Showing papers by "Michael Hughes published in 2012"

Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children.

Abstract: Background Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established. Methods In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24. Results A total of 288 children were enrolled; the median p...

Dynamics of the resting CD4(+) T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age.

Abstract: OBJECTIVES Identification of HIV infection in exposed infants facilitates early therapy, which may limit viral reservoirs that maintain HIV infection under HAART. METHODS The dynamics of the resting CD4 T-cell latent HIV reservoir was determined over the first 2 years of life in 17 HIV-infected infants initiating lopinavir/ritonavir-based HAART at a median age of 8.1 weeks and achieving adequate suppression of plasma viral load by 24 weeks. RESULTS The resting CD4 T-cell latent HIV reservoir was detected in 12 of 14 (86%) infants tested at 24 weeks of HAART [median frequency 1.88 infectious units per million (IUPM); range <0.22 to 81.7), and remained measurable (median IUPM = 0.32; range <0.22 to 3.25) in six of 10 (60%) children retested at 96 weeks. The reservoir declined, from 24 to 96 weeks of HAART, at an estimated mean rate of 0.028 log10 IUPM/month, corresponding to a half-life of 11 months (95% confidence interval 6-30 months]. A strong relationship was found between the frequency of latently infected CD4 T cells at 96 weeks of HAART and time to first undetectable plasma viral load (Spearman r = 0.91, P < 0.001). CONCLUSION Although the resting CD4 T-cell latent reservoir remains detectable over the first 2 years of HAART in a substantial proportion of infants, its size is associated with time to first undetectable viral load. To minimize HIV reservoirs in infants, rapid curtailment of viremia may limit HIV reservoirs and should be a therapeutic goal of early HAART in infants.

Nevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub-Saharan African women.

Abstract: Objectives To estimate nevirapine pharmacokinetics and examine its association with rash and/or hepatotoxicity in women starting antiretroviral treatment in the ACTG A5208/OCTANE study in Africa.

Nevirapine- versus lopinavir/ritonavir-based initial therapy for HIV-1 infection among women in Africa: a randomized trial.

Abstract: Background Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.

Genotype assays and third-line ART in resource-limited settings: A simulation and cost-effectiveness analysis of a planned clinical trial

Abstract: Objectives To project the clinical and economic outcomes of a genotype assay for selection of third-line antiretroviral therapy (ART) in resource-limited settings, as per the planned international A5288 trial (MULTI-OCTAVE).

Next-generation, high-density, low-cost, multimode optical backplane interconnect

Abstract: This paper describes the development, termination and performance of next generation optical backplane interconnect components. This low cost, dense optical interconnect technology combined with recent advances in 10G/lane and beyond, miniature imbedded Tx/Rx devices is driving bandwidth density to unprecedented levels. A monolithic, multi-fiber ferule with integrated collimating lenses was designed with the same overall footprint as a traditional MT-type, multi-fiber rectangular ferrule. The new optical ferrule was designed with precision micro holes for alignment to the lens array allowing for incorporation of multiple rows of fibers into single ferrule unit. The design supports up to four rows with as many as 16 fibers per row for a total potential lane count of up to 64 within in a single ferrule. A low cost termination is achieved by securing precision-cleaved fiber arrays into the rear of the ferrule with a quick-cure, index matched, UV light activated epoxy. The elimination of a polished fiber array greatly reduces the cost and complexity associated with physical contact based multi-fiber interconnects. With the same overall footprint as an MT ferrule, the new, lens-based ferrule can be used in conjunction with MPO and other MT based connectors. However, by eliminating the need for physical contact via the use of collimated light beams, the connection force per ferrule required is greatly reduced, paving the way for high ferrule counts and mass insertion of dense optical backplanes. Mated pairs of the new ferrule were tested for insertion loss with the substitution method and all channels were <1dB.

HIV-1 Protease Inhibitors and Clinical Malaria: a Secondary Analysis of the AIDS Clinical Trials Group A5208 Study

Abstract: HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART We calculated hazard ratios and 95% confidence intervals We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up Of these 137, 72 (53%) were randomized to LPV/r-based ART Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 111 [079 to 156]) The results were similar in the recurrent events analysis Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted

Infected Calcinosis of the Knee in Limited Cutaneous Systemic Sclerosis

Abstract: Calcinosis is a fairly common complication of systemic sclerosis (SSc) and a major cause of morbidity. Sometimes, surgical intervention is indicated. A 41-year-old woman with limited cutaneous SSc (lcSSc) presented with pain and erythema of the anterior aspect of the right knee, and a blistering lesion filled with white colored fluid (Figure 1A). She had known calcinosis of the …

Factors affecting timing of antiretroviral treatment initiation based on monitoring CD4 counts.

Abstract: OBJECTIVE To evaluate factors affecting antiretroviral therapy (ART) start time when triggered by a CD4 count <350 cells/μL while monitoring counts over time. Measurement frequency, requirement for confirmatory counts, and precision and accuracy of CD4 enumeration technology were considered. METHODS Using a model of CD4 count trajectories among seroconverters in the Multicenter AIDS Cohort Study, sequences of counts were simulated for a large hypothetical population monitored for 5 years from seroconversion. Time of first count <350 cells/μL was defined as ART start time. The simulation was adapted to evaluate the effect of the above factors on these times. ART initiation was considered "very late" among patients whose underlying trajectory declined less than 200 cells/μL during the period simulated if no previous observed count was <350 cells/μL. RESULTS For 12-, 6-, 4-, and 3-monthly measurements, median start time was 48, 36, 32, and 30 months after seroconversion and proportion of patients starting ART very late was 11.5%, 1.6%, 0.2%, and 0.1%. For 6-monthly measurements, requiring confirmation increased the median to 49 months and proportion to 8.9%. Changes in standard deviation of short-term variability in counts of 25% and measurement bias for a novel technology of ±10% changed median time by ±6 months with modest change in the proportion very late (range, 0.5%-3.2%). CONCLUSION : 6-monthly measurements appear adequate in achieving low rates of very late ART whereas confirmation affects rates adversely. Studies comparing new versus standard measurement technologies should focus on ruling out modest bias, particularly proximal to important thresholds for treatment management.