Antiretroviral Dosing Research Articles

Long-Acting, Injectable Antiretroviral Therapy for the Management of HIV Infection: An Update on a Potential Game-Changer

The efficacy of daily oral antiretroviral (ARVs), even when combined with supplemental adherence strategies, remains limited by non-adherence. Resistance and treatment failure resulting from missed ARV doses continue to hamper efforts to curb the epidemic. This commentary argues that we must simplify ARV regimens even further, and highlights the potential for long-acting injectable (LAI) formulations to facilitate weekly, monthly, and multi-month ARV regimens in both resource rich and resource poor settings. We summarize the latest progress in LAI development and reflect on the potential of LAIs to revolutionize HIV management and define the next frontier of HIV medicine.

Individualized Texting for Adherence Building (iTAB): Improving Antiretroviral Dose Timing Among HIV-Infected Persons with Co-occurring Bipolar Disorder

HIV+ persons with co-occurring bipolar disorder (HIV+/BD+) have elevated rates of medication nonadherence. We conducted a 30-day randomized controlled trial of a two-way, text messaging system, iTAB (n = 25), compared to an active comparison (CTRL) (n = 25) to improve antiretroviral (ARV) and psychotropic (PSY) adherence and dose timing. Both groups received medication adherence psychoeducation and daily texts assessing mood. The iTAB group additionally received personalized medication reminder texts. Participants responded to over 90 % of the mood and adherence text messages. Mean adherence, as assessed via electronic monitoring caps, was high and comparable between groups for both ARV (iTAB 86.2 % vs. CTRL 84.8 %; p = 0.95, Cliff's d = 0.01) and PSY (iTAB 78.9 % vs. CTRL 77.3 %; p = 0.43, Cliff's d = -0.13) medications. However, iTAB participants took ARVs significantly closer to their intended dosing time than CTRL participants (iTAB: 27.8 vs. CTRL: 77.0 min from target time; p = 0.02, Cliff's d = 0.37). There was no group difference on PSY dose timing. Text messaging interventions may represent a low-burden approach to improving timeliness of medication-taking behaviors among difficult-to-treat populations. The benefits of improved dose timing for long-term medication adherence require additional investigation.

Electrospun solid dispersions of Maraviroc for rapid intravaginal preexposure prophylaxis of HIV.

The development of topical anti-human immunodeficiency virus (HIV) microbicides may provide women with strategies to protect themselves against sexual HIV transmission. Pericoital drug delivery systems intended for use immediately before sex, such as microbicide gels, must deliver high drug doses for maximal effectiveness. The goal of achieving a high antiretroviral dose is complicated by the need to simultaneously retain the dose and quickly release drug compounds into the tissue. For drugs with limited solubility in vaginal gels, increasing the gel volume to increase the dose can result in leakage. While solid dosage forms like films and tablets increase retention, they often require more than 15 min to fully dissolve, potentially increasing the risk of inducing epithelial abrasions during sex. Here, we demonstrate that water-soluble electrospun fibers, with their high surface area-to-volume ratio and ability to disperse antiretrovirals, can serve as an alternative solid dosage form for microbicides requiring both high drug loading and rapid hydration. We formulated maraviroc at up to 28 wt% into electrospun solid dispersions made from either polyvinylpyrrolidone or poly(ethylene oxide) nanofibers or microfibers and investigated the role of drug loading, distribution, and crystallinity in determining drug release rates into aqueous media. We show here that water-soluble electrospun materials can rapidly release maraviroc upon contact with moisture and that drug delivery is faster (less than 6 min under sink conditions) when maraviroc is electrospun in polyvinylpyrrolidone fibers containing an excipient wetting agent. These materials offer an alternative dosage form to current pericoital microbicides.

Antiretroviral dose reduction: good for patients and rollout

Of the 35 million people living with HIV, almost a third are already on antiretroviral therapy, and the current aim is to increase substantially the number of people on medication during the next 5–10 years.1 WHO recommends a regimen of the non-nucleoside reverse transcriptase inhibitor efavirenz, and the nucleotide and nucleoside reverse transcriptase inhibitors tenofovir and lamivudine (or emtricitabine), as the preferred primary fixed-drug combination treatment.2 This recommendation is based on extensive evidence supporting efficacy, simplicity, and tolerability, and allows for one drug procurement schema that is affordable, can be safely used in pregnancy, can be combined with tuberculosis drugs, and is effective against hepatitis B virus.

