Suchergebnisse

BackgroundDuring HAART, HIV RNA can be detectable (>50 cop/mL) in CSF when it is undetectable in plasma, a condition termed CSF viral escape (CVE). The aim of the current analysis was to determine the prevalence and risk factors for CVE in two large US cohorts.Methods1,264 volunteers enrolled in CHARTER or HNRP at their most recent visit between 2003 and 2011 were included in this cross‐sectional analysis if their HIV RNA level in plasma was undetectable while on stable HAART (>6 months) and if they had CSF collected. Potential risk factors were identified using univariable and multivariable analysis. Odds ratios for detected risk factors were calculated.ResultsMean age was 46 years, 82% were men, 70% had AIDS, 22% were HCV+, 49% were Caucasians, median CD4 nadir was 129, and 38% were cognitively impaired. CVE was present in 55 (4.35%) with a median HIV RNA in CSF of 155 (IQR 80‐283). The table summarizes the main analysis results. CVE was associated with longer durations of HIV disease, higher platelet count, higher total serum protein, and higher CSF white blood cells (WBCs). CVE was also associated with treatment‐associated factors, including use of boosted PIs and unboosted atazanavir.













Variable
Measure
CSF viral load >50 (n=55)
CSF viral load <50 (n=1209)
Univariable analysis
Multivariable analysis
Odds ratio
Odds ratio info




Age (years)
Mean±SD
45.3±7.48
46±9.50
p=0.663





Gender (male)
n (%)
43 (78.18)
978 (81.98)
p=0.486





Ethnicity (white)
n (%)
25 (45.45)
590 (49.50)
p=0.692





Years since first HIV+
Median [IQR]
16.02 [11.55–19.9]
12.72 [6.79–18.24]
p=0.018
p=0.016
1.367 [1.058–1.785]
(each 5 years)


HCV (positive)
n (%)
10 (22.22)
219 (22.42)
p=0.976





CD4 nadir (cells/mL)
Median [IQR]
71 [8.75–188.5]
133 [27.5–240]
p=0.025





AIDS (CDC)
n (%)
41 (83.67)
775 (69.07)
p=0.021





Cognitively impair (Yes)
n (%)
21 (38.18)
447 (37.69)
p=0.914





Global Deficit Score
Median [IQR]
0.4 [0.11–0.87]
0.33 [0.11–0.72]
p=0.943





CD4 in blood (cells/mL)
Median [IQR]
506 [268–711]
508.5 [340.25–710]
p=0.678





Hb in blood (mg/dL)
Median [IQR]
14 [12.9–15.1]
14.4 [13.4–15.3]
p=0.104





Platelets in blood (x103/mL)
Median [IQR]
232 [202–283]
230 [189–273]
p=0.056
p=0.022
1.314 [1.041–1.645]
(each 50,000)


Protein in serum (g/dL)
Median [IQR]
7.7 [6.90–8.30]
7.4 [7–7.9]
p=0.013
p=0.035
1.649 [1.036–2.614]
(each 1 g/dL)


WBC in CSF (cells/mL)
Median [IQR]
4 [2.5–16.5]
2 [1–3]
p≤0.001
p≤0.001
3.416 [2.204–5.582]
(each 10 cells)


Protein in CSF (mg/dL)
Median [IQR]
47 [31.5–55.5]
38 [30–48]
p=0.002





Glucose in CSF (mg/dL)
Median [IQR]
62 [57.5–68.5]
63 [58–68]
p=0.740





Previous blips (Y/N)
n (%)
6 (10.91)
111 (9.2)
p=0.677





Months VL <50 in plasma
Median [IQR
13.07 [6.04–37.66]
18.63 [7.51–40.8]
p=0.543





Months on current HAART
Median [IQR]
13.07 [6.05–29.78]
18.32 [6.7–35.89]
p=0.18





Months on HAART ever
Median [IQR]
77.55 [39.65–124.15]
72.87 [34.94–117.07]
p=0.419





CPE score
Median [IQR]
7 [6–8]
7 [7–9]
p=0.625





NNRTI+NRTIs
n (%)
8 (14.55)
438 (36.23)
p<0.001





PI/r + NRTIs
n (%)
31 (56.36)
501 (41.47)
p=0.03
p=0.006
2.749 [1.340–5.976]
(Yes vs No)


ATV + NRTIs
n (%)
4 (7.27)
27 (2.23)
p=0.052
p=0.024
6.006 [1.302–21.57]
(Yes vs No)


Other HAART regimens
n (%)
12 (21.82)
243 (20.07)
p=0.747







ConclusionsIn this large, cross‐sectional analysis, CVE was uncommon in subjects on effective HAART. A combination of disease and treatment factors were associated with CVE. The associations with higher levels of CSF WBCs, blood platelets, and serum total protein may reflect greater immune activation. Treatment with PI‐based HAART was particularly associated with CVE, especially if unboosted atazanavir was part of the regimen. CVE was not associated with neurocognitive impairment. Prospective analyses are needed for better characterization of CVE.

