To examine the association between nutritional markers at initiation and during follow up in two different cohorts of HIV-infected adults initiating highly active antiretroviral therapy (HAART) in West Africa.The ATARAO study was a one year prospective study carried in Mali. It consisted of a sample of consecutive patients initiating HAART in one of four participating centers during that period. Data were collected at time of treatment initiation (baseline) and every 3 months thereafter. The ANRS 1290 study followed Senegalese patients recruited in similar conditions. Bivariate analyses were used to identify nutritional and immunological covariates of malnutrition at baseline. Longitudinal trajectories of body mass index, hemoglobin and albumin, and their associated factors, were evaluated using mixed linear models.2, nearly 60% were anemic and 47.4% hypoalbuminemic at time of treatment initiation. At baseline, low hemoglobin, hypoalbuminemia and low CD4 levels were associated with a BMI < 18.5 kg/m2. Similarly, low BMI, low albumin and low CD4 counts were linked to anemia; while, hypoalbuminemia was associated with low hemoglobin levels and CD4 counts. In ANRS, out of the 372 participants retained for analyses, 31% had a low BMI and almost 70% were anemic. At baseline, low BMI was associated with low hemoglobin levels and CD4 counts, while anemia was associated with low CD4 counts and female sex. While treatment contributed to early gains in BMI, hemoglobin and albumin in the first 6 months of treatment, initial improvements plateaued or subsided thereafter. Despite HAART, malnutrition persisted in both cohorts after one year, especially in those who were anemic, hypoalbuminemic or had a low BMI at baseline.In ATARAO, 250 participants were retained for analyses; of which, 36% had a BMI < 18.5 kg/mIn ATARAO and ANRS, malnutrition was common across all indicators  and persisted despite treatment. Low BMI, anemia and hypoalbuminemia were associated with attrition, and with a deficient nutritional and immunological status at baseline, as well as during treatment. In spite of therapy, malnutrition is associated with negative clinical and treatment outcomes which suggests that HAART may not be sufficient to address co-existing nutritional deficiencies. In sub-Saharan Africa (SSA), malnutrition is endemic and affects 12-26% of the populations of Mali and Senegal ,4. In SSLow BMI reflects low energy stores and chronic energy deficiency ,11. BetwIn PLA, anemia is highly frequent, affecting up to 95% of those in advance stages of the disease ,18. Its In LMIC, up to 55% of PLA suffer from hypoalbuminemia -25. AlbuDespite a high prevalence of malnutrition in treated PLA in LMIC, few studies have described post HAART nutritional trajectories in these patients. In two different West African contexts, we examined malnutrition amongst individuals in their first year of treatment by investigating the association between nutritional markers at treatment initiation by and examining nutritional trajectories post HAART.ATARAO  was a one-year cohort that aimed at identifying the determinants of therapeutic success in treatment naïve PLA at two hospitals and two community centers in Bamako and Sikasso, Mali. Attending physicians at participating sites consecutively invited all patients who qualified for ART initiation during the recruitment period to join the cohort. Details concerning inclusion criteria are contained in Table  and Canadian  ethics committees. has been described elsewhere [Detailed methodology of the ANRS 1290/1215 lsewhere . BrieflyDemographic data were collected at baseline. Every 3 months, BMI was measured by the same staff member (ATARAO) or by the treating physician (ANRS). Blood samples were collected at each trimester for albumin assessment (ATARAO only). Hemoglobin and CD4 values were measured every 6 months in both studies.Participants were considered LFTU if they missed ≥ 2 consecutive visits (ATARAO) or if they could not be contacted for ≥ 6 months (ANRS). Efforts taken to locate patients, determine their vital status and causes of death of ANRS LTFU patients are described elsewhere . SimilarBMI : Body weight was measured in grams and height was measured to the nearest 0.5 cm using a stadiometer. BMI cutoffs of 18.5 kg/m2 and 16 kg/m2 were used to identify mild and severely malnourished patients, respectively [ectively .Albumin: Albumin was only available in ATARAO. Albumin was measured in Canada in frozen plasma samples collected in Mali. Albumin levels were estimated using QuantiChrom™ BCG Albumin Assay Kit (BioAssay Systems). Albumin values under 3.5 g/dl and <2.5 g/dl indicate moderate and severe hypoalbuminemia, respectively [ectively .Hemoglobin : Hemoglobin was measured locally by automated hematology analyzer. Because > 95% of patients were at least mildly anemic, we chose to use a more severe definition of anemia. Consequently, a cutoff value of ≤ 11 g/dl was used. According to World Health Organization (WHO), this cutoff identifies individuals with moderate and severe anemia [e anemia .CD4 : CD4 cell counts were measured by FACS count (Flow Cytometry Assay) (Becton Dickinson) locally. Only CD4 values measured within a month of the interview’s date were kept for analyses.Bayesian Information Criterion (BIC). For graphic purposes, identical mixed linear models were generated using non-centered variables. Analyses were performed using SPSS 18.Tests for linear trends in proportions were carried out to identify covariables of malnutrition at time of treatment initiation. Mixed linear models were used to examine longitudinal changes in BMI, hemoglobin and albumin. In these equations, the intercept represented the baseline value of the dependent variable and the time coefficient indicated its rate of change in time. A significant quadratic time term indicated the presence of a nonlinear accelerating pattern. The intercepts, linear and quadratic time terms were examined, and treated as random if significant. All models were adjusted for age, sex, time since entry in the cohort, as well as variables found to be associated with the nutritional status at baseline (p < 0.20). Continuous variables were centered to the mean. Interactions between baseline predictors and time were examined. Model selection was done using the Patients with less than two data entry (including baseline) were excluded from multivariate analyses. Consequently, between 20-34% were excluded from multilevel analyses because of incomplete BMI, hemoglobin or albumin data in ATARAO. In ANRS, 13% of the original cohort were excluded from multilevel analyses because of incomplete BMI or hemoglobin data.(data not shown).Respectively, 273 and 404 patients from ATARAO and ANRS were initially recruited. Of which, 250 and 372 were retained in analyses Table . During 2 (IQR: 17.7-22.4) in ATARAO, and 20.0 kg/m2 (18.0-22.3) in the ANRS. In both cohorts, a vast proportion of patients suffered from anemia (median Hb = 10.5(ATARAO), 10.6(ANRS); IQR = 9.4-11.8(ATARAO), 9.5-11.9(ANRS)). In ATARAO, median albumin level at baseline was 3.67 (IQR = 2.67-5.10). Finally, median CD4 counts were 163 (IQR = 54–275) in ATARAO and 120 (IQR = 46–214) cells/mm3 in ANRS. At treatment initiation, mean BMI, hemoglobin and CD4 counts did not differ significantly across studies.In both cohorts, baseline malnutrition was frequent, irrespective of the indicator analyzed Table . Median At baseline, the proportion of individuals with a low BMI augmented with worsening of anemia or hypoalbuminemia statuses Table . A simil(data not shown).Pooled data from both cohorts were used to examine associations between nutritional markers  according to CD4 counts . In spite of stratification, associations between BMI and hemoglobin maintained their significance Table 2. While this proportion decreased to 6.9% at 12 months in Mali, as many Senegalese (17.8%) were malnourished according to their BMI status at the end of the first year of treatment. Most of these (>70%) had a BMI <18.5 kg/m2 at HAART initiation in both populations (data not shown).In model 1, random and fixed linear and quadratic time terms were significant in both cohorts (p < 0.001) indicating a positive change in BMI in the first months followed by a later decline. Women initiated treatment with higher BMI, but gained in a similar fashion to men over time . Sex was excluded as it failed to improve the fit of the model.In ATARAO, albumin increased similarly for both men and women during the first 9 months of treatment, but declined in the course of the last trimester . These hemoglobin gains were less impressive in terms of absolute increase and sustainability compared to previous reports [Similarly, in both ATARAO and ANRS, about a third of patients continued to be anemic at 6 and 12 months despite initial improvements; most of whom were already identified as such at baseline  reports . Interac reports .Finally, after 6 months of treatment, less than 6% of participants were hypoalbuminemic compared to 48% at baseline. These early improvements in albumin levels could indicate lessening of the HIV associated inflammatory processes in response to HAART’s action on viral replication . HoweverOur results indicate that malnutrition either subsists or appears despite HAART. Weight or BMI loss, but also the absence of weight gain in the months following treatment initiation, are risk factors of mortality , especiaAssociations between nutritional markers persisted even after stratification by baseline CD4 counts, contrary to previous reports from LMIC. These earlier studies observed a positive significant covariation between BMI and hemoglobin/albumin at low, but not at high CD4 counts, suggesting that they were markers of more advanced disease and inflammation, rather than a nutritional marker .Finally, immunodeficiency appeared to be strongly linked to malnutrition at time of treatment initiation, but the predictive value of baseline CD4 was somewhat weaker in multilevel modeling. Many conflicting reports have emerged concerning the interrelation between immunity and malnutrition in HAART treated patients. Some have found positive links ,30,44; oThe main limitations of our study were 1) attrition, and 2) missing data, especially biochemical and hematological. Both cohorts suffered from high mortality and LTFU rates. Nonetheless, these rates approximated that observed elsewhere in LMIC ,47. In tAs observed in ATARAO and ANRS, low BMI, anemia or hypoalbuminemia, at time of initiation or in the first year of therapy, have an impact on the health of patients as they put them at risk of persistent malnutrition, LTFU and mortality. Independently of treatment and level of immunosuppression, malnutrition persisted among patients receiving HAART. Antiretrovirals alone may not be sufficient to overcome malnutrition and death in treated PLA. Pharmaceutical interventions should be complemented, if not preceded, with programs to fight undernutrition and food insecurity.