Text message intervention designs to promote adherence to antiretroviral therapy (ART): a meta-analysis of randomized controlled trials.

BackgroundThe efficacy of antiretroviral therapy depends on patient adherence to a daily medication regimen, yet many patients fail to adhere at high enough rates to maintain health and reduce the risk of transmitting HIV. Given the explosive global growth of cellular-mobile phone use, text-messaging interventions to promote adherence are especially appropriate. This meta-analysis synthesized available text messaging interventions to promote antiretroviral therapy adherence in people living with HIV.MethodsWe performed Boolean searches of electronic databases, hand searches of recent year conference abstracts and reverse searches. Included studies (1) targeted antiretroviral therapy adherence in a sample of people living with HIV, (2) used a randomized-controlled trial design to examine a text messaging intervention, and (3) reported at least one adherence measurement or clinical outcome.ResultsEight studies, including 9 interventions, met inclusion criteria. Text-messaging interventions yielded significantly higher adherence than control conditions (OR = 1.39; 95% CI = 1.18, 1.64). Sensitivity analyses of intervention characteristics suggested that studies had larger effects when interventions (1) were sent less frequently than daily, (2) supported bidirectional communication, (3) included personalized message content, and (4) were matched to participants’ antiretroviral therapy dosing schedule. Interventions were also associated with improved viral load and/or CD4+ count (k = 3; OR = 1.56; 95% CI = 1.11, 2.20).ConclusionsText-messaging can support antiretroviral therapy adherence. Researchers should consider the adoption of less frequent messaging interventions with content and timing that is individually tailored and designed to evoke a reply from the recipient. Future research is needed in order to determine how best to optimize efficacy.

Pre-exposure prophylaxis for the prevention of HIV infection in high risk populations: a meta-analysis of randomized controlled trials.

BackgroundNearly ten randomized controlled trials (RCTs) of pre-exposure prophylaxis (PrEP) have been completed or are ongoing worldwide to evaluate the effectiveness of PrEP in HIV transmission among HIV-uninfected high risk populations. The purpose of this study was to evaluate the role of PrEP to prevent HIV transmission through a Mata-analysis.MethodsA comprehensive computerized literature search was carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wan Fang, CNKI and related websites to collect relevant articles (from their establishment date to August 30, 2013). The search terms were “pre-exposure prophylaxis”, “high risk population”, “HIV infection”, “reduction”, “relative risk” and “efficacy”. We included any RCT assessing PrEP for the prevention of HIV infection in high risk populations. Interventions of the studies were continuously daily or intermittent doses of single or compound antiretrovirals (ARVs) before HIV exposure or during HIV exposure. A meta-analysis was conducted using Stata 10.0. A random-effects method was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI) for all studies included.ResultsSeven RCTs involving 14,804 individuals in high risk populations were eligible for this study. The number of subjects in the experimental groups was 8,195, with HIV infection rate of 2.03%. The number of subjects in the control groups was 6,609, with HIV infection rate of 4.07%. The pooled RR was 0.53 (95% CI = 0.40∼0.71, P<0.001). The re-analyzed pooled RR were 0.61 (95% CI = 0.48∼0.77, P<0.001), 0.49 (95% CI = 0.38∼0.63, P<0.001), respectively, by excluding the largest study or two studies without statistical significance. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 1,022.ConclusionThese results show that PrEP is an effective strategy for reducing new HIV infections in high risk populations.

