Antiretroviral Therapy In Resource-limited Settings Research Articles

Rates of emergence of HIV drug resistance in resource-limited settings: a systematic review.

The increasing availability of antiretroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance. This review summarizes the available information on drug resistance in adults in resource-limited settings. The online databases PubMed and Google Scholar, pertinent conference abstracts and references from relevant articles were searched for publications available before November 2011. Data collected after ART rollout were reviewed. A total of 7 studies fulfilled the criteria for the analysis of acquired drug resistance and 22 fulfilled the criteria for the analysis of transmitted drug resistance (TDR). Acquired resistance was detected in 7.2% of patients on ART for 6-11 months, 11.1% at 12-23 months, 15.0% at 24-35 months, and 20.7% at ≥ 36 months. Multi-class drug resistance increased steadily with time on ART. The overall rate of TDR in all resource-limited countries studied was 6.6% (469/7,063). Patients in countries in which ART had been available for ≥ 5 years were 1.7 × more likely to have TDR than those living in a country where ART had been available for <5 years (P<0.001). The reported prevalence of TDR was 5.7% (233/4,069) in Africa, 7.6% (160/2,094) in Asia and 8.4% (76/900) in Brazil. The emergence of drug resistance following access to ART in resource-limited settings resembles what was seen in resource-rich countries and highlights the need for virological monitoring for drug failure, drug resistance testing and alternative drug regimens that have proven beneficial in these resource-rich settings.

Scaling up antiretroviral therapy in resource-limited settings

This review describes the evolution of WHO guidelines for antiretroviral therapy (ART) in HIV-infected individuals, considering the key epidemiological, scientific, programmatic, and political changes over the last decade, and highlights the major trends for the management of the HIV disease in future guidelines revisions. In the last few years, new evidence has emerged supporting the potential preventive benefit of ART in reducing HIV transmission. This, together with the potential clinical benefits of earlier initiation of therapy, has led to the consideration of the broader strategic use of ART, taking into account the clinical and public health benefit, and programmatic feasibility. In 2002, WHO established its first guidelines for ART use, primarily focused on a public health approach for resource-limited settings. These recommendations were updated in 2003, 2006, and 2010, incorporating progressive changes reflecting progressive increase in the knowledge of HIV pathogenesis, development of new drugs and diagnostics, and increased experience of HIV treatment and prevention programs. The impact of several international political commitments and scale-up initiatives such as the 3 by 5 Initiative, Universal Access targets, and the Treatment 2.0 Strategy were also important drivers of the global response, increasing the treatment coverage and catalyzing the necessary environment for the establishment of operational and programmatic components for an expanded and sustainable global response to HIV/AIDS.

Optimizing Treatment Switch for Virologic Failure during First-Line Antiretroviral Therapy in Resource-Limited Settings

We evaluated adult Nigerian patients with antiretroviral switch to second-line treatment with ritonavir-boosted protease inhibitor (PI/r)-based regimens due to virologic failure (confirmed HIV-1 RNA viral load [VL] >1000 copies/mL) during first-line antiretroviral therapy. Proportion of patients with VL >400 copies/mL and characteristics associated with nonsuppression during second-line treatment are described. Approximately 15% of patients (34 of 225) had VL >400 copies/mL at 1-year after treatment switch to PI/r-based regimens. In adjusted analyses, VL ≥5 log10 copies/mL at treatment switch (odds ratio [OR] 2.90 [confidence interval (CI) 1.21-6.93]); duration of first-line treatment after virologic failure >180 days (OR 2.56 [CI 1.0-6.54]); and PI/r regimen adherence <90% (OR 3.27 [CI 1.39-7.68]) were associated with VL >400 copies/mL at 1 year of second-line treatment. We therefore recommend that the maximum permissible time between suspicion of virologic failure and completion of antiretroviral treatment switch should not exceed 6 months when patients develop first-line antiretroviral failure in resource-limited settings.