Treatment of HIV infection in adolescents is challenging due to long duration of therapy and poor adherence. Recently, the integrase strand transfer inhibitor dolutegravir (DTG) has been approved for the use in adolescents with HIV, but evidence in clinical practice is very limited.We describe six cases of HIV-infected children/adolescents successfully treated with DTG-based regimen. Data relative to children/adolescents managed at the Referral Center for Pediatric HIV/AIDS of the University of Naples were reviewed. Patients were tested before introduction of DTG, after 1 month and every 3 months in the first 2 years to assess virologic and immunological response, tolerance and development of side effects. Families were asked to report any suspected adverse events.+ cell count was observed. Four patients showed a persistent suppression after 2 years of follow-up, and 2 patients at about 1 year. One month after the introduction of DTG, the patient enrolled because of severe dyslipidaemia and hyper-transaminasemia showed a complete normalization of laboratory values. During follow-up  no adverse events were reported and most patients demonstrated a good adherence to treatment.Six patients  were started on DTG-based anti-retroviral regimen due to low adherence to anti-retroviral treatment (ART), multiple drug resistance mutations, or development of ART-related side effects. Within 4–8 weeks after DTG treatment onset, a complete viral suppression and a concomitant increase of CD4DTG-based treatments demonstrated efficacy and good safety profile in adolescents. All patients demonstrated a rapid virologic and immunological response within 4–8 weeks, with good adherence and absence of side effects. The treatment of adolescents with vertically-acquired HIV infection is particularly challenging  due to sSeveral studies have identified both pill burden and lifestyle issues  as major barriers to effective adherence. Choosing the simplest regimen possible, reducing dose frequency and pill number and selecting a regimen that fits well to daily patients and family activities, are important strategies to achieve.Recently, the integrase strand transfer inhibitors (INSTIs) have been approved as preferred regimens for treating children and adolescents with HIV infection , 5. DoluRecently DTG, in combination with other anti-retroviral drugs, was effective in dramatically reducing viral replication without side effects in two patients, an adult  and a chWe performed a retrospective review of adolescents with HIV infection treated with DTG at the Regional Referral Center for Pediatric HIV of the University of Naples Federico II in collaboration with consultants from the Unit of Viral Diseases. Clinical and laboratory data were retrieved through manual chart reviewing. All patients aged ≤ 18 years old were tested before ART switch (T0), at 1 month (T1), and successively every 3 months after introduction of new ART regimen to assess virologic and immunological response and the potential development of side-effects.Viral load was evaluated by using a real time-PCR . Caregivers of children were required to report any suspect adverse event to the Reference Center after ART switch. Other potential side effects were specifically looked for during follow-up visits.DTG was prescribed according to recent guidelines for the management of HIV infection in children and adolescent , 5.No ethical committee opinion was requested because the use of this drug in adolescents is suggested by international guidelines. All procedures performed in this study were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. An informed consent for sharing anonymous patient data was obtained from families and/or caregivers. All drugs were provided by the University Hospital Pharmacy and paid by the National Health Care System according to Italian legislation. No direct contact with drug companies was taken.Since January 2015 a DTG-based ART was prescribed to 6 paediatric patients  due to previous treatment failure, development of side effects, presence of multiple viral resistance or low adherence to ART (Tables All but one patients were classified as stage 3 according to the 2014 Center for Disease Control and Prevention (CDC) Classification for paediatric HIV/AIDS  and noneThe clinical management of patient 1 and patient 2, both female in stage 3, was complicated by missed medical visits, a sustained low compliance to ART and the development of multiple genetic resistance mutations. They received various anti-retroviral drugs combined in different regimens: zidovudine (ZDV), stavudine (D4T), lamivudine (3TC), efavirenz (EFV), nelfinavir (NFV), lopinavir/ritonavir (LPV/r), tenofovir (TDF), emtricitabine (FTC).The last ART regimen was LPV/r and TDF/FTC, which was poorly tolerated due to persistent gastrointestinal side effects in both patients. Particularly, although other alternative regimens including PI were considered, patient 1 experienced severe and frequent side effects related to PI, with recurrent abdominal and epigastric pain, nausea, episodes of vomiting and anorexia. Because of the persistence of virologic failure associated with a decrease of CD4+ cells, on January 2015, a once-daily regimen with DTG and TDF/FTC was started with the aim of increasing compliance and immunological and virologic response.Patient 3 was a 12-year-old male admitted to our Department for acute pancreatitis whose mother died 8 years before due to AIDS-related meningitis, and he never underwent testing because of parental refusal. At the time of HIV diagnosis, he presented with 190 CD4+ cells/μl (8%) with a viral load of 19.800 copies/ml. Since the patient was naïve to anti-retroviral therapy, we started anti-retroviral treatment with LPV/r and ABC plus 3TC, according to Pediatric Guidelines for HIV infection . After 4Patient 4 was a 16-year-old Italian male who was on LPV/r + TDF/FTC in the last 4 years of follow-up, and subsequently developed chronic (not infectious) diarrhoea as side effect of ART. This was responsible for a progressive decrease in treatment adherence and he was switched to DTG-based regimen.Patient 5 was an 18-year-old female treated with FPV + TDF/FTC + ATV + RTV due to a complex mutation profile. A DTG-based regimen was introduced in order to simplify the ART.Patient 6 was a 17-year-old female from Ukraine treated with EFV + FTC + TDF. In order to improve compliance, a DTG-based regimen was started.Patients 1, 3 and 4 experienced full viral suppression  within the first 4 weeks. Patient 2 demonstrated a significative reduction (2 logs) after 4 weeks and a complete viral suppression after 8 weeks of treatment. Patients 5 and 6, who already had undetectable viral load under previous ART regimen, maintained a suppressed HIV load after treatment switch , discontinued ART and required unscheduled clinical visits that showed viral load peaks of 1779 copies/ml (patient 1) and 4100 copies/ml (patient 2). After discussions with both patients regarding the importance of adherence and the risks of acquiring further drug resistance mutations, we observed virologic suppression at subsequent visits, resulting from improved adherence to ART and rapid response to DTG-based ART.A progressive increase in CD4+ cells was observed in all but one patients Fig.  b.Patient 3, who showed a major reduction in viral load during LPV/r-based regimen, demonstrated full viral suppression  and an increase in CD4+ cells after three weeks of DTG-based treatment Fig.  a/b.Patient 5, who was started on DTG-based regimen with a high percentage of CD4+, had a slight reduction of CD4+ at first control (from 44% to 36% with no significant reduction in absolute CD4+ lymphocyte count) and then remained substantially stable.The 6 patients were followed during the last two years with a median follow-up of 24 months (range 9–24 months). All patients are still in follow-up at our institution and DTG-based treatment is still ongoing. Neither side effects or treatment failure were observed during follow-up visits. Two patients reported a transient reduction in ART adherence.Patient 3, who received DTG-based regimen due to the presence of serious side effects, had a complete normalization of total (142 mg/dl) and LDL (80 mg/dl) cholesterol, triglycerides (74 mg/dl) concentrations and liver markers  within one month after ART switch.Despite excellent efficacy, safety and tolerability in adults, the effects of DTG in children and adolescents are poorly documented. DTG is approved for patients ≥ 12 years of age (recently anticipated at 6 years) and the IMPAACT study showed that 70% of adolescents (12 to < 18 years old) treated with DTG achieve a complete viral suppression .In our experience, two patients who in the last five years never achieved a viral suppression with several ART regimens, showed a rapid and good response to DTG-based regimen. Both experienced a viral suppression and increase of CD4+ cells, although their adherence to ART was not optimal as demonstrated by a temporary viremia relapse. As reported in adult patients , due to Patient 3, the only one receiving DTG-based regimen for serious ART-related side effects, reached a complete normalization of dyslipidaemia and hyper-transaminasemia, in association with a complete viral suppression, as previously reported in a large adult population . The draOne limitation of this study is that drug resistance profiles were available for 4 of 6 patients. In adult patients, DTG monotherapy is associated with an increased risk of virological failure and DTG resistance . FurtherIn conclusion, this small size series indicates that children and adolescents may benefit from DTG- based regimen achieving a complete control of HIV infection with no side effects. The major advantages of DTG-based regimen are the possibility to reduce the pill burden to two pills once a day, the increasing treatment adherence and the low or absent risk of additional drug resistance mutations. Good safety profile was observed up to a maximum of 24 months in our patients.