The new European Guidelines of Dislipidemia Management of the European Societies of Cardiology and Arteriosclerosis consider HIV+ as patients at high risk of developing cardiovascular events and deaths. The objective of the study was to evaluate cardiovascular events and deaths in a series of HIV+ patients. Observational, cross‐sectional study, including a cohort of HIV+ and HIV− patients from 2008. CVR was calculated using the SCORE‐CVR chart. Variation on lipid profile and incidence of cardiovascular events, cardiovascular death or death related to any cause were recorded. Data was analyzed using SPSS version 20.0 for MAC. 154 HIV+ and 155 HIV− patients were included. Mean age: 44.8±9.5 vs 55.2±14.3 y and 69.5% vs 49% males respectively (p<0.01). Mean time since HIV+ diagnosis was 11±6.2 y. Mean BMI and systolic blood pressure were lower in HIV+ (25.1±6.7 kg/m2 vs 28.7±5.1 kg/m2, (p<0.01) and 119.6±19.4 vs 124.7±14.7 mmHg, (p=0.044; respectively)). A lower proportion of hypertense, diabetic and obese patients was observed in HIV+ (25.5% vs 6.5%; 20.6% vs 3.9% and 36.8% vs 12.3%) but a larger proportion of smokers (68.8% vs 29.7%) was observed (p<0.01 in all cases). Mean cholesterol and LDLc were lower in HIV+ (191.2±41.4 vs 218.5±44.6 mg/dl and 109.5±33.9 vs 134.6±37.7 mg/dl; p<0.01; respectively) but with a lower mean HDLc and higher TG (50.3±19 mg/dl vs 55.2±14.9 mg/dl; p=0.013 and 156.7±85.7 vs 135.8±66.2 mg/dl; p=0.017; respectively). There was no significant difference in mean CVR‐SCORE (3.5±3.6% vs 4.4±3.8%; p=0.091). With this SCORE, 5.2±5.3 and 6.7±5.8 cardiovascular events or deaths should be expected in HIV+ and HIV− respectively at 10 y. Four years later cholesterol, LDLc, HDLc, TG in HIV+ and HIV− patients did not vary compared with those obtained 4 y before. 5 events and 1 death were seen at 4 y follow‐up in HIV+, and in HIV− patients. The incidence of events in HIV+ patients is similar to the expected according to their SCORE at 10 y. We could suppose that once the 10 y follow‐up is reached, this incidence would be higher. On the other side, in HIV− at 4 y just 3 events ocurred, far from the 6.7 events expected. There were no significant differences between lipid profiles in any of the cohorts. Lipid profile with low HDLc and high TG is persistent in HIV+ patients at 4 y follow‐up. Understimation of CVR in HIV+ patients by SCORE charts could be present as soon as 4 y after the first assesment. This supports the stratification of HIV+ patients as high‐risk patients in new guidelines.

Purpose of the studyPregnant women experience physiological changes during pregnancy resulting in clinically significant alterations in antiretroviral pharmacokinetics (PK). Therefore, achieving and maintaining optimal plasma concentrations of antiretroviral drugs is essential for maternal health and minimising the risk of mother‐to‐child transmission of HIV. The aim of this study is to describe atazanavir/ritonavir (ATV/r) PK during pregnancy.MethodsPregnant HIV‐positive women received ATV/r as part of their routine pre‐natal care. Demographic and clinical data were collected, and ATV plasma concentrations [ATV] were determined in the first (T1), second (T2) and third (T3) trimester using HPLC‐MS/MS (LLQ=0.05 µg/mL). Postpartum (PP) sampling was performed where applicable. Antepartum (AP) and PP PK parameters were compared using a one‐way ANOVA.Summary of resultsFrom January 2007, 44 women (37 black African) were enrolled in the study. All received ATV/r at a standard dose of 1 tablet once daily (300/100 mg od). 24 women were receiving ART prior to pregnancy, and 20 women initiated ATV/r during pregnancy. Median (range) gestation at treatment initiation in these patients was 23.5 weeks (7–35). At the time nearest to delivery 31 patients had an undetectable plasma viral load (pVL), 6 patients had detectable pVL and 2 were unavailable. [ATV] were determined in 11/44 (T1); 25/44 (T2); 35/44 (T3) and 28/44 (PP) patients. Time of TDM sampling, gestation time and [ATV] (geometric mean; 95% CI) are given in the Table. 6 patients were either below or approaching the ATV MEC (0.15 µg/mL) during pregnancy; of these, 4/6 achieved undetectable pVL at the time of delivery (1=pVL of 291 copies/mL; 1 unavailable). [ATV] were significantly lower at T2/T3 relative to T1/PP. Equally, in a paired analysis of 28 patients (T2/T3 vs. PP), [ATV] were significantly reduced at T2/T3 (P=0.003).












