Search

The article presents the 2011 guidelines of the British HIV Association for tuberculosis (TB)/HIV coinfection treatment. It says that the guidelines have been created to help physicians in managing TB/HIV coinfection patients in which the guidelines suggests that coinfected patients should be managed by a multidisciplinary team. It explores several diagnostic tests for TB patients such as the tuberculin skin testing in which it the test can identify patients with latent infection.

Background: Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1.Objective: To describe the efficacy and safety of tenofovir disoproxil fumarate (tenofovir DF) compared with placebo in patients with detectable viral replication despite current antiretroviral therapy.Design: Randomized, double-blind, placebo-controlled study through 24 weeks. After 24 weeks, all patients received open-label tenofovir DF for the remainder of the 48-week study.Setting: 75 North American, European, and Australian HIV clinics.Patients: 552 HIV-1-infected adults who were receiving antiretroviral therapy and had stable HIV-1 RNA levels ranging from 400 to 10,000 copies/mL.Measurements: Change in HIV-1 RNA level (time-weighted average from baseline through week 24); proportion of patients with grade 3 or 4 laboratory abnormalities and adverse events; and genotypic HIV-1 resistance testing in a separate substudy at baseline, week 24, and week 48.Results: A statistically significant decrease in HIV-1 RNA level through week 24 (the primary end point) was observed in the tenofovir DF group versus the placebo group (-0.61 log10 copies/mL vs. -0.03 log10 copies/mL, respectively [P < 0.001]; difference, -0.58 log10 copies/mL [95% CI, -0.68 to -0.49 log10 copies/mL]). In a virologic substudy, 94% of 253 patients had plasma isolates expressing reverse transcriptase mutations associated with nucleoside resistance mutations at baseline. Through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and those receiving tenofovir DF (14% vs. 13%). No evidence of tenofovir DF-related toxicity was seen through week 48.Conclusion: In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated antiviral effectiveness and safety of doravirine (DOR)-based regimens in people with HIV (PWH) in routine clinical practice., Design: A retrospective, noninterventional study across 16 sites in five European countries [United Kingdom (UK), France, Spain, Belgium, Netherlands]., Methods: The study was conducted in both treatment-experienced and treatment-naive PWH who either switched to, or initiated DOR-containing antiretroviral therapy (ART). The primary endpoints were virological success (defined as the percentage of participants with HIV RNA <50 copies/ml, using FDA Snapshot method) and virological failure (FDA Snapshot, HIV RNA ≥50 copies/ml) at 48 weeks after initiation of DOR regimen., Results: Between August 2017 and February 2022, 394 participants were enrolled, 63 naive and 331 treatment-experienced. 75.4% were men, with a median age of 45 years, and 92.2% received DOR in combination with tenofovir disoproxil fumarate and lamivudine or emtricitabine. The proportion of participants with virological success at week 48 after initiation of DOR regimen was 90.6% [95% confidence interval (CI) 87.3-93.3] overall, 87.3% (95% CI 76.5-94.4) in the ART-naive group, and 91.2% (95% CI 87.7-94.1) in the switch group. The proportion of participants with virological failure was 3.3% (95% CI 1.8-5.6) overall, 1.6% (95% CI 0-8.5) in the ART-naive group and 3.6% (95% CI 1.9-6.2) in the switch group. Of the 394 included participants, two (0.5%) were lost to follow-up and 13 (3.3%) discontinued the DOR regimen, four (1%) due to adverse events., Conclusion: Our results show high levels of efficacy and low levels of side effects in DOR-containing regimens in both treatment-naive and treatment-experienced PWH., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Large randomised studies of new long-acting medications for the prevention and treatment of HIV have shown high effectiveness and acceptability. Although modelling studies indicate these agents could be fundamental in HIV elimination, coordination of their entry into health-care markets is crucial, especially in low-income and middle-income countries with high HIV prevalence, where coordination is low despite UNAIDS flagging that global HIV targets will not be met. Research and implementation projects are tightly controlled by originator pharmaceutical companies, with only a small percentage of eligible people living with or affected by HIV benefiting from these projects. WHO, financial donors, manufacturers, and governments need to consider urgent coordinated action from stakeholders worldwide, akin to the successful introduction of dolutegravir into treatment programmes across low-income and middle-income countries. Without this immediate coordination, large-scale access to long-acting agents for HIV will be delayed, potentially extending into the 2030s. This delay is unacceptable considering the established global HIV targets., Competing Interests: Declaration of interests WDFV receives grants paid to University of the Witwatersrand from the Bill & Melinda Gates Foundation, South African Medical Research Council, National Institutes of Health (NIH), Unitaid, Foundation for Innovative New Diagnostics, Children's Investment Fund Foundation, United States Agency for International Development (USAID), ViiV Healthcare, and Merck; drug donations from Gilead Sciences, ViiV Healthcare, Merck, and Johnson and Johnson; honoraria for educational talks and advisory board membership from Gilead Sciences, ViiV Healthcare, Mylan-Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson and Johnson, Sanofi, and Virology Education; conducts commercial drug studies for Merck and Novo Nordisk; and is a member of the international NIH HIV data safety monitoring board and WHO and Southern African HIV Clinicians Society HIV guideline committees. MG is supported financially by NIH. SLB is a member of the AIDS Vaccine Advocacy Coalition board, a Global Coalition of Tuberculosis Activists fiscal sponsor, and is a member of the Global Public Investment Network and Global Fund Advocate Network steering committees. LJ is financially supported by USAID and the Bill & Melinda Gates Foundation. BH receives grant support from ViiV Healthcare to amFAR. MW's receives support from the Bill & Melinda Gates Foundation to the AIDS Vaccine Advocacy Coalition. KM has received honoraria from Johnson and Johnson. LG-B has received honoraria for advisories to Merck, ViiV Healthcare, and Gilead Sciences; is an unpaid board member for Access to Medicine Foundation, AIDS Vaccine Advocacy Coalition, and International AIDS Vaccine Initiative; and her unit (Desmond Tutu HIV Centre) has received a study drug from ViiV Healthcare and Johnson and Johnson for studies funded by the Bill & Melinda Gates Foundation. AO reports consulting fees for Gilead Sciences, ViiV Healthcare, and Assembly Biosciences; and is Director and Chief Science Officer for Tandem Nano, with patents issued and pending in drug delivery. AP receives grants paid to NEAT ID from NIH, National Heart, Lung, and Blood Institute, the EU (via the VERDI Consortium), Gilead Sciences, ViiV Healthcare, and Merck for commercial drug studies; receives honoraria for educational talks and advisory board membership from Gilead Sciences, ViiV Healthcare, Merck, and Virology Education; is on a data safety monitoring board for MRC–PENTA studies; is a member of the European AIDS Clinical Society and British HIV Association HIV treatment guidelines panels; is the President of NEAT ID; and is a board member of Doctor's with Africa CUAMM UK. PR has received grants from ViiV Healthcare and consulted for Gilead Sciences. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: ALP receives grants from NIH, NHLBI, the EU (via the VERDI Consortium), Gilead, ViiV Healthcare, and Merck for commercial drug studies paid to the organisation NEAT ID; receives honoraria for educational talks and advisory board membership from Gilead, ViiV Healthcare, Merck, and Virology Education; is on a data safety monitoring board for MRC–PENTA studies; is a member of the EACS and BHIVA HIV treatment guidelines panels; is the President of NEAT ID; and is a board member of CUAMM UK. WDFV receives grants from the Bill & Melinda Gates Foundation, SA Medical Research Council, NIH, Unitaid, Foundation for Innovative New Diagnostics, Children's Investment Fund Foundation, USAID, ViiV Healthcare, and Merck, paid to the institution; receives drug donations from Gilead, ViiV Healthcare, Merck, and Johnson & Johnson; does commercial drug studies for Merck and Novo; receives honoraria for educational talks and advisory board membership for Gilead, ViiV Healthcare, Mylan–Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Sanofi, and Virology Education; and is a member of the International NIH HIV data safety monitoring board and WHO and SAHCS HIV guideline committees.

