Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda

OBJECTIVE: To evaluate adherence, treatment interruptions, and outcomes in patients purchasing antiretroviral fixed-dose combination (FDC) therapy. DESIGN: Ninety-seven participants were recruited into a prospective 24-week observational cohort study of HIV-positive, antiretroviral-naive individuals initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. Adherence was measured by monthly structured interview, unannounced home pill count, and electronic medication monitors (EMM). Treatment interruptions were measured as continuous intervals greater than 48 h without opening the EMM. The primary outcomes were survival with viral suppression below 400 copies/ml, CD4 cell increases, and genotypic drug resistance at 24 weeks. RESULTS: The median baseline CD4 cell count was 56 cells/microl and median log10 copies RNA/ml was 5.54; mean adherence ranged from 82 to 95% for all measures but declined significantly over time. In an intent-to-treat analysis, 70 (72%) patients had an undetectable plasma HIV-RNA level at week 24. Sixty-two of 95 (65%) individuals with continuous EMM data had a treatment interruption of greater than 48 h. Treatment interruptions accounted for 90% of missed doses. None of 33 participants who did not interrupt treatment for over 48 h had drug resistance, whereas eight of 62 (13%) participants who did interrupt therapy experienced drug resistance. Antiretroviral resistance was seen in 8% of individuals and overall mortality was 10% at 24 weeks. CONCLUSION: HIV-positive individuals purchasing generic FDC antiretroviral therapy have high rates of adherence and viral suppression, low rates of antiretroviral resistance, and robust CD4 cell responses. Adherence is an important predictor of survival with full viral suppression. Treatment interruptions are an important predictor of drug resistance.     

Factors associated with intention to conceive and its communication to providers among HIV clients in Uganda

Persons living with HIV/AIDS (PLHA) must discuss their fertility intentions with healthcare providers to receive the support needed to have children safely and limit transmission risks. However, few quantitative studies have examined correlates of fertility intentions, let alone the communication of such intentions with providers. We examined the prevalence and correlates of intentions to have children, and comfort discussing such plans with one’s providers, in HIV clients at two HIV clinics in Uganda. Cross-sectional self-report data were collected from 233 patients who had primary partners. Bivariate correlates significant at the P < 0.10 level were included in logistic regression analysis. Of the 233 participants, 103 (44%) reported an intention to conceive a child in the near future. In multivariate analysis, younger age of both the patient and their partner, better physical health functioning and higher internalized HIV stigma were associated with having fertility intentions. One-third (35%) of those with fertility intentions expressed having difficulty discussing these intentions with their providers, which was associated with receiving care at the rural clinic and greater internalized HIV stigma. These findings highlight the need for reproductive health services that help clients accept themselves as PLHA and their fertility rights, thus promoting patient-doctor communication needed to promote safe child conception and delivery outcomes.     

Second-line antiretroviral treatment successfully resuppresses drug-resistant HIV-1 after first-line failure: prospective cohort in Sub-Saharan Africa

Little is known about the effect of human immunodeficiency virus type 1 (HIV-1) resistance mutations present at time of regimen switch on the response to second-line antiretroviral therapy in Africa. In adults who switched to boosted protease inhibitor-based regimens after first-line failure, HIV-RNA and genotypic resistance testing was performed at switch and after 12 months. Factors associated with treatment failure were assessed using logistic regression. Of 243 participants, 53% were predicted to receive partially active second-line regimens due to drug resistance. The risk of treatment failure was, however, not increased in these participants. In this African cohort, boosted protease inhibitors successfully resuppressed drug-resistant HIV after first-line failure.     

Depression in the Pathway of HIV Antiretroviral Effects on Sexual Risk Behavior Among Patients in Uganda

HIV antiretroviral therapy (ART) can increase safe sex or lead to disinhibition and less condom use. We conducted one of the first controlled studies of ART effects on sexual risk behavior in sub-Saharan Africa, and the potential explanatory roles of physical and mental health. Participants (302 non-ART, 300 ART) were followed for the first 12?months of HIV care in Uganda. Multivariate intention-to-treat regression analysis showed that frequency of sex increased significantly in both groups, but more among ART patients; when added to the model in separate analyses, changes in physical health functioning and depression were both significant predictors, as was time in HIV care, but there was no longer an ART effect. Both ART and non-ART groups had similar dramatic increases in consistent condom use over time; however, change in depression, unlike physical health functioning, was a significant predictor of consistent condom use when added to this model, and there remained a similar level of increased condom use among ART and non-ART patients. HIV care and ART increase sexual activity and condom use, but depression undercuts the prevention benefits of ART, highlighting the need to integrate mental health services into HIV care.     

