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: Introduction: Tenofovir‐based oral pre‐exposure prophylaxis is currently approved for HIV prevention; however, adherence in women has been low. A vaginal gel containing tenofovir (TFV) demonstrated partial protection to HIV but protection was not confirmed in additional studies. Vaginal rings offer user‐controlled long‐acting HIV prevention that could overcome adherence and protection challenges. TFV may also help prevent herpes simplex virus type 2 acquisition when delivered intravaginally. We evaluated the pharmacokinetics, safety, adherence and acceptability of a 90‐day TFV ring. Methods: Between January and June 2019, Microbicide Trials Network (MTN)‐038 enrolled 49 HIV‐negative participants into a phase 1, randomized (2:1) trial comparing a 90‐day ring containing 1.4 grams (g) TFV to a placebo ring. TFV concentrations were quantified in plasma, cervicovaginal fluid (CVF), rectal fluid and cervical tissue, and TFV‐diphosphate (TFV‐DP) in cervical tissue. Used rings were analysed for residual TFV. Safety was assessed by adverse events (AEs); acceptability and adherence by self‐report. Results: Mean age was 29.5; 46 identified as cisgender‐female and three gender non‐conforming. There were no differences in the proportion of participants with grade ≥2 genitourinary AEs in the TFV versus placebo arms (p = 0.41); no grade ≥3 AEs were reported. Geometric mean TFV concentrations increased through day 34 in CVF/rectal fluid and day 59 in plasma, but declined across compartments by day 91. Geometric mean TFV‐DP tissue concentrations exceeded the 1000 fmol/mg target through day 56, but fell to 456 fmol/mg at day 91. Among 32 rings returned at the end of the study, 13 had no or low ( Conclusions: The 90‐day TFV ring was well‐tolerated, acceptable and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies are needed to characterize the higher release from TFV rings in some participants and the optimal duration of use., INTRODUCTION Over half of the 38 million people living with human immunodeficiency virus (HIV) worldwide are women [1]. In sub‐Saharan Africa, women and girls accounted for 63% of new HIV [...]

PE11.01 Rates of undiagnosed HIV infection among racial/ethnic subgroups in a large nationwide cohort study of sexual minority men in the U.S.: Evidence for reframing from disparities to inequities H.J. [...]

Introduction: Persistence on preexposure prophylaxis for HIV prevention (PrEP) medication has rarely been reported for periods greater than one year, or in real-world settings. This study used pharmacy fill records for PrEP users from a national chain pharmacy to describe persistence on PrEP medication over a two-year period, and to explore correlates with PrEP medication persistence in a real-world setting. Methods: We analysed de-identified pharmacy fill records of 7148 eligible individuals who initiated PrEP in 2015 at a national chain pharmacy. A standard algorithm was employed to identify TDF-FTC use for PrEP indication. We considered three time periods for persistence, defined as maintaining refills in PrEP care: year 1 (zero to twelve months), year 2 (thirteen to twenty-four months) and initiation to year 2 (zero to twenty-four months). Individuals with 16 or more days of TDF-FTC PrEP dispensed in a 1-month period for at least three-quarters of a given time period (e.g. nine of twelve months or eighteen of twenty-four months) were classified as persistent on PrEP medication for the period. Results: Persistence was 56% in year 1, 63% in year 2 and 41% from initiation to year 2. Individuals aged 18 to 24 had the lowest persistence, with 29% from initiation to year 2. Men had higher persistence than women, with 42% compared to 20% persistent from initiation to year 2. Individuals with commercial insurance and individuals who utilized a community-based specialty pharmacy from the national chain also had higher persistence. Male gender, age >18 to 24 years, average monthly copay of $20 or less, commercial insurance, and utilization of a community-based specialty pharmacy were positively associated in adjusted models with persistence in year 1 and from initiation to year 2; the same correlates, with the exception of utilization of a community-based specialty pharmacy, were associated with higher persistence in year 2. Conclusions: We found substantial non-persistence on PrEP medication in both year 1 and year 2. Across the entire 2-year period, only two out of every five users persisted on PrEP. Demographic, financial and pharmacy factors were associated with persistence. Further research is needed to explore how social, structural or individual factors may undermine or enhance persistence on PrEP, and to develop interventions to assist persistence on PrEP. Keywords: PrEP; retention; prevention; medication persistence; preventative medicine; HIV, 1 | INTRODUCTION Preexposure prophylaxis (PrEP) for HIV prevention with daily oral use of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) is well-tolerated and highly effective [1-8]. PrEP is still relatively [...]

