Predictors of incomplete adherence, virologic failure, and antiviral drug resistance among HIV-infected adults receiving antiretroviral therapy in Tanzania.

BACKGROUND: Access to antiretroviral therapy is rapidly expanding in sub-Saharan Africa. Identifying the predictors of incomplete adherence, virologic failure, and antiviral drug resistance is essential to achieving long-term success. METHODS: A total of 150 subjects who had received antiretroviral therapy for at least 6 months completed a structured questionnaire and adherence assessment, and plasma human immunodeficiency virus (HIV) RNA levels were measured. Virologic failure was defined as an HIV RNA level >400 copies/mL; for patients with an HIV RNA level >1000 copies/mL, genotypic antiviral drug resistance testing was performed. Predictors were analyzed using bivariable and multivariable logistic regression models. RESULTS: A total of 23 (16%) of 150 subjects reported incomplete adherence. Sacrificing health care for other necessities (adjusted odds ratio [AOR], 19.8; P<.01) and the proportion of months receiving self-funded treatment (AOR, 23.5; P=.04) were associated with incomplete adherence. Virologic failure was identified in 48 (32%) of 150 subjects and was associated with incomplete adherence (AOR, 3.6; P=.03) and the proportion of months receiving self-funded antiretroviral therapy (AOR, 13.0; P=.02). Disclosure of HIV infection status to family members or others was protective against virologic failure (AOR, 0.10; P=.04). CONCLUSIONS: Self-funded treatment was associated with incomplete adherence and virologic failure, and disclosure of HIV infection status was protective against virologic failure. Efforts to provide free antiretroviral therapy and to promote social coping may enhance adherence and reduce rates of virologic failure.     

Are there differences in disease progression and mortality among male and female HIV patients on antiretroviral therapy? A meta-analysis of observational cohorts

Studies examining the sex differences in morbidity and mortality among HIV/AIDS patients have yielded inconsistent results. We conducted a meta-analysis of sex differences in disease progression and mortality among HIV/AIDS patients. Medical literature databases from inception to August 2014 were searched for published observational studies assessing sex differences in immunologic and virologic response, disease progression and mortality among HIV-infected patients. Random effects meta-analyses of 115 eligible studies were conducted to obtain pooled estimates of outcomes and heterogeneity was explored in sub-group analyses. Pooled estimates showed an increased risk of progression to AIDS (relative risk [RR]=1.11,95% CI=1.02–1.21) and all-cause mortality (RR=1.23, 95% CI=1.17–1.29) among males compared to females. All-cause mortality differed by sex only in low and middle income countries. The risk of AIDS-related mortality (RR=1.03, 95% CI=0.82–1.30), immunologic failure (RR=1.19,95% CI: 0.97–1.47), virologic suppression (RR=0.98, 95% CI=0.84–1.14), virologic failure (RR=1.26, 95% CI=0.99–1.61) and the change in CD4 cell count (Weighted mean difference [WMD] = ?5.15, 95% CI= ?13.57 to 3.28) did not differ by sex. These findings were modified by disease severity, adherence and use of highly active antiretroviral therapy. We conclude that HIV-related disease progression and survival outcomes are poorer in males.     

Simple adherence assessments to predict virologic failure among HIV-infected adults with discordant immunologic and clinical responses to antiretroviral therapy

