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Enhanced Solubility and Bioavailability of Dolutegravir by Solid Dispersion Method: In Vitro and In Vivo Evaluation-a Potential Approach for HIV Therapy

Chaudhary S, Nair AB, Shah J, Gorain B, Jacob S, Shah H, et al.

AAPS PharmSciTech, 2021 Apr 09;22(3):127.
PMID: 33835317 DOI: 10.1208/s12249-021-01995-y

Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased Cmax (14.56 μg/mL) when compared to the physical mixture (4.12 μg/mL) and pure drug (3.45 μg/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99±10.07 μg/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45±6.58 μg/h/mL) and pure drug (49.27±6.16 μg/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy

Yong YK, Shankar EM, Solomon A, Spelman T, Fairley CK, Elliott JH, et al.

AIDS, 2016 09 10;30(14):2159-68.
PMID: 27281059 DOI: 10.1097/QAD.0000000000001179

BACKGROUND: Chronic HIV infection leads to marked depletion of CD4 T cells in the gastrointestinal tract and increased microbial translocation measured by an increase in circulating lipopolysaccharide (LPS) levels. Here, we hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor 4 (TLR4) and CD14, the principal receptors for LPS, were associated with CD4 T-cell recovery postantiretroviral therapy (ART).
METHODS: Prospective study of predominantly white HIV-infected participants receiving suppressive ART for at least 12 months. We analysed the CD14 SNPs C-260T and the TLR4 SNPs A+896G, C+1196T. We also determined the levels of LPS and soluble CD14 in plasma samples collected pre-ART and post-ART initiation. CD4 T-cell recovery was assessed by linear mixed models.
RESULTS: Following ART, individuals with a TT genotype compared with a CT or CC genotype for CD14 C-260T SNP showed higher levels of soluble CD14 (P = 0.008 and 0.003, respectively). The CC genotype for the CD14 C-260T SNP, compared with CT or TT, and the TLR4 SNP (AC/GT), compared with the homozygous genotype (AA/CC), were both independently associated with enhanced long-term CD4 T-cell recovery (>3 months; P HIV-infected individuals post-ART.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line therapy

Martin A, Moore C, Mallon PW, Hoy J, Emery S, Belloso W, et al.

AIDS, 2013 Sep 24;27(15):2403-11.
PMID: 23921615 DOI: 10.1097/01.aids.0000432534.47217.b4

To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals

HIV-CAUSAL Collaboration, Ray M, Logan R, Sterne JA, Hernández-Díaz S, Robins JM, et al.

AIDS, 2010 Jan 02;24(1):123-37.
PMID: 19770621 DOI: 10.1097/QAD.0b013e3283324283

OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.
DESIGN: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication.
RESULTS: Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001).
CONCLUSION: We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

Matched MeSH terms: HIV Infections/drug therapy
Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy

Lim A, Tan D, Price P, Kamarulzaman A, Tan HY, James I, et al.

AIDS, 2007 Jul 31;21(12):1525-34.
PMID: 17630546

To examine the relationships between blood CD4 natural regulatory T (Treg) cells, plasma HIV RNA level, CD4 T-cell count and immune activation in untreated HIV-infected patients and immunodeficient patients beginning antiretroviral therapy (ART), using a novel phenotype to define Treg cells (CD25CD127CD4). Data were compared with established Treg cell markers (FoxP3, CTLA-4 and GITR).

Matched MeSH terms: HIV Infections/drug therapy
Fulltext Material security and adherence to antiretroviral therapy among HIV-positive people who use illicit drugs