Comparative study of patients in correct usage of and preference for the swinghaler and turbuhaler multidose inhalers

Objective. Current dry powder inhalers (DPIs), introduced to overcome problems associated with pressurized metered dose inhalers (pMDIs), possess not only difficulties originating from their designs but also other barriers that prevent their correct usage. The authors of this study investigated the ease and correctness of use of Swinghaler, a new device in the form of multidose DPI, as well as the preference of the study participants for either a Swinghaler or a Turbuhaler. Methods. A total of 260 patients from Korea, China, Indonesia, the Philippines, Taiwan, and Thailand were prospectively recruited. Patients who had stable asthma, were more than 12 years old, had no experience with DPIs, and provided informed consents were included, whereas those with limited physical or intellectual ability and prior experience with any DPIs were excluded. Results. There were no group or time effects between the patients who were assigned to use a Swinghaler or a Turbuhaler first. Forty-one (16.1%) participants correctly performed the inhalation maneuver with a Swinghaler, whereas 28 (10.9%) did so with a Turbuhaler; the difference was not statistically significant. The overall assessment on the precise use of the devices indicated that there were no differences between Swinghaler and Turbuhaler usage. Comparing the preference scales between the two devices, the participants gave higher scores to the Swinghaler for all assessment items and were more satisfied with the Swinghaler compared with the Turbuhaler (78.5% vs. 55.0%, p < .001). Conclusions. The participants showed no difference in their ability to correctly use a Swinghaler when compared with a Turbuhaler and preferred the Swinghaler. These results suggest that the Swinghaler may be an effective and valuable tool for the management of airway diseases.     

A secular increase in BMD in Chinese women

Population-based studies have revealed a decline in the incidence of age-adjusted hip fractures in southern Chinese women during the past decade. To determine whether there was a secular change in population characteristics that accounted for this decline, we compared the bone mineral density (BMD) and lifestyle habits of two cohorts of women who were more than 50 years of age and who were recruited from 1995 to 2000 and 2005 to 2010. The BMD levels in the 2005–2010 cohort were significantly higher at the spine and hip and ranged from 3.6 to 17.8 % among the different age groups. Additionally, a significantly lower prevalence of subjects with osteoporosis and osteopenia was observed. Longer reproductive years, higher levels of physical activity, higher estradiol and 25(OH) vitamin D levels, and lower alkaline phosphatase levels were found in the 2005–2010 cohort. After adjusting for bone-determining factors, significant differences were detected in the BMD levels at the lumbar spine, femoral neck, and total hip (4.17, 9.02, and 9.34 %, respectively) in women >50 years of age but not in women ≤50 years of age. The secular increase in BMD and healthier lifestyles most likely led to the decline in the incidence of age-adjusted fractures.     

Rational identification of a novel peptide for targeting nanocarriers to 9L glioma

Traditional therapies for high grade gliomas are limited in part by collateral damage to normal tissues. Selective delivery of therapies to tumors is, therefore, needed. Here, we report that liposomal nanocarriers coated with a novel oligopeptide enhance uptake by 9L gliosarcoma. A targeting nine amino acid peptide sequence (RSI) was identified by differential panning of random peptide phage display libraries on 9L cells and rat blood cells and plasma. Peptides were coupled to the surface of liposomal nanocarriers which were subsequently loaded with doxorubicin. The ability of RSI coated liposomes to facilitate drug uptake and cytotoxicity was compared with conventional liposomal nanocarriers and controls. In addition, plasma clearance profiles of the RSI peptide coupled liposomal nanocarriers were evaluated in adult immuno-competent rats. RSI peptide-coupled liposomal nanocarriers enhanced drug uptake by 9L cells by 500% compared with conventional liposomal nanocarriers, and significantly increased cytotoxicity. The plasma half-lives confirmed that the presence of the RSI peptide on the liposomal nanocarriers did not compromise circulation time in the blood in comparison with Stealth liposomal nanocarriers. These data suggest that phage-identified oligopeptides could lead to the development of new tumor selective nanocarriers.