HIV Highly Active Antiretroviral Therapy Research Articles

Tenofovir-Based Highly Active Antiretroviral Therapy Is Associated with Superior CD4 T Cells Repopulation Compared to Zidovudine-Based HAART in HIV 1 Infected Adults.

Tenofovir-based highly active antiretroviral therapy (HAART) is one of the preferred first-line therapies in the management of HIV 1 infection. Ghana has since 2014 adopted this recommendation; however there is paucity of scientific data that reflects the safety and efficacy of the tenofovir-based therapy compared to zidovudine in the Ghanaian health system. This study sought to assess the comparative immune reconstitution potential between tenofovir and zidovudine-based HAART regimens, which includes lamivudine and efavirenz in combination therapy. It also aimed to investigate the adverse drug reactions/events (ADREs) associated with pharmacotherapy with these agents in a total of 106 HAART naïve HIV patients. The study included 80 patients in the tenofovir cohort while 26 patients were on the zidovudine regimen. The occurrence of HIV comorbidities profile was assessed at diagnosis and throughout the study period. The baseline CD4 T cells count of the participants was also assessed at diagnosis and repeated at a median period of five months (range 4–6 months), after commencing treatment with either tenofovir- or zidovudine-based HAART. After five months of the HAART, the tenofovir cohort recorded higher CD4 T cell count change from baseline compared to the zidovudine cohort (p < 0.0001). The patients on the tenofovir-based HAART and female sex however appeared to be associated with more multiple ADREs.

Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients

PurposeTo assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40∶01 carriage with HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS).MethodsThree-hundred and thirty-six patients, 187 with HALS and 149 without HALS, and 72 uninfected subjects were recruited. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Polymorphisms in the thymidylate synthase (TS) and methylene-tetrahydrofolate reductase (MTHFR) genes were determined by direct sequencing, HLA-B genotyping by PCR-SSOr Luminex Technology, and intracellular levels of stavudine triphosphate (d4T-TP) by a LC-MS/MS assay method.ResultsHALS was associated with the presence of a low expression TS genotype polymorphism (64.7% vs. 42.9%, OR = 2.43; 95%CI: 1.53–3.88, P<0.0001). MTHFR gene polymorphisms and HLA-B*40∶01 carriage were not associated with HALS or d4T-TP intracellular levels. Low and high expression TS polymorphisms had different d4T-TP intracellular levels (25.60 vs. 13.60 fmol/106 cells, P<0.0001). Independent factors associated with HALS were(OR [95%CI]: (a) Combined TS and MTHFR genotypes (p = 0.006, reference category (ref.): ‘A+A’; OR for ‘A+B’ vs. ref.: 1.39 [0.69–2.80]; OR for ‘B+A’ vs. ref.: 2.16 [1.22–3.83]; OR for ‘B+B’ vs. ref.: 3.13, 95%CI: 1.54–6.35), (b) maximum viral load ≥5 log10 (OR: 2.55, 95%CI: 1.56–4.14, P = 0.001), (c) use of EFV (1.10 [1.00–1.21], P = 0.008, per year of use).ConclusionHALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*40∶01 carriage in Caucasian patients with long-term exposure to stavudine.

AIDS malignancy consortium (AMC) study 061: A phase I/PK study of sunitinib (S) with highly active antiretroviral therapy (HAART) in HIV+ patients with solid tumors.

2591 Background: Rates of non-AIDS defining cancers (NADCs) now exceed those of AIDS-defining cancers in HIV+ patients taking HAART. Treatment of NADCs may be complicated by drug-drug interactions between HAART and chemotherapy, including HAART induction or inhibition of metabolizing enzymes, especially CYP3A4. We present findings from the first of a series of studies by the AMC of new targeted therapies and HAART in HIV+ cancer pts. Methods: Pts were stratified into two arms to determine the MTD of S: (1) non-ritonavir based HAART or (2) ritonavir-based HAART. Pts in arm 1 received the standard dose of S (50mg). Arm 2 used a phase I, 3+3 dose escalation design (25, 37.5, and 50mg). S was taken daily on a 4 wk on/2 wk off cycle. PK monitoring of S and its active metabolite (S-M) were performed throughout cycle one, and normalized based on dose level, to calculate AUC-24, Cmax, and trough level. Results: Between 8/09 and 1/11, 16 patients were enrolled and completed cycle 1 (9 on arm 1, 7 on arm 2). Following enrollment of the first 6 pts, Arm 1 was expanded to include additional pts on efavirenz, a potent inducer of CYP3A4. Cancer types included Kaposi’s Sarcoma (7), lung (2), anal (2), NHL (1), and other solid tumors (4). Median cycles was 2 (range 1-6). Pts on arm 1 tolerated standard treatment with no DLTs. One pt in arm 2 at the 37.5 mg level had a DLT (wound dehiscence). Enrollment continues at that expanded dose level. No patient had a CR or PR. Five patients (31%) had stable disease for >2 cycles. Grade 3/4 toxicities at any time during treatment were: neutropenia (13%), fatigue (13%), anemia (6%), hand/foot (6%), and wound complications (6%). PK analysis showed significant inter-patient variability of S and S-M. There was no PK alterations of S between the arms, but there were significant alterations in the PK of S-M. Efavirenz resulted in a 315% and 150% increase, whereas ritonavir caused a 69% and 72% decrease in the Cmax and AUC-24 of S-M, respectively. Conclusions: S 50mg was well tolerated in pts on non-ritonavir based HAART regimens. Dose reduction of S may be warranted in pts on ritonavir-based HAART regimens. HAART therapy affected the PK of S-M but not S. Final results will be presented.