T1 (n=11)
T2 (n=25)
T3 (n=35)
PP (n=28)
P value




[ATV], µg/mL
1.07 (0.15–1.99)
0.68 (0.39–0.97)
0.63 (0.47–0.78)
1.22 (0.96–1.49)
0.002


CV, %
102
83
61
49
–


Time of sampling, h
12.0 (8.8–15.3)
18.2 (15.8–20.5)
18.9 (17.2–20.7)
18.9 (16.5–21.3)
0.003


Gestation/PP, weeks
9 (6–12)
20 (14–26)
32 (25–39)
10.5 (5–50)
–




ConclusionsThis study represents one of the larger cohorts of women undergoing TDM for ATV in pregnancy. Lower [ATV] were seen in T2 and T3 when compared to T1. However, such findings were not associated with viral breakthrough or HIV transmissions. Nonetheless, careful monitoring of women in pregnancy is required, and if there is concern for inadequate levels, dose adjustment of ATV upward from 300 mg to 400 mg may be an option.

Antiretroviral (ARV) therapy during pregnancy is recommended to reduce the risk of mother‐to‐child transmission (MTCT). Physiologic changes during pregnancy can affect PK. We present the PK of total and unbound (pharmacologically active) DRV in HIV‐1‐infected pregnant women receiving twice‐daily (bid) DRV/ritonavir (rtv). This Phase IIIb study enrolled HIV‐1‐infected pregnant women≥18 years old in the 2nd trimester of pregnancy receiving DRV/rtv 600/100 mg bid and other ARVs. DRV (total and unbound) and rtv (total) plasma concentrations were obtained predose and 1, 2, 3, 4, 6, 9 and 12 hours postdose during the 2nd and 3rd trimesters and postpartum. Total DRV and rtv plasma concentrations were determined using a previously validated HPLC‐MS/MS assay (lower limit of quantification 5.00 ng/mL). Unbound DRV was determined by fortifying plasma samples with 14‐C DRV and separating total and unbound DRV using ultrafiltration. Total and unbound 14‐C DRV were measured using liquid scintillation counting. Total and unbound PK parameters were derived using a noncompartmental analysis. Safety and efficacy were investigated at each visit and summarized using descriptive statistics. Sixteen women (10 black, 4 Hispanic, 2 white) were enrolled; 11 had evaluable PK data. Total DRV AUC12h was 24% and 17% lower during 2nd and 3rd trimesters, respectively, vs postpartum (Table). Unbound DRV AUC12h was unchanged during 2nd and 3rd trimesters vs postpartum. Total and unbound DRV Cmin increased by 43% and 10%, respectively, during 2nd trimester and by 86% and 14%, respectively, during 3rd trimester vs postpartum. Unbound DRV was above the EC50 (27.5 ng/mL) for PI‐resistant HIV in all patients. Albumin and α1‐acid glycoprotein (AAG) concentrations were 22%–29% lower during pregnancy vs postpartum. Viral load decreased and CD4+ count increased over time. One serious adverse event was reported (increased transaminase). Three of 12 infants were born prior to 37 weeks (30, 36 and 36 weeks), and all 12 infants were HIV‐1‐negative by standard PCR testing. Total DRV and rtv PK decreased during pregnancy likely due to pregnancy‐related dilution of albumin and/or AAG. No clinically relevant change in unbound DRV AUC12h and Cmin occurred during pregnancy, and there was no MTCT; therefore no dose adjustment is required for DRV/rtv 600/100mg bid in pregnant women. This ongoing trial will further evaluate the effects of pregnancy on DRV/rtv once daily, etravirine and rilpivirine PK.