The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT).This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts.Baseline quality of life, measured with the MOS-HIV score, was very good  and suffered no change during the study in any of the arms , without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects  improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT.In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens. With the introduction of highly active antiretroviral therapy (HAART), HIV-1 infection has evolved from a fatal disease to a manageable chronic condition. Central goals of current HIV research are to avoid side effects associated with long-term therapy, promote patient comfort and compliance, and reduce economic costs. The standard treatment with three antiretroviral agents, usually two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a boosted protease inhibitor (PI), an integrase inhibitor (II), or a non-nucleoside reverse transcriptase inhibitor (NNRTI) , 3. FurtDuring the last decade, the use of simplification regimens , initiatHowever, poor treatment satisfaction is a significant risk factor for loss of viral control in patients undergoing antiretroviral therapy, including MT , 26. To The primary objective was to compare quality of life in patients who started MT with LPV/r versus patients continuing on TT containing a PI.Secondary objectives were to compare MT vs TT with regard to treatment satisfaction, adherence, tolerability, regimen safety and virological and immunologic efficacy.This was a phase IV national, open-label, multicentre, controlled, randomized (2:1), 24-week follow-up trial in HIV infected patients. The study was conducted at 31 different Spanish hospitals and was sponsored by the Sociedad Andaluza de Enfermedades Infecciosas (SAEI). The trial protocol was approved in advance by Ethics Committees from each participating hospital, and by a Reference Ethics Committee, representing all of them, the CCEIBA  in November 2009. It met the ethical principles specified in the Declaration of Helsinki and international good clinical practice guidelines, and was registered in December 2009 under EudraCT number 2009-014430-25. The authors confirm that all ongoing and related trials for this drug/intervention are registered. Written informed consent was obtained from each patient prior to any study procedures being performed. A pseudorandom number generator algorithm , 28 was Patients over 18 years of age, with a positive HIV-1 antibody and/or PCR test, receiving any TT containing a boosted PI, and with undetectable VL  during the six months prior to enrolment were eligible for this study. For women with childbearing potential, a negative urine pregnancy test in the initial screening was mandatory. Patients were ineligible if any of the following conditions were present: pregnancy or nursing, acute hepatitis, documented resistance to LPV/r or failure on a PI therapy, concomitant therapy with drugs contraindicated for use with LPV/r, known history of drug addiction or chronic alcohol consumption, current active opportunistic infection or documented infection within 4 weeks of screening, renal disease with creatinine clearance <60 mL/min, concomitant use of nephrotoxic or immunosupressor drugs including corticosteroids, interleukin-2 or chemotherapy, prior medical history of psychiatric disorders such as depressive syndrome, schizophrenia or psychotic disease. Patients took Kaletra (lopinavir 200mg/ritonavir 50mg), 2 tablets bid. A protocol amendment modified the initial exclusion criterion (CD4 cell count nadir < 100 cells/μL) to allow any CD4 cell nadir, provided that the current CD4 count was > 250 cells/μL. In total, 46 patients had a nadir < 100 cells/μL.ad-hoc questionnaire developed to assess satisfaction in patients switching to a simplified regimen, addressing general health status, treatment, illness control, side effects, number of pills and doses, and dietary differences. This questionnaire has two dimensions, the first one related to the degree of treatment satisfaction and the second one to the assessment of factors determining patient satisfaction [Patients’ overall quality of life was assessed using the Medical Outcomes Study HIV Health Survey (MOS-HIV) and EQ-5D questionnaires . The MOSsfaction .Safety was determined by the incidence of treatment adverse events, differences between arms in vital signs and clinical laboratory data, especially regarding HIV-1 RNA levels and CD4 cell counts. Adverse events were graded according to Common Toxicity Criteria . SeriousThe virological efficacy was assessed in different ways. Strict virological failure was defined by two consecutive measurements of plasma HIV-1 RNA > 500 copies/mL separated by at least two weeks. During virological failure, HIV genotyping was performed to determine resistance mutations. In the MT arm, virological rebounds were not considered as therapeutic failure if there was no evidence of LPV/r genotypic resistance and viral suppression could be reinduced with the addition of two NRTIs, leading to a subsequent decrease in VL of at least tenfold in four weeks and to < 50 copies/mL of HIV-1 RNA after 16 weeks. However, an ITT analysis in which analogous reintroduction meant a failure was also performed. The ability of the two strategies to maintain VL lower than 50 and 200 copies/mL was also assessed, and major virological efficacy was defined as undetectable VL during the whole follow-up period and at week 24.Patients were assessed at baseline, week 12, and week 24. At each time point, the following were obtained: a clinical assessment, list of concomitant medications, adverse events, GEEMA, VAS and CESTA questionnaires, VL, CD4 cell count, liver enzymes, biochemistry and hematologic values. MOS-HIV and EQ-5D questionnaires were completed at the first and last assessments. An extra set of data was collected on week 4 for the experimental arm, that included VL and CD4 cell count, GEEMA, VAS, and CESTA questionnaires, and information on concomitant medications and adverse events.P = 0.05. Baseline characteristics of study groups were also compared using an analysis of variance (ANOVA). The main endpoint was ascertained from all the MOS-HIV scores and EQ-5D questionnaire outcomes. The odds ratio of virological rebound was calculated.Sample size calculations for the current study were based on the expected difference between the two treatment arms. It was estimated, according to the literature , that inFor all analyses, the primary population included all patients from the control arm and those from the experimental arm who received at least one dose of LPV/r . In some particular cases, such as MOS-HIV evaluation, an analysis of covariance (ANCOVA) was used for comparisons between both treatment arms, including baseline values, sex, and age as covariates.Between February 2010 and June 2011, 225 patients were identified as eligible for the study and were randomized: 146 patients switched to MT and 79 patients remained on TT. At the beginning of the study, 77.2% of patients in the TT arm were taking lopinavir/ritonavir, while the remaining patients were taking fosamprenavir, saquinavir, atazanavir, darunavir, and nelfinavir. Furthermore, 90% of them were using two NRTIs, the most common being TDF/FTC (53%), followed by ABC/3TC (19%). Overall, 129 patients in the MT arm and 68 patients in the TT arm were still in the study at week 24 . Of the Baseline characteristics of the patients included in the study were not significantly different between the two groups, TT and MT, in the majority of measured parameters . Mean agAt baseline, the mean MOS-HIV overall scores were 83.0 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm . An analConcerning the EQ-5D questionnaire, the baseline scores were 81.8 ± 18.2 in the MT arm and 82.6 ± 15.7 in the TT arm . The ANCAdherence rates  were similar in both boosted PI-based regimens with no significant change over time . At the beginning and end of the study, 74.1% and 70.1% of patients in the MT arm and 70% and 69.4% of patients in the TT arm were fully adherent to treatment, respectively. When all the items included in the GEEMA questionnaire were analysed separately, there were statistical differences only in the number of doses missed within the last week, which were more numerous in the TT arm  . In the Comparing both treatment arms, there was a significant difference in the mean score measuring the change in dimension 1 , and specifically, a significantly greater satisfaction with the number of pills taken daily (P <0.001) among the patients in the monotherapy arm versus the TT arm .There was no significant difference in the incidence of adverse events between treatment arms. Total and serious adverse events were reported in 17.8% and 4.1% of patients from MT versus 14.3% and 1.3% from TT (P = 0.573 and P = 0.426). The non-serious adverse events were mild in 81.1% and 58.8% in MT and TT arms respectively and considered unrelated to treatment in 83.8% and 82.4% of cases .There were no significant differences for haematological parameters, vital signs and anthropometric measures over time either in each arm or between arms.As to maintaining virological suppression, there were no significant differences between MT and TT arms. In the ITT analysis , the percentages of patients with undetected VL (< 50 copies/mL) at any time during the study period were similar in both treatment arms . Likewise, there was a similar percentage of subjects who, at the end of the study, had VL < 50 copies/mL . No significant differences were found in the virological failure rate considering VL > 500 copies/mL , VL > 200 copies/mL , or VL > 50 copies/mL , nor for the percentage of patients with VL < 200 copies/mL at any time during the study . Furthermore, there were no statistical differences in adherence and virological failure between arms .Furthermore, the number of detectable VLs over time did not show significant differences . The risk of virological rebound was similar for both arms: the OR of MT versus TT was 1.429 (CI 95% 0.772–2.646) for VL > 50 copies/mL; and 1.762 (CI 95% 0.584–5.315) for VL > 200 copies/mL.Genotype testing showed no LPV/r resistance in MT patients with virological failure. All of them regained virological suppression after restarting prior antiretroviral treatment.Regarding the development of the immune response, although there was no statistical difference in total cell counts of CD4 cells/μl, the CD4 percentage of total lymphocytes showed a significant difference between arms .LPV/r monotherapy is one of the best known options of tailored therapeutic approaches for patients with persistently suppressed HIV viremia in which fewer than the recommended standard of three antiretrovirals are used . The priIt is well known that adherence is a determinant factor of antiretroviral treatment efficacy and, as such, it is an important variable that must be determined. High rates of adherence were observed in all patients. The GEEMA and VAS questionnaires did not show any statistical difference between the two arms.The degree of patient satisfaction with the monotherapy regimen, measured by the dimension 