (HAART) regimen after January 1, 1998. Assessment was continued until death in patients who maintained a virologic suppression, with right-censoring of their follow-up time if they had an HIV RNA > 500 copies/ml. Cox proportional hazards regression was used to assess statin use as a time-varying covariate, as well as other demographic and clinical factors.ResultsA total of 1538 HIV-infected patients fulfilled eligibility criteria, of whom 238 (15.5%) received a statin while taking HAART. There were 85 deaths (7 in statin users, 78 in non-users). By multivariate Cox regression, statin use was associated with a relative hazard of 0.33 (95% CI: 0.14, 0.76; P = 0.009) after adjusting for CD4, HIV-1 RNA, hemoglobin and cholesterol levels at the start of HAART, age, race, HIV risk group, prior use of ART, year of HAART start, NNRTI vs. PI-based ART, prior AIDS-defining illness, and viral hepatitis coinfection. Malignancy, non-AIDS-defining infection and liver failure were particularly prominent causes of death.DiscussionStatin use was associated with significantly lower hazard of dying in these HIV-infected patients who were being effectively treated with HAART as determined by virologic suppression. Our results suggest the need for confirmation in other observational cohorts, and if confirmed, the need for a clinical trial of statin use in HIV infection.