Pharmacokinetic parameters a LS mean ratio, (90% CI)
2nd trimester vs postpartum
3rd trimester vs postpartum





Darunavir (total)





N
11b vs 11
11 vs 11



Cmin
1.43 (0.39, 5.22)
1.86 (0.49, 7.04)



Cmax
0.72 (0.61, 0.86)
0.81 (0.69, 0.96)



AUC12h
0.76 (0.63, 0.90)
0.83 (0.72, 0.97)



Darunavir (unbound)





N
6d vs 11
7e vs 11



Cmin
c
1.10 (0.59, 2.06)
1.14 (0.59, 2.20)



Cmax
0.78 (0.52, 1.18)
0.82 (0.57, 1.16)



AUC12h
0.92 (0.66, 1.30)
0.93 (0.69, 1.24)



Ritonavir (total)





N
11f vs 11
11g vs 11



Cmin
1.08 (0.31, 3.81)
1.22 (0.41, 3.59)



Cmax
0.66 (0.41, 1.08)
0.63 (0.40, 0.98)



AUC12h
0.72 (0.44, 1.17)
0.67 (0.43, 1.04)



Efficacy parameters Parameter
Baseline, n=15

h

2

nd

trimester, n=14
3

rd

trimester, n=11


Log10 viral load, mean (SD)
2.17 (0.770)
1.99 (0.514)
1.88 (0.598)


CD4+ cell count, cells/mm3,  median (range)
419 (104, 793)
429 (81, 933)
470 (103, 960)


Virologic response (HIV RNA  <50 copies/mL), n (%)
5 (33.3)
9 (64.3)
9i (81.8)





aOne patient was excluded from the PK analysis due to low adherence;
bn=10 for AUC12h;
cn=10 for postpartum;
dn=9 for Cmin and n=7 for Cmax;
en=8 for Cmin and Cmax;
fn=12 for Cmax;
gn=10 for Cmin;
hn=14 for CD4+ cell count;
i1 patient had VL 50–<400 copies/mL and 1 patient had VL≥1000 copies/mL; LS, least squares;
CI, confidence interval; Cmin, minimum plasma concentration;
Cmax, maximum plasma concentration; AUC12h, area under the plasma concentration‐time curve over 12 hours;
SD, standard deviation; PK, pharmacokinetic.

ObjectiveMultiple therapies are common in HIV‐infected children on highly active antiretroviral therapy (HAART). These children are at risk for clinically significant drug interactions (CSDIs). While CSDIs are under‐recognized in developed countries, data are lacking for developing African countries. We aimed to investigate the prevalence of CSDIs between antiretrovirals (ARVs) and co‐prescribed drugs for children attending a large HIV clinic in Lagos, Nigeria.MethodsWe retrospectively assessed the risk for clinically significant drug interactions in children on HAART. Of the 417 patients enrolled for treatment, 80 were eligible for inclusion. We defined CSDIs as 'major' (capable of causing severe or permanent damage, contraindicated, avoid or not recommended by the manufacturer, or requiring dose modification) or 'moderate' (manufacturers advise caution, or close monitoring, or capable of causing clinical deterioration).ResultsA total of 60 (75%) patients were at risk for a CSDI resulting in major interactions in 13 (16.3%) patients and could potentially lower the plasma concentration of antiretroviral drugs in 9 (15%) patients. Major interactions most frequently involved rifampicin in 9 (11.3%) patients and artemisinin combination therapies (ACTs) in 8 (10%) patients whereas moderate interactions frequently involved ACTs (48.8%), fluconazole (36.3%), and rifampicin (11.3%). Age (p = 0.392), gender (p = 0.813), and moderate (p = 0.692) or severe (p = 0.788) malnourished state of the children were not associated with risk for CSDIs.ConclusionsThree‐quarters of children receiving ARV drugs are at risk for CSDIs. Strategies are needed to be put in place to prevent important drug interactions and to manage unavoidable interactions.

The western Africa is the origin of the HIV2 infection where Guinea Bissau has been the country where the rate of infection is higher. This infection have extended to Europe through the relationship established between European countries and there African colonies in the past. At 2010, 1.295 cases of HIV 2 infection were notified in Portugal, which represents nearly 3.3% of all HIV infections. Almost 510 of these cases are classified as AIDS. Although the majority of notified cases is from African patients there is still a significant contribution of the Portuguese people in these numbers. Retrospective analysis of HIV2 infected women and men followed at Faro's Hospital HIV/AIDS consult between January 1992 and June 2012. In this sample were included every patient older than 15 years and were excluded every patient than haven't been at the consult for a period superior to 18–24 months. Deceased patients and address change were also exclusion factors. Of all 1500 patients followed in consult, 35 of them were infected with HIV2 (2.3%); 18 women and 17 men. There were 3 patients that were co‐infected with HIV1 and HIV2. Mean age were 52.9 years. 19 of the infected patients were leucodermic and 16 were melanodermic. The majority of patients (19 cases) were Portuguese. The rest of them were from Africa where Guinea Bissau were the only country represented. In opposition to the HIV1 infection, the sexual transmission is by far the more common way of being infected. There's no case of vertical transmission known in our population. At the first contact, the majority of patients appear asymptomatic (16 cases) while a minority (4 cases) manifest themselves by AIDS. There is an AIDS case that result from HIV1 and HIV2 co‐infection (only one intravenous drug user in the group). The more common treatment is the association of NRTI and PI. The HIV2 infection is characterized by a longer clinical evolution when compared to the HIV1 infection. That fact explains why the mean age of patients is higher in the first case. This study shows that there isn't a gender incidence difference between men and women. Despite what happens at a national level, at local level the HIV2 infection is more prevalent among patients born in Portugal. It's important to notice that the HIV1 and HIV2 co‐infection is rising and that leads to some questions like viral synergism with consequent rapid disease progression.