Earlier Initialization of Highly Active Antiretroviral Therapy Is Associated With Long-Term Survival and Is Cost-Effective

Raising the guidelines for the initiation of antiretroviral therapy in resource-limited settings at CD4 T-cell counts of 350 cells per microliter raises concerns about feasibility and cost. We examined costs of this shift using data from Uganda for almost 10 years. We projected total costs of earlier initiation with combined antiretroviral therapy, including inpatient and outpatient services, antiretroviral treatment and treatment for limited HIV-related opportunistic diseases, and benefits expressed in years-of-life-saved over 5- and 30-year time horizons using a deterministic economic model to examine the incremental cost-effectiveness ratio (ICER), expressed in cost per year-of-life-saved (YLS). The model generated ICERs for 5- and 30-year time horizons. Discounting both costs and benefits at 3% annually, for the 5-year analysis, the ICER was $695/YLS and $769 in the 30-year analysis. The results were most sensitive to program cost and the discount rate applied, but they were less sensitive to opportunistic infection treatment costs or the relative-risk reduction from earlier initiation. Program costs varied from 25% to 125%, and the ICER for the lower bound decreased to $491/YLS at 5-years and $574/YLS at 30 years. For the upper bound, the ICER increased to $899 for 5-years and $964 at 30-years. The budget impact of adoption, assuming the same level of program penetration in the community, is $261,651,942 for 5 years and $872,685,561 for 30 years. Our model showed that earlier initiation of combined antiretroviral therapy in Uganda is associated with improved long-term survival and is highly cost-effective, as defined by WHO-CHOICE.

Article Commentary: Antiretroviral Therapy in Resource-Limited Settings: Is There Still a Role for Stavudine?

Phanuphak et al. compared three strategies for first-line antiretroviral therapy in 150 Thai patients: initiating therapy with zidovudine (AZT), tenofovir disoproxil fumarate (TDF), or a 24-week lead-in phase with stavudine (d4T) followed by a switch to AZT. Those taking d4T had higher haemoglobin levels and CD4(+) T-cell counts without an increase in neuropathic symptoms, peripheral neuropathy or lipoatrophy compared with those on AZT. Because AZT is associated with more short-term side effects and toxicity than d4T, and because most d4T toxicity occurs only after long-term use, this approach may have advantages over initial use of AZT. However, TDF-based regimens, while more expensive, are more effective, better tolerated, less toxic, less likely to lead to cross-resistance, and possibly more cost-effective. The goal in resource-limited settings should be to move away from use of thymidine analogues in first-line regimens.

Cryptococcal Antigen Screening and Preemptive Therapy in Patients Initiating Antiretroviral Therapy in Resource-Limited Settings

HIV-associated cryptococcal meningitis (CM) is estimated to cause over half a million deaths annually in Africa. Many of these deaths are preventable. Screening patients for subclinical cryptococcal infection at the time of entry into antiretroviral therapy programs using cryptococcal antigen (CRAG) immunoassays is highly effective in identifying patients at risk of developing CM, allowing these patients to then be targeted with "preemptive" therapy to prevent the development of severe disease. Such CRAG screening programs are currently being implemented in a number of countries; however, a strong evidence base and clear guidance on how to manage patients with subclinical cryptococcal infection identified by screening are lacking. We review the available evidence and propose a treatment algorithm for the management of patients with asymptomatic cryptococcal antigenemia.

Viral load monitoring in resource-limited settings

When antiretroviral therapy (ART) scale up began in Africa a decade ago, there was concern that lack of laboratory monitoring for patients receiving antiretroviral drugs would be an obstacle to providing treatment. To address this concern, the first set of World Health Organization (WHO) guidelines for ART in resource-limited settings rightly recommended that programmes should primarily use clinical criteria for monitoring treatment efficacy [1].

What Is the Optimal First Line Antiretroviral Therapy in Resource-Limited Settings?

A perspective by Chris Kenyon and Robert Colebunders discusses policy implications for use of first line antiretroviral therapies in resource-limited settings, emerging from a new research study conducted by Campbell and colleagues.

Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings

To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs). An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000 copies/ml. Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100 mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r. Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400 copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40 copies/ml and 30 had levels 40-200 copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400 copies/ml. In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.

Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings.

