Treatment of HIV infection with once-daily regimens

Introduction: Treatment for HIV infection requires a lifetime antiretroviral therapy. In order to improve adherence, once daily (OD) is thus a preferred regimen.

Areas covered: Evidence-based information and most recent guidelines recommendation, both from resource-rich and resource-limited settings, on antiretroviral regimens that can be administered OD will be reviewed. Sources of evidences were from the late clinical development studies (Phase III and II) published in Medline or major international conferences.

Expert opinion: Nine OD US FDA-approved regimens and one new integrase inhibitor OD regimen have been shown to be efficient and well tolerated. For the fixed-dose single-tablet regimens (STRs), there are two currently approved regimens: Atripla® and Complera®. Another STR elvitegravir/cobicistat/emtricitabine/tenofovir (QUAD, Stribild®) is recently approved by the US FDA (August 20, 2012), whereas two additional SRTs, including abacavir/lamivudine/dolutegravir and darunavir/cobicistat/emtricitabine/GS-7340 are undergoing Phase III and II trials, respectively. Three OD regimens are currently recommended by the US DHHS guidelines as the preferred regimens for treatment-naïve patients (efavirenz, boosted atazanavir and boosted darunavir). EFV-based regimen is the only OD regimen available for resource-limited countries. Nevertheless, it should be noted that each of these OD regimens has its own advantages and disadvantages and therefore should be selected accordingly.     

Treatment adherence following national antiretroviral rollout in South Africa

The national antiretroviral (ARV) programme in South Africa commenced in 2004. ARV drugs became readily available to all South Africans due to the concerted efforts of ‘access to all’ campaigns. This study investigates medication adherence among a sample of South Africans after the ARV rollout in order to gain insight into the adherence challenges they face. A semi-structured questionnaire was completed by 439 participants from across the country. The results show that only 40% of the respondents were able to reach the optimum adherence level of 90% or above. The patients who displayed below-optimum adherence often had not been part of an ARV-preparation programme, did not have HIV-treatment supporters, lacked general knowledge about drug adherence, and felt unsupported by healthcare providers in their day-to-day effort to adhere to their medications. They often had no money for food or transportation, ran out of ARVs for various reasons, suffered from HIV-treatment fatigue, battled with depression, abused alcohol, could not disclose to sexual partners that they were on ARVs, and often had to hide or skip ARV dosages because they feared stigma and discrimination. Suggestions to assist patients to adhere to their ARV medications are made.     

Value of the use of absolute lymphocyte as surrogate for CD4 count in resource poor situations

Background:

The initiation of antiretroviral (ARV) drugs and monitoring of human immunodeficiency virus (HIV) treatment in developing nations such as sub-Sahara Africa is based on the clinical stage and level of CD4 count. Clinical stages can easily be determined using the World Health Organisation (WHO) criteria, this is not so with CD4 count where the right equipment and expertise are not easily available. This lead to various studies being carried out in search of surrogates for CD4 count with use of total lymphocyte count (TLC) being suggested by some studies.

Objective:

In situation where determination of CD4 cell count is not available or feasible, lymphocyte count is believed to be one alternative method for immunological classification of Acquired Immunodeficiency Syndrome (AIDS). Such assumption may not be true of every population. The objective is, therefore, to examine the correlation between the absolute lymphocyte count and the CD4+ lymphocyte count in HIV positive patients.

Materials and Methods:

One hundred and sixty-five consecutive HIV positive patients were recruited for the study before the commencement of ARV drugs over a period of 13 months. The haemotological parameters such as the CD4 count was done by flow cytometry using Partec cyflow counter machine made in Germany, with strict adherence to the manufacturer''s standard operating procedure. TLC were also determined using Sysmex haematology blood analyser, following the manufacturer''s standard operating procedure. Patients were then grouped into CD4 and Total lymphocyte (TLC) categories. These were then compared to determine if there is any correlation as shown in previous studies. Statistical analysis of data was done using Statistical Package for Social Sciences (SPSS) and statistical significance of data was based on P value of less than 0.05. There was significant positive correlation (P value 0.000) between TLC and CD4 count.