Purpose of the studyRilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) is a new single‐tablet regimen (STR) approved for the initial treatment of HIV‐1 infection. The aim of this study was to estimate the impact on the State Budget of this new STR introduction in the Portuguese Health System (PHS) using secondary data from official statistics and observational studies.MethodsThe analysis considers a time frame of three years, does not include mortality, assumes a constant flow of new patients, and deals only with antiretroviral therapy (ART) costs. Values are not discounted. The stock and flow data of total HIV‐1 patients comes from official statistics from the National Committee for HIV/AIDS. The model starts with recent historical data on the percentage of different ART drugs used for the treatment of naïve patients. Estimates from an observational study also provide 1) the probability that a patient in a given regimen switches to another therapy and 2) the probability distribution for the new therapy choices given that the patient has switched. The penetration of the new STR is also linked with the prevalence of adverse effects of other ART, in particular teratogenic effects, central nervous systems effects and possible interactions with methadone. The distribution of patients according to ART drug, together with price information, allow us to estimate average costs of treatment per year and per patient for each class of ART. Estimates of patients' numbers for the second and third years assume the same inflow as in the first year, a given annual percentage of non‐switchers from RPV/FTC/TDF and additional flows from patients switching to non‐nucleoside reverse transcriptase inhibitors from other third‐agent classes.Summary of resultsThe model predicts a flow of 245 new naïve patients on RPV/FTC/TDF per year, with 209 and 194 of these patients staying with RPV/FTC/TDF in the second and third years, respectively. Given that the average cost of treatment is lower in the scenarios with RPV/FTC/TDF (because the percentage of patients on the more expensive PI class are lower), the overall budget impact consists in savings of about €2.3 million.ConclusionsThe introduction of the new STR RPV/FTC/TDF in the PHS will lead to cost savings in the resources spent on the anti‐retroviral therapy of HIV‐1.

BackgroundPatients with a discordant response to cART, defined as persistent CD4 + T‐cell counts <200 cells/mm3 and lack CD4 increase despite virologic suppression on HAART, have an increased risk of morbidity and mortality. Several studies have suggested a potential benefit of intensification with maraviroc (MVC) on CD4+T‐cell recovery.MethodsA 24‐week prospective, open‐label, randomized, controlled study. Subjects on cART, plasma HIV RNA <37 copies/mL for at least 12 months, and CD4 < 200 cells/L, with CD4‐gain in the previous 12 months <50 cells/µL, were randomized to add MVC (A) or continuing same cART (B). Randomisation was stratified by the presence of liver cirrhosis (CH) (n = 10) and non‐CH (n = 28). We measured by flow cytometry changes in the following parameters of CD4 + and CD8 + T‐cell subsets: activation (CD38, HLA‐DR), senescence (CD28, CD57, CD45RA and RO), coreceptors (CCR5 and CXCR4) and apoptosis (Annexin‐V).ResultsThirty‐eight subjects were included at the final analysis. Median values were: age 51 years (IQR, 44–57), time with VL < 37 copies/mL before entry 43 months (IQR 24–62 months), baseline CD4 + T‐cell count 144 cells/µL (IQR 106–181). Four subjects were lost of follow‐up (3 in A, 1 in B). One subject from group B experienced confirmed virologic failure at week 24. Adverse events were similar in both arms. Median increase in CD4 + T‐cell count from baseline to weeks 2,4 and 24 in both groups were +15.5 vs ‐1 (p = 0.025); +16.5 vs ‐2.5 (p = 0.158); +46.5 vs + 6.50 (p = 0.190). Similar trend towards a higher CD4 increase were seen in both CH and non‐CH individuals. At W24, 8 subjects from arm A vs 1 subject from arm B achieved a CD4 + T‐cell count above 200 cells/µL (p < 0.05). Markers of immune activation (CD38 and HLA‐DR) decreased during MVC intensification, especially in CD8+ T cells (p < 0.01) whereas apoptosis did not. Additionally CCR5 expression tended to increase (p = 0.051) in CD8 T cells from arm A subjects. No significant differences were found in the immunological assay between cirrhotic and non cirrhotic individuals.ConclusionsMVC intensification was safe and was associated with a significant a trend towards increasing CD4 + T‐cell counts both in cirrhotic as well as non‐cirrhotic patients with discordant response. The addition of MVC was associated with a decrease in markers of immune activation in both groups.