We evaluated the association between two antiretroviral therapy (ART) adherence measurements--the medication possession ratio (MPR) and patient self-report--and detectable HIV viremia in the setting of rapid service scale-up in Lusaka, Zambia. Drug adherence and outcomes were assessed in a subset of patients suspected of treatment failure based on discordant clinical and immunologic responses to ART. A total of 913 patients were included in this analysis, with a median time of 744 days (Q1, Q3: 511, 919 days) from ART initiation to viral load (VL) measurement. On aggregate over the period of follow-up, 531 (58%) had optimal adherence (MPR > or =95%), 306 (34%) had suboptimal adherence (MPR 80-94%), and 76 (8%) had poor adherence (MPR <80%). Of the 913 patients, 238 (26%) had VL > or =400 copies/ml when tested. When compared to individuals with optimal adherence, there was increasing risk for virologic failure in those with suboptimal adherence [adjusted relative risk (ARR): 1.3; 95% confidence interval (CI): 1.0, 1.6] and those with poor adherence (ARR: 1.7; 95% CI: 1.3, 2.4) based on MPR. During the antiretroviral treatment course, 676 patients (74%) reported no missed doses. The proportion of patients with virologic failure did not differ significantly among those reporting any missed dose from those reporting perfect adherence (26% vs. 26%, p = 0.97). Among patients with suspected treatment failure, a lower MPR was associated with higher rates of detectable viremia. However, the suboptimal sensitivity and specificity of MPR limit its utility as a sole predictor of virologic failure.     

Caregiver-reported antiretroviral therapy non-adherence during the first week and after a month of treatment initiation among children diagnosed with HIV in Ethiopia

To achieve optimal virologic suppression for children undergoing antiretroviral therapy (ART), adherence must be excellent. This is defined as taking more than 95% of their prescribed doses. To our knowledge, no study in Ethiopia has evaluated the level of treatment adherence at the beginning of the child’s treatment. Our aim was therefore to evaluate caregiver-reported ART non-adherence among children and any predictors for this during the early course of treatment. We conducted a prospective cohort study of 306 children with HIV in eight health facilities in Ethiopia who were registered at ART clinics between 20 December 2014 and 20 April 2015. The adherence rate reported by caregivers during the first week and after a month of treatment initiation was 92.8% and 93.8%, respectively. Our findings highlight important predictors of non-adherence. Children whose caregivers were not undergoing HIV treatment and care themselves were less likely to be non-adherent during the first week of treatment (aOR?=?0.17, 95% CI: 0.04, 0.71) and the children whose caregivers did not use a medication reminder after one month of treatment initiation (aOR?=?5.21, 95% CI: 2.23, 12.16) were more likely to miss the prescribed dose. Moreover, after one month of the treatment initiation, those receiving protease inhibitor (LPV/r) or ABC-based treatment regimens were more likely to be non-adherent (aOR?=?12.32, 95% CI: 3.25, 46.67). To promote treatment adherence during ART initiation in children, particular emphasis needs to be placed on a baseline treatment regimen and ways to issue reminders about the child’s medication to both the health care system and caregivers. Further, large scale studies using a combination of adherence measuring methods upon treatment initiation are needed to better define the magnitude and predictors of ART non-adherence in resource-limited settings.     

Cumulative exposure to stimulants and immune function outcomes among HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study

We examined associations between stimulant use (methamphetamine and cocaine) and other substances (nicotine, marijuana, alcohol and inhaled nitrites) with immune function biomarkers among HIV-seropositive (HIV +) men taking highly active antiretroviral therapy (ART) and HIV-seronegative (HIV-) men in the Multicenter AIDS Cohort Study. Among HIV + men, cumulative adherence to ART (4.07, 95% confidence interval [CI]: 3.52, 4.71, per 10 years of adherent ART use), and recent cohort enrolment (1.38; 95% CI: 1.24, 1.55) were multiplicatively associated with increase in CD4+/CD8+ ratios. Cumulative use of methamphetamine (0.93; 95% CI: 0.88, 0.98, per 10 use-years), cocaine (0.93; 95% CI: 0.89, 0.96, per 10 use-years) and cumulative medical visits (0.99; 95% CI: 0.98, 0.99, per 10 visit-years), each showed small negative associations with CD4+/CD8+ ratios. Among HIV- men, cumulative medical visits (0.996; 95% CI: 0.993, 0.999), cumulative number of male sexual partners (0.999; 95% CI: 0.998, 0.9998, per 10 partner-years) and cigarette pack-years (1.10; 95% CI: 1.02, 1.18, per 10 pack-years) were associated with CD4+/CD8+ ratios over the same period. ART adherence is associated with a positive immune function independent of stimulant use, underscoring the influence of ART on immune health for HIV+ men who engage in stimulant use.     