Results:

Majority of the patients with TLC less than 1000/mm^[3] had CD4 count <200 cells/μl. Using TLC <1000/mm^[3] threshold, there was high sensitivity of 81.8% but low specificity and positive predictive value of 47.5% and 19.4%, respectively, for CD4 count <200 cells/μl. Further assessment using TLC of <1,200/mm^[3] for the currently accepted CD4 count cut-off of <350 cells/μl for initiation of antiretroviral drugs, the sensitivity, specificity, positive predictive value were found to be 76.5%, 26.7%, 21.3%, respectively.

Conclusions:

Considering the low specificity and positive predictive value, it was concluded that the use of TLC of as a surrogate for CD4 count is unreliable. However, where there is no alternative, it could be used with caution bearing in mind its limitations.     

The development of virus-free labile blood derivatives — A review

Human blood plasma derived coagulation factor concentrates carry a substantial risk of virus transmission as traditionally prepared. Intensive investigations during the past 5 years have led to the development of several virus sterilization procedures which can be applied to these concentrates as well as to other labile protein derivatives. This review summarizes detailed information which is now available establishing the virucidal potency of these procedures, particularly with regard to the contaminating viruses of most concern: hepatitis B, non-A, non-B hepatitis and the AIDS virus.Currently utilized virus sterilization procedures have greatly reduced or eliminated the transmission of AIDS virus, HIV. The transmission of non-A, non~B hepatitis virus (NANBHV) has also been greatly reduced by some but not all of these procedures. Additional virus safety data in man will be required to establish whether any of the procedures gives products which arc totally safe from NANBHV transmission and to assess their impact on other blood-borne-viruses.Corresponding author.     

Knowledge,attitudes, and practices regarding antiretroviral management,reproductive health,sexually transmitted infections,and sexual risk behavior among perinatally HIV-infected youth in Thailand

More than 30% of perinatally HIV-infected children in Thailand are 12 years and older. As these youth become sexually active, there is a risk that they will transmit HIV to their partners. Data on the knowledge, attitudes, and practices (KAP) of HIV-infected youth in Thailand are limited. Therefore, we assessed the KAP of perinatally HIV-infected youth and youth reporting sexual risk behaviors receiving care at two tertiary care hospitals in Bangkok, Thailand and living in an orphanage in Lopburi, Thailand. From October 2010 to July 2011, 197 HIV-infected youth completed an audio computer-assisted self-interview to assess their KAP regarding antiretroviral (ARV) management, reproductive health, sexual risk behaviors, and sexually transmitted infections (STIs). A majority of youth in this study correctly answered questions about HIV transmission and prevention and the importance of taking ARVs regularly. More than half of the youth in this study demonstrated a lack of family planning, reproductive health, and STI knowledge. Girls had more appropriate attitudes toward safe sex and risk behaviors than boys. Although only 5% of the youth reported that they had engaged in sexual intercourse, about a third reported sexual risk behaviors (e.g., having or kissing boy/girlfriend or consuming an alcoholic beverage). We found low condom use and other family planning practices, increasing the risk of HIV and/or STI transmission to sexual partners. Additional resources are needed to improve reproductive health knowledge and reduce risk behavior among HIV-infected youth in Thailand.     

The evolution of haematological and biochemical indices in HIV patients during a six-month treatment period

Objective

To assess haematological and biochemical parameters in Human Immunodeficiency Virus (HIV) patients under going antiretroviral therapy.

Methods

We enrolled HIV patients from, 18–65 years, who were under first line antiretroviral therapy and followed them for six months from February 2010 for changes in haematological and biochemical parameters. Profiles for ALAT, creatinine, amylase, cholesterol, CD4+ and total lymphocytes, haemoglobin, and monocytes were studied every three months.

Results

There was an increase of both, CD4+ lymphocyte counts from 233.57 cells/mm³ to 336.45 cells/mm³ and total lymphocytes from 45 to 46.6 10³ cells /µl, after six months. The haemoglobin level dropped from 8.8 g/L to 7.52 g/L. We observed an increase in ALAT from 40.27 to 47.42 U/L, amylase from 178.9 to 193.97 U/L, and cholesterol from 5.88 to 8.40 mmol/L. Creatinine levels decreased from 117.4 to 115.0 µmol/L.