Comprehensive information on combined antiretroviral therapy (cART) regimens in rural Sub‐Saharan Africa over time is scarce, particularly on the use of stavudine (d4T) and second‐line regimens. Since 2010, World Health Organization (WHO) guidelines discourage using stavudine in first‐line regimens due to frequent and severe side‐effects. This study examined the practical adaption of this phasing‐out and described trends in use of various cART combinations in a rural Tanzanian setting. We analyzed longitudinal, prospectively collected data of HIV‐1‐infected adults initiating cART within the Kilombero Ulanga Antiretroviral Cohort (KIULARCO) in Ifakara, Tanzania from 2007–2011. This analysis included data of 3068 patients over a 5‐year period. Of these subjects, 1997 (66.9%) were female, median age was 37 (interquartile range [IQR] 31–44) years and median CD4 cell count at enrollment was 178 cells/µl (IQR 88‐291). The percentage of prescriptions containing stavudine in initial regimens (Table 1) fell from a peak of 75% in 2008 to 12.2% in 2011 (p for trend<0.001). TDF/FTC/EFV became available in 2009 and was used in 117 (41.6%) patients initiating cART in 2011. An overall on‐treatment analysis (Figure 1) revealed that d4T/3TC/NVP and AZT/3TC/EFV were the most prescribed combinations in each year, including 2011 (684 [32.5%] and 642 [30.5%] patients respectively). Of those on d4T/3TC/NVP in 2011, 632 (92.4%) were initiated in earlier years. The ratio of second‐line to total regimens remained stable over time (p for trend=0.19) with a maximum of 34 (1.2%) patients in 2011, whereof 32 (94.1%) received a combination of ABC/ddI/LPVr.Overall on‐treatment count of patients on cART combinations by year.image

Initial cART combinations prescribed by year.











2007
2008
2009
2010
2011




d4T/3TC/NVP
426 (66.6%) 536
536 (71.2%)
362 (46.8%)
93 (19.4%)
52 (12.2%)


d4T/3TC/EFV
25 (3.9%)
29 (3.8%)
25 (3.2%)
6 (1.2%)
0 (0%)


AZT/3TC/EFV
177 (27.7%)
174 (23.1%)
324 (41.9%)
160 (33.4%)
138 (32.4%)


AZT/3TC/NVP
7 (1.1%)
10 (1.3%)
5 (0.6%)
21 (4.4%)
54 (12.7%)


TDF/FTC/EFV
2 (0.3%)
2 (0.2%)
57 (7.3%)
199 (41.5%)
177 (41.6%)


Total
639
752
773
479
425




 Initial cART with stavudine declined to low levels according to recommendations but the overall use of stavudine remains substantial. The usage of second‐line treatment is unusually low in view of expected therapeutic failure rates, indicating potential difficulties in management of suspected treatment failure cases. Monitoring of prescription trends is a simple and feasible approach to identify deficits in the implementation of treatment guidelines for optimal outcomes.

Hepatitis C (HCV) and HIV are commonly acquired through intravenous drug use (IDU). Treatment of HCV is beneficial in reducing hepatic complications and likely decelerating the rate of progression of HIV. HCV therapy in HCV/HIV co‐infected individuals is increasingly being reported to be feasible. However, re‐infection is emerging as an important concern, especially in the prison population where likely related to surreptitious IDU. In this study, we report the re‐infection rate of inmates in the Pacific region of Canada who have HCV/HIV and were successfully treated for HCV. Retrospective medical chart reviews of 57 co‐infected inmates with a history of IDU who received HCV therapy between April 2003 and June 2012. All received standard doses of pegylated interferon alpha 2a or 2b and weight‐base ribavirin for durations of 24–48 weeks depending on genotypes. After successfully attaining SVR, inmates are routinely monitored for re‐infection every 6–12 months with HCV RNA qualitative analysis. Of the 57 inmates with HCV/HIV, 48 (82.8%) were Caucasians and 10 (17.2%) were First Nations. 94.7% (54) of the study population were males. The mean age at the start of treatment was 39.6±7.5 years. 100% (inclusion criteria) admitted to IDU before treatment and 7 (12.1%) admitted IDU after treatment. Genotype 1 made up 56.1% (32), followed by genotype 3 at 35.1% (20) and genotype 2 at 8.8% (5). Treatment was discontinued due to adverse side effects in 4 (6.9%) and discontinued due to no response in 9 (15.5%) inmates. 2 (3.7%) were lost to follow up due to discharge to community. SVR was attained in 33 (56.9%) inmates and of those 30.3% (10) were re‐infected. These re‐infected cases were noted mainly in genotype 3 (60%) and genotype 1 (40%). Six had viral relapsed. SVR results are pending for three. Achieving a SVR is encouraging in HCV/HIV co‐infected. Our study revealed that 30.3 % of the inmate population became re‐infected after treatment. Of note, these numbers are relatively small. However, it is important that counseling regarding harm reduction and strategies should be provided before, during and after treatment to help reduce the rate of re‐infection.

