Impact on hemoglobin of starting combination antiretroviral therapy with or without zidovudine in anemic HIV-infected patients

OBJECTIVE: To evaluate, among anemic patients with HIV, the impact on hemoglobin (Hb) of initiating zidovudine (AZT)-containing and non-AZT-containing combination antiretroviral therapy (cART). METHODS: We used medical records data collected in 11 US cities from 1998 to 2004. Baseline anemia was described as mild (10 < Hb < or = 12 [women] or 14 [men] g/dL), moderate (8 < Hb < or = 10 g/dL), or severe (Hb < or = 8 g/dL). Improvement of anemia was a > or =1-g/dL increase in Hb, with a decrease in categoric severity. We excluded patients previously treated with erythropoietin or transfusion, and used Cox proportional hazards regression to describe factors associated with hazard of improvement of anemia. RESULTS: For 1620 patients initiating cART, more than half (54%) of patients had improvement of anemia. Time to improvement of anemia was longer for those initiating AZT-containing regimens and blacks and was shorter for those with moderate and severe anemia or CD4 counts <200 cells/microL. CONCLUSIONS: Most anemic patients initiating cART (with or without AZT) had increases in Hb-especially those with more severe anemia or immunosuppression. Initiation of AZT-containing cART may be considered, even for patients with preexisting anemia; however, improvement of anemia may be delayed for black patients and for patients with mild disease.     

Hepatitis B virus seroprevalence among HIV-infected patients receiving combination antiretroviral therapy three decades after universal neonatal hepatitis B immunization program in Taiwan

Background/purposeThis multicenter study aimed to evaluate the seroprevalence of hepatitis B virus (HBV) and the use of combination antiretroviral therapy (cART) among patients receiving HIV care in Taiwan.MethodsWe retrospectively reviewed the medical records of HIV-infected adult patients who initiated cART at 11 designated hospitals in Taiwan between 2012 and 2016. The clinical information collected included serological profiles on HBV, hepatitis C virus (HCV), and syphilis, plasma HIV RNA load, nadir CD4 cell count, and antiretrovirals with activity against both HBV and HIV (tenofovir disoproxil fumarate [TDF], lamivudine [LAM], and emtricitabine [FTC]).ResultsWe analyzed 1800 HIV-infected patients; 1742 (96.8%) were male and 794 (44.1%) were born after July, 1986, when nationwide universal neonatal HBV vaccination was implemented. HBsAg positive results were 11.6% (209/1800), which decreased significantly from 18.1% (182/1006) in those born before July 1986 to 3.4% (27/794) in those born after. In multivariable analysis, HBsAg positivity was significantly associated with age (adjusted odds ratio [aOR] 1.06, 95% confidence interval [CI] 1.05–1.08), CD4≧200 cells/μL (aOR 0.73, 95% CI 0.53–0.99), and HCV seropositivity (aOR 1.62, 95% CI 1.06–2.50). Of 209 HBV/HIV-coinfected patients, 31.1% started cART containing only LAM with anti-HBV activity, while 68.9% started cART containing TDF plus LAM or coformulated TDF/FTC.ConclusionsThe overall prevalence of HBV/HIV coinfection remained high among HIV-infected patients in Taiwan. Despite recommendations of the HIV treatment guidelines for the management of HBV infection, a substantial proportion of HIV/HBV-coinfected patients received cART containing only LAM for HBV infection.     

Sexual dysfunction in HIV-infected patients treated with highly active antiretroviral therapy

Sexual disturbances develop in some patients treated with highly active antiretroviral therapy (HAART). To evaluate sexual dysfunction and the influence that different antiretrovirals could have on those parameters, we conducted a prospective study in patients with stable clinical condition attending an HIV outpatient clinic. A total of 351 evaluations were performed in 189 HIV-infected men, who were interviewed about symptoms of sexual dysfunction. Sexual hormones as well as other clinical and laboratory parameters were also measured at the time of each evaluation. The mean CD4 count was 451.1 x 10(6) cells/L, and viral load was undetectable in two thirds of the determinations. The prevalence of sexual dysfunction was 19.5% overall, but it was influenced by treatment, particularly (although not exclusively) by protease inhibitors (PIs) (27.1% vs. 3.8% for untreated patients). Sexual dysfunction was not related to hypophyseal or gonadal hormonal values. Although several parameters were associated with sexual dysfunction in the univariate analysis, only antiretroviral treatment was significantly predictive of this disorder in a logistic regression analysis. Sexual dysfunction is common in HIV-infected patients in stable clinical condition receiving HAART, and all antiretroviral drugs, particularly PIs, seem to be related to it. Sexual dysfunction in these patients is not related to hormonal causes.     