1 of the CESTA questionnaire, was significantly greater than in the TT arm. This dimension registers satisfaction with general health status and treatment, disease control, absence of side effects, number of pills, dosage schedule, and dietary restrictions. This result could reflect the advantages of treatment simplification. Particularly, there was greater acceptance of the number of pills taken by the patients in the experimental arm.In this study, there were no significant differences in adverse events and viral rebounds between treatment arms. In contrast with other studies, a low lymphocyte nadir (less than 200 or less than 100 cells/μl) was not shown to be a risk predictor for VL detection or for virological failure.However, although the difference was not significant, TT has been shown to be more efficient than monotherapy in maintaining HIV-1 suppression, with fewer blips and viral rebounds . As in oWith regard to development of the immune response, the fact that the fraction of CD4/total lymphocytes increased to a greater extent in the TT arm has uncertain significance, and no conclusions can be drawn. Although an increase in the percentage of CD4 cells may be associated in some cases with a decrease in the percentage of CD8 cells, and thus with a decrease in immunological activation, no other activation parameters were measured to further evaluate this feature.Almost 85% of ITT population in the MT arm had a VL of < 50 copies/mL at the end of the study. This outcome could be an indication that the monotherapy simplification strategy with LPV/r in stable, controlled HIV-1 patients is safe and efficient. While this conclusion is not novel, it reinforces results from previous studies  and suppPreviously, the MONARK trial had analysed quality of life as a secondary endpoint in antiretroviral-naive patients in MT , with tha priori. Longer follow-up periods and a greater number of patients may be needed to demonstrate any change. There has also been a delay in the publication of this article due to the desire to elaborate on virological data outcomes. This prolonged the data collection period to perform a post-hoc analysis and rewrite the article for publication. This delay has led to a loss of interest in the study drug since the study was carried out. However, this study is important as it offers new data on the efficacy and safety of MT that could be extrapolated to darunavir.The slight differences in patients’ treatment adherence, quality of life, and satisfaction shown by our study suggest that switching from standard TT to MT may be beneficial. However, a more obvious gain in quality of life was expected in the monotherapy arm, considering the simplification of the treatment, despite the twice-a-day administration. These results may also be due to limitations, such as a reduced statistical power due to sample size, the subjective nature of the assessment tools, short follow-up and cohort characteristics. Indeed, the study was carried out on patients who were already tolerating a stable antiretroviral regimen, with a high quality of life at baseline (VAS score over 80%), so the probability of showing differences was low In summary, we showed that both regimens exhibited high overall health scores, satisfaction and treatment adherence, and did not lead to significant differences from baseline in VL or CD4 cell counts. Our results are in general agreement with previous studies and support the effectiveness of LPV/r as a suitable LDR for some patients, in light of the evidence for maintained HIV-1 suppression and potential to avoid the side effects associated with nucleoside analogue-containing regimens. This strategy also preserves future treatment options in case of failure, and reduces the economic costs of antiretroviral therapy, while maintaining a very good quality of life.S1 Fig(DOC)Click here for additional data file.S1 TableSome of the questions from the last visit, for the ITT population.(DOC)Click here for additional data file.S2 TableQuestions from dimension 1 at last visit. Intent-to-treat analysis.(DOC)Click here for additional data file.S1 File(DOC)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.S4 File(XLSX)Click here for additional data file.S5 File(XLSX)Click here for additional data file.


Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression.Methods: Cross-sectional data on 5152  patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients’ characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used.Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL , viral load < 5 log copies/mL at care entry , baseline lymphocyte CD4 count ≥200 cells/µL  and negative HCV serology . For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL  and negative HCV status .Conclusions: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions. Antiretroviral treatment leading to virologic suppression is considered not only the most effective treatment option to preserve immune system function but also to decrease the risk of HIV- and non-HIV-associated co-morbidities and death –3. ContrIn Poland, approximately 0.1% of population is infected with HIV with >21,000 diagnosed cases as of January 2017. Approximately ten years ago, the dominant route of transmission shifted from intravenous drug use, with high number HCV coinfections, to men who have sex with men (MSM) with continuous expansion of epidemics in this group –13. DespModern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral replication in majority of treated cases, with the WHO target of 90% viral suppression among people on antiretroviral therapy to be reached by 2020 . To meetaids@aids.gov.pl)] followed up in 14/17 Polish HIV treatment centres. The following treatment centres participated in the study : Białystok , Bydgoszcz , Chorzów , Gdańsk , Kraków , Lublin , Łódź , Opole , Ostróda , Szczecin , Wrocław , Warsaw [two centres: Hospital for Infectious Diseases  and Medical University ], Zielona Gora .Cross-sectional data on the antiretroviral treatment efficacy were collected for 5152 patients . Data on the antiretroviral treatment history were not collected. For the final analyses the following treatment groups were used: 2NRTI+NNRTI, 2NRTI+PI, 2NRTI+InI, nucleos(t)ide sparing PI/r+InI as well as combined category for all patients treated with three drug class regimens. All data were extracted from the patient files.Statistical comparisons were performed using the Chi-square tests for categorical variables. As all continuous variables were distributed in the non-linear manner U-Mann Whitney test was used for analyses. Computations were performed with Statistica 12.0 PL software . HIV viral load at baseline, lymphocyte CD4 count and age were analysed both as continuous variables and as predefined categories. HIV-1 viral load was categorized using a threshold of 5 log copies/mL, baseline and nadir lymphocyte CD4 count with a threshold of 200 cells/µL and last lymphocyte CD4 count of 500 cells/µL. Additionally, age at diagnosis was subdivided into six categories  similarly to the classification of age categories for European cohorts . To verin = 2285, 44.35%) cases, followed by 2NRTI plus NNRTI  and 2NRTI plus integrase inhibitor (InI) . NRTI sparing regimen of PI/r+InI was used in 89 (1.73%) patients, while other combinations in 301 (5.84%) individuals , NRTI+PI/r+NRTI  and protease inhibitor monotherapy  . As at the time of data collection 196 (3.8%) patients received three drug regimens a separate cumulative category was created for them and added to the statistical analyses.In the analysed data set the most commonly used regimen combined 2NRTI and one PI . Last lymphocyte CD4 count in the range of 200–499 copies was noted in 1778 (34.51%) cases, and <200 cells/µL among 271 (5.26%) patients. Notably, antiretroviral treatment efficacy was significantly higher, for both HIV-RNA thresholds (<50 copies/mL and <200 copies/mL) for MSM, patients with no history of AIDS, anti-HCV negative, cases with higher lymphocyte CD4 counts at care entry, nadir and last analysis as well as for individuals with lower baseline viral load. Additionally, for the threshold <200 copies/mL male gender was associated with higher virologic success rate  was observed in 4672 (90.68%) individuals. Furthermore, among 262 (5.09%) antiretroviral treated patients last HIV-1 viral load was in the range of 50–200 copies/mL indicating 95.77% overall treatment efficacy if threshold <200 copies/mL was adopted . At the n = 204) were ≤20 years of age. For the majority of cases HIV diagnosis was established between 21 and 30  and 31–40  years of age. Diagnoses at ages between 41–50 years were noted among 414 cases (13.7%), while between 51–60 among 155 (5.13%) patients and >60 years among 50 (1.65%) of individuals.For 3023 patients with available data on the age at diagnosis, 6.75% (p = 0.28). Applying the <200 copies/mL virologic efficacy threshold, higher rate of treatment failure was observed for patients aged ≤20 years at diagnosis (93.14% with viremia <200 copies/mL) compared to other age categories . For <200 copies/mL threshold, median age at diagnosis was also notably lower [median: 28 (IQR:23–36)] among virologically failing patients compared to the suppressed ones [median: 32 (IQR: 26–39)], p = 0.007.Treatment success rates for the threshold of 50 HIV-RNA copies/mL were similar across all age categories . This difference was less pronounced for the threshold of 200 copies/mL (p = 0.0036) (not presented in For the <50 copies/mL threshold notable differences across regimen types were observed. For this threshold significantly higher virologic success rate was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) ). HoweveSignificant differences in the demographic, clinical, immunologic as well as virologic characteristics were observed for the five analysed treatment combinations  when compared separately (see Treatment with nucleos(t)ide plus non-nucleoside reverse transcriptase inhibitors was associated with the most favourable clinical, immunological and virologic characteristics compared to other analysed antiretroviral combinations: the least common history of AIDS, the highest baseline, nadir and last lymphocyte CD4 counts, as well as the lowest baseline HIV-1 viral load . Distribution of transmission routes was similar for 2NRTI+NNRTI- and 2NRTI+InI-based treatments.Among 2NRTI+PI-treated patients AIDS history was notably more common while baseline and nadir lymphocyte CD4 counts were lower compared to 2NRTI+InI, with similar last lymphocyte CD4 count and baseline HIV-1 viral loads. Also the percentage of 2NRTI+PI-treated female as well as anti-HCV-positive individuals was significantly higher compared to 2NRTI+NNRTI and 2NRTI+InI. Age at HIV diagnosis and antiretroviral treatment initiation was similar for all three  most common regimens.Nucleos(t)ide-sparing PI/r+InI combinations were commonly used among patients with history of AIDS as well as injection drug use, both with similar frequency to 2NRTI+PI-based regimens. These patients were notably older at HIV diagnosis compared to any other combination (except for the similar age of the therapy initiation for patients on triple class