Conclusion

The use of ARVs boosts CD4+ and total lymphocyte counts. Prolonged use of antiretroviral drugs (ARVs) is associated with variable degrees of liver and pancreatic damage, hypercholesteremia, and anaemia in some patients. Since many of these side effects are multi-factorial, management of HIV patients should take into consideration such side effects in making treatment decisions based on periodic evaluation of these parameters     

Biopsia líquida y cáncer de próstata. Evidencia actual aplicada a la clínica

ContextDespite being a validated source of biomarkers, liquid biopsy has not yet succeeded in becoming part of the standard clinical practice in prostate cancer patients. Few biomarkers undergo adequate validation, prospective and independent, of their predictive and/or prognostic value, which results in a lack of the different available tests in the clinical practice.ObjectiveTo carry out a pragmatic synthesis of current scientific evidence on liquid biopsy for prostate cancer patients.Evidence acquisitionNon-systematic literature review, narrowing the search to papers on liquid biopsy from blood samples in prostate cancer patients. We mainly selected works evaluating clinical endpoints in prostate cancer.Evidence synthesisThe most clinically advanced forms of liquid biopsy are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Both CTCs and ctDNA have demonstrated their prognostic value in metastatic disease. ARV7 determination is the first predictive biomarker of the disease. Its implementation into routine clinical practice requires methodological standardization and adequate clinical validation of the different available ways to detect it. The detection of CTCs in the early stages of the disease still depends on the optimization of the diagnostic methods and on the development of the biological characterization of these cells. The biological information provided by CTCs and ctDNA is different; therefore, the study of its adequate combination is the object of cutting-edge research.ConclusionsThe absence of protocols and methodological standards is the limiting factor when aiming to reach conclusions that could have a potential impact on clinical practice. Therefore, the real short-term challenge for liquid biopsy is the establishment of consensus and common criteria.     

Uncovering ART adherence inconsistencies: An assessment of sustained adherence among adolescents in South Africa

IntroductionAntiretroviral treatment (ART) adherence rates are lower among adolescents living with HIV (ALHIV) than among adults and children, but more evidence is needed on long‐term sustained ART adherence among ALHIV. This study assesses rates of sustained ART adherence in a cohort of adolescents in South Africa.MethodsA prospective cohort of adolescents (10‐19 years) living with HIV (baseline sample N = 1 046, 55% female, mean age 13.6) in the Eastern Cape Province in South Africa were interviewed at baseline (2014‐15) and followed‐up twice (2015‐16, 2017–18). All adolescents ever initiated on treatment in 52 government health facilities were traced (with 90% uptake, 94% retention at Wave 2, and 97% retention at Wave 3, 3.4% mortality) and their clinic records were extracted where available. We investigate sustained ART adherence among adolescents interviewed at all three waves of data collection (N = 933). To quantify adherence at each study wave, we used self‐reported past‐week adherence (including weekdays and weekends). Self‐reported adherence was validated using HIV‐1 RNA viral load (>50 copies/mL cut‐off) reported in clinic records, in a random‐intercept logistic regression.Results and discussionAt baseline, approximately 66% (N = 615) of adolescents reported past‐week ART adherence, and of these 45.3% reported adherence at both baseline and follow‐up. Only 37.1% of the sample reported sustained past‐week ART adherence over the three waves of the study. Most adolescents (N = 587, 62.9%) report inconsistent adherence across time (including 6.4% disengaged from care). Older (P = 0.007) and adolescents with horizontally acquired HIV (P = 0.002) were more likely to report inconsistent adherence across time. Controlling for socio‐demographic characteristics, past‐week adherence was associated with non‐detectable viral load (aOR 1.72, 95%CI 1.14‐2.59, P = 0.009). Overall, of the adolescents with viral load measurements at study Wave 1 and Wave 2, 50.6% maintained undetectable viral load for the preceding year.ConclusionsAdolescents living with HIV reported very low rates of sustained ART adherence. Adherence reported at a single time may mask high rates of variability in adherence over time. These findings highlight the urgent need for enhanced and effective interventions to assist ALHIV with ART adherence through the challenging years of adolescence.