Mohd Salleh NA, Van Draanen J, Nosova E, Barrios R, Milloy MJ, Richardson L

AIDS, 2020 06 01;34(7):1037-1045.
PMID: 32073444 DOI: 10.1097/QAD.0000000000002501

OBJECTIVE: To examine the relationship between poverty, operationalized using a novel material security measure, and adherence to antiretroviral therapy (ART) among people who use illicit drugs (PWUD) in a context of universal access to HIV care.
DESIGN: We analyzed data from a community-recruited prospective cohort in Vancouver, Canada (n = 623), from 2014 to 2017.
METHODS: We used multivariable generalized mixed-effects analyses to estimate longitudinal factors associated with mean material security score. We then estimated the association between achieving at least 95% adherence to ART and overall mean material score, as well as mean score for three factors derived from a factor analysis. The three-factor structure, employed in the current analyses, were factor 1 (basic needs); factor 2 (housing-related variables) and factor 3 (economic resources).
RESULTS: Recent incarceration [β-coefficient (β) = -0.176, 95% confidence interval (95% CI): -0.288 to -0.063], unmet health needs [β = -0.110, 95% CI: -0.178 to -0.042), unmet social service needs (β = -0.264, 95% CI: -0.336 to -0.193) and having access to social services (β= -0.102, 95% CI: -0.1586 to -0.0465) were among the factors associated with lower material security scores. Contrary to expectations that low levels of material security in this population would lead to poor ART adherence, we did not observe a significant relationship between adherence and overall material security score, or for each factor individually.
CONCLUSION: Our findings highlight the potentially important role of no-cost, universal access to HIV prevention and treatment, in mitigating the impact of socioeconomic disadvantage on ART adherence.

Matched MeSH terms: HIV Infections/drug therapy*
Major health impact of accelerated aging in young HIV-infected individuals on antiretroviral therapy

Rajasuriar R, Chong ML, Ahmad Bashah NS, Abdul Aziz SA, Mcstea M, Lee ECY, et al.

AIDS, 2017 06 19;31(10):1393-1403.
PMID: 28358731 DOI: 10.1097/QAD.0000000000001475

BACKGROUND: Aging among HIV-infected individuals on antiretroviral therapy (ART) is a significant clinical challenge; however, studies assessing multidimensional aspects of aging are lacking. We characterized 10 geriatric conditions encompassing multiple functional domains, its health impact and associated risk factors in HIV-infected and age-matched uninfected controls.

METHODS: HIV-infected individuals were recruited from the outpatient clinic in University Malaya Medical Centre, Malaysia and controls from the community. All participants were aged at least 25 years of age with no acute illness, and HIV-infected individuals were on stable ART. Geriatric conditions were assessed and the burden scored as a composite of geriatric conditions present in an individual (total score = 10). Multivariate regression analysis was performed to determine the risk factors and health impact associated with the burden of geriatric conditions.

RESULTS: We analyzed data from 336 HIV-infected individuals (total HIV+), of whom 172 were matched for age, sex, and ethnicity with 172 HIV-uninfected controls (matched subset). In the total HIV-positive cohort, median (interquartile range) age was 44 (38-51) years and CD4 T-cell count was 562 (398-737) cells/μl. The burden of geriatric conditions was significantly higher in the HIV-infected group compared with controls (P HIV-infected group compared with matched controls. Both sociobehavioural and HIV-related clinical factors were independently associated with an increasing burden of geriatric condition in HIV.

CONCLUSIONS: A high burden of geriatric conditions with significant impact on health outcomes, including mortality risk scores are observed among HIV-infected individuals on ART in a resource-limited setting.

Study site: Outpatient clinic, University Malaya Medical Centre (UMMC)

Matched MeSH terms: HIV Infections/drug therapy*
Assessment of sarcopenia in virally suppressed HIV-infected Asians receiving treatment

Abdul Aziz SA, Mcstea M, Ahmad Bashah NS, Chong ML, Ponnampalavanar S, Syed Omar SF, et al.

AIDS, 2018 05 15;32(8):1025-1034.
PMID: 29547442 DOI: 10.1097/QAD.0000000000001798

OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes.
DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging.
METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals.
RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004).
CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext The Influence of Medication Attitudes on Utilization of Antiretroviral Therapy (ART) in Indonesian Prisons

Culbert GJ, Bazazi AR, Waluyo A, Murni A, Muchransyah AP, Iriyanti M, et al.