Effects of Counselling on Adherence to Antiretroviral Treatment Among People with HIV in Estonia: A Randomized Controlled Trial

To assess the efficacy of an education- and strengths-based counselling programme to promote antiretroviral therapy (ART) adherence in a cohort of HIV-infected individuals with high prevalence of injection drug use in Estonia. Parallel-group randomized (1:1) controlled trial (RCT). Adults receiving ART in two clinics were followed for 12 months. The trial compared: (i) an intervention (three sessions) incorporated into routine clinic visits, providing education about HIV, ART, the role of adherence, and tailoring regimen to daily routines using problem-solving skills to address adherence barriers versus (ii) usual care (control). Primary and secondary outcomes were self-reported ART adherence (3-day recall) and viral load (respectively). 519 patients were randomized and 82% completed the study. Recent optimal ART adherence (3-day recall ≥95%) was reported by 75.6% in the intervention group and 72.9% of controls at baseline and 76.7% and 67.5%, respectively, at 12 months (RR 1.14, 95% CI 1.00–1.28; adjusted RR 1.13, 95% CI 1.00–1.27). There was no difference in the proportion of patients with undetectable viral load. At 12 months the intervention group reported significantly higher perceptions of ART necessity versus ART concerns [mean ART necessity-concerns differential: intervention group 1.32 (SD 1.22) vs control group 1.08 (SD 1.12); p = 0.048]. All-cause mortality among study participants was 27.7 per 1000 person years (95% CI 15.6–44.8). A brief, clinic-based adherence intervention alone may assist with adherence but lacks impact on viral load at 12 months.     

Understanding the Reasons for Deferring ART Among Patients Diagnosed Under the Same-Day-ART Policy in Johannesburg,South Africa

We aimed to examine the correlates of antiretroviral therapy (ART) deferral to inform ART demand creation and retention interventions for patients diagnosed with HIV during the Universal Test and Treat (UTT) policy in South Africa. We conducted a cohort study enrolling newly diagnosed HIV-positive adults (≥?18 years), at four primary healthcare clinics in Johannesburg between October 2017 and August 2018. Patients were interviewed immediately after HIV diagnosis, and ART initiation was determined through medical record review up to six-months post-test. ART deferral was defined as not starting ART six months after HIV diagnosis. Participants who were not on ART six-months post-test were traced and interviewed telephonically to determine reasons for ART deferral. Modified Poisson regression was used to evaluate correlates of six-months ART deferral. We adjusted for baseline demographic and clinical factors. We present crude and adjusted risk ratios (aRR) associated with ART deferral. Overall, 99/652 (15.2%) had deferred ART by six months, 20.5% men and 12.2% women. Baseline predictors of ART deferral were older age at diagnosis (adjusted risk ratio (aRR) 1.5 for 30–39.9 vs 18–29.9 years, 95% confidence intervals (CI): 1.0–2.2), disclosure of intentions to test for HIV (aRR 2.2 non-disclosure vs disclosure to a partner/spouse, 95% CI: 1.4–3.6) and HIV testing history (aRR 1.7 for? >?12 months vs?<?12 months/no prior test, 95% CI: 1.0–2.8). Additionally, having a primary house in another country (aRR 2.1 vs current house, 95% CI: 1.4–3.1) and testing alone (RR 4.6 vs partner/spouse support, 95% CI: 1.2–18.3) predicted ART deferral among men. Among the 43/99 six-months interviews, women (71.4%) were more likely to self-report ART initiation than men (RR 0.4, 95% CI: 0.2–0.8) and participants who relocated within SA (RR 2.1 vs not relocated, 95% CI: 1.2–3.5) were more likely to still not be on ART. Under the treat-all ART policy, nearly 15.2% of study participants deferred ART initiation up to six months after the HIV diagnosis. Our analysis highlighted the need to pay particular attention to patients who show little social preparation for HIV testing and mobile populations.