therapy) and presented with the highest baseline HIV-1 viral loads. Despite the fact that baseline and nadir lymphocyte CD4 count was lower for nucleos(t)ide-sparing PI/r+InI regimens compared to 2NRTI+NNRTI or 2NRTI+InI the last lymphocyte CD4 count was similar to any nucleos(t)ide-based combinations.It should also be observed that in the group treated with three drug class combinations, the highest percentage of women, individuals with history of AIDS or injection drug use and anti-HCV-positive cases was noted. Also median baseline, nadir and last lymphocyte CD4 count were the lowest in this group compared to any other treatment combination. This group also commonly presented with high viral load, comparable only to the group on nucleoside sparing regimens, with viral load >5 log copies/mL observed in 57.62% of cases and 63.51% for both combinations, respectively.Lastly, differences for the number of years on antiretroviral treatment were notable across all analysed categories, except between nucleoside sparing PI/r+InI and three drug class regimens. As expected, the shortest time was noted for nucleos(t)ide plus integrase inhibitor [median: 2 (IQR:1–6) years] combinations followed by nucleos(t)ide plus non-nucleoside reverse transcriptase inhibitors [median: 4 (2–8) years], nucleos(t)ide plus protease inhibitors [median: 5 (3–8) years], nucleos(t)ide sparing PI/r+InI [median: 7 (4–12) years] and finally, three drug class treatments [median: 9.5 (6–13) years].In multivariate model, adjusted for AIDS history, lymphocyte CD4 baseline and nadir <200 cells/µL, last lymphocyte CD4 < 500 cells/µL, HIV viral load at baseline <5 log copies/mL and transmission route, virologic treatment efficacy, expressed as HIV-1 viral load <50 copies/mL proved similar across the analysed treatment groups . BaselinThis study presents national data on antiretroviral treatment efficacy for the majority of patients in care in Poland and represents the largest data set published so far, based on 56.92% of all countrywide treated patients for the time of analysis. The highest proportion of cases received nucleos(t)ide backbone treatment combined with PIs, followed by combinations containing NNRTI and InI. These results are similar to other European cohorts ,19. PrevAntiretroviral treatment efficacy exceeded 90% and 95% for the thresholds of 50 and 200 HIV-RNA copies/mL, respectively. Observed differences in the ratio of virologic success were largely dependent on the baseline patient characteristics and less favourable clinical, immunologic and virologic profile reflected by increased odds ratios of failures associated with the history of AIDS, lower baseline lymphocyte CD4 count, higher HIV viral load at care entry or hepatitis C coinfection and is likely associated with delayed linkage to care. Virologic suppression rates >90% are consistent with the WHO 90–90–90 target and similar to the ones observed for European high income countries such as UK (94% for the threshold of 200 copies/mL) , Sweden In our study virologic efficacy for the threshold of <200 copies/mL was lower for patients aged ≤20 years at diagnosis. Similarly in the Cohere study group, virological success rates were notably lower among individuals aged ≤20 years at diagnosis, which is likely related to adherence issues among adolescents and young adults or may reflect underlying psychological, social, addiction or mental problems in this group ,30. In tIt should be noted that our data revealed notable differences in the frequency of viral suppression rates related to the last antiretroviral treatment option using univariate statistics, mitigated in the multivariate models by the initial clinical (history of AIDS), virologic  and immunologic (baseline lymphocyte CD4 count of 200 cells/µL) patient characteristics and the status of HCV coinfection. Some of the treatment efficacy differences reflect selection of patients with more favourable profile – which is clearly the case of the 2NRTI+NNRTI-based regimens. This group presented with the lowest median HIV-1 viral load, the highest baseline and nadir lymphocyte counts and the least frequent history of AIDS – variables known to affect treatment efficacy –38. AlsoDue to special clinical interest analysis included two additional treatment groups: nucleoside-sparing PI/r+InI-treated cases and three drug class treated individuals. Switching off the nucleos(t)ide tends to be selected in aging patients with increasing risk of NRTI-related adverse events, especially kidney injury and loss of bone mineral density . VirologFinally, combination of at least two active antiretroviral compounds is required to achieve virologic control among treatment-experienced cases. In the setting of treatment failure and emerging drug resistance it may be necessary to combine three or more classes of antiretroviral drugs ,50–52. IThe study has the following limitations: Firstly, only the individuals with viral load assessment performed within the last six months from database closure were investigated, which may have led to overestimation of the virological success rates based only on the patients who remained in the close care. Some of early discontinuations might have been missed by this criterion; however, HIV viral loads are assessed every three to six months and such a criterion best reflected clinical practice in Poland. Secondly, for this study it was not possible to assess the history of the antiretroviral regimen changes; therefore, statistics was based on the last recorded antiretroviral treatment combination. This limitation is related to the unavailability of electronic records reflecting treatment changes. Both limitations are at least partially mitigated by the group size which strengthens validity of the presented results.To sum up, presented data indicate high efficacy of the antiretroviral treatment in Poland, fully in line with the millennium WHO 90% target and reflects success of comprehensive HIV management in Poland. Differences in the antiretroviral treatment efficacy are based on the patient characteristics and reflect individualized treatment decisions related to variety of clinical conditions such as infection status, age or adherence. It should be noted, however, that presented high frequency of virologic suppression does not result in the decrease of the number of new cases – HIV epidemics in Poland is expanding, especially among MSM ,35. Whil


The introduction of Bedaquiline, the first new antimycobacterial drug in over 40 years, has highlighted the critical importance of medication adherence in drug-resistant tuberculosis (DR-TB) treatment to prevent amplified drug-resistance and derive sustained benefit. Real-time electronic dose monitoring (EDM) accurately measures adherence and allows for titration of adherence support for anti-retroviral therapy (ART). The goal of this study was to evaluate the accuracy and acceptability of a next-generation electronic pillbox (Wisepill RT2000) for Bedaquiline-containing TB regimens.Eligible patients were DR-TB/HIV co-infected adults hospitalized for the initiation of Bedaquiline-containing treatment regimens in KwaZulu-Natal, South Africa. A one-way crossover design was used to evaluate levels of adherence and patient acceptance of EDM. Each patient was given a Wisepill device which was filled with ART, Levofloxacin or Bedaquiline over three consecutive weeks. Medication adherence was measured using Wisepill counts, patient-reported seven-day recall, and weekly pill count. An open-ended qualitative questionnaire at the end of the study evaluated participant acceptability of the Wisepill device.p = 0.02). Patients reported positive experiences with Wisepill and expressed willingness to use the device during a full course of DR-TB treatment. There were no concerns about stigma, confidentiality, or remote monitoring.We enrolled 21 DR-TB/HIV co-infected inpatients admitted for the initiation of Bedaquiline from August through September 2016. In aggregate patients were similarly adherent to Bedaquiline (100%) compared to Levofloxacin (100%) and ART (98.9%) by pill count. Wisepill was more sensitive (100%) compared to seven-day recall (0%) in detecting non-adherence events (In this pilot study patients were highly adherent to Bedaquiline by all adherence measures. However, there was lower adherence to ART by pill count and Wisepill suggesting a possible challenge for adherence with ART. The use of EDM identified significantly more missed doses than seven-day recall. Wisepill was highly acceptable to DR-TB/HIV patients in South Africa, and is a promising modality to support and monitor medication adherence in complex treatment regimens. Tuberculosis (TB) is the leading cause of death globally from a single infectious pathogen having surpassed HIV in estimated mortality in 2015 . OutcomeMycobacterium tuberculosis (MTB) , it’s like driving on a road where there are traffic cops, I understand that they are there to control and to make sure that people are safe on our roads.This form of monitoring encouraged them to take their medications at the prescribed times, as explained by one patient:I do not have a problem because I am a person who can take medication without supervision. But being monitored also motivated me to make sure that I take medication.However, a few participants were worried about failing to adhere to the specified dosing time: “if you miss the correct time you become very scared.”Participants were asked about how their use of the device may be perceived by others around them. No participant felt the device would invite stigma or a loss of confidentiality about their HIV or TB status. Indeed, several patients believed the device helped to maintain their confidentiality.Yes I would love to use [the device] especially because people undermine and discriminate you when you are on ARVs, so the device is very helpful because nobody can see what is inside.Most participants also believed that their fellow patients “liked” or “wished they were also given” an electronic device, and nearly all of them were confident that their family and friends – even if inquisitive – would accept them using this device when they were discharged home.A few participants acknowledged that the device was likely to cause some curiosity at home, particularly because of the flashing light, and were concerned if it were to be discovered and used by their children, or altogether misplaced during travel.We asked participants about their personal preferences for Wisepill medications. Most indicated that Wisepill was easiest and most convenient for ARVs because they were already accustomed to taking these medications independently, without a nurse’s supervision.I enjoyed using [Wisepill] more when ARVs were loaded because they are the only of medications I take at my own time. Unlike other meds which I must take together with what is going to be administered by the nurse.Among the anti-TB drugs, patients preferred to pack Bedaquiline into the Wisepill device, because they felt it was conducive to the drug’s unique thrice weekly dosing; all other medications were taken daily. Time in the study was also a factor; several patients felt the longer they used