AIDS Behav, 2016 05;20(5):1026-38.
PMID: 26400080 DOI: 10.1007/s10461-015-1198-4

Negative attitudes toward HIV medications may restrict utilization of antiretroviral therapy (ART) in Indonesian prisons where many people living with HIV (PLH) are diagnosed and first offered ART. This mixed-method study examines the influence of medication attitudes on ART utilization among HIV-infected Indonesian prisoners. Randomly-selected HIV-infected male prisoners (n = 102) completed face-to-face in-depth interviews and structured surveys assessing ART attitudes. Results show that although half of participants utilized ART, a quarter of those meeting ART eligibility guidelines did not. Participants not utilizing ART endorsed greater concerns about ART efficacy, safety, and adverse effects, and more certainty that ART should be deferred in PLH who feel healthy. In multivariate analyses, ART utilization was independently associated with more positive ART attitudes (AOR = 1.09, 95 % CI 1.03-1.16, p = 0.002) and higher internalized HIV stigma (AOR = 1.03, 95 % CI 1.00-1.07, p = 0.016). Social marketing of ART is needed to counteract negative ART attitudes that limit ART utilization among Indonesian prisoners.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext Social Network Strategies to Address HIV Prevention and Treatment Continuum of Care Among At-risk and HIV-infected Substance Users: A Systematic Scoping Review

Ghosh D, Krishnan A, Gibson B, Brown SE, Latkin CA, Altice FL

AIDS Behav, 2017 Apr;21(4):1183-1207.
PMID: 27125244 DOI: 10.1007/s10461-016-1413-y

Social network analysis (SNA) and social network-based interventions (SNI) are important analytical tools harnessing peer and family influences critical for HIV prevention and treatment among substance users. While SNA is an effective way to measure social network influences, SNI directly or indirectly involves network members in interventions. Even though these methods have been applied in heterogeneous ways, leading to extensive evidence-based practices, systematic reviews are however, lacking. We searched five bibliographic databases and identified 58 studies involving HIV in substance users that had utilized SNA or SNI as part of their methodology. SNA was used to measure network variables as inputs in statistical/mathematical models in 64 % of studies and only 22 % of studies used SNI. Most studies focused on HIV prevention and few addressed diagnosis (k = 4), care linkage and retention (k = 5), ART adherence (k = 2), and viral suppression (k = 1). This systematic review highlights both the advantages and disadvantages of social network approaches for HIV prevention and treatment and gaps in its use for HIV care continuum.

Matched MeSH terms: HIV Infections/drug therapy
Fulltext Is forced migration a barrier to treatment success? Similar HIV treatment outcomes among refugees and a surrounding host community in Kuala Lumpur, Malaysia

Mendelsohn JB, Schilperoord M, Spiegel P, Balasundaram S, Radhakrishnan A, Lee CK, et al.

AIDS Behav, 2014 Feb;18(2):323-34.
PMID: 23748862 DOI: 10.1007/s10461-013-0494-0

In response to an absence of studies among refugees and host communities accessing highly active antiretroviral therapy (HAART) in urban settings, our objective was to compare adherence and virological outcomes among clients attending a public clinic in Kuala Lumpur, Malaysia. A cross-sectional survey was conducted among adult clients (≥18 years). Data sources included a structured questionnaire that measured self-reported adherence, a pharmacy-based measure of HAART prescription refills over the previous 24 months, and HIV viral loads. The primary outcome was unsuppressed viral load (≥40 copies/mL). Among a sample of 153 refugees and 148 host community clients, refugees were younger (median age 35 [interquartile range, IQR 31, 39] vs 40 years [IQR 35, 48], p HIV strategic plans of host countries with a view to expanding access in accordance with national guidelines for HAART.
Study site: Infectious Diseases Clinic, Hospital Sungai Buloh, Selangor, Malaysia

Matched MeSH terms: HIV Infections/drug therapy*
Adherence to Antiretroviral Therapy Among Incarcerated Persons with HIV: Associations with Methadone and Perceived Safety

Culbert GJ, Waluyo A, Wang M, Putri TA, Bazazi AR, Altice FL

AIDS Behav, 2019 Aug;23(8):2048-2058.
PMID: 30465106 DOI: 10.1007/s10461-018-2344-6

With adequate support, people with HIV (PWH) may achieve high levels of adherence to antiretroviral therapy (ART) during incarceration. We examined factors associated with ART utilization and adherence among incarcerated PWH (N = 150) in Indonesia. ART utilization was positively associated with HIV status disclosure (adjusted odds ratio [aOR] = 5.5, 95% CI 1.2-24.1, p = 0.023), drug dependency (aOR = 3.9, 95% CI 1.2-12.6, p = 0.022), health service satisfaction (aOR = 3.2, 95% CI 1.7-6.2, p

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext Early suboptimal ART adherence was associated with missed clinical visits in HIV-infected patients in Asia

Jiamsakul A, Kerr SJ, Kiertiburanakul S, Azwa I, Zhang F, Chaiwarith R, et al.