Relationship between HIV/Highly Active Antiretroviral Therapy (HAART)–Associated Lipodystrophy Syndrome and Stavudine‐Triphosphate Intracellular Levels in Patients with Stavudine‐Based Antiretroviral Regimens

The link between human immunodeficiency virus/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS) and the use of thymidine analogues has been well established. However, to our knowledge, no relationship has been proven between intracellular levels of stavudine (d4T) and HALS. We measured peripheral blood mononuclear cell intracellular levels of d4T-triphosphate (TP) in patients who were receiving d4T as part of their antiretroviral regimens. d4T-TP levels were determined by a validated liquid chromatography-tandem mass spectrometry assay method. The diagnosis of HALS was made in accordance with the criteria of a lipodystrophy severity grading scale. The Student t test, Pearson correlations, 1-way analysis of variance with Bonferroni correction, and stepwise logistic regression were used for statistic analyses. This was a cross-sectional study. There were 33 patients: 17 with HALS and 16 without HALS. The median concentration of d4T-TP for patients with HALS was 20.60 femtomoles (fmol)/1 x 10(6) cells (interquartile range [IQR], 14.90-26.92 fmol/1 x 10(6) cells) and for patients without HALS was 13.85 fmol/1 x 10(6) cells (IQR, 8.65-20.15 fmol/1 x 10(6) cells) (P=.013). The median d4T-TP intracellular level in patients who had developed an AIDS-defining condition was 22.50 fmol/1 x 10(6) cells (IQR, 15.80-27.37 fmol/1 x 10(6) cells) and in those who had not was 14.40 fmol/1 x 10(6) cells (IQR, 10.80-20.40 fmol/1 x 10(6) cells) (P=.037). There were no statistically significant differences in d4T-TP intracellular levels with respect to the presence of metabolic syndrome, the clinical form of HALS (pure lipoatrophic vs mixed), the degree of facial lipoatrophy, the presence of hepatitis C virus infection, and the pair of nucleosides in HAART. d4T-TP levels correlated only with cumulative d4T exposure in time and dose. d4T-TP intracellular levels were independently associated with HALS (odds ratio, 1.58; 95% confidence interval, 1.08-2.32; P=.019). Intracellular levels of d4T-TP are strongly associated with the development of HALS.

Incident Depression Symptoms Are Associated With Poorer HAART Adherence: A Longitudinal Analysis From the Nutrition for Healthy Living Study

To determine the relationship between incident depression symptoms and suboptimal adherence to HIV highly active antiretroviral therapy (HAART). Participants in a cohort study of persons with HIV on HAART with at least 4 consecutive semiannual study visits were included (n = 225). Incident depression was defined as having 2 visits with a negative depression screening test followed by 2 visits with a positive test. Comparison group participants had 4 consecutive visits with a negative depression screening test. Suboptimal adherence was defined as missing >5% of HAART doses in the past 7 days. We compared suboptimal adherence rates in those with and without incident depression symptoms and estimated the relative risk and 95% confidence intervals of suboptimal adherence at visit 4 in those adherent at baseline (n = 177), controlling for sociodemographic, behavioral, and clinical variables. Twenty-two percent developed depression symptoms. Those developing depression symptoms had higher rates of suboptimal adherence at follow-up (45.1% vs. 25.9%, P < 0.01). Among those with optimal baseline adherence, those with incident depression were nearly 2 times more likely to develop suboptimal adherence (Adjusted relative risk =1.8, 95% confidence interval =1.1 to 3.0) at follow-up. Incident depression symptoms were associated with subsequent suboptimal HAART adherence. Ongoing aggressive screening for, and treatment of, depression may improve HAART outcomes.