BackgroundChanges in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART.MethodNaïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART.Results3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12.ConclusionIn routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

Genotype assays and third-line ART in resource-limited settings

To project the clinical and economic outcomes of a genotype assay for selection of third-line antiretroviral therapy (ART) in resource-limited settings, as per the planned international A5288 trial (MULTI-OCTAVE). We used the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-International Model to compare three strategies for patients who have failed second-line ART in South Africa: sustained second-line: no genotype assay, all patients remain on second-line ART; A5288: genotype to determine the resistance profile and assign an appropriate regimen; or population-based third-line: no genotype, all patients switch to a potent third-line regimen. Model inputs are from published data in South Africa. Resistance profiles, ART regimens, and efficacy data were those used for trial planning. Projected life expectancy for sustained second-line, A5288, and population-based third-line are 61.1, 103.8, and 104.2 months. Compared to sustained second-line ($12 ,460), per person lifetime costs increase for the A5288 ($39, 250) and population-based ($44, 120) strategies. The incremental cost-effectiveness ratio of A5288, compared to sustained second-line, is $7500/year of life saved (YLS), and for population-based third-line, compared to A5288, is $154 ,500/YLS. In the A5288 strategy, very late presentation to care, coupled with lengthy delays to obtain the genotype, dramatically reduces 5-year survival, making the population-based third-line strategy more attractive. We project that, whereas the public health approach to third-line therapy is unaffordable, genotype assays and third-line ART in resource-limited settings will increase survival and be cost-effective compared to the population-based approach, supporting the value of an efficacy study.

Impact of malnutrition and social determinants on survival of HIV-infected adults starting antiretroviral therapy in resource-limited settings

Determining the impact of malnutrition, anaemia and social determinants on survival once starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in a rural HIV care centre in Sihanoukville, Cambodia. Retrospective and descriptive cohort study of adults starting ART between December 2004 and July 2009. We used the Kaplan-Meier and Cox regression survival analyses to identify predictors of death. Out of 1002 patients, 49.7% were men; median age was 40; median time of follow-up was 2.4 years and 10.4% died during the follow-up. At baseline, median CD4 cell count was 83 cells/μl, 79.9% were at WHO stage III or IV. In multivariate analysis, malnutrition appeared to be a strong and independent risk factor of death; 11.2% had a BMI less than 16 kg/m and hazard ratio was 6.97 [95% confidence interval (CI), 3.51-13.89], 21.5% had a BMI between 16 and 18 kg/m and hazard ratio was 2.88 (95% CI, 1.42-5.82), 30.8% had a BMI between 18 and 20 kg/m and hazard ratio was 2.18 (95% CI, 1.09-4.36). Severe anaemia (haemoglobin≤8.4 g/dl) and CD4 cell count below 100 cells/μl also predicted mortality, hazard ratio were 2.25 (95% CI, 1.02-4.34) and 2.29 (95% CI, 1.01-2.97), respectively. Social determinants were not significantly associated with death in univariate analysis. Malnutrition and anaemia are strong and independent prognostic factors at the time of starting ART. Nutritional cares are essential for the clinical success of HIV programs started in developing countries.

Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings

A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings. Two reviewers independently searched four databases and three conference websites. Full text articles were screened and data extracted using a standardized data extraction form. We retrieved 5812 citations, of which 19 studies reporting second-line failure rates in 2035 patients across low-income and middle-income countries were eligible for inclusion. The cumulative pooled proportion of adult patients failing virologically was 21.8, 23.1, 26.7 and 38.0% at 6, 12, 24 and 36 months, respectively. Most studies did not report adequate information to allow discrimination between drug resistance and poor adherence as reasons for virological failure, but for those that did poor adherence appeared to be the main driver of virological failure. Mortality on second-line was low across all time points. Rates of virological failure on second-line therapy are high in resource-limited settings and associated with duration of exposure to previous drug regimens and poor adherence. The main concern appears to be poor adherence, rather than drug resistance, from the limited number of studies accessing both factors. Access to treatment options beyond second-line remains limited and, therefore, a cause for a concern for those patients in whom drug resistance is the identified cause of virological failure.

A Model for Reduced HIV-1 Viral Load Monitoring in Resource-Limited Settings

Viral load monitoring of antiretroviral therapy in low-income countries is rarely used because of high costs. Reducing the frequency of monitoring may make it financially feasible. We modeled three testing schemes: reduced viral load monitoring (RVLM) with CD4 count at baseline and viral load testing at 6, 36, and 60 months; United States Department of Health and Human Services (US DHHS) Treatment Guidelines; and World Health Organization (WHO) Guidelines using a cohort of 313 HIV-infected patients using Kaplan-Meier analysis. Median time to detection of antiretroviral therapy (ART) failure using RVLM was 147 days; using US DHHS, it was 115 days; and using WHO guidelines, it was 1110 days. Median time for the development of first thymidine analog mutation was 594 days. The cost of RVLM was significantly lower than US DHHS. RVLM detected failure significantly sooner than CD4 count monitoring alone at a lower cost than US DHHS monitoring. RVLM is a potentially effective method of monitoring ART in resource-limited settings.