     

The effectiveness of treatment supporter interventions in antiretroviral treatment adherence in sub-Saharan Africa: a systematic review and meta-Analysis

ABSTRACT

This systematic review and meta-analysis evaluated the effectiveness of treatment supporter interventions (TSI) in improving ART adherence and viral suppression among adults living with HIV (PLWH) in sub-Saharan Africa. This review included ten randomized controlled trials (RCT) and six cohort studies comparing treatment support interventions to the standard of care (SOC). Primary outcomes include pill count ART adherence and viral load suppression (VLS). Pooled relative risk ratios (PRR) with 95% confidence intervals were generated using random-effects models. Stratified analyses and meta-regressions were conducted to determine the effect of study type, follow-upperiod, and patient treatment supporters on ART adherence. Treatment supporters included partners, friends, family members, trained community health workers, and HIV positive peers. TSIs were associated with a 7.6% higher ART adherence compared to the SOC group (PRR = 1.076, [95% CI = 1.005, 1.151]). VLS was 5% higher in the treatment group compared to the SOC group (PRR = 1.05, [95% CI = 1.061, 1.207]). There was a significant, positive association between TSIs and VLS in community-based delivery settings but not in facility-based settings. TSIs were statistically significant for VLS in cohort study designs (RR = 1.073, [95% CI = 1.028, 1.121]) but not in RCTs. Findings suggest that TSIs critical in facilitating optimal ART adherence and VLS among PLWHs.     

Voluntary HIV counseling and testing acceptance, sexual risk behavior and HIV incidence in Rakai, Uganda

OBJECTIVE: To assess the acceptance of voluntary HIV counseling and testing (VCT) and the effects of VCT on sexual risk behavior and HIV acquisition in Rakai, Uganda. METHODS: In a rural cohort, 10 694 consenting adults were interviewed, provided blood for HIV testing and were offered free VCT by community resident counselors. The proportions receiving VCT and the adjusted risk ratio (adj. RR) of VCT acceptance were estimated by log binomial regression. Risk behaviors and HIV incidence per 100 person-years (PY) in HIV-negative acceptors and non-acceptors of VCT were assessed prospectively. RESULTS: Although 93% initially requested HIV results, 62.2% subsequently accepted VCT. VCT acceptance was lower among persons with no prior VCT [Adj. RR = 0.88; 95% confidence interval (CI), 0.85-0.90], individuals with primary education (adj. RR = 0.94; 95% CI, 0.90-0.99) or higher (adj. RR = 0.91; 95% CI, 0.87-0.97), individuals who were HIV-positive (adj. RR = 0.72; 95% CI, 0.68-0.76), and persons reporting condom use in the past 6 months (inconsistent users, adj. RR = 0.95; 95% CI, 0.90-0.99; consistent users, adj. RR = 0.88; 95% CI, 0.82-0.95). VCT acceptance was higher among the currently married (adj. RR = 1.14; 95% CI, 1.08-1.20) and previously married (adj. RR = 1.11; 95% CI, 1.04-1.18). Receipt of results was not significantly associated with age, gender, and self-perception of HIV risk. There were no significant differences in sexual risk behaviors, or in HIV incidence between acceptors (1.6/100 PY) and non-acceptors (1.4/100 PY) of VCT. CONCLUSION: In this rural cohort where VCT services are free and accessible, there is self-selection of individuals accepting VCT, and no impact of VCT on subsequent risk behaviors or HIV incidence.     

Adherence to HIV antiretroviral therapy in HIV+ Ugandan patients purchasing therapy

Our objective was to determine the level of adherence and reasons for non-adherence to antiretroviral therapy (ART) among HIV-positive (HIV+) people on ART in a resource-limited setting. Patients receiving ART were recruited into the cross-sectional study from three treatment centres in Kampala, Uganda. The number of missed doses over the last three days was assessed by structured patient interviews and dichotomized at +/-95% adherence. Reasons for non-adherence were assessed with both structured patient interviews and unstructured qualitative interviews. Independent predictors of non-adherence were assessed with multivariate logistic regression. In all, 304 HIV-infected persons on ART were enrolled into the study. Factors associated with non-adherence were marital status (odds ratio (OR) = 2.93, 95% confidence interval (CI) 1.32-6.50) and low monthly income <50 US$ [OR = 2.77, 95% CI 1.64-4.67]. We concluded that levels of self-reported adherence in patients receiving ART in Kampala are comparable to levels in resource-rich settings with inability to purchase and secure a stable supply as a major barrier to adherence.     