Difficulties reported by HIV-infected patients using antiretroviral therapy in Brazil

OBJECTIVE: To describe the degree of difficulty that HIV-infected patients have with therapy treatment. INTRODUCTION: Patients perceptions about their treatment are a determinant factor for improved adherence and a better quality of life. METHODS: Two cross-sectional analyses were conducted in public AIDS referral centers in Brazil among patients initiating treatment. Patients interviewed at baseline, after one month, and after seven months following the beginning of treatment were asked to classify and justify the degree of difficulty with treatment. Logistic regression was used for analysis. RESULTS: Among 406 patients initiating treatment, 350 (86.2%) and 209 (51.5%) returned for their first and third visits, respectively. Treatment perceptions ranged from medium to very difficult for 51.4% and 37.3% on the first and third visits, respectively. The main difficulties reported were adverse reactions to the medication and scheduling. A separate logistic regression indicated that the HIV-seropositive status disclosure, symptoms of anxiety, absence of psychotherapy, higher CD4+ cell count (> 200/mm3) and high (> 4) adverse reaction count reported were independently associated with the degree of difficulty in the first visit, while CDC clinical category A, pill burden (> 7 pills), use of other medications, high (> 4) adverse reaction count reported and low understanding of medical orientation showed independent association for the third visit. CONCLUSIONS: A significant level of difficulty was observed with treatment. Our analyses suggest the need for early assessment of difficulties with treatment, highlighting the importance of modifiable factors that may contribute to better adherence to the treatment protocol.     

Anemia in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Anemia is common in HIV infection, particularly in advanced disease states. We wished to determine how highly active antiretroviral therapy (HAART) and other factors affected the level of hemoglobin in HIV infection. METHODS: We analyzed data from 905 patients receiving care at Johns Hopkins in Baltimore, Maryland after July 1, 1996. Analyses were done of hemoglobin levels obtained at baseline and during 1 year of follow-up in patients who received and did not receive a HAART regimen. Use of HAART and other demographic and clinical factors were examined. RESULTS: Eleven percent of patients had a hemoglobin count <10 g/dL, 27% had a hemoglobin count 10 to 12 g/dL, and 21% had a hemoglobin count of >14 g/dL at baseline before HAART was started. During 1 year of follow-up, use of HAART was associated with a hemoglobin levels >14 g/dL in 42% of patients, irrespective of use of zidovudine as part of HAART regimen, compared with 31% of patients who did not use HAART. In multivariate analysis, use of HAART was strongly associated with not having anemia during 1 year of follow-up, adjusting for patient gender, race, injection drug use history, baseline CD4 and HIV-1 RNA levels, and anemia treatments. CONCLUSIONS: HAART is an effective treatment of the anemia of HIV infection. Patients who continue to have symptomatic anemia while receiving HAART may need additional intervention.     

Changes in lymphocyte subsets in depressed HIV-infected patients without antiretroviral therapy

The authors studied the effects of major depression on lymphocyte subsets by comparing depressed and matched control subjects in a population of HIV-seropositive outpatients not treated with antiretroviral therapy. Twelve patients with major depression, as determined by the Structured Clinical Interview for DSM-III-R, were assessed in comparison with 15 matched nondepressed control subjects. Flow cytometric analysis of peripheral blood lymphocyte subsets together with immunological parameters were performed. In HIV-infected patients, major depression was significantly (P=0.001) associated with a reduction in natural killer cell absolute count and percentage. This report suggests that depression may alter the natural killer cell population that provides a cytotoxic defense against HIV infection.     

The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Background

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.

Objective

To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.

Methods

Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.

Results

From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.

Conclusion

Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.     