AIDS Care, 2018 12;30(12):1560-1566.
PMID: 30021450 DOI: 10.1080/09540121.2018.1499859

Missed clinic visits can lead to poorer treatment outcomes in HIV-infected patients. Suboptimal antiretroviral therapy (ART) adherence has been linked to subsequent missed visits. Knowing the determinants of missed visits in Asian patients will allow for appropriate counselling and intervention strategies to ensure continuous engagement in care. A missed visit was defined as having no assessments within six months. Repeated measures logistic regression was used to analyse factors associated with missed visits. A total of 7100 patients were included from 12 countries in Asia with 2676 (37.7%) having at least one missed visit. Patients with early suboptimal self-reported adherence <95% were more likely to have a missed visit compared to those with adherence ≥95% (OR = 2.55, 95% CI(1.81-3.61)). Other factors associated with having a missed visit were homosexual (OR = 1.45, 95%CI(1.27-1.66)) and other modes of HIV exposure (OR = 1.48, 95%CI(1.27-1.74)) compared to heterosexual exposure; using PI-based (OR = 1.33, 95%CI(1.15-1.53) and other ART combinations (OR = 1.79, 95%CI(1.39-2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (OR = 1.27, 95%CI(1.06-1.52)). Patients aged >30 years (31-40 years OR = 0.81, 95%CI(0.73-0.89); 41-50 years OR = 0.73, 95%CI(0.64-0.83); and >50 years OR = 0.77, 95%CI(0.64-0.93)); female sex (OR = 0.81, 95%CI(0.72-0.90)); and being from upper middle (OR = 0.78, 95%CI(0.70-0.80)) or high-income countries (OR = 0.42, 95%CI(0.35-0.51)), were less likely to have missed visits. Almost 40% of our patients had a missed clinic visit. Early ART adherence was an indicator of subsequent clinic visits. Intensive counselling and adherence support should be provided at ART initiation in order to optimise long-term clinic attendance and maximise treatment outcomes.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext Adherence to antiretroviral therapy, stigma and behavioral risk factors in HIV-infected adolescents in Asia

Prasitsuebsai W, Sethaputra C, Lumbiganon P, Hansudewechakul R, Chokephaibulkit K, Truong KH, et al.

AIDS Care, 2018 06;30(6):727-733.
PMID: 29336591 DOI: 10.1080/09540121.2018.1425363

We studied behavioral risks among HIV-infected and uninfected adolescents using an audio computer-assisted self-interview. A prospective cohort study was initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected adolescents were matched to uninfected adolescents (4:1) by sex and age group (12-14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5 years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1 years) adolescents. At enrollment, HIV-infected adolescents were on antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14% had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV-infected and 26 (44%) uninfected adolescents reported having ever smoked cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected adolescents reported having initiated sexual activity; 6 of the HIV-infected adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among adolescents, with few differences between those with and without HIV.

Matched MeSH terms: HIV Infections/drug therapy*
Calanolide looks promising

AIDS Patient Care STDS, 2000 Apr;14(4):225-6.
PMID: 10806645
Matched MeSH terms: HIV Infections/drug therapy*
Antiretroviral Resistance After First-Line Antiretroviral Therapy Failure in Diverse HIV-1 Subtypes in the SECOND-LINE Study

Lam EP, Moore CL, Gotuzzo E, Nwizu C, Kamarulzaman A, Chetchotisakd P, et al.

AIDS Res Hum Retroviruses, 2016 09;32(9):841-50.
PMID: 27346600 DOI: 10.1089/AID.2015.0331

We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01_AE (n = 109, 22%), G (n = 25, 5%), and CRF02_AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p HIV-1 subtypes in this study are consistent with knowledge derived from subtype B, with some exceptions. Patterns of resistance after failure of a first-line ta-N(t)RTI regimen support using TDF in N(t)RTI-containing second-line regimens, or using N(t)RTI-sparing regimens.