Treatment optimization

In this issue of Current Opinion, the Guest Editors and their colleagues provide a comprehensive overview of current activities aimed at optimizing global HIV treatment. In this introduction, we outline current goals and approaches that will be described in more detail elsewhere in this issue. Two recent conferences, the first and second Conference on Antiretroviral Drug Optimization (CADO), brought together experts from academia, governments, foundations, the pharmaceutical industry, and community activists to develop a global HIV-treatment research agenda for the coming decade focused on better therapies and how to make them accessible to a broader population of people living with HIV. Important recommendations included a focus on more efficient process chemistry for antiretroviral drugs, investigation of antiretroviral dose reduction as a possible optimization strategy, recognition of the increasing importance of concurrent infections and comorbidities especially tuberculosis and aging-related diseases, and identifying a highly effective and affordable nontoxic, once-daily fixed-dose combination regimen for first-line treatment. HIV treatment optimization is a process intended to enhance the long-term efficacy, adherence, tolerability, safety, convenience, and affordability of combination ART. The ultimate goal of this process is to expand access to well tolerated and effective lifetime treatment to all those in need.

Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients

Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population. We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the US Food and Drug Administration (FDA) Guidance for industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared with recommended dosages based on the level of estimated kidney function, 3-19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation. The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing-related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function.

Optimizing HIV treatment

There are at least seven million people eligible for antiretroviral treatment but not receiving it. An additional 19 million people will need to start treatment in the future, as their HIV disease progresses. Funding for Universal Access to HIV treatment has been restricted by the Global Financial Crisis. There are three large randomized trials ongoing, designed to establish the efficacy of lower than approved doses of antiretrovirals. If successful, the results of these trials could lower costs of antiretrovirals and improve the safety profiles. Clinical trials evaluating efavirenz, atazanavir, ritonavir and stavudine are discussed. The costs of these and other antiretrovirals are presented. The results of these trials could significantly lower the costs of Universal Access. Assuming 15 million people on antiretroviral treatment, the reduction in unit costs of tenofovir (TDF)/3TC/efavirenz from dose optimization of efavirenz to 400 mg once daily would save US$16 per person, leading to an overall saving of US$192 million per year. The switch from zidovudine (ZDV)/3TC/atazanavir (ATV)/r 300/100 once daily to dolutegravir along with ATV/r 200/50 once daily would save US$267 per person, leading to an overall saving of US$801 million. The combined saving in costs from first- and second-line treatment would therefore be US$993 million per year.

Impact of antiretroviral dosing frequency and daily pill burden on virological success rates in patients of the ICoNA cohort starting their first ART

Complexity of antiretroviral treatment (ART) is a reason for non‐adherence and may impact treatment outcome. The association between daily dosing and pill burden and chance of virological success (VS) of first ART has been rarely assessed. 3,674 naïve patients who started treatment after January 2000 were identified from the ICoNA cohort. Number of daily doses and pills were estimated on the basis of the drugs used to rank first ART complexity: 1–2 daily pills once a day (low‐pills QD [lpQD]); 3–6 daily pills QD (high‐pills QD [hpQD]); 2–5 daily pills BID (low‐pills BID [lpBID]); &gt;6 daily pills BID (high‐pills BID [hpBID]). VS was the date of first HIV RNA &lt;50 cp/ml. Follow‐up was censored at the date of VS or last available HIV RNA. Kaplan‐Meier curves estimated probability of achieving VS according to ART complexity. Univariable and multivariable Cox regression stratified by clinical site was used to identify variables associated with VS. ITT principle was applied, using competing risk approach for death. Population: male 75%; median age 37 y (IQR, 32–44); HIV transmission heterosexual 43%, homosexual 33%, drug use 16%; Italian origin 86%; CDC group C 17%; median pre‐ART CD4 and log HIV‐RNA were 271/mm3 (range, 0–1672) and 4.84 cp/ml (1.70–6.38), respectively. Regimens were started in ‘00–‘02 24%,‘03–‘05 17%,‘06–‘08 17%,‘09–‘12 42% and based on NNRTI in 40%, PI/r 43%, PI 8%, other ART 10%. Frequencies in complexity ranks were: 19% lpQD, 23% hpQD, 32% lpBID, 26% hpBID. VS was achieved by 85% of patients with an overall median time to VS of 5.6 months (95% CI: 5.4–5.8). Median months to VS were shorter with decreasing complexity: hpBID 6.5; lpBID 6.0; hpQD 5.3, lpQD 4.5. Kaplan‐Meier curves are shown (Figure).imageAfter stratifying for clinical site and adjusting for age, gender, origin, transmission route, CDC group C, HCV/HBV infection, years of HIV, pre‐cART CD4 and HIV‐RNA, type of regimen a significantly reduced likelihood of achieving VS was found for ART complexity (hpQD: HR 0.76 95% CI 60–0.96; lpBID: 0.74, 0.59–0.94) when compared with lpQD. The chance of VS was higher in people starting ART more recently (RH 1.28 [95% CI 1.09–1.51] for ‘03–‘05; RH 1.64 [1.27–2.10] for ‘09–‘12; vs. ‘00–‘02) and was lower in people with previous AIDS (RH 0.85 [0.73–0.98]). Once‐a‐day dosing of ART, especially when combined with low daily pill burden, seems to be one of main factors contributing to the higher rate of success of ART in recent years.

Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naïve HIV patients

There are few data on the impact of antiretroviral therapy (ART) regimen factors on adherence in ART-naïve HIV patients on contemporary once- or twice-daily regimens. Ninety-nine newly diagnosed patients in a prospective observational cohort study completed a visual analogue scale to assess their ART adherence. Adherence by type of ART and dosing frequency were compared by Brown-Mood median tests. Participants taking once-daily regimens had higher adherence (n = 70, 99.5%) compared with participants taking twice-daily regimens (n = 29, 94%; P = 0.01). Adherence of participants taking the fixed dose combination efavirenz-emtricitabine-tenofovir (n = 34, 100%) compared with those taking once-daily regimens of two or more pills was no different (n = 36, 99.3%; P = 0.34). Among a cohort of newly diagnosed ART-naïve patients, once-daily dosing of ART resulted in higher adherence than twice-daily dosing. Pill burden among once-daily regimens did not predict adherence, suggesting that factors other than pill burden should drive regimen selection.

Stable Virologic Suppression during Raltegravir plus Atazanavir Dual-Therapy Taken Every other Day: A Case Report

Adherence to Highly Active Antiretroviral Therapy can be affected by a number of factors limiting the outcome of the treatment. We report the case of a 39 year-old HIV-HCV co-infected woman in stable virologic suppression and immune recovery during a raltegravir plus unboosted atazanavir dual-therapy taken every other day. Measurement of HIV-1 RNA plasma levels (viral load), CD4+ T-cell counts and the therapeutic drug monitoring through validated high-performance liquid chromatography methods, were performed to assess the effectiveness of this regimen. Our data on raltegravir pharmacokinetics in association with atazanavir show adequate minimum effective concentrations of raltegravir throughout 36 and 48 hours despite the every other day intake of the drug. Further studies are recommended in order to identify the determinants that could enable a reduction in antiretroviral dosing frequency in case of difficult management of HIV-infected patients due to low adherence to therapy. By reporting our medical experience, we focused on the utility of performing therapeutic drug monitoring especially in cases of poor adherence, drug and/or alcohol abuse, co morbidities and co-administration of other drugs.

584: Once-daily versus twice-daily antiretroviral dosing in HIV-infected pregnant women

Current recommendations for antiretroviral-naive patients support initiating nonpregnant HIV-infected patients on a once-daily (QD) regimen. However, seropositive pregnant women are often initiated or changed to a twice-daily (BID) regimen due to the historical preference and traditional dosing of zidovudine. We aimed to compare the efficacy and safety between QD and BID regimens in HIV-infected pregnant women.

Pharmacokinetics of Lamivudine and Lamivudine-Triphosphate after Administration of 300 Milligrams and 150 Milligrams Once Daily to Healthy Volunteers: Results of the ENCORE 2 Study