Purpose of the studyTo know the main epidemiological, virological and therapeutic characteristics of HCV infection and the degree of hepatic fibrosis in a cohort of HIV‐HCV co‐infected patients in a health area of southeastern of Spain.MethodsProspective cohort of co‐infected HIV‐HCV patients followed in the University Hospital of Saint Lucia (Spain), which describes the main epidemiological characteristics, degree of liver fibrosis assessed by transient elastography and the level of response to treatment for HCV during the period November 30, 2011–February 28, 2012.Summary of resultsThe cohort included 109 patients, of whom 27 were females (25%) and 82 males (75%), with a mean age of 45.8 (SD: 6.2) years and a mean time of infection of 18.8 (SD: 5.7) years. The main route of transmission was in this order: IDUs in 90 patients (83%), 13 (12%) by heterosexual intercourse and 3 (2.8%) in MSM. There were no statistically significant differences between the years of evolution of HCV based on the route of transmission (p=0.36). In the genotypic analysis, 55 patients were genotype 1a (51%), 13 genotype 1b (13%), 19 genotype 3 (17%) and 9 genotype 4 (8.3%). The median HCV viral load was 868,000 IU/ml (6.15 log10). In this cohort 31 patients (28%) received antiviral therapy for HCV: 2 (1.8%) Interferon (INF) non‐pegylated, 3 (2.8%) INF non‐pegylated with Ribavirin (RBV) and 25 (23%) INF pegylated with RBV. In 6 cases (19%) were achieved sustained viral response (SVR). In the 25 cases without SVR (81%), 9 (36%) were partial responders, 7 (28%) null responders, 6 (24%) relapsers and 3 (12%) discontinued treatment due to problems of tolerability. In 108 patients were determined the degree of liver fibrosis by transient elastography: 48 patients (44%) had significant fibrosis (F3–F4;>9.5 kpascal) and 30 (28%) liver cirrhosis (F4;>14.5 kpascal). In patients with F4, 5 (17%) had values between 14.5–20 kpascal, 14 (47%) values between 21–40 kpascal and 11 (37%) values over 40 kpascal.ConclusionsIn our cohort, the gender predominant was male and the abuse of intravenous drugs was the main cause of HCV transmission. Most patients had genotype 1a, high viral load (>800,000 UI/mL) and a poor rate of SVR (19.3%), predominating the partial response rate among non‐responders. A high proportion of patients (28%) had liver cirrhosis (F4), of which, a significant proportion of subjects (37%) were at high risk of hepatic decompensation (>40 kpascal).

Scale‐up of HIV services in countries such as Uganda has resulted in a rapid increase in facilities offering antiretrovirals (ARVs) and an increase in healthcare workers trained to deliver care. Consequently, evaluating medication safety is increasingly important in these settings. Data from developed countries suggest that drug‐drug interactions (DDIs) involving ARVs are common, occurring at rates of 14–58%. Few data are available from low resource settings, however a study of 996 Kenyan patients found that 33.5% were at risk of clinically significant DDIs. We evaluated the prevalence and type of ARV DDIs and the patients most at risk in an African outpatient setting. A random sample of patients taking current ARVs and accessing care at the Infectious Diseases Institute, Makerere University, Kampala was selected from the clinic database. The most recent prescription for each patient was screened for DDIs using www.hiv‐druginteractions.org. Clinical significance of DDIs was assessed by two of us using a previously developed technique evaluating: likelihood of interaction, therapeutic index of affected drug and severity of potential adverse effect. From 1000 consecutive patients 99.6% were taking≥1 co‐medication alongside their ARV regimen (mean 1.89). 24.5% had≥1 potential DDI, with a total of 335 DDIs observed. Of these, 255 DDIs were considered clinically significant, affecting 18.8% of patients. Only 0.3% of DDIs involved a contraindicated combination. There was a higher rate of potential DDIs observed in patients taking TB treatment (p=0.0047), who were WHO stage 3 or 4 (p=0.001), or patients taking ≥2 co‐medications alongside ARVs (p<0.0001) (Fishers exact test). Patient age, gender, CD4 count and weight did not affect risk for DDIs. Co‐medications commonly associated with potential DDIs were antibiotics (6.2% of 1000 patients), anthelminthics (4.6%) and antifungals (3.5%). Potential DDIs involving ARVs occur at similar rates in resource‐limited settings and developed countries. Drug combinations which most frequently cause DDIs, however, differ between settings; for example CNS and cardiovascular drugs in the UK and anti‐infectives in Kenya and Uganda. Development of tools which are relevant to particular settings are essential for recognition of DDIs. Initiatives such as incorporation of WHO essential medicines into the Liverpool DDI database and the AIDS Treatment Information Centre in Uganda are important in achieving this.

Moderate intensity aerobic activity reduces the risk of cardiovascular disease, diabetes and metabolic syndrome in the general population and has a potential in preventing bone loss. We evaluated the effects of brisk walking, with or without strength exercise, on bone mineral density in HIV‐infected treated persons. Twenty‐eight HIV‐infected, cART‐treated, sedentary subjects with VL<50 c/mL were enrolled in a 12‐week exercise program, consisting of 3 outdoor sessions/week of 60 min walking at 67–70% of HR (heart rate) max±30 min circuit training at 65% of 1‐RM (repetition maximum). Subjects were examined at baseline (BL) and 12 weeks (W12) by 6‐minute walking test (6MWT) and by counting the number of repetitions for each strength exercise; and by dual energy X‐ray absorptiometry (DEXA) to evaluate lumbar spine and femoral bone mineral density with t‐ and z‐scores ‐ in addition to morphometric (BMI, waist, hip and leg circumference) and blood examination (cytometry, fasting total, HDL and LDL cholesterol, triglycerides, glucose, insulin; AST/ALT, ALP, gGT, creatinine, CPK, HbA1c; CD4+ and CD8+, plasma HIV‐RNA). Differences over time were tested by Wilcoxon‐signed rank test and between groups by Mann‐Whitney test. Twenty‐seven (96%) participants (19M, 8F; median 48 y‐o, IQR 43–54; median CD4+624/µL, IQR 478–708; ART with PI: 13 patients, with NNRTI: 7 patients, and including TDF: 15 patients) completed the 12‐week program with a median adherence of 61% (IQR 50–70): 18 in the 'walk only' only group and 9 in the 'walk and strength' group. At W12, participants showed significant improvement of distance by 6MWT (Table), and of performance in all strength exercises (crunch p=0.023, lat machine p=0.016, chest press p=0.016, leg extension p=0.016, sitting calf p=0.008, leg press p=0.016). DEXA spine z‐score improved significantly in the whole group, and femoral z‐scores in the 'walk only' group. There was no z‐score difference at BL between patients with/out PIs, NNRTIs or TDF. However, spine z‐score improved significantly in patients receiving TDF. At W12 BMI, waist circumference, and LDL also improved significantly in the whole group, whereas no significant changes were observed for the other variables, The above 12‐week program improved fitness and bone density in HIV‐infected treated subjects, in addition to some morphometric variables and serum LDL. Brisk walking, with or without strength exercise, might help control the long‐term consequences of cART.










BL‐median (IQR)
W12‐median (IQR)
p




Distance at 6MWT (m)
658 (605–691)
715 (IQR 690–830)
<0.0001


DEXA spine (z‐score)
−1.15 (−1.7/−0.7)
−1.05 (−1.4/−0.3)
0.002


DEXA spine (z‐score)(TDF‐treated pts)
−1.4 (−1.7/−0.7)
−1.3 (−1.55/−0.5)
0.002


DEXA femoral neck (z‐score)(walk only)
−0.8 (−1.4/−0.2)
−0.5 (−1.2/−0.2)
0.047


DEXA femoral ward (z‐score)(walk only)
−1 (−1.9/−0.6)
−0.75 (−1.4/−0.2)
0.004


BMI
25.7 (24.6–26.3)
24.9 (21.4−26)
0.0016


Waist circumference (cm)
93 (87−100)
92 (85.5−98.5)
0.029


LDL cholesterol (mg/dL)
126 (113−154.5)
116 (96–137.5)
0.0003