Adherence, drug use, and treatment failure in a methadone-clinic-based program of directly administered antiretroviral therapy

Supervised dosing is a cornerstone of tuberculosis treatment. HIV treatment strategies that use directly administered antiretroviral therapy (DAART) are increasingly being assessed. In a prospective single-arm clinical trial, we enrolled methadone-maintained, HIV-infected participants to receive supervised doses of antiretroviral therapy (ART) on days when they received methadone. Other ART doses were self-administered. In this analysis we examined factors associated with retention to DAART, adherence to supervised doses, and virologic failure. Factors associated with retention to DAART were assessed with the Kaplan-Meier method and Cox proportional hazards models. Factors associated with nonadherence with supervised dosing and with virologic failure were assessed by logistic regression and techniques for longitudinal data analysis. A total of 16,453 supervised doses were administered to 88 participants over a median follow-up of 9.4 months. The median participant adherence with supervised dosing was 83%. Active drug use, determined by urine drug screens, was associated twofold increased risks of both intervention dropout and nonadherence with supervised doses. Adherence with supervised doses was strongly associated with virologic failure. Because DAART was administered only on methadone dosing days, fewer than half of the total ART doses were scheduled to be supervised in most participants. The percent of doses that was scheduled to be supervised was not associated with either adherence or with virologic failure. Given that a relatively small proportion of the total ART doses were supervised in many patients, future studies should assess how DAART affects adherence with nonsupervised doses and retention to ART.     

Risk factors for treatment denial and loss to follow-up in an antiretroviral treatment cohort in Kenya

OBJECTIVES: To evaluate risk factors for treatment denial and loss to follow-up in an antiretroviral treatment (ART) cohort in a rural African setting in western Kenya. METHOD: Sociodemographic and clinical data of patients enrolled in an ART cohort were collected within 18 months of an observational longitudinal study and analysed by logistic and Cox regression models. RESULTS: Of 159 patients with treatment indication 35 (22%) never started ART. Pregnancy [adjusted odds ratio (AOR) 3.60, 95% confidence interval (CI) 1.10-11.8; P = 0.035] and lower level of education (AOR 3.80, 95% CI 1.14-12.7; P = 0.03) were independently associated with treatment denial. The incidence of total loss of patients under therapy was 43.2 per 100 person years (pys) (mortality rate 19.2 per 100 pys plus drop out rate 24 per 100 pys). Older age [adjusted hazard ratio (AHR) 1.06, 95% CI 1.01-1.12; P = 0.04], AIDS before starting treatment (AHR 5.83, 95% CI 1.15-29.5; P = 0.03) and incomplete adherence to treatment (AHR 1.05, 95% CI 1.03-1.07; P < 0.001) were independent risk factors for death. Incomplete adherence also independently predicted drop out because of other reasons (AHR 1.06, 95% CI 1.04-1.09; P < 0.001). CONCLUSION: Pregnancy and lower level of education, higher age, advanced AIDS stage and impaired compliance to ART were identified as risk factors for treatment denial and death, respectively. Adequate counselling strategies for patients with these characteristics could help to improve adherence and outcome of treatment programmes in resource-limited settings.     