Apoptosis-associated gene expression in HIV-infected patients in response to successful antiretroviral therapy

The simultaneous expression of 19 apoptosis-related genes was analyzed by RNA-protection assay in peripheral blood mononuclear cells of HIV-infected patients before and during successful antiretroviral therapy (ART). After 12 months of therapy, the expression of the pro-apoptotic genes FAS, FAS-L, FAF-1, FADD, CASPASE-8, DR3, TRAIL, TNFR-1, TRADD, and BAX was significantly downregulated with respect to time 0, while that of BCL-2, BCL-XL, and MCL-1 was significantly upregulated. The data suggest that inhibition of cell death in HIV-positive patients under successful therapy is the result of a complex network of multifactor signaling, correlated with both death and survival of lymphocytes.     

Non-AIDS-defining malignancies among HIV-infected patients in the highly active antiretroviral therapy era

In the highly active antiretroviral therapy (HAART) era, the incidence of AIDS-defining malignancies (ADMs) has declined significantly. On the other hand, the incidence of other malignancies not known to be associated with immunosuppression (non-ADMs) has not changed and remains significantly higher than in the general population. Some recent controlled studies even suggest that the incidence of selected non-ADMs has increased in the HAART era. These trends warrant a high index of suspicion for malignancies among HIV care providers and a renewed focus on understanding the mechanisms underlying the increased rates. Potential explanations for the higher non-ADM rates include longer survival of patients with HIV on HAART, with only partial immune recovery achieved in most patients; high incidence of human papillomavirus, Epstein-Barr virus, and hepatitis C virus coinfection in patients with HIV infection; and potential oncogenicity of long-term HIV infection or of long-term HAART.     

Disturbance of apolipoprotein B100 containing lipoprotein metabolism in severe hyperlipidemic and lipodystrophic HIV patients on combined antiretroviral therapy: evidences of insulin resistance effect

The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB (1.49+/-1.11 vs 0.51+/-0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7+/-42.2 vs 22.6+/-23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44+/-1.62 vs 1.60+/-0.61, p<0.05). They exhibited an increase in VLDL (1.24+/-0.33 vs 0.80+/-0.21 mg/kg/h, p<0.05), decrease in IDL (0.20+/-0.10 vs 0.48+/-0.24 mg/kg/h, p<0.05) and no difference in LDL (0.38+/-0.19 vs 0.45+/-0.25 mg/kg/h) production rate. LD subject also showed a dramatic decrease in transformation of VLDL to IDL (0.013+/-0.010 vs 0.258+/-0.206 h(-1), p<0.005) and IDL to LDL (0.088+/-0.093 vs 0.366+/-0.189 h(-1), p<0.05) and a decrease in fractional catabolic rate (FCR) of VLDL (0.199+/-0.132 vs 0.555+/-0.398 h(-1), p<0.05), IDL (0.110+/-0.08 vs 0.523+/-0.275 h(-1), p<0.05) and LDL (0.010+/-0.005 vs 0.025+/-0.014 h(-1), p<0.05). These disturbances, overproduction and an overall delayed catabolism of apoB, are similar to those observed using the same protocol in insulin resistant subjects. Our study suggests that metabolic disturbance of apoB100 observed in lipodystrophic HIV in combined antiretroviral therapy are consecutive to insulin resistance induced by the treatment.     

Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients

BACKGROUND: Antiretroviral regimens for HIV-infected patients require strict adherence. Untreated depression has been associated with medication nonadherence. We proposed to evaluate the effect of antidepressant treatment (ADT) on antiretroviral adherence. METHODS: Data were retrieved for HIV-infected patients seen at an urban health care setting (1997-2001) from chart review and administrative and pharmacy files. Antiretroviral adherence was determined for depressed patients stratified by receipt of and adherence to ADT. Antiretroviral adherence was compared before and after initiation of ADT. RESULTS: Of 1713 HIV-infected patients, 57% were depressed; of those, 46% and 52% received ADT and antiretroviral treatment, respectively. Antiretroviral adherence was lower among depressed patients not on ADT (vs. those on ADT; P = 0.012). Adherence to antiretroviral treatment was higher among patients adherent to ADT (vs. those nonadherent to antidepressant treatment; P = 0.0014). Antiretroviral adherence improved over a 6-month period for adherent, nonadherent, and nonprescribed ADT groups; however, the mean pre- versus post-6-month change in antiretroviral adherence was significantly greater for those prescribed antidepressants. CONCLUSIONS: Depression was common, and antiretroviral adherence was higher for depressed patients prescribed and adherent to ADT compared with those neither prescribed nor adherent to ADT. Attention to diagnosis and treatment of depressive disorders in this population may improve antiretroviral adherence and ultimate survival.