it, the more comfortable they became using the device.When participants were probed about their suggestions for future use, many of them requested increasing the size of the device to hold more medications. Other popular suggestions included adding an alarm reminder for taking medication. One participant suggested such devices should be reserved for “dedicated people, not people who will open it and throw away the tablets.”This pilot study of medication adherence in DR-TB/HIV co-infected patients demonstrates that use of real-time electronic adherence monitoring is effective in capturing non-adherence events and is highly acceptable to patients. In this study, the Wisepill RT2000 device provided real-time feedback on adherence to the online server that was highly correlated with pill count and superior to self-report at capturing non-adherence events when using pill count as a reference standard. Given that Wisepill measures suggested a greater number of missed doses than self-report as well as pill count, electronic adherence monitoring may capture more non-adherence events and its superiority and efficacy to measure adherence and guide adherence support interventions for DR-TB/HIV treatment should be evaluated in future studies.Electronic device monitoring was able to capture adherence data equally for Bedaquiline, Levofloxacin, and ART suggesting that it is capable of effective monitoring for TB medications as well as the HIV medications, for which electronic adherence monitoring has been previously studied –20. In tThe use of an electronic device for dispensing HIV or DR-TB medications was a positive experience for all patients in this study and there were few technical issues reported. Several studies of HIV treatment have demonstrated the acceptability of Wisepill devices; in support of the current literature, this pilot study shows that monitoring was not a concern for patients and this level of supervision was viewed as a sign of caring or a means of motivation –19. PartThis study was limited by the short duration of follow-up on the patients and potential biases introduced by the order of medications by week. The temporal bias may have affected adherence to ART (the first week) as compared to other medications, though this is less concerning given the high acceptability and ease of use regardless of medication reported in qualitative assessment. In addition, the small sample size and hospital inpatient monitoring may limit generalizability to the outpatient setting. Other limitations include incomplete qualitative assessment and possible confounding due to unmeasured variables, such as education. For this pilot study, qualitative data was limited to descriptive content analysis; contextual factors such as education and role of the clinic environment were not fully explored. We plan to address these limitations in a future larger study .There are a variety of electronic health devices used in studies for adherence monitoring. The Wisepill RT2000 device used in this study is one of several Wisepill devices available. The Wisepill evriMED500 and evriMED1000 are table top dispensers with USB only or 2G network access to data, respectively. They are also loaded with 5–10 different medications at a time. The characteristics and goals of this pilot study supported the use of the Wisepill RT2000 device for evaluation of adherence of one medication at a time with a smaller device.N = 4173), comparison of 4 study arms  showed that the use of text messages as reminders for TB medication adherence was not effective in decreasing missed doses (p = 0.649), but electronic medication packaging (with recorded pillbox openings) succeeded in improving TB medication adherence (p = 0.008) [Electronic health interventions, including mobile health, have been used in supporting TB treatment adherence with mixed results. In the largest randomized controlled trial to date (= 0.008) . Next-ge= 0.008) . On the = 0.008) . Similar= 0.008) . This stThe results of this pilot study are encouraging for the use of electronic monitoring adherence in DR-TB/HIV drug regimens. These results will inform a larger study on the effect of electronic monitoring on adherence, feasibility, and acceptability of this device for second-line TB medications. With increasing use of Bedaquiline for the treatment of DR-TB, further studies on adherence to TB regimens will be required and essential for protecting the efficacy of this new and long-awaited drug.The Wisepill device shows promise in providing real-time adherence information in a way that is effective and acceptable to the patient. It has the potential to identify lapses in adherence and possibly improve adherence with real-time intervention before these lapses can lead to a negative impact on treatment success. Self-report and pill count depend on patients continuing to attend clinic visits, do not provide data on potential non-adherence in real-time, may be inferior to Wisepill in capturing non-adherence (self-report), and may not provide the reported confidentiality of the Wisepill device. Thus, the use of electronic monitoring devices appears to be applicable to DR-TB treatment in addition to ART, and may have significant advantages to other commonly utilized adherence monitoring methods.


Highly Active Antiretroviral therapy (HAART) reverses the effect of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) by durably suppressing viral replication. This allows CD4 gain to levels that are adequate enough to restore the body’s capability to fight against opportunistic infections (OIs). Patients with poor immune recovery have been shown to have higher risk of developing both AIDS and non AIDS related clinical events. This study aimed at assessing the proportions and risk factors of poor immune recovery in adult HIV-infected patients on 48 months of HAART attending care and treatment center (CTC) in northwestern Tanzania.A retrospective analysis of adult HIV patients’ data attending CTC at Sekou Toure hospital and who initiated HAART between February 2004 and January 2008 was done. Poor immune recovery was defined as a CD4 count less than 350 cells/µl on follow up as used in other studies.A total of 734 patients were included in the study. In this study 50.25% of patients attending CTC at Sekou Toure hospital were found to have poor immune recovery. The risk of developing inadequate immune recovery was independently associated with male gender, age older than 50 years, low baseline CD4 counts, and advanced World Health Organization (WHO) clinical stage.Poor immune recovery is prevalent among adult HIV patients attending CTC at Sekou Toure hospital in Northwestern part of Tanzania and opportunistic infections are common in this sub group of patients. Clinicians in resource limited countries need to identify these patients timely and plan them for targeted viral assessment and close clinical follow up to improve their long term clinical outcome. HIV is known to infect CD4 positive cells and its replication in these immune cells causes progressive lysis and reduction of the number and quality of functional immune cells –3. With This was a retrospective study involving all adult HIV positive patients (age ≥18 years) who started on antiretroviral therapy at Sekouture hospital care and treatment center. Children and adult patients who were yet to be on ART were excluded. Sekouture is a regional referral hospital located in Mwanza, in north western part of Tanzania. A retrospective analysis of 4 years data of HIV patients initiated on HAART between 20th February 2004 and 20th January 2008 was done. In this study HAART was referred to as a combination of 2 Nucleoside reverse transcriptase and one non nucleoside reverse transcriptase inhibitor or a protease inhibitor with or without a pharmacological booster.p values less than 0.05 were considered for inclusion in the multivariate model. A stepwise approach was used to derive a Parsimonious model, and all associated factors in the final model were considered significant if the p value was less than 0.05.The variables collected included age, sex, marital status, occupation, baseline CD4 count, occurrence of opportunistic infections within 4 years of follow up at CTC, body weight and CD4 count at 48 months of follow up. Data were managed using Epi Data 3.1  and analysis was done using STATA version 12 . The baseline CD4 counts were categorized into two using cut off point CD4 of 200 cells/µl and patients with CD4 counts of less than 200 cells/µl at base line were referred as presenting with severe immune suppression. The immune response at 48 months of follow up was also divided into two groups with cut off point CD4 of 350 cells/µl as used in other studies . Immune In total 734 patients were included in this study; in which most patients were females (66.76%), with a median age of 39.0321–60) years. Most of patients (52%) were married, unemployed (89%) and in WHO clinical stage 3 and 4 (57.49%). Of these patients 722 (98.4%) had recorded baseline CD4, where more than 75 percent; 545 (75.48%) had baseline CD4 counts of less than 200 cells/µl, while 670 (92.27%) had baseline CD4 counts <350 cells/µl as summarized in Table –60 yearsThe aim of this study was to determine the proportion and risk factors of poor immunological response to HAART in adult HIV patients attending CTC in northwestern Tanzania for 48 months. Of the 593 patients who had records of their CD4, 289 (50.25%) did not reach an immunological threshold of ≥350 cells/µl at 4 years of HAART. This prevalence seems slightly higher than those reported from developed countries. In one study in Australia Kaufmann et al. indicated that about 14% of the virologically suppressed patients didn’t reach an immunological cut off point of 350 cells/µl at four years of HAART . While aThis study had a number of limitations. It was a single site clinic based study and therefore findings may not be generalizable to the general population. Being a retrospective study, the data was obtained from patients’ files; these are most of times incomplete; some of the important variables were missing including information on compliance to medications and missing CD4 counts at 48 months. In this study about 141(19.21%) patients had missing CD4 records at 48 month, on a sub analysis (not shown) most of them 98(70.5%) had baseline CD4 <200 cells/µl indicating that they were more likely to have poor immune response at 48 months of follow up and this could have made the burden of poor immune recovery probably more worse. However even with these limitations our study has a number of strengths inclusive of being a relatively large sample size study that describes immune recovery in patients initiated on HAART at low baseline CD4 counts.Poor immune recovery is common in Northwestern Tanzania. This is strongly associated with male gender, older age than 50 years, low baseline CD4 count, advanced clinical stage and occurrence of opportunistic conditions. Clinicians from resource limited settings should identify potential patients and plan them for a much closer clinical follow up and targeted plasma viral load since this subgroup of patients have poor clinical outcomes.