Rate,causes, and clinical implications of presenting with low CD4+ cell counts in the era of highly active antiretroviral therapy

Of patients attending HIV clinics, neither the proportion with CD4(+) cell counts below 200 cells/microl, and therefore at risk for developing opportunistic infections (OIs), nor the reasons for the persistence of low CD4(+) cell counts are well known in the era of highly active antiretroviral therapy (HAART). In an effort to gather data concerning this issue, the charts of all outpatients who attended two reference HIV clinics in Spain throughout the year 2001 were retrospectively reviewed. Of 1897 subjects, 213 (11%) had at least one CD4(+) cell count determination below 200 cells/microl during 2001. The main reasons for presenting with low CD4(+) cell counts were as follows: (1) poor treatment adherence, 64 (30%); (2) poor immune recovery despite complete virus suppression for longer than 1 year on HAART, 47 (22%); (3) virologic failure under HAART, 33 (15%); (4) no antiretroviral therapy, 23 (11%); (5) initiation of HAART within the current year in subjects with very low CD4(+) cell counts, 17 (8%); (6) impediment in using HAART due to toxicity, 17 (8%); and (7) drug-induced myelotoxicity, 12 (6%). During the period under review, one or more OIs developed in 52 of the 213 (24%) patients with low CD4(+) cell counts. They occurred more frequently in subjects who were naive for antiretroviral drugs or who initiated therapy recently (RR, 6.45; 95% CI, 2.43-17.12; p < 0.001), and conversely tended to be less frequent among subjects with poor immune reconstitution despite complete virologic suppression while on HAART (RR 0.86; 95% CI, 0.28-2.62; p = 0.79). A lower lifetime CD4(+) cell count nadir was associated with a greater risk of developing an OI (RR, 0.98; 95% CI, 0.97-0.99; p < 0.001). We conclude that, despite the availability of HAART, more than 10% of patients currently attending HIV clinics have CD4(+) cell counts <200 cells/microl, and continue to be at risk for developing OIs. Poor treatment adherence and lack of immune recovery despite complete virus suppression while on HAART account for more than half of cases.     

Homelessness as a structural barrier to effective antiretroviral therapy among HIV-seropositive illicit drug users in a Canadian setting

Despite the advent of effective antiretroviral therapy (ART), HIV-seropositive injection drug users (IDU) continue to suffer from elevated levels of morbidity and mortality. Evidence is needed to identify social- and structural-level barriers to effective ART. We investigated the impact of homelessness on plasma HIV RNA response among illicit drug users initiating ART in a setting with free and universal access to HIV care. We accessed data from a long-running prospective cohort of community-recruited IDU linked to comprehensive HIV clinical monitoring and ART dispensation records. Using Cox proportional hazards with recurrent events modeling, we estimated the independent effect of homelessness on time to plasma HIV viral load suppression. Between May 1996 and September 2009, 247 antiretroviral na?ve individuals initiated ART and contributed 1755 person-years of follow-up. Among these individuals, the incidence density of plasma HIV RNA suppression less than 500 copies/mm(3) was 56.7 (95% confidence interval [CI]: 46.9-66.0) per 100 person-years. In unadjusted analyses, homelessness was strongly associated with lower rates suppression (hazard ratio = 0.56, 95% CI: 0.40-0.78, p = 0.001), however, after adjustment for adherence this association was no longer significant (adjusted hazard ratio = 0.79, 95% CI: 0.56-1.11, p = 0.177). Homelessness poses a significant structural barrier to effective HIV treatment. However, since this relationship appears to be mediated by lower levels of ART adherence, interventions to improve adherence among members of this vulnerable population are needed.     

The impact of antiretroviral treatment on mortality trends of HIV‐positive adults in rural Uganda: a longitudinal population‐based study, 1999–2009