Preferred antiretroviral drugs for the next decade of scale up

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.

The impact of first year adherence to antiretroviral therapy on long-term clinical and immunological outcomes in the DART trial in Uganda and Zimbabwe

To describe associations between different summaries of adherence in the first year on antiretroviral therapy (ART) and the subsequent risk of mortality, to identify patients at high risk because of early adherence behaviour. We previously described an approach where adherence behaviour at successive clinic visits during the first year on ART was seen as a Markov chain (MC), and the individually estimated transition probabilities between 'good', 'poor' and 'non-response' adherence states were used to classify HIV-infected adults in the DART trial into subgroups with similar behaviour. The impact of this classification and classifications based on traditional 'averaged' measures [mean drug possession ratio (DPR) and self-reported adherence] were compared in terms of their impact on longer-term mortality over the 2-5 years on ART using Cox proportional hazards models. Of 2960 participants in follow-up after 1 year on ART, 29% had never missed pills in the last month and 11% had 100% DPR throughout the first year. The poorest adherers by self-reported measures were more likely to have only none/primary education (P < 0.01). Being in the poorest adherence subgroup by MC and DPR was independently associated with increased mortality [HR = 1.57 (95% CI 1.02, 2.42); 1.82 (1.32, 2.51) respectively]. Classification based on dynamic adherence behaviour is associated with mortality independently of DPR. The classifications could be useful in understanding adherence, targeting focused interventions and improving longer-term adherence to therapy.

Home-Based HIV Counseling and Testing as a Gateway to Earlier Initiation of Antiretroviral Therapy

Timely access to combination antiretroviral therapy (ART) represents the single most effective intervention in reducing mortality and morbidity among patients with human immunodeficiency virus (HIV) infection or AIDS. Until recently, the threshold for initiating ART in resource-limited settings was set at a CD4 T-cell count #200 cells/mm, a conservative threshold that had been abandoned in wealthier settings several years earlier [1]. Randomized trial data [2] and cohort evaluations [3] that demonstrate improved survival when ART is initiated earlier provided convincing evidence for the World Health Organization to revise guidance for resource-limited settings to initiate ART at a CD4 T-cell count #350 cells/mm. Most developing countries have now adopted or strive for this target threshold. More recent studies have validated this shift by demonstrating the broader benefits of earlier initiation of ART, including reduced incidence of tuberculosis [4], reduced rates of hospitalization [5], reduced likelihood of HIV transmission [6], and increased life expectancy [7]. Changing the threshold for initiation was seen as a daunting task, and a common refrain in discussions about early ART initiation in resource-limited settings was that raising the threshold would overwhelm healthcare systems by increasing the number of new patients requiring a clinician’s time [8]. It has often been pointed out that most patients in sub-Saharan Africa present too late as it is, with an average CD4 T cell count of only 111 cells/mm [9]. For the most part, however, the reasons that patients present late to care have nothing to do with initiation thresholds at the clinic. Rather, they are related to a lack of awareness of their HIV status [10] or disincentives to accessing care, such as high costs [11] or distances from clinics [12]. There is no convincing evidence that individuals arrive late to care because they have been ‘‘crowded out’’ by patients who are not as sick. Earlier treatment means that patients do not become as sick and thus need less-complex care. Evidence from programs to date suggests that earlier initiation supports access to care by promoting delivery of ART by nurse-led primary care clinics and reducing demands for more-specialized and inpatient clinical care [5]. Although considerable research attention has been paid to demonstrating the relative merits of earlier ART initiation, the question of how to encourage persons to seek treatment earlier has to date been almost entirely neglected. Recently, the need for better retention in care between testing and initiation of treatment for eligible patients has been recognized [13]. An important prior concern is to identify patients as early as possible, both to decrease the likelihood of transmission between partners and to provide an early opportunity to engage patients into care. Home-based counseling and testing (HBCT) represent an important strategy for identifying patients before their CD4 T cells are severely depleted. It is also a strategy to engage underrepresented populations in HIV/AIDS testing. Populations such as men, the elderly, and adolescents [14, 15] are regularly excluded from testing campaigns and are thus underrepresented in ART treatment programs, leading to worse overall mortality for these groups [16]. Designers of targeted HBCT that aim to broadly involve either the entire population in a setting or an accurate sample of it need to consider whether these groups are likely to be identified through HBCT or more likely to be located outside the home [17]. The study by Wachira and colleagues provides compelling evidence that widespread HIV counseling HBCT helps identify Received 21 September 2011; accepted 26 September 2011. Correspondence: Edward J. Mills, PhD, University of Ottawa, 43 Templeton, Ottawa, Ontario, K1N 6X1, Canada 778317 8530 (edward.mills@uottawa.ca). Clinical Infectious Diseases 2012;54(2):282–4 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cir812

