Journal of AIDS & Clinical Research

Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are currently an essential part of highly active antiretroviral therapy (HAART) for the treatment of HIV. However, the use of some dideoxynucleotide analogues may be limited by mitochondrial toxicity leading to distal symmetric polyneuropathy (DSP). Acetyl-L-Carnitine (ALCAR) has been investigated for the treatment of existing DSP but the potential for ALCAR to prevent DSP is unknown.

Methods: In this double blind, placebo controlled trial 43 HIV infected, antiretroviral naïve individuals were randomised to receive either ALCAR or placebo in addition to stavudine (as stavudine-XR, a sustained release formulation), tenofovir and efavirenz for 48 weeks. Development of DSP was assessed clinically and histologically by Protein Gene Product (PGP) staining of the epidermis. Quality of life (QOL) was measured during the study with the MOS-HIV Health Survey and the QUROQOL Score questionnaires.

Results: Twenty one subjects in each treatment arm were followed through 48 weeks. Discontinuation rates for stavudine and ALCAR versus placebo were similar in both groups. No differences were found for histological examination or clinical assessment of DSP; whilst the safety profile of ALCAR was comparable to placebo.

Conclusions: At 48 weeks the prophylactic administration of ALCAR with HAART to prevent DSP was no different than placebo, with a similar safety profile.

In a 24-week phase 4, non-randomized, open-label, single-arm study, 19 HIV-infected patients receiving amprenavir (APV)-based highly active antiretroviral therapy (HAART) for 1.3-4.2 years (mean, 3.1 years) were switched to equimolar fosamprenavir (FPV) doses with no other changes in their treatment regimens. Most patients (74%) received APV/ ritonavir 600mg/100mg twice daily at screening. All but one were switched to FPV/ritonavir 700mg/100mg twice daily. Between baseline and week 24 after switching, clinical status generally remained stable or improved: median viral load 751 vs 71 copies/mL; CD4+ count 570 vs 622/mm3; proportion with viral load <400 copies/mL 47% vs 71%, and <50 copies/mL, 32% vs 35%. In 13 patients whose baseline HIV-1 RNA was >50 copies/mL, eight remained at this level and three were below it at week 24 (the other two were lost to follow-up). No study drug-related adverse events were reported and laboratory values did not notably change.

The purpose of this study was to measure adherence and to identify specific factors facilitating or constraining adherence to anti-retrovirals (ARVs) among HIV/AIDS patients. A cross sectional study on ARV adherence was conducted in two Tanzanian regions, Arusha and Dar es Salaam, in June and July 2005, involving 7 healthcare facilities in these regions. A multi-disciplinary team of researchers collected the data from two populations: the ARV users and the health care providers. The data was collected from the ARV users through exit interviews, semi structured interviews, adherence measures, focus group discussion and key informants interviews. From the health care staff, the tools used were semi structured interviews, observation of staff conducting consultations, and pharmacy stock check-ups. A total of 207 ARV users were studied, 26 observations were made, 28 health staff were interviewed, 8 focus group discussions and 10 key informant interviews were conducted, and 6 pharmacy stock checks were done in healthcare facilities.

Results from the qualitative discussions, individual as well as institutional factors contributed to non-adherence. For many food, long waiting time, transportation, social supports, lack of education about anti-retroviral therapy (ART) or ARVs, lack or inadequate counseling, drug related side effects, and even knowledge about AIDS were barriers. Structural impediments such as stigma by untrained hospital care workers towards clients, over worked health care staff, and lack of space for confidential consultations, lack of availability of diagnostic and laboratory equipments were also sited as barriers. However, according to health staff, adherence was interpreted to mean using medicines as prescribed, at the right time and at the correct dosage, and attending the facilities as scheduled for follow-up checks.

Many patients are appreciative of the government and of the health care workers involved in the programs. Yet, close attention and adequate supplies and resources to overcome the external barriers and attempts to try to mitigate the internal negative social determinants which prohibit adherence are needed. Unless due attention is paid to the critical issue of adherence, the emergence of drug-resistance will be accelerated and the expected early treatment achievements could be reversed.

Objective: To determine the influence of nevirapine (NVP) and lopinavir/ritonavir (LPV/r) on the efficacy of pegylated interferon (peg-IFN) plus ribavirin (RBV) among HIV/HCV-coinfected patients.

Methods: All HIV/HCV-coinfected patients who received peg-IFN plus RBV while under a three-drug antiretroviral regimen including tenofovir (TDF) plus lamivudine (3TC) or emtricitabine (FTC) along with NVP or along with LPV/r at twenty hospitals in Spain were included in this retrospective study. Sustained virological response (SVR) rates in both groups were compared.

Results: A total of 165 patients were included in the study, 71 (43%) receiving NVP and 94 (57%) LPV/r. Significantly more patients on LPV/r had a baseline HCV-RNA load ≥600000 IU/mL (44% vs. 73%, p=0.001). Forty (56%) individuals included in the NVP group and 35 (37%) in the LPV/r group showed SVR (p=0.015). In the NVP group, 19 (43%) patients carrying genotype 1-4 and 21 (78%) subjects with genotype 2-3 achieved SVR. In the LPV/r group, the corresponding figures were 25% (p=0.04) and 59% (p=0.1). In the subpopulation of individuals with baseline HCV viral load ≥600,000 IU/mL, 18 (58%) of those taking NVP vs. 21 (31%) who were given LPV/r reached SVR (p=0.01). HCV genotype 2-3, adherence to HCV therapy >80% and use of NVP during peg-IFN plus RBV were independently associated with SVR in the multivariate analysis.

Conclusions: HIV/HCV-coinfected patients who receive NVP respond better to peg-IFN plus RBV than those individuals receiving LPV/r. Lower HCV viral load due to NVP treatment may account for the former differences.