Objective To investigate trends in all‐cause adult mortality after the roll‐out of an antiretroviral therapy (ART) programme in rural Uganda. Methods Longitudinal population‐based cohort study of approximately 20 000 residents in rural Uganda. Mortality in adults aged 15–59 years was determined for the 5‐year period (1999–2003) before introduction of ART in January 2004 and for the 5‐year period afterwards. Poisson regression was used to estimate mortality rate ratios (RRs) for the period before ART, 1 year after ART introduction (from January 2004 to January 2005) and more than 1 year after ART introduction. Trends in mortality were analysed by HIV status, age and sex. Results Before ART became available, the mortality rate (deaths per 1000 person‐years) was 4.0 (95% CI = 3.3–4.8) among HIV‐negative individuals and 116.4 (95% CI = 101.9–133.0) among HIV‐positive individuals. During the period January 2004–end November 2009, 279 individuals accessed ART. In the year after ART was introduced, the mortality rate (deaths per 1000 person‐years) among HIV‐negative individuals did not change significantly (adjusted RR = 0.95, 95% CI = 0.61–1.47), but among HIV‐positive individuals dropped by 25% to 87.4 (adjusted RR = 0.75, 95% CI = 0.53–1.06). In the period 2005–2009, the mortality rate (deaths per 1000 person‐years) among HIV‐positive individuals fell further to 39.9 (adjusted RR = 0.33, 95% CI = 0.26–0.43). The effect was greatest among individuals aged 30–44 years, and trends were similar in men and women. Conclusion The substantially reduced mortality rate among HIV‐positive individuals after ART roll‐out lends further support to the intensification of efforts to ensure universal access to ART.     

Adherence and plasma drug concentrations are predictors of confirmed virologic response after 24-week salvage highly active antiretroviral therapy

Data from 197 patients for whom highly active antiretroviral therapy (HAART) failed, who started a new regimen chosen under the guide of resistance testing results interpreted by experts, were retrospectively studied, provided that at least 2 determinations of adherence and plasma drug concentrations were performed during the follow-up. Univariate and multivariable logistic regression analyses were conducted, using confirmed virologic response at week 24 as outcome measure (i.e., achievement of undetectable HIV plasma viral load at any time point before week 24 and its maintenance up to week 24). Suboptimal drug concentrations (odds ratio [OR]: 0.3; 95% confidence interval [CI] 0.2-0.7; p = 0.006) and suboptimal adherence (OR: 0.4; 95% CI 0.2-0.8; p = 0.014) were both negative independent predictors of sustained virologic response, while the use of boosted protease inhibitor-containing regimens resulted to be protective (OR: 2.4; 95% CI 1.1-5.3; p = 0.032).     

Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa

Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.     

Discontinuation of antiresorptive therapies: a comparison between 1998-2001 and 2002-2004 among osteoporotic women

CONTEXT: Studies having reported high rates of discontinuation of antiresorptive therapies (ART) may not reflect their actual use. OBJECTIVES: We compared probability of discontinuation among women aged 70 yr or older with a diagnosis of osteoporosis or recent osteoporotic fracture having started ART (alendronate, risedronate, cyclical etidronate, raloxifene, nasal calcitonin) between 1998-2001 or 2002-2004. PATIENTS AND METHODS: We constructed two cohorts of women using Régie de l'Assurance Maladie du Québec databases. Discontinuation was defined as a lapse of 30 d or longer after completion of a refill. Switching from one ART to another was allowed. Probability of discontinuation was estimated using Kaplan-Meier analysis. Multivariate Cox models were used to identify potential determinants of ART discontinuation over 1 yr. RESULTS: After 1 yr, probability of discontinuation was slightly lower in the 2002-2004 cohort than the 1998-2001 cohort (52.2 vs. 57.5%; P < 0.001). This difference remained significant after adjusting for determinants [adjusted rate ratio (RR) 0.92, 95% confidence interval (CI) 0.87-0.98]. Significant determinants of ART discontinuation within 1 yr included bone mineral density testing (RR 0.77; CI 0.73-0.82) performed within 2 yr prior to initiation of therapy and having consulted more than two pharmacies (RR 1.15; CI 1.06-1.25) in the year before starting therapy. In the 2002-2004 cohort, when switching was allowed, women initiating a once-weekly regimen of alendronate or risedronate did not show a 1-yr risk of discontinuation different from women initiating daily regimens of the same drugs (RR 0.90; CI 0.82-1.00). CONCLUSIONS: Even if new dosing regimens were introduced, discontinuation of ART among osteoporotic women remains high.