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We develop a differential diagnosis and diagnostic approach to a possible drug-drug interaction between a cART based on boosted atazanavir and newly given drugs. History taking should not only encompass prescribed but also over-the-counter medication. Exchange of information between attending physicians as to therapeutic changes, documented side effects and adherence, therapeutic drug monitoring of cART and evaluation by pharmacologist in complex situations are the diagnostic tools at hand. [ABSTRACT FROM AUTHOR]

The development of resistance mutations in drug-targeted HIV-1 genes compromises the success of antiretroviral therapy (ART) programs. Genotyping of these mutations enables adjusted therapeutic decisions both at the individual and population level. We investigated over time the prevalence of HIV-1 primary drug resistance mutations in treatment-naive patients and described the HIV-1 subtype distribution in a cohort in rural Tanzania at the beginning of the ART rollout in 2005-2007 and later in 2009. Viral RNA was analyzed in 387 baseline plasma samples from treatment-naive patients over a period of 5 years. The reverse transcriptase (RT) and protease genes were reversely transcribed, polymerase chain reaction (PCR) amplified, and directly sequenced to identify HIV-1 subtypes and single nucleotide polymorphisms associated with drug resistance (DR-SNPs). The prevalence of major DR-SNPs in 2005-2007 in the RT gene was determined: K103N (5.0%), Y181C (2.5%), M184V (2.5%), and G190A (1.7%), and M41L, K65KR, K70KR, and L74LV (0.8%). In samples from 2009 only K103N (3.3%), M184V, and T215FY (0.8%) were detected. Initial frequencies of subtypes C, A, D, and recombinants were 43%, 32%, 18%, and 7%, respectively. Later similar frequencies were found except for the recombinants, which were found twice as often (15%), highlighting the subtype diversity and a relatively stable subtype frequency in the area. DR-SNPs were found at initiation of the cohort despite very low previous ART use in the area. Statistically, frequencies of major mutations did not change significantly over the studied 5-year interval. These mutations could reflect primary resistances and may indicate a possible risk for treatment failure.

Background: Nevirapine (NVP) is a widely used non-nucleoside reverse transcriptase inhibitor. A once-daily extended-release (XR) formulation would potentially increase adherence and thus efficacy., Objective: The aim of this study was to investigate the steady-state bioavailability of 2 once-daily tablet formulations of NVP XR (containing 25% or 20% hypromellose; NVP XR25 and NVP XR20, respectively) in 400- or 300-mg tablets compared with twice-daily immediate-release (IR) NVP 200-mg tablets., Methods: This Phase Ib multinational, multicenter, open-label trial was conducted in patients aged 18 to 60 years, infected with HIV-1 (viral load, ≤50 copies/mL), and treated for ≥12 weeks with twice-daily NVP IR 200 mg. Patients were switched to NVP XR25 400 or 300 mg or NVP XR20 400 or 300 mg for 19 days. Plasma samples were collected over 24-hour periods at steady state. Primary end points were AUC(0-24,ss), C(max,ss), and C(min,ss), analyzed using an ANOVA statistical model on the logarithmic scale and 2-sided 90% CI. Sample size was determined assuming an intrasubject %CV of 20% for C(max). Adverse events (AEs) and viral loads were monitored., Results: Ninety-two patients were enrolled (NVP XR25 400 mg, 24 patients; NVP XR20 400 mg, 24; NVP XR25 300 mg, 21; NVP XR20 300 mg, 23). Compared with NVP IR, the AUC(0-24,ss) values of the NVP XR formulations were lower (test/reference ratios: 79.5% [90% CI, 73.0-86.7; P = 0.544], 71.0% [90% CI, 63.3-79.7; P = 0.956], 90.3% [90% CI, 80.4-101.4; P = 0.044], and 83.7% [90% CI, 77.9-89.9; P = 0.148] with NVP XR25 400 mg, NVP XR20 400 mg, NVP XR25 300 mg, and NVP XR20 300 mg, respectively). The relative bioavailability of NVP XR25 was greater compared with that of NVP XR20. C(max,ss) values were lower with all NVP XR formulations compared with NVP IR. For C(min,ss), NVP XR25 400 and 300 mg were not significantly different from NVP IR, with 90% CIs within the range of 80% to 125% (P = 0.039 and P = 0.017, respectively). All AEs were mild or moderate, with no significant differences between treatment groups. No virologic failures (viral load, >50 copies/mL over 2 consecutive readings) were observed., Conclusions: Extent of bioavailability was lower and t(max,ss) was delayed with all NVP XR formulations compared with NVP IR. The bioavailability of the NVP XR25 formulations was greater than that of the NVP XR20 formulations. C(min,ss) with NVP XR25 was similar to that with NVP IR. All of the NVP XR formulations were well tolerated. The 400-mg NVP XR25 formulation was selected for further development., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Background: Data on combination antiretroviral therapy (cART) in remote rural African regions is increasing., Methods: We assessed prospectively initial cART in HIV-infected adults treated from 2005 to 2008 at St. Francis Designated District Hospital, Ifakara, Tanzania. Adherence was assisted by personal adherence supporters. We estimated risk factors of death or loss to follow-up by Cox regression during the first 12 months of cART., Results: Overall, 1,463 individuals initiated cART, which was nevirapine-based in 84.6%. The median age was 40 years (IQR 34-47), 35.4% were males, 7.6% had proven tuberculosis. Median CD4 cell count was 131 cells/μl and 24.8% had WHO stage 4. Median CD4 cell count increased by 61 and 130 cells/μl after 6 and 12 months, respectively. 215 (14.7%) patients modified their treatment, mostly due to toxicity (56%), in particular polyneuropathy and anemia. Overall, 129 patients died (8.8%) and 189 (12.9%) were lost to follow-up. In a multivariate analysis, low CD4 cells at starting cART were associated with poorer survival and loss to follow-up (HR 1.77, 95% CI 1.15-2.75, p=0.009; for CD4<50 compared to >100 cells/μl). Higher weight was strongly associated with better survival (HR 0.63, 95% CI 0.51-0.76, p<0.001 per 10 kg increase)., Conclusions: cART initiation at higher CD4 cell counts and better general health condition reduces HIV related mortality in a rural African setting. Efforts must be made to promote earlier HIV diagnosis to start cART timely. More research is needed to evaluate effective strategies to follow cART at a peripheral level with limited technical possibilities.