HIV-associated primary non-Hodgkin's lymphoma of ovary: A case report

Background. Although there have been few case series of primary non-Hodgkin's lymphoma (NHL) of ovary, no patient with AIDS-related primary ovarian lymphoma has been described in the literature. Case. We report a case of human immunodeficiency virus infected female with primary ovarian NHL for which she could not receive standard NHL combination chemotherapy and standard HIV highly active antiretroviral therapy (HAART) and succumbed to death within 7 months after diagnosis. Conclusions. Primary ovarian lymphoma is rare as compared with other ovarian tumors and has similar presentation to other common ovarian malignancies. The patients from developing countries cannot afford standard NHL combination chemotherapy and HAART as these drugs are expensive and are not provided freely to all patients, in state government run public hospitals.

Papel diferencial de las subpoblaciones de linfocitos T CD4+ y CD8+ sobre la replicación del virus de la inmunodeficiencia humana y la función tímica en niños

We intended to study the relationship between T-cell subsets with plasmatic detectable viral load (VL) and T-receptor excision circles (TREC). Twenty HIV-infected children on highly active antiretroviral therapy (HAART) were recruited in a 1-year longitudinal retrospective study. We analyzed the relationship between changes in peripheral blood T-cell subsets, VL and TREC markers by lineal regression. Memory and activated CD4+ T-cells increases had a negative association with log10 TRECs increases. However, naive CD4+ T-cells increases had a positive association with log10 TRECs increases. In contrast, memory, activated and effector CD8+ T-cells increases positively correlated with log10 VL increases. On the other hand, naive CD8+ T-cells increases had a negative association with log10 VL increases. CD4+ and CD8+ T-cells subsets change in a different way as a response to the changes produced by HAART in HIV vertically infected children. CD4+ T-cells are more dependent on thymic function and CD8+ T-cells are more dependent on viral replication. Thus, the decline in cellular activation would allow the production of more naive T-cells by the thymus.

HIV-associated primary cervical non-Hodgkin’s lymphoma and two other cases of primary pelvic non-Hodgkin’s lymphoma☆

Background Although there have been few case series of primary pelvic non-Hodgkin’s lymphoma (NHL) reported over the past two decades, no patient with acquired immunodeficiency syndrome (AIDS)-related primary pelvic NHL has been reported. Cases We report a human immunodeficiency virus (HIV)-infected patient with primary cervical NHL. After surgical biopsy, she received standard NHL combination chemotherapy plus standard HIV highly active antiretroviral therapy (HAART), and remains disease free 38 months since therapy. We also report two other cases of primary pelvic NHL. Conclusions Primary pelvic NHL is rare, with clinical presentation similar to other common gynecologic malignancies. It is treated with combination chemotherapy and pelvic radiotherapy, and generally has good prognosis. Adding HAART to other standard therapies for patients with AIDS-related pelvic lymphoma may improve the prognosis of this category of patients.

Access to and Use of HIV Antiretroviral Therapy: Variation by Race/Ethnicity in Two Public Insurance Programs in the U.S.

To examine access to and use of HIV highly active antiretroviral therapy (HAART) by race/ethnicity in Medicaid and the AIDS Drug Assistance Program (ADAP) in 1998 in four states. The authors analyzed reimbursement claims and AIDS surveillance data in California, Florida, New York, and Texas. Study subjects were identified using diagnostic or medication codes specific to HIV. The race/ethnicity of program enrollees was compared to representation in the HIV epidemic to examine access. Claims for antiretroviral (ARV) use were compared to U.S. Public Health Service treatment guidelines to assess HAART use. The authors identified 151,000 HIV-infected individuals in these two programs in the four states. Evidence of AIDS or symptomatic HIV was present in 78%-88% of enrollees in Medicaid, versus 31%-48% in ADAP. African Americans participated in Medicaid 10%-53% above and in ADAP 17%-31% below representation in the epidemic. Non-Latino whites exhibited the opposite pattern, being in Medicaid 5%-38% below and in ADAP 9%-65% above epidemic representation. Latinos participated more in ADAP (7%-31%), except in New York. HAART use over 90 days (July-September) ranged from 38% to 76% by program and state. Differences by race/ethnicity were inconsistent and small: African Americans had lower HAART use by 6%-14% in California and Florida Medicaid, and Latinos had higher HAART use by 2%-11% in ADAP and in Texas Medicaid. African Americans were more likely to access HIV drugs through Medicaid than through ADAP, which may reflect differences in program eligibility criteria as well as care seeking later in HIV disease. Differences in the use of HAART by race/ethnicity within state programs were small.