There is interest in evaluating the efficacy of lower doses of certain antiretrovirals for clinical care. We determined here the bioequivalence of plasma lamivudine (3TC) and intracellular 3TC-triphosphate (3TC-TP) concentrations after the administration of two different doses. ENCORE 2 was a randomized crossover study. Subjects received 3TC at 300 and 150 mg once daily for 10 days (arm 1; n = 13) or vice versa (arm 2; n = 11), separated by a 10-day washout. Pharmacokinetic (PK) profiles (0 to 24 h) were assessed on days 10 and 30. Plasma 3TC and 3TC-TP levels in peripheral blood mononuclear cells were quantified by high-performance liquid chromatography-tandem mass spectrometry. Within-subject changes in PK parameters (the area under the concentration-time curve from 0 to 24 h [AUC(0-24)], the trough concentration of drug in plasma at 24 h [C(24)], and the maximum concentration of drug in plasma [C(max)]) were evaluated by determining the geometric mean ratios (GMRs) adjusted for study arm, period, and intra-individual variation. Regimens were considered bioequivalent if the 90% confidence interval (90% CI) fell within the range of 0.8 to 1.25. A total of 24 subjects completed the study. The GM (90% CI) 3TC AUC(0-24)), expressed as ng·h/ml, for the 300- and 150-mg doses were 8,354 (7,609 to 9,172) and 4,773 (4,408 to 5,169), respectively. Bioequivalence in 3TC PK following the administration of 300 and 150 mg was not demonstrated: the GMRs for AUC(0-24), C(24), and C(max) were 0.57 (0.55 to 0.60), 0.63 (0.59 to 0.67), and 0.56 (0.53 to 0.60), respectively. The GM (90% CI) 3TC-TP AUC(0-24) values (pmol·h/10(6) cells) for the 300- and 150-mg doses were 59.5 (51.8 to 68.3) and 44.0 (38.0 to 51.0), respectively. Bioequivalence in 3TC-TP PK following the administration of 300 and 150 mg was not demonstrated: the GMRs for AUC(0-24), C(24), and C(max) were 0.73 (0.64 to 0.83), 0.82 (0.68 to 0.99), and 0.70 (0.61 to 0.82), respectively. We found that 3TC at 150 mg is not bioequivalent to the standard regimen of 300 mg, indicating that saturation of cytosine phosphorylation pathways is not achieved at a dose of 150 mg.

Mathematical analysis of an HIV model with impulsive antiretroviral drug doses

In this paper, we incorporate the periodic therapy from antiretroviral drugs for HIV into the standard within-host virus model, and study the stability and bifurcation of the system. It is shown that when the basic reproduction number of virus is less than one, there is an infection-free equilibrium which is globally stable. Further, if it is greater than one, the HIV infection is uniformly persistent. Besides, subharmonic bifurcation occurs under suitable conditions, and chaotic attractor may emerge through period doubling routes, which can be used to explain the HIV patients’ unpredictable unstable health states, even after a long and hard treatment.

Social meanings of adherence to antiretroviral therapy in Cambodia

Global expansion of antiretroviral therapy (ART) programmes for people living with HIV is the largest public health undertaking to date. Antiretroviral therapy adherence drives individual and programme outcomes, yet little is known regarding the determinants of these behaviours. We investigated beliefs and practices associated with ART use in Cambodia. In-depth interviews were conducted during 2005 with 27 people living with HIV who were recruited using a theoretical sampling strategy and analysed in Khmer and English using an inductive approach to code data and identify themes. Limited access to ART generated a sense of ART as rare and precious, with access granted by doctors once patients proved themselves dependable. The social construction of ART use was strict, precise and modern with ritualistic preparation and dosing procedures. Experiences of life-saving efficacy in self and others built a deep sense of trust. For many, ART was simply equated to life. Antiretroviral therapy dosing was prioritized and supported by an ever-present sense of remembering, reminder devices and social networks. Healthcare workers set norms and provided various forms of adherence support. Antiretroviral therapy use in Cambodia is shaped by the relationship between individuals and social and healthcare networks that set, encourage and enforce precise norms of ART use.

Newborn outcomes in a cohort of premature babies born to HIV infected mothers: a single centre experience

BackgroundPremature babies born to HIV positive mothers are at an increased risk of vertical transmission. This is complicated by the limited choice and the absence of adequate antiretroviral dosing and...