Matched MeSH terms: HIV Infections/drug therapy*
Short communication: low prevalence of genotypic drug resistance mutations among antiretroviral-naive HIV type 1 patients in Malaysia

Tee KK, Kamarulzaman A, Ng KP

AIDS Res Hum Retroviruses, 2006 Feb;22(2):121-4.
PMID: 16478392

To assess the prevalence of mutations associated with drug resistance in antiretroviral-naive patients in Kuala Lumpur, Malaysia, genotypic resistance testing was conducted among drug-naive HIV-1 patients attending the University Malaya Medical Center (UMMC) between July 2003 and June 2004. Reverse transcriptase (RT) and protease genes of plasma virions were sequenced from 100 individuals. The majority of the patients were recently diagnosed. Codons 20-255 of the RT and 1-96 of the protease gene were examined for major and minor mutations associated with antiretroviral resistance reported by the International AIDS Society- USA (IAS-USA) Drug Resistance Mutations Group. The prevalence of patients with at least one major mutation conferring drug resistance was 1%, with only one patient having a Y181C amino acid substitution in the RT gene that confers high-level resistance to nevirapine and delavirdine. Minor mutations were detected in high prevalence in the protease gene. Amino acid substitutions I13V, E35D, and M36I were associated with CRF01_AE while L63P, V77I, and I93L were associated with subtype B. Baseline prevalence of major mutations associated with resistance to antiretroviral drugs was low among antiretroviral-naive HIV-1 patients, suggesting that routine drug resistance testing may be unnecessary for all individuals newly diagnosed with HIV or all patients beginning antiretroviral therapy.

Matched MeSH terms: HIV Infections/drug therapy
Fulltext Short Communication: Impact of Viral Load Use on Treatment Switch in Perinatally HIV-Infected Children in Asia

Jamal Mohamed T, Teeraananchai S, Kerr S, Phongsamart W, Nik Yusoff NK, Hansudewechakul R, et al.

AIDS Res Hum Retroviruses, 2017 03;33(3):230-233.
PMID: 27758114 DOI: 10.1089/AID.2016.0039

We sought to assess the impact of routine HIV viral load (VL) monitoring on the incidence of switching from a first- to a second-line antiretroviral therapy (ART) regimen, and to describe factors associated with switch. Data from a regional cohort of 16 clinical programs in six Asian countries were analyzed. Second-line switch was defined as a change from a non-nucleoside reverse transcriptase inhibitor (NNRTI) to a protease inhibitor (PI) or vice versa, and ≥1 of the following: (1) reported treatment failure by local criteria, (2) switch of ≥1 additional drug, or (3) a preceding HIV VL ≥1,000 copies/ml. Routine VL was having ≥1 test after ≥24 weeks of ART and ≥1 time/year thereafter. Factors associated with time to switch were evaluated with death and loss to follow-up as competing risks. A total of 2,398 children were included in this analysis. At ART initiation, the median (interquartile range) age was 6.0 (3.3-8.9) years, more than half had WHO stage 3 or 4, the median CD4 was 189 (47-456) cells/mm3, 93% were on NNRTI-based first-line ART, and 34% had routine VL monitoring. Treatment switch occurred in 17.6% of patients, at a median of 35 (22-49) months. After adjusting for country, sex, first ART regimen, and CD4% at ART initiation, children with routine VL monitoring were 1.46 (95% confidence interval 1.11-1.93) times more likely to be switched (p = .007). Scale-up of VL testing will lead to earlier identification of treatment failure, and it can help guide earlier switches to prevent resistance.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings

Kiertiburanakul S, Boettiger D, Ng OT, Van Kinh N, Merati TP, Avihingsanon A, et al.

AIDS Res Ther, 2017;14:27.
PMID: 28484509 DOI: 10.1186/s12981-017-0151-1

BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome.
METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created.
RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2(OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p 350 cells/mm3(OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p 2000 cells/mm3(OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p 25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients.
CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.

Matched MeSH terms: HIV Infections/drug therapy*
Fulltext A multi-step pace towards a cure for HIV: kick, kill, and contain

López M

AIDS Rev, 2013 Jul-Sep;15(3):190-1.
PMID: 24002204

The 7th IAS Conference held in July 2013 in Kuala Lumpur, Malaysia, heard about a number of cases of "functional cure" in people who had started antiretroviral therapy soon after HIV infection, including a German case that can now be added to the "Mississippi baby" report presented at CROI 2012 and 14 individuals of the French VISCONTI cohort. All these persons maintained an undetectable viral load after coming off antiretrovirals.

Matched MeSH terms: HIV Infections/drug therapy*

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