Background: People living with human immunodeficiency virus (PLHIV) have a similar prevalence of psoriasis as the general population, though incidence and severity correlate with HIV viral load. Adequately treating HIV early renders the infection a chronic medical condition and allows PLHIV with a suppressed viral load (PLHIV-s) to live normal lives. Despite this, safety concerns and a lack of high-level data have hindered the use of systemic psoriasis therapies in PLHIV-s., Objectives: We aim to provide a structured framework that supports healthcare professionals and patients discussing the risks and benefits of systemic psoriasis therapy in PLHIV-s. Our goal was to address the primary question, are responses to systemic therapies for the treatment of psoriasis in PLHIV-s similar to those in the non-HIV population?, Methods: We implemented an inference-based approach relying on indirect evidence when direct clinical trial data were absent. In this instance, we reviewed indirect evidence supporting inferences on the status of immune function in PLHIV. Recommendations on systemic treatment for psoriasis in PLHIV were derived using an inferential heuristic., Results: We identified seven indirect indicators of immune function informed by largely independent bodies of evidence: (1) functional assays, (2) vaccine response, (3) life expectancy, (4) psoriasis manifestations, (5) rate of infections, (6) rate of malignancies, and (7) organ transplant outcomes., Conclusions: Drug-related benefits and risks when treating a patient with systemic psoriasis therapies are similar for non-HIV patients and PLHIV with a suppressed viral load and normalized CD4 counts. Prior to initiating psoriasis treatment in PLHIV, HIV replication should be addressed by an HIV specialist. Exercise additional caution for patients with a suppressed viral load and discordant CD4 responses on antiretroviral therapy., (© 2022. The Author(s).)

Background: Both tenofovir disoproxil fumarate (TDF)/emtricitabine and tenofovir alafenamide (TAF)/emtricitabine demonstrate excellent efficacy and safety overall, but concerns remain over specific changes in markers of bone and renal function. Lower plasma tenofovir concentrations are seen with TAF and in unboosted regimens. We assess TAF vs. TDF safety with and without booster coformulation., Methods: A previous systematic review was updated with recent clinical trials. TAF vs. TDF efficacy and safety were compared in boosted and unboosted subgroups. Efficacy was measured by viral suppression. Key safety endpoints included all adverse events, serious adverse events, Grades 3-4 adverse events and adverse event discontinuation. Further specific renal and bone markers were also assessed., Results: A total of 14 clinical trials comparing TDF and TAF regimens were identified. A significant difference (P = 0.0004) in efficacy was shown in the boosted subgroup in favour of TAF, but no difference was seen in the unboosted subgroup. There were no significant differences between TAF and TDF for any of the key safety endpoints analysed. No differences were seen for the bone markers analysed. No difference was found for renal tubular events. There was a difference in risk for discontinuation due to renal adverse events when boosted (P = 0.03), but none when unboosted., Conclusion: Across all main safety endpoints, no differences between TAF and TDF are seen. Boosted TDF regimens were associated with lesser comparative efficacy than boosted TAF and a higher risk of renal event discontinuation. However, modern antiretroviral regimens are more commonly unboosted. This study finds no difference in efficacy or safety in unboosted TAF vs. TDF.

Background: The Botswana Tsepamo study reported neural tube defects (NTDs) in 4 of 426 (0.94%) infants of women receiving preconception dolutegravir (DTG) antiretroviral therapy (ART) vs 14 of 11 300 (0.12%) receiving preconception non-DTG ART. Data are needed to investigate this potential safety signal. Clinicians, patients, and pharmaceutical companies can report adverse drug reactions (ADRs) to pharmacovigilance databases. Data from ADRs reported to various pharmacovigilance databases were searched for NTDs., Methods: Four pharmacovigilance databases (World Health Organization [WHO] VigiAccess; United Kingdom Medicines Health Regulatory Authority [UK MHRA]; European Medicines Agency [EMA] EudraVigilance; US Food and Drug Administration Adverse Event Reporting System [FAERS]) with online data availability were analyzed for NTD reports for 4 integrase inhibitors (DTG, raltegravir, elvitegravir, bictegravir), 2 protease inhibitors (darunavir, atazanavir), and 2 nonnucleoside reverse transcriptase inhibitors (nevirapine, efavirenz). Reports in the system organ class "congenital or familial disorders" were searched for NTDs., Results: NTDs have been reported among infants born from women taking a wide range of antiretrovirals in 4 pharmacovigilance databases (WHO VigiAccess, 116 reactions; UK MHRA, 8 cases; EMA EudraVigilance, 20 cases; FAERS, 44 cases). Six NTDs were identified for DTG across the pharmacovigilance databases. Cases were very hard to interpret, given the lack of clear denominators., Conclusions: Pharmacovigilance databases have many limitations, most importantly lack of a clear denominator for patients exposed to the drug of interest and duplicate cases that are difficult to identify. Given widespread use of new antiretroviral drugs worldwide and anticipated use of new drugs, prospective follow-up of pregnant women and birth surveillance studies such as Tsepamo are critically needed., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomized trials; however, the comparative incidence of clinically significant renal events remains unclear., Design: We used a pooled data approach to increase the person-years of drug exposure analysed, maximizing our ability to detect differences in clinically significant outcomes., Methods: We pooled clinical renal safety data across 26 treatment-naive and antiretroviral switch studies to compare the incidence of proximal renal tubulopathy and discontinuation due to renal adverse events between participants taking TAF-containing regimens vs. those taking TDF-containing regimens. We performed secondary analyses from seven large randomized studies (two treatment-naive and five switch studies) to compare incidence of renal adverse events, treatment-emergent proteinuria, changes in serum creatinine, creatinine clearance, and urinary biomarkers (albumin, beta-2-microglobulin, and retinol binding protein-to-creatinine ratios)., Results: Our integrated analysis included 9322 adults and children with HIV (n = 6360 TAF, n = 2962 TDF) with exposure of 12 519 person-years to TAF and 5947 to TDF. There were no cases of proximal renal tubulopathy in participants receiving TAF vs. 10 cases in those receiving TDF (P < 0.001), and fewer individuals on TAF (3/6360) vs. TDF (14/2962) (P < 0.001) discontinued due to a renal adverse event. Participants initiating TAF-based vs. TDF-based regimens had more favourable changes in renal biomarkers through 96 weeks of therapy., Conclusion: These pooled data from 26 studies, with over 12 500 person-years of follow-up in children and adults, support the comparative renal safety of TAF over TDF.

Introduction: The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk-benefit messaging when a safety signal is identified., Discussion: The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll-out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high-quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified., Conclusions: The response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk-benefit trade-offs in a variety of contexts; guidance to transform this risk-benefit balance into effective and agreed-upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Rifabutin, a rifamycin of equivalent potency to rifampicin, has several advantages in its pharmacokinetic and toxicity profile, particularly in HIV co-infected patients on combined antiretroviral therapy (cART). In this commentary, we evaluate evidence supporting increased global use of rifabutin and highlight key recommendations for action., Discussion: Although extrapolation of data from HIV uninfected patients would suggest non-inferiority, there has been no randomized controlled study comparing rifabutin versus rifampicin in the outcomes of relapse-free cure, in drug susceptible tuberculosis (TB), in HIV co-infected patients on currently utilized cART regimens or in paediatric populations. An important advantage of rifabutin is that compared to the dose adjustments required with rifampicin, it can be co-administered with the integrase strand transfer inhibitors raltegravir or dolutegravir without the need for dose adjustments. This strategy would be easier to implement in a programmatic setting and would save costs. We have assessed cost incentives to utilize rifabutin and have estimated generic costs for a range of rifabutin dosage scenarios. Where facilities are present for drug re-challenge and monitoring for drug toxicity and cross-reactivity, rifabutin offers a switch alternative for adverse drug reactions (ADR)s attributed to rifampicin. This would negate the need to prolong treatment in the absence of a rifamycin as part of short-course multidrug therapy. There is evidence of incomplete cross-resistance to rifampicin and rifabutin. Rifabutin may be useful in rifampicin-resistant TB, in an estimated 20% of cases, based on phenotypic or genotypic rifabutin susceptibility testing., Conclusions: Rifabutin should be available globally as a first-line rifamycin in HIV co-infected individuals and as a switch option in cases of rifampicin associated ADRs. Further studies are needed to ascertain the utility of rifabutin in rifampicin-resistant rifabutin-susceptible TB., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)-based regimen to a dolutegravir (DTG)-based regimen may improve lipid profile., Methods: European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)-infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs)., Results: Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, -.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P < .001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata., Conclusions: Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile., Clinical Trials Registration: NCT02098837 and EudraCT: 2013-003704-39.

Purpose of Review: Results from nonrandomized cohort studies suggest higher risks of CNS adverse events for dolutegravir, versus other ARVs. There have been two case reports of myocarditis on dolutegravir. Integrase inhibitors have been associated with IRIS in two cohort studies. Meta-analysis of randomized trials can be used to cross-check potential safety signals. This systematic review of drug safety used an EMBASE and MEDLINE search combined with serious adverse event (SAE) reports on the website www.clinicaltrials.gov. Cardiovascular, CNS or IRIS-associated adverse events were analysed for dolutegravir versus other ARVs. Relative risks for the comparison between dolutegravir and other antiretrovirals were calculated for each adverse event. Meta-analyses applied Mantel-Haenszel random-effects models., Recent Findings: There was a higher risk of Grade 1-4 insomnia adverse events for DTG (6.1%) versus other ARVs (4.5%; P = 0.02). There was no significant difference between DTG and other ARVs in the risk of cardiovascular serious adverse events. In the SINGLE and SPRING-1 trials comparing DTG with efavirenz, there were 5/465 patients with reported suicidality SAEs on DTG (1.1%) versus 6/469 (1.3%) on EFV. In other studies, serious adverse events of suicidality were reported for 15/2250 patients on DTG (0.7%) versus 9/2257 patients on other ARVs (0.4%). Risks of IRIS were low, but event rates were low and the main trials excluded CDC stage C disease., Summary: In this meta-analysis, there was no significant effect of dolutegravir on the risk of cardiac, IRIS or suicide-related serious adverse events. There was a higher risk of insomnia for DTG. Other completed randomized trials should be included in new evaluations of DTG safety. Continued pharmacovigilance, with regular meta-analyses, should be used to monitor safety.

Objective: To compare the efficacy, safety, and impact on lipid fractions of switching from a ritonavir-boosted protease inhibitor (PI/r) to a dolutegravir (DTG) regimen., Methods: HIV type 1-infected adults more than 50 years or with a Framingham score more than 10% were eligible if plasma HIV RNA less than 50 copies per ml for at least 24 weeks while on a PI/r regimen. Patients were randomized to switch to DTG or to remain on PI/r. Primary endpoints were: proportion maintaining HIV RNA less than 50 copies per ml and percentage change from baseline of total cholesterol at week 48., Results: In total, 415 patients (32 sites in six European countries) were randomized: 205 to DTG and 210 to continue PI/r. About 89% were men, 87% more than 50 years, 74% had a Framingham score more than 10%, with a median CD4 cell count of 617 cells per μl and suppressed viremia for a median of 5 years. At week 48, in the intent-to-treat analysis, treatment success rate was 93.1% in DTG group and 95.2% in PI/r group (difference -2.1%, 95% confidence interval -6.6 to 2.4, noninferiority demonstrated). There were four virological failures with DTG and one with PI/r with no emergent resistance mutations. There was no significant difference in severe adverse events or grade 3 or 4 adverse events or treatment modifying adverse events. Total cholesterol and other lipid fractions (except high-density lipoprotein cholesterol) improved significantly (P < 0.001) in the DTG group regardless of PI/r at baseline., Conclusion: Switching to a DTG regimen in virologically suppressed HIV type 1 patients with high cardiovascular disease risk was noninferior, and significantly improved lipid profiles.

Purpose of Review: Tenofovir disoproxil fumarate (TDF) is a standard first-line therapy for HIV. Recently, tenofovir alafenamide (TAF), a different prodrug for the same active moiety, has been approved. In this review, we have conducted a meta-analysis comparing efficacy and safety data for TDF and TAF, to inform a discussion of which drug would be best for a proposed 'universal antiretroviral (ARV) regimen'., Recent Findings: We identified 10 randomized controlled trials comparing TDF with TAF (6969 patients, 8043 patient-years of follow-up). Meta-analysis found no difference in treatment efficacy, resistance, or adverse events. There were significant differences favouring TAF in bone mineral density measures and renal function measures, but no significant difference in bone fracture events or discontinuations because of bone toxicity or renal toxicity. TAF arms showed higher lipid levels, and were associated with a slightly greater risk of being started on lipid-lowering therapy., Summary: TAF has lesser detrimental effects on renal and bone markers, but no difference in adverse events. Data are unavailable for TAF safety in pregnancy, tuberculosis coinfection, and low CD4 count. Data for these groups, and an affordable price, will be required before it can be recommended as part of a 'universal ARV regimen'.

Purpose of Review: To discuss barriers and opportunities for the introduction of new antiretrovirals into national treatment programmes in low-income and middle-income countries to support further treatment scale-up. Invitees to a WHO Think Tank in February 2017 evaluated recently published results., Recent Findings: There is not sufficient clinical experience of dolutegravir (DTG), tenofovir alafenamide (TAF) or efavirenz 400 mg (EFV400) to recommend their use in pregnancy. Outcomes from births and assessment of congenital anomalies need to be evaluated from several hundred pregnant women. Clinical experience of these treatments during rifampicin-based treatment for tuberculosis is also required. This could be difficult for TAF, which is currently contraindicated with TAF. Changes in second-line treatment from two nucleoside analogues + protease inhibitor plus ritonavir will require new randomized trials of alternative combinations., Conclusion: Additional safety and efficacy data on DTG, TAF and EFV400 in some subpopulations are needed before a large introduction in national treatment programmes. There is currently limited support for the introduction of TAF as part of first-line antiretroviral treatment in low-income and middle-income settings. There was an overall agreement for 6-monthly reviews of safety and efficacy data, in parallel with a phased introduction of the new antiretrovirals.

Background: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings., Objectives: We examined darunavir DRMs emerging in clinical practice in the UK., Patients and Methods: Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls., Results: Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group., Conclusions: Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Aim: To determine the frequency of detection of ocular and extraocular Chlamydia trachomatis (CT) infection in non-high myopes with rhegmatogenous retinal detachment (RRD)., Methods: This was a single-center, nonrandomized, prospective, case-control study. One hundred and four patients were divided into a study group with RRD (n=63) and a control group with traumatic retinal detachment (n=41). Samples of subretinal fluid (SFR), conjunctival, urethral/cervical swabs, and blood were collected. The frequency of detection of CT infection in SRF samples was determined by polymerase chain reaction (PCR), direct fluorescence assay (DFA) and cell culture, whereas that in conjunctival swabs was determined by PCR and DFA, and those in urethral/cervical swabs and blood were determined by DFA. Yates Chi-square test (with Bonferroni correction) and two-tailed Student's t-test were used for statistical analysis., Results: SRF CT infection was detected more frequently in the study group (50.8%-71.4%) than in the control group (9.8%-12.2%) by all the methods used (P<0.01). The frequency of detection of conjunctival CT infection by DFA was higher in the RRD patients compared with the controls (81.0% vs 24.4%, P=0.004). The PCR detected conjunctival CT infection more often in the study group than in the controls (46.0% vs 9.8%, P=0.007). The DFA detected CT in blood specimens almost as frequently as in urogenital specimens, for the RRD patients (61.2% vs 63.5%) and the controls (7.3% vs 9.8%)., Conclusion: CT infection is detected with high frequency in non-high myopes with RRD.

Thanks to the emergence of combination antiretroviral therapy, HIV/AIDS has been transformed into a manageable, chronic condition in just 30 years and the life expectancy of patients living with HIV is now comparable to those without. Recent data (START) support the strategy of starting all HIV-positive patients regardless of CD4 count. However, patients and physicians want more than just viral control: they want better tolerability, convenience, and few drug-drug interactions. Are the guidelines right in recommending an integrase inhibitor-based regimen as the first-line treatment of choice?

Purpose: To investigate latent conjunctival Chlamydia trachomatis (CT) and Bacteroides fragilis (BF) infections as potential risk factors for posttrabeculectomy bleb failure., Patients and Methods: This retrospective observational study included 50 primary open-angle glaucoma eyes of 50 patients who were submitted to trabeculectomy without cytostatics from September 2010 to June 2011 and were followed up for at least a year. Preoperatively, conjunctival scrapings were taken and their specimens subjected to polymerase chain reaction, direct fluorescent assay and cell culture testing for CT, and culture for BF on blood agar medium. Serum CT-specific IgG and IgA and tear interleukin (IL)-1β and IL-8 concentrations were measured with enzyme-linked immunosorbent assay. We defined bleb failure as intraocular pressure >21 mm Hg with antiglaucoma medications, resulting from reduced bleb filtration capacity due to bleb fibrosis, fistula obstruction, flattened bleb, or encapsulated bleb, and no earlier than 2 weeks after surgery. At the time of the reintervention, a scleroconjunctival biopsy was obtained for histopathology (including direct fluorescent assay testing for CT). Eyes were divided into a failure group and a nonfailure group, depending on whether they developed bleb failure (required reintervention) or not within a follow-up year., Results: In the failure group (n=18), the frequencies of detection of CT and BF in conjunctival specimens were 27.8% and 66.7%, respectively, versus 0% and 9.4% in the nonfailure group (n=32). CT and BF were detected in 11.1% and 11.1%, respectively, of scleroconjunctival biopsies. IgG and IgA seropositivity to CT was found in 66.7% and 33.3%, respectively, of the failure group patients, versus 9.4% and 0% of the nonfailure group patients. Tear IL-1β and IL-8 levels were markedly elevated in the failure group (468.83±80.43 and 107.89±15.11 pg/mL, respectively) versus the nonfailure group (22.34±5.43 and 9.34±2.83 pg/mL, respectively)., Conclusion: Being a contributor to low-grade conjunctival inflammation, latent conjunctival CT, and BF infections in primary open-angle glaucoma patients represent risk factors for posttrabeculectomy bleb failure.

Introduction: There have been several important developments in antiretroviral treatment in the past two years. Randomized clinical trials have been conducted to evaluate a lower dose of efavirenz (400 mg once daily). Integrase inhibitors such as dolutegravir have been approved for first-line treatment. A new formulation of tenofovir (alafenamide) has been developed and has shown equivalent efficacy to tenofovir in randomized trials. Two-drug combination treatments have been evaluated in treatment-naïve and -experienced patients. The novel pharmacokinetic booster cobicistat has been compared to ritonavir in terms of pharmacokinetics, efficacy and safety. The objective of this commentary is to assess recent developments in antiretroviral drug treatment to determine whether new treatments should be included in new international guidelines., Discussion: The use of first-line treatment with tenofovir and efavirenz at the standard 600 mg once-daily dose should remain the first-choice standard of care treatment. Evidence supporting a switch to efavirenz 400 mg once daily or integrase inhibitors is sufficient to consider these drugs as alternative first-line options, but more data are needed on their use in pregnant women and people with TB co-infection. The use of new formulations of tenofovir is currently too preliminary to justify immediate adoption and scale-up across HIV programmes in low- and middle-income countries. The evidence supporting use of two-drug combinations is not considered strong enough to justify changed recommendations from use of standard triple drug combinations. Cobicistat does not offer significant safety advantages over ritonavir as a pharmacokinetic booster., Conclusions: For continued scale-up of antiretroviral treatment in low- and middle-income countries, use of first-line triple combinations including efavirenz 600 mg once daily is supported by the largest evidence base. Additional studies are underway to evaluate new treatments in key populations, and these results may justify changes to these recommendations.

Human immunodeficiency virus type-1 (HIV-1) and human T lymphotropic virus type-1 (HTLV-1) infections have complex effects on adaptive immunity, with specific tropism for, but contrasting effects on, CD4 T lymphocytes: depletion with HIV-1, proliferation with HTLV-1. Impaired T lymphocyte function occurs early in HIV-1 infection but opportunistic infections (OIs) rarely occur in the absence of CD4 lymphopenia. In the unusual case where a HIV-1 infected individual with a high CD4 count presents with recurrent OIs, a clinician is faced with the possibility of a second underlying comorbidity. We present a case of pseudo-adult T cell leukemia/lymphoma (ATLL) in HIV-1/HTLV-1 coinfection where the individual fulfilled Shimoyama criteria for chronic ATLL and had pulmonary Mycobacterium kansasii, despite a high CD4 lymphocyte count. However, there was no evidence of clonal T-cell proliferation by T-cell receptor gene rearrangement studies nor of monoclonal HTLV-1 integration by high-throughput sequencing. Mutually beneficial interplay between HIV-1 and HTLV-1, maintaining high level HIV-1 and HTLV-1 viremia and proliferation of poorly functional CD4 cells despite chronicity of infection is a postulated mechanism. Despite good microbiological response to antimycobacterial therapy, the patient remained systemically unwell with refractory anemia. Subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of CD4 T lymphocytosis as well as HIV-1 viral suppression and decreased HTLV-1 proviral load. This is proposed to be the result of attenuation of immune activation post-HIV virological control. This case illustrates the importance of screening for HTLV-1 in HIV-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on HIV-1/HTLV-1 adaptive immunity., Competing Interests: The authors have no conflicts of interest to disclose.