Factors Associated with Complete Adherence to HIV Combination Antiretroviral Therapy

Purpose: To assess factors associated with adherence, particularly pill burden, to combination antiretroviral therapy (cART) using multivariate models. Method: A cross-sectional survey of US adults with a self-reported diagnosis of HIV/AIDS was conducted between April and May 2007. Respondents on a cART regimen of at least 2 nucleoside reverse transcriptase inhibitors plus at least 1 protease inhibitor or non-nucleoside reverse transcriptase inhibitor (n = 461) were included in the analytic sample. Multiple logistic regression models determined independent predictors of complete adherence (defined as never missing or skipping an antiretroviral dose). Results: Fifty-four percent of respondents reported complete adherence to cART. Adherent respondents reported a lower percentage of hospitalizations (11% vs 28%; P < .0001) and emergency room visits (26% vs 34%; P < .09). Respondents taking the single tablet efavirenz/emtricitabine/tenofovir fixed-dose regimen were significantly more likely to have complete adherence than respondents taking other cART regimens (odds ratio [OR] 2.1, P < .05), and higher imputed daily HIV pill count was associated with lower likelihood of complete adherence (OR 0.93, P < .05). Conclusion: This study shows the negative impact of higher pill burden on medication adherence, an important factor associated with treatment outcomes in patients with HIV/AIDS.

Factors associated with non-adherence to antiretroviral therapy in the SUN study

Background. Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality. Methods. We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006, in a multicenter, longitudinal, prospective cohort study (the SUN study). Using multiple logistic regression, we examined independent risk factors for non-adherence, defined as reporting having missed one or more antiretroviral doses in the past three days on the baseline questionnaire. Results. Of 528 participants (22% female, 28% black, median age 41 years, and median CD4 cell count 486 cells/mm3), 85 (16%) were non-adherent. In the final parsimonious multivariate model, factors independently associated with non-adherence included black race (adjusted odds ratio (aOR): 2.08, 95% confidence interval (CI): 1.20–3.60 vs. white race), being unemployed and looking for work (aOR: 2.03, 95% CI: 1.14–3.61 vs. all other employment categories), having been diagnosed with HIV ≥5 years ago (aOR: 1.95, 95% CI: 1.18–3.24 vs. being HIV-diagnosed <5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02–2.91 vs. drinking <3 drinks per day), and having not engaged in any aerobic exercise in the last 30 days (aOR: 2.13, 95% CI: 1.25–3.57). Conclusion. Although the above factors may not be causally related to non-adherence, they might serve as proxies for identifying HIV-infected patients at greatest risk for non-adherence who may benefit from additional adherence support.

Correlation between lamivudine plasma concentrations and patient self-reported adherence to antiretroviral treatment in experienced HIV patients

BackgroundAdherence to antiretroviral treatment (ART) is important to achieve treatment success in human immunodeficiency virus (HIV)-infected patients. Most HIV clinics apply the patient self-report (PSR) method. However, the reliability of this method in experienced HIV patients remains questionable.PurposeTo validate the PSR method for measuring adherence to ART using lamivudine (3TC) plasma concentrations in experienced HIV patients.MethodsThe study was conducted in Dar Es Salaam and involved 220 patients who were receiving ART services at HIV clinics for more than 12 months. Self-reported adherence information to ART was obtained on the day of HIV clinic visit. The patients were asked to mention the number of doses missed within the past 7 days. In addition, blood samples (2 mL) were collected from each patient on the same day. The blood samples were determined for 3TC plasma concentrations. The target 3TC plasma concentration as indicator concentration for adherent patients was determined in 20 patients who took their evening dose of antiretrovirals under supervision. The blood from these patients was drawn 3 hours after drug administration.ResultsComplete drug levels of 3TC and self-reported adherence data was obtained in 200 treatment-experienced HIV patients. Lamivudine plasma concentrations obtained in these patients ranged between 0.02–17.36 μg/mL. The mean time from dose administration to blood drawing was 3.1 ± 1.2 hours with coefficient of variation >39%. The mean 3TC plasma concentration obtained in 20 patients who took their antiretroviral dose under supervision was found to be 0.67 ± 0.46 μg/mL, range 0.25–2.33 μg/mL. As many as 82.5% of experienced HIV patients had PSRs in agreement with their 3TC plasma concentrations.ConclusionPSR adherence is still a valid method for ascertaining adherence to ART in treatment-experienced HIV patients.