Reliability of absolute lymphocyte count as a marker to assess the need to initiate antiretroviral therapy in HIV-infected children

CD4 counts are a standard laboratory measure of disease progression in HIV-infected children. However, CD4 counting is done by flow cytometry and may not always be possible in every centre treating HIV-infected children in resource-limited countries. Absolute Lymphocyte Count (ALC) can be derived easily by performing a routine white blood cell count. The World Health Organization (WHO) in 2006 had recommended ALC to identify HIV-infected children in need of ART in resource-limited settings, when CD4 cell count is not available. This study aims to assess the reliability of using ALC as a marker for starting antiretroviral therapy (ART) in HIV-infected children in a tertiary hospital setting. Retrospective analysis of 46 HIV-infected children who presented at a pediatric HIV clinic at a tertiary referral centre from 2002-2005. Using WHO 2006 guidelines for cutoff values of ALC and 2008 guidelines for CD4% as a comparative standard, a retrospective analysis was done on ART-naοve HIV-infected children who underwent baseline CD4% and ALC, and sensitivity and specificity of ALC was calculated. Fischer exact two-tailed analysis was used to correlate ALC and CD4 and need for starting ART. Sensitivity of ALC was 27.6% (72.4% were false negatives), specificity was 70.6%, with positive predictive value of 61.5%. On comparison across all clinical stages of disease, only 13/46 children (28.2%) would have been started on ART according to ALC cutoffs versus 29/46 children (63.04%) using CD4 criteria (P value=0.0015). In children with WHO clinical Stage 1 or 2 of disease, only 1/11 (9.1%) children were identified by ALC as requiring ART as opposed to 6/11 (54.5%) children by CD4% (P=0.0635). ALC is an unreliable marker to determine the need for starting ART in HIV-infected children.

Correlation between Health-Related Quality of Life and Various Therapeutic Monitoring Parameters of Ivorian HIV-Infected Patients

Background: Health-related quality of life (HRQOL) is an important issue for HIV-infected patients on antiretroviral therapy (ART). The purpose of our study was to highlight particular items of HRQOL correlated to some monitoring parameters during ART in resource-limited settings (RLS): mean CD4 count, adherence, drug side effects (DSE), cotrimoxazole prophylaxis, self-medication and opportunistic infections. Methods: HRQOL and self-medication were evaluated cross sectionally at eighteenth month of ART with 231 Ivorian HIV-infected patients. Our survey was performed using the MOS-HIV questionnaire for HRQOL. The mean CD4 count during ART was determined with values measured at sixth month (M6), twelfth month (M12), eighteenth month (M18). Routine data from clinical visit at M6, M12, and M18 were used to assess longitudinally the quality of adherence, the occurrence of drug side effects and opportunistic infections during ART. These parameters were evaluated by each patient’s physician. Results: Regardless of CD4 counts, scores of HRQOL items attached to them were homogeneous, (patients had an equivalent quality of life). Good adherence was significantly correlated with high general health perception scores, and overall quality of life component scores. Physical functioning and cognitive functioning were significantly influenced by the occurrence of DSE; scores of these items were higher without DSE. Considering the global HRQOL scores, the existence or not of cotrimoxazole prophylaxis did not influence differently the HRQOL scores. Patients who practiced self-medication had global HRQOL scores not significantly different from those who did not practice it. However, we found significant correlations between the practice of self-medication and mental health, energy/ fatigue and cognitive functioning. The scores of these items were greater in patients not practicing self-medication. Conclusion: Information about therapeutic risks related to incomplete adherence, DSE and self-medication must be a crucial element integrated in counseling for HIV-infected patients to help optimize their HRQOL in RLS.

Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings

Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings