Bruno Spire

Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment

BACKGROUND The recording of outcomes from large-scale, simplified HAART (highly active antiretroviral therapy) programmes in sub-Saharan Africa is critical. We aimed to assess the effectiveness of such a programme held by Médecins Sans Frontières (MSF) in the Chiradzulu district, Malawi. METHODS We scaled up and simplified HAART in this programme since August, 2002. We analysed survival indicators, CD4 count evolution, virological response, and adherence to treatment. We included adults who all started HAART 6 months or more before the analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed on a subsample of patients, and antiretroviral resistance mutations were analysed in plasma with viral loads greater than 1000 copies per mL. Analysis was by intention to treat. FINDINGS Of the 1308 patients who were eligible, 827 (64%) were female, the median age was 34.9 years (IQR 29.9-41.0), and 1023 (78%) received d4T/3TC/NVP (stavudine, lamivudine, and nevirapine) as a fixed-dose combination. At baseline, 1266 individuals (97%) were HAART-naive, 357 (27%) were at WHO stage IV, 311 (33%) had a body-mass index of less than 18.5 kg/m2, and 208 (21%) had a CD4 count lower than 50 cells per muL. At follow-up (median 8.3 months, IQR 5.5-13.1), 967 (74%) were still on HAART, 243 (19%) had died, 91 (7%) were lost to follow-up, and seven (0.5%) discontinued treatment. Low body-mass index, WHO stage IV, male sex, and baseline CD4 count lower than 50 cells per muL were independent determinants of death in the first 6 months. At 12 months, the probability of individuals still in care was 0.76 (95% CI 0.73-0.78) and the median CD4 gain was 165 (IQR 67-259) cells per muL. In the cross-sectional survey (n=398), 334 (84%) had a viral load of less than 400 copies per mL. Of several indicators measuring adherence, self-reported poor adherence (<80%) in the past 4 days was the best predictor of detectable viral load (odds ratio 5.4, 95% CI 1.9-15.6). INTERPRETATION These data show that large numbers of people can rapidly benefit from antiretroviral therapy in rural resource-poor settings and strongly supports the implementation of such large-scale simplified programmes in Africa.

On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection

BACKGROUND Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy

In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.

Adherence to HAART in French HIV-infected injecting drug users : The contribution of buprenorphine drug maintenance treatment

ObjectivesTo assess adherence to highly active antiretroviral therapies (HAART) in a cohort of French patients infected by HIV through injection drug use (IDU), and the impact on adherence of buprenorphine ambulatory drug maintenance treatment (DMT) which has been widely introduced since 1996. DesignAdherence assessment at first visit after initiation of HAART in the MANIF2000 cohort study. MethodsPatients face-to-face and self-administered questionnaires. Univariate and logistic regression adjusted odds ratios (OR) to compare characteristics of non-adherent versus adherent patients. ResultsOf the 164 patients, 34.8% took less than 80% of the prescribed HAART doses during the previous week. Decrease in viral load titres after initiation of HAART was significantly lower among non-adherent patients. After adjustment by logistic regression, non-adherence was associated with younger age, alcohol consumption, frequency of negative life-events during the prior 6 months and active drug use. However, IDU in buprenorphine DMT reached higher levels of adherence (78.1%) than ex-IDU (65.5%), although this difference did not reach statistical significance. ConclusionPrescription of buprenorphine DMT may increase adherence to HAART among HIV-infected opiate-dependent patients. Reducing the negative impact of stressful life-events through psychosocial interventions should be considered, even for those who have stopped using drugs.

Self-Reported Symptoms After Initiation of a Protease Inhibitor in HIV-Infected Patients and Their Impact on Adherence to HAART

Abstract Purpose: The purpose of our study was to assess short-term self-reported symptoms in patients who were started on two nucleoside reverse transcriptase inhibitors and one protease inhibitor (PI) in the multicenter APROCO cohort (N = 336) and to assess the influence of these symptoms on adherence. Method: Adherence and patient’s reported symptoms were measured at 1 and 4 months (M) after initiation of highly active antiretroviral therapy (HAART) through self-administered questionnaires. Results: Most patients reported at least one symptom (94.0% at M1; 88.0% at M4); fatigue and diarrhea were the most often reported symptoms. Respectively, 81.3% and 75.0% of patients were strictly adherent to HAART during the 4 days prior to M1 and M4 visits. After adjustment for younger age, history of antiretroviral treatment, unstable housing, poor social support, and alcohol consumption, patients who reported a high number of symptoms at M1 were more likely to be nonadherent at M4 (odds ratio per symptom = 1.13; 95% CI = 1.03-1.24). Conclusion: Patients reporting a high number of symptoms soon after HAART initiation are at higher risk of future nonadherence and could be targeted for interventions to achieve good levels of adherence and to improve treatment outcome.

The dynamic of Adherence to highly active antiretroviral therapy : Results from the French National APROCO cohort

Objectives: Our objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20‐month period and its relationship with virologic success. Methods: Self‐reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitorcontaining regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined. Results: Among the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was “always,” 225 (51.6%) “sometimes,” and 74 (17.0%) “never” “highly adherent” during follow‐up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64‐5.58]) or sometimes (OR [95% CI], 2.15 [1.24‐3.74]) “highly adherent.” Conclusion: Adherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.

Nonadherence among HIV-infected injecting drug users: the impact of social instability.

Summary: The authors tested the impact of social instability on adherence to highly active antiretroviral therapy (HAART) among patients infected with HIV through injection drug use (IDU; MANIF2000 cohort). In the study, they analyzed sociodemographic baseline characteristics to develop an indicator of social instability. Information concerning adherence to HAART was collected through questionnaires during a 2‐year follow‐up period. Factors associated with nonadherence were studied in two different groups: 1) patients who had stopped injection drug use (ex‐IDUs) and who were not in drug maintenance programs (DMT) during the entire follow‐up period, and 2) those who were still opiate dependent. Among the 210 eligible patients, 114 were classified as ex‐IDUs and 96 as opiate dependent. Ex‐IDUs reported nonadherence behaviors in 96 of 384 visits (25.0%), while opiate‐dependent patients were nonadherent in 111 of 308 visits (36.0%; p = .02). Among ex‐IDUs, the only factor associated with nonadherence was social instability, while among opiate‐dependent patients, injection behavior was the only determinant of nonadherence behavior. For opiate‐dependent patients, DMT may enhance adherence to HAART, but only if it is successful in reducing abuse of injection practices. For ex‐IDUs, it is very important that the management of social difficulties be taken into account to increase adherence to HAART.

Health-related quality of life after 1 year of highly active antiretroviral therapy.

Objective: We investigated the impact of the first year of highly active antiretroviral therapy (HAART) on health‐related quality of life (HRQL). Methods: Medical data for patients in the French APROCO cohort were collected at enrollment (MO) and month 12 (Ml2). A self‐administered questionnaire gathered information about HRQL (Medical Outcome Study 36‐Item Short Form Health Survey) and toxicity‐related symptoms. Using the twenty‐fifth percentile of HRQL scales in the French population as a threshold, patients with normal values in at least three mental and three physical scales were considered to have a “normal HRQL.” Results: Of the 1053 patients followed through M12, HRQL data at M0 and M12 were available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%) experienced a deterioration of HRQL at M12. Among the 421 patients with a low baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that factors independently associated with a normal HRQL at M12 were normal baseline HRQL, baseline CD4 count <500 cells/mm3, time since HIV diagnosis <8 years, undetectable HIV‐RNA at M12, and lower number of self‐reported symptoms at M12. Conclusion: An assessment of HRQL should be integrated to efficacy outcomes to evaluate and compare long‐term strategies properly and to optimize the durability of response to antiretroviral therapy.

ANTIMONIOTUNGSTATE (HPA 23) TREATMENT OF THREE PATIENTS WITH AIDS AND ONE WITH PRODROME

The antiviral activity of HPA 23 was assessed by viral isolation studies in the lymphocytes of 4 patients with acquired immunodeficiency syndrome (AIDS) or related syndromes. HPA 23 reduced lymphadenopathy-associated virus (LAV) in all 4 patients. LAV could no longer be detected in peripheral blood lymphocytes during or after treatment. Assays of infectivity showed that HPA 23 was inhibiting virus replication without killing virus infected cells. LAV was not isolated for 1 month after the end of treatment in 2 patients; in the remaining 2 patients LAV was detectable by co-cultivation indicating incomplete inhibition. This is the 1st demonstration of inhibition of the growth of LAV in AIDS patients. Particularly significant is the clinical improvement observed in the study subject who has been followed for 1 year after the end of HPA 23 treatment--an AIDS patient with cerebral toxoplasmosis. On the other hand it remains to be established whether antiviral drugs can cure AIDS. Inhibition of LAV replication may not completely correct complex autoimmune dysfunctions.

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the groups strategy.