Purpose: To verify the effectiveness of a pharmaceutical care model developed by the Specialized Municipal Assistance Service in Sorocaba, Brazil, on adherence to ART among patients infected with HIV.Methods: A cohort study compared adherence to ART in two groups of patients: intervention group  and non-intervention group . Antiretroviral adherence was measured by the number of pharmacy refill records in a six-month period. The relationship between the use of other drugs for the treatment of opportunistic infections and the adherence rate in the intervention group and the correlation between adherence and viral load and CD4 lymphocytes were also assessed.Results: Higher adherence rates were observed in the intervention group (p<0.05). The use of others drugs did not influence adherence to ART (p=0.30). There was a positive correlation between adherence and the percentage of patients in the intervention group with undetectable viral loads (p=0.0004) and higher levels of CD4 lymphocytes (p=0.0024).Conclusion: The pharmaceutical care model developed by the SAME improved patient adherence to ART as well as clinical outcomes. This model consists of a pharmaceutical consultation that seeks information regarding medications and provides explanations to patients about their treatment, enhancing co-responsibility and contributing to adherence to therapy. To date, no study has been conducted in the SAME to verify the clinical benefit of these models. The present study aimed to describe the effectiveness of this model of pharmaceutical care in supporting adherence to antiretroviral therapy. Also, the relationship between adherence and viral load and CD4 lymphocyte values was evaluated.In 1996, Brazil was the first country to guarantee to HIV/AIDS patients the right to receive all of the drugs needed for their treatment free of charge through the public system.A cohort study that followed the patients over a period of six-months. The study was developed at the SAME, in Sorocaba, State of São Paulo, Brazil. The service has a multi-disciplinary team.The study population consisted of all patients infected with HIV and taking antiretroviral therapy enrolled in the pharmacy SICLOM (Digitized System of Drug Logistic Control) during the period of study. Patients aged over 12 years infected with HIV and receiving antiretroviral therapy for at least one year and registered at SICLOM were included. Patients, who transferred to other services, received antiretroviral therapy for a short interval, were pregnant, or died during the study period, were excluded.The patients were divided into two groups: pharmaceutical intervention  and non-intervention group .This model consisted of one pharmaceutical consultation with patients or parent or guardian of minor patients. During the consultation, a chart was prepared for each patient with information regarding their medical prescription and their antiretroviral treatment-taking habits. The table contained information that oriented patients to the appropriate times to ingest their drugs, the number of pills to take, and images of the antiretrovirals. Possible interactions between drugs and food were explained verbally and separated in the schedules at different times. The pharmacist explained the main adverse effects that occur with the use of antiretroviral therapy and how to manage them. At the consultation, self-adhesive tags with standardized drawings were placed in vials and blisters of drugs with the intent of reinforcing the information given to the patient as far as time, dosage and interval of drug usage.6 in a six-month period. Patients who received all six refills (100%) were classified as adherent. Those that received five monthly refills (80.0%) were classified into the minimum effective adherence. Patients who received between one and four refills (below 66.7%) were classified into the low adherence category. Finally, patients who did not refill their medications during the study were classified as non-adherents.7 The association between adherence to antiretroviral therapy and the prescription of drugs for the treatment of opportunistic infections was verified in the intervention group only since SICLOM does not permit access to this information.Adherence to antiretroviral therapy was verified by the number of pharmacy refill recordsViral load and CD4 lymphocyte values were collected from the clinical charts of patients in the intervention group at close to the day of pharmaceutical consultation and six months after consultation. It was not possible to obtain the viral load values in the non-intervention group and some of the patients in the intervention group due to the absence of this information in their clinical charts.Patients were classified into: patients with an undetectable viral load (less than 40 copies/ml), patients with at least a 90% reduction in the viral burden , and patients with an unsatisfactory response to ART. The correlation between adherence to ART and viral load levels six months after the initial pharmaceutical consultation was measured based on the above data.9 The correlation between adherence to ART and increase in CD4 levels (>500 cells/mm³) was measured six months after the initial pharmaceutical consultation.The CD4 cell count was considered in this study because it is a classic marker of disease progression, with increased measurement challenges in advanced phases of infection. The values were considered to be altered when the results were below 500 cells/mm³ in proportion to the total number of lymphocytes.Chi-square tests were used to evaluate levels of adherence among the groups. The correlation between adherence and the levels of viral load and CD4 lymphocytes was established by the Spearman correlation coefficient. Statistical analyses were performed using Bioestat software 5.3, Institute of Sustainable Development Mamirauá, p=5%.The sample consisted of 359 patients, with 130 in the intervention group and 229 in the non-intervention group. The majority of patients were adults. Approximately 50.7% of patients were male, and 49.3% were female. It was observed that the pharmaceutical care model developed in the SAME was associated with higher rates of adherence to ART and decreased the rates of treatment abandonment.6 showed that the most common methods of adherence assessment were based on medication refill records, followed by patient self-report and electronic drug monitoring using medication event monitoring systems. The Brazilian studies that utilized SICLOM to gather data about antiretroviral adherence considered the system as an important tool for monitoring irregular adherence patterns or risk of treatment abandonment.10The results of a systematic review by Saberi et al11 evaluated patient adherence to antiretrovirals using the same methods employed in this study. The study verified the association between adherence, as assessed by pharmacy refill records, and virologic failure to develop a clinical tool for use in antiretroviral programs in low-middle income settings. They observed that the risk of virologic failure fell by 73% with each 10% increase in adherence measured using pharmacy refill records over a four-month period.Court et al12 also verified improved adherence to antiretroviral therapy among patients accompanied by the pharmacy service in the Department of Health Services of California. These patients were more likely to remain on one type of drug regimen throughout the year and had a fewer change in regimens.The present study demonstrated that the intervention of a pharmaceutical consultation aided the monitoring of patients by SICLOM reduced treatment abandonment rates. Hirsch et alIn the intervention group, a positive and significant correlation coefficient was observed between treatment adherence and undetectable viral load values and increased CD4 lymphocyte levels. Patients with maximum levels of treatment adherence showed the highest levels of undetectable viral load at 86.0% .13 observed results consistent with the findings of our study. The study evaluated the efficacy of a clinical pharmacist intervention and verified the decrease or maximum suppression of the viral load and the increase in CD4 lymphocytes. Patients who had less than 70% adherence to antiretroviral treatment showed a five-fold increase in disease progression risk. Comparatively, patients who showed greater than 90% adherence had an increased length of time to viral failure, increased CD4 lymphocyte counts, and less disease progression risk and posterior death.14 However, there is conflicting evidence on defining the minimum threshold of adherence for the effectiveness of antiretroviral therapy. HIV care providers continue to aim to achieve adherence levels of 95% or more, although the clinical significance to the patient of maintaining a particular adherence percentage remains unclear.15Ma et alAlthough our results demonstrate the benefits of a pharmaceutical care model implemented by the SAME, the rate of patients with the ideal adherence can be improved. This model is the main tool used by the clinical pharmacist at the SAME and is in the process of further improvement. We noted that teenagers, who composed only approximately 5% of participants of the study, had increased doubts regarding treatment, suggesting that the model requires adaptation to the needs of different subpopulations, such as modification in drug therapy, among others.One disadvantage of the pharmaceutical care model was the inability to verify if the drugs were correctly administered. Even vials with sensors for the electronic monitoring of medication-taking can be altered. However, information regarding the most recent refill records made it possible to estimate the adherence of patients to ART, and if needed, reinforcement of medication-taking could be provided during the refill encounter. This study described the pharmaceutical service of the SAME and demonstrated the benefits of the model for adherence to therapy and response to certain clinical parameters. This tool could help identify patients who require intervention to improve the adherence.The pharmaceutical care model developed at the SAME positively influenced patient’s adherence to antiretroviral therapy as well as reduced viral loads and increased CD4 lymphocytes levels.The authors would like to acknowledge the Specialized Municipal Assistance Service (SAME) in HIV/AIDS, Sorocaba, Brazil.The study was approved by the Committee on Ethics in Research on Human Beings of the University of Sorocaba (number. 18/2011).The authors declare no conflict of interests.