In a prospective influenza-vaccination trial we show that HIV-infected individuals with CD4 T-cell counts less than 350 microl were distinct from HIV-infected individuals with more than 350 CD4 T-cell counts/microl, and from HIV-negative individuals, in that an influenza-specific immunoglobulin M-response was absent and expansion of interferon-gamma-secreting CD4 T cells was impaired. By contrast, immunoglobulin G-responses were induced in all study groups. These data suggest that establishing broad influenza-specific (immunoglobulin G) B-cell memory prior to severe immunodeficiency is important.

Objective: To evaluate the impact of a national HIV voluntary counselling and testing (VCT) campaign on presentation to HIV care in a rural population in Tanzania., Methods: Retrospective analysis of data of the VCT and of the National AIDS Control Programme registers of the St. Francis Designated District Hospital at Ifakara for the two 6-month periods before (2007) and after (2008) the National VCT Campaign., Results: There were 4354 individuals presenting at St. Francis Hospital tested for HIV; 2065 (47.4%) before the VCT Campaign and 2289 (52.6%) afterwards. The overall HIV test positivity was 24.6% and higher in 2007 than in 2008 (26%vs. 23%, P = 0.034). This rate was much higher than the Tanzanian National HIV prevalence of 5.7%. Of 1069 individuals who tested HIV-positive, the proportion of married, divorced or widowed individuals and those who lived further than 10 km from the hospital increased from 2007 to 2008. In 356 HIV-infected persons with available data, the median CD4 cell count increased from 137 to 163 cells/mm(3) (P = 0.058), while the WHO clinical stage was similar in both periods. Enrolling into the National AIDS Control Programme was significantly more common in 2008 (42%vs. 30%, P < 0.001). In a multivariate analysis, the only positive predictor of testing HIV positive when presenting for care after the National VCT Campaign was being married (OR 1.61, 95%CI 1.21-2.15, P = 0.001) or divorced/widowed compared to single (OR 4.58, 95% CI 3.00-8.12, P < 0.001)., Conclusions: Our results suggest that the National VCT Campaign raised awareness and readiness to test for HIV in a remote rural setting and that the HIV-positive test rate is much higher in conjunction with a specific HIV care programme.

Papular pruritic eruption (PPE) is a frequent HIV-comorbidity in tropical countries. Because of constant itching and social stigma, effective treatment is highly valued. In our HIV cohort in rural Tanzania with 12% prevalence of PPE, we have retrospectively analyzed responses to available treatments. Oral promethazine improved itching (P < 0.0058) and clinical scores (P < 0.032) significantly more than topical steroids. Disease activity did not correlate with CD4+ and CD8+ T cell counts and was independent of anti-retroviral medication. Therefore, oral antihistamines are an effective first-line treatment for PPE.

Background: Yellow fever vaccine (17DV) has been investigated incompletely in human immunodeficiency virus (HIV)-infected patients, and adequate immunogenicity and safety are of concern in this population., Methods: In the Swiss HIV Cohort Study, we identified 102 patients who received 17DV while they were HIV infected. We analyzed neutralization titers (NTs) after 17DV administration using the plaque reduction neutralization test. NTs of 1:>or=10 were defined as reactive, and those of 1:<10 were defined as nonreactive, which was considered to be nonprotective. The results were compared with data for HIV-uninfected individuals. Serious adverse events were defined as hospitalization or death within 6 weeks after receipt of 17DV., Results: At the time of 17DV administration, the median CD4 cell count was 537 cells/mm(3) (range, 11-1730 cells/mm(3)), and the HIV RNA level was undetectable in 41 of 102 HIV-infected patients. During the first year after vaccination, fewer HIV-infected patients (65 [83%] of 78; P = .01) than HIV-uninfected patients revealed reactive NTs, and their NTs were significantly lower (P < .001) than in HIV-uninfected individuals. Eleven patients with initially reactive NTs lost these reactive NTs

Objective: To assess the incidence and epidemiological pattern of respiratory viruses in HIV-infected patients and to evaluate their potential clinical impact., Design and Methods: A prospective population-based cohort study was conducted at three Swiss university hospitals. Study participants were HIV-infected patients who underwent a bronchoalveolar lavage to rule out an opportunistic event. All bronchoalveolar lavage specimens were screened using a set of real-time reverse transcriptase-polymerase chain reaction assays targeting 17 different respiratory viruses., Results: Between November 2003 and November 2006, 59 bronchoalveolar episodes from 55 HIV-infected patients were analysed. Eleven of 59 episodes (18.6%) were positive for at least one respiratory virus. Coronavirus OC43 was identified in three cases (27.3%) followed by influenza A in two (18.2%). Parainfluenza virus (PIV) 2, PIV 3, PIV 4, bocavirus, human rhinovirus A and human metapneumovirus were each identified in one case (9%). In the majority of these cases (63.6%) no other concomitant microorganism was isolated., Conclusions: Clinical investigation of respiratory viral infections in HIV-infected patients should not be restricted to prototype viruses and also need to target all the different family of viruses as it seems likely that these viruses contribute to pulmonary complications and morbidity in this population.