The aims of this study were: (i) to determine the factors associated with HRQOL at baseline in our cohort, and (ii) to evaluate if there are differences in baseline HRQOL measures by antiretroviral treatment.The Short Form 36 (SF-36) was administered between 2006 and 2010 among members of the United States HIV Natural History Study cohort (NHS), and participants who completed the SF-36 were included in the study. Physical component summary (PCS) and mental component summary (MCS) scores were computed based on standard algorithms. Multivariate linear regression models were constructed for PCS and MCS to estimate the association between selected variables and HRQOL scores.3 , mental comorbidity , medical comorbidity , AIDS diagnosis . Others were gender, military rank, marital status, and age. Factors independently associated with MCS were CD4+ count < 200 cells/mm3 , mental comorbidity , age , and being African American .Antiretroviral therapy (ART) was not independently associated with HRQOL scores. Factors associated with PCS were CD4+ count < 200 cells/mmAmong military active duty and beneficiaries with HIV, modifiable factors associated with HRQOL measures included advanced HIV disease, and mental or medical comorbidity. Addressing these factors may improve quality of life of HIV-infected individuals in the NHS cohort. The annual estimated rate of new human immunodeficiency virus (HIV) infections in the United States between 2008 and 2011 remained stable at 15.8 per 100,000 while the rate for HIV stage 3 or acquired immune deficiency syndrome (AIDS) was 10.3 per 100,000 during the same period, 5.HRQOL is a multidimensional and dynamic concept that is well recognized as an end-point in assessing the well-being of individuals living with HIV/AIDS–9. SeverThe relationship between HIV/AIDS, HAART and HRQOL is complex. While HAART helps to prevent disease progression and results in better quality of life and well-being in HIV-infected individuals, the prolonged use of medication that is necessary to continually keep viral suppression below detection levels may lead to adverse effects that may reduce an individual’s HRQOL. Such side effects of HAART, including lipodystrophy, diarrhea and other medication-related symptoms, have also been shown to affect HRQOL–27. AlthSome predictors of HRQOL in HIV-infected individuals in the general US population, such as lack of access to healthcare due to lack of insurance, access to and maintenance of antiretroviral medications, and injection drug use may not play an equally important role as determinants of HRQOL of HIV-infected individuals in the United States Military. HRQOL has not been previously evaluated in the U.S. Military HIV Natural History Study (NHS), which is one of the oldest open-enrollment dynamic HIV cohorts in the country and provides a unique opportunity to evaluate HRQOL in the setting of equal access to healthcare. Furthermore, racial diversity and equal access to medication are other advantages of our cohort. Also, previous study in the military shows that injection drug use is rare among military personnel, 34. TheThe U.S. Military HIV Natural History Study has been approved centrally by the Uniformed Services University Institutional Review Board (IRB) and at each participating site and is conducted according to the principles expressed in the Declaration of Helsinki. Written informed consent was obtained from the participants. This analysis was approved by the central IRB and Drexel University.The NHS is a prospective multicenter continuous enrollment observational cohort of HIV-infected active duty military personnel and other beneficiaries  from the Army, Navy/Marines and Air Force enrolled since 1986, 35–37. The RAND Short Form 36 (SF-36) questionnaires were administered annually to NHS participants from April 2006 to September 2010. However, a few participants had more than one completed questionnaire in a year, and for these participants the last completed questionnaire for that year was used. Baseline was defined as the first ever HRQOL measure irrespective of when the participant was first enrolled in the NHS.Variable selection was based on the literature on HRQOL in HIV-infected individuals in the United States and other high income countries, 10, on We computed the norm-based physical (PCS) and mental (MCS) component summary scores from the eight health domains in the Short Form 36 (SF-36) questionnaire in line with the recommended scoring algorithm for the RAND 36-item health survey 1.0, 39. TheHAART was defined as a combination of at least three full dose antiretroviral agents similar to previous investigations for this cohort. HAART t3, 200–499 cells/mm3 and >499 cells/mm3), medical comorbidity, mental comorbidity, AIDS-defining illnesses (1993 CDC criteria), HIV duration, and calendar year. We used the CD4+ cell count and pVL values closest in time to the HRQOL measure used. Although most of the participants were not new to the NHS, administration of the HRQOL questionnaire began in 2006 and continued until 2010. We therefore included calendar year to adjust for any temporal variations in participants’ characteristics upon entry into the HRQOL study. Medical comorbidity referred to concurrent chronic medical conditions such as diabetes mellitus, hypertension and cancers the participants had at the time of the study. Similarly, mental comorbidity included such conditions as major depressive disorder, general anxiety disorder, bipolar disorder and alcohol abuse. Both medical and mental comorbidities were extracted from the participants’ medical record using the central electronic health-records system of the US Military. Medical comorbidity was classified as having “no” for participants who had no medical comorbidity or “yes” for those with one or more medical comorbidity. Mental comorbidity was similarly classified.Covariates considered for inclusion in our models were based on previous studies as well as on the demographic and clinical characteristics that were captured in the NHS cohort. These covariates included gender , age, military rank , marital status , race/ethnicity , pVL (>50 copies/mL or ≤50 copies/mL), CD4+ cell count , and covariates. Finally, we checked for any evidence of multi-collinearity for all covariates using the variance inflation factor (VIF). All statistical analyses were performed using SAS 9.3 .Baseline demographic and clinical characteristics by HAART group for participants with SF-36 data are displayed in Tables 3, lower military rank or being civilian/retired, presence of medical and mental comorbidities, AIDS diagnosis, and being married. Being male was associated with a higher PCS score. Also, participants who were administered the HRQOL questionnaire in 2007 had a higher PCS score compared to their 2006 counterparts but there were no statistically significant differences in PCS scores for participants enrolled in 2008 to 2010 compared to their 2006 counterparts. The PCS scores of participants receiving protease inhibitors were significantly lower than those receiving non-protease inhibitors in the unadjusted model  but not in the adjusted model. The PCS scores of participants in the Off-HAART group were also significantly lower than those receiving non-protease inhibitors in the unadjusted model  but not in the adjusted model . Compared to participants receiving non-protease inhibitors, HAART-naivety was associated with a higher PCS scores by 1.99  in the unadjusted model but not in the adjusted model. Similarly, PCS scores in the PI-HAART group was significantly different from those of in the Off-HAART group and the HAART-naïve in the unadjusted model but not after adjustment  and mental comorbidity . Plasma viral load >50 copies/mL and AIDS diagnosis were associated with lower MCS scores in the unadjusted models but not in the adjusted model. The MCS scores of participants receiving protease inhibitors were not significantly different from those of receiving non-protease inhibitors. MCS scores were 1.44 and 2.34 significantly lower for the HAART-Naïve and Off-HAART groups respectively compared to those on NPI-HAART. These differences were no longer significant after adjustment. On the other hand, the PI-HAART group did not show any differences in MCS scores before and after adjustment with the HAART-naïve and Off-HAART groups . Plasma viral load was, however, not associated with PCS similar to findings by others[Akin to the literature, we found that CD4+ cell count <200 cells/mmPCS score, 21, 44.by others, 14. Theby others, 46. Thiby others, 46. AndThe presence of medical and mental comorbidities was negatively associated with physical functional health similar to findings by others, 22, 40.We found that being male was significantly associated with a 2.2 point higher PCS score compared to being female in our cohort, a finding similar to what has been reported in the literature, 15, 48 Being married was associated with lower PCS score in our cohort, a finding similar to that reported by Smith et al for a non-HIV military cohort. AlthougOur findings indicate that there were statistically significant differences in PCS scores among HAART treatment groups in the unadjusted models Tables  and 4 bu3, mental comorbidity, and race/ethnicity. We found a positive association between increasing age and MCS in our cohort similar to that in the military[3 was independently associated with lower MCS score similar to the findings by others[3 is associated with faster disease progression in HIV-infected individuals, this will tend to cause distress that may negatively impact MCS[Factors independently associated with MCS scores in our cohort were age, CD4+ cell count <200 cells/mm military and in H military. The rel military, making  military. We alsoby others, 17, 52 by others, which fmpact MCS. There wmpact MCS, 45, 46.mpact MCS we did nmpact MCS.Mental comorbidity had a dramatic impact on mental functional health in our cohort , which clearly shows the need for greater attention by both clinicians and policy makers in addressing mental health issues in this population of military personnel. The need for frequent and regular evaluation of the mental health of participants is further supported by the high prevalence of mental comorbidity in our cohort (over 25%). And as we stated earlier, depression was by far the most significant mental comorbidity in our cohort. There was no association between medical comorbidity and MCS. In our cohort, being African-American was positively associated with higher mental functional health which is similar to the findings in a non-HIV Military cohort which reported a higher MCS score among African-Americans compared to Caucasians. While tSome of the limitations of our study include its cross-sectional nature, which may preclude conclusions on causality. Our study population was predominantly male (>90%) so generalizability to female should be applied cautiously. We also did not control for variables such as route of transmission as this was not captured at the time the surveys were administered due to the military “Don’t Ask, Don’t Tell” policy in place at the time. It is wOur study had some major advantages. One, we simultaneously examined the differences in HRQOL measures in a large cohort of individuals on PI-HAART and NPI-HAART, as well as those who were HAART-naïve or Off-HAART. Because of the large sample size, we were able to adjust for many important confounding or mediating variables in our models. Our study also had a good representation of minority groups including African-Americans and Hispanics/other races. Also, the use of a norm-based generic HRQOL questionnaire (RAND SF-36) makes it easy for direct comparisons with different populations and settings including the general US population, non-HIV-infected US military population, other HIV cohorts as well as those of other chronic diseases that have used similar instruments. Finally, our models were fairly robust requiring removing only one influential observation from the PCS model and none from the MCS model.3. Medical comorbidity and AIDS were only associated with poorer physical functional health. Addressing these risk factors may help improve the physical and mental functional health status of HIV-infected individuals in the United States’ Military.In conclusion, our study showed that modifiable risk factors associated with negative physical and mental functional health were mental comorbidity and CD4+ cell count <200 cells/mm