Introduction: Discontinuations of HIV preexposure prophylaxis (PrEP) by at-risk individuals could decrease the effectiveness of PrEP Our objective was to characterize patterns of, reasons for, and clinical outcomes associated with PrEP discontinuations in primary care. Methods: We conducted medical chart reviews for patients prescribed PrEP during 2011 to 2014 at a Boston community health centre specializing in healthcare for sexual and gender minorities. Patients were followed through 2015. We characterized patients' sociodemographics, relationship status, behavioural health conditions, patterns of and reasons for PrEP discontinuations, and HIV seroconversions. Cox proportional hazards models were used to assess patient factors associated with PrEP discontinuations. Results: Of the 663 patients prescribed PrEP, the median age was 33 years, 96% were men who have sex with men (MSM) and 73% were non-Hispanic white; 40% were in committed relationships and 15% had HIV-infected partners. Patients either used PrEP continuously (60%), had 1 or more discontinuations (36%), or did not initiate PrEP (4%). Discontinuations were most often due to a decrease in HIV risk perception (33%), non-adherence to care plans (16%), or insurance barriers (12%). Of the 7 (1.1%) PrEP patients diagnosed with HIV, 1 was HIV-infected at baseline, 2 seroconverted while using PrEP, and 4 seroconverted after discontinuations. In a multivariable model adjusted for race/ethnicity, relationship status, substance use disorders, and insurance status, those who were less than 30 years old (aHR 2.0, 95% CI 1.4 to 2.9 for ages 18 to 24, aHR 2.2, 95% CI 1.6 to 3.1 for ages 25 to 29, vs. ages 30 to 39 years), who identified as transgender women (aHR 2.0, 95% CI 1.2 to 3.4, vs. cisgender men), and who had mental health disorders (aHR 1.2, 95% CI 1.1 to 1.4 for each additional disorder) were more likely to have discontinuations. Conclusions: Discontinuations of PrEP use among this American sample of predominately MSM were common, particularly among patients who were younger, identified as transgender women, or had behavioural health issues. As HIV seroconversions occurred after discontinuations of PrEP, strategies to prevent inappropriate discontinuations are needed. Keywords: HIV; PrEP; primary care; discontinuations; adherence; community health center; men who have sex with men, 1 | INTRODUCTION As there are nearly 40,000 new HIV infections each year in the US [1], there is a need to implement and optimize effective HIV-prevention strategies. Randomized-controlled studies [...]

Several clinical trials have demonstrated that antiretroviral (ARV) drugs taken as pre-exposure prophylaxis (PrEP) can prevent HIV infection, with the magnitude of protection ranging from -49 to 86% (refs. ). Although these divergent outcomes are thought to be due primarily to differences in product adherence, biological factors likely contribute. Despite selective recruitment of higher-risk participants for prevention trials, HIV risk is heterogeneous even within higher-risk groups. To determine whether this heterogeneity could influence patient outcomes following PrEP, we undertook a post hoc prospective analysis of results from the CAPRISA 004 trial for 1% tenofovir gel (n = 774 patients), one of the first trials to demonstrate protection against HIV infection. Concentrations of nine proinflammatory cytokines were measured in cervicovaginal lavages at [greater than] 2,000 visits, and a graduated cytokine score was used to define genital inflammation. In women without genital inflammation, tenofovir was 57% protective against HIV (95% confidence interval (CI): 7-80%) but was 3% protective (95% CI: -104-54%) if genital inflammation was present. Among women who highly adhered to the gel, tenofovir protection was 75% (95% CI: 25-92%) in women without inflammation compared to -10% (95% CI: -184-57%) in women with inflammation. Immunological predictors of HIV risk may modify the effectiveness of tools for HIV prevention; reducing genital inflammation in women may augment HIV prevention efforts., Author(s): Lyle R McKinnon (corresponding author) [1, 2, 3]; Lenine J Liebenberg [1, 3]; Nonhlanhla Yende-Zuma [1]; Derseree Archary [1, 3]; Sinaye Ngcapu [1, 3]; Aida Sivro [1, 2, 3]; [...]

Introduction: Men who have sex with men (MSM) and transgender women (TGW) in Brazil experience high rates of HIV infection. We examined the clinical and economic outcomes of implementing a pre-exposure prophylaxis (PrEP) programme in these populations. Methods: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model of HIV prevention and treatment to evaluate two strategies: the current standard of care (SOC) in Brazil, including universal ART access (No PrEP strategy); and the current SOC plus daily tenofovir/emtracitabine PrEP (PrEP strategy) until age 50. Mean age (31 years, SD 8.4 years), age-stratified annual HIV incidence (age [less than or equal to] 40 years: 4.3/100 PY; age > 40 years: 1.0/100 PY), PrEP effectiveness (43% HIV incidence reduction) and PrEP drug costs ($23/month) were from Brazil-based sources. The analysis focused on direct medical costs of HIV care. We measured the comparative value of PrEP in 2015 United States dollars (USD) per year of life saved (YLS). Willingness-to-pay threshold was based on Brazil's annual per capita gross domestic product (GDP; 2015: $8540 USD). Results: Lifetime HIV infection risk among high-risk MSM and TGW was 50.5% with No PrEP and decreased to 40.1% with PrEP. PrEP increased per-person undiscounted (discounted) life expectancy from 36.8 (20.7) years to 41.0 (22.4) years and lifetime discounted HIV-related medical costs from $4100 to $8420, which led to an incremental cost-effectiveness ratio (ICER) of $2530/YLS. PrEP remained cost-effective ( Conclusion: Daily tenofovir/emtracitabine PrEP among MSM and TGW at high risk of HIV infection in Brazil would increase life expectancy and be highly cost-effective. Keywords: HIV; pre-exposure prophylaxis; men who have sex with men; Brazil; cost-effectiveness, 1 INTRODUCTION A growing body of evidence supports the use of tenofovir/emtracitabine pre-exposure prophylaxis (PrEP) to prevent HIV infection, particularly in high-risk populations. A 2016 meta-analysis of 18 PrEP-related studies [...]

: Introduction: Event‐driven pre‐exposure prophylaxis (edPrEP) with oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective for preventing HIV acquisition in men who have sex with men (MSM) and is preferred over daily PrEP by some MSM. However, it is largely unknown how well MSM adhere to edPrEP. We then aimed to assess PrEP protection during CAS among MSM using edPrEP and participating in the Amsterdam PrEP demonstration project (AMPrEP). Methods: We analysed data from participants enrolled in AMPrEP who were taking edPrEP. We measured adherence through (1) a mobile application in which sexual behaviour and PrEP‐use were recorded daily, (2) three‐monthly self‐completed questionnaires and (3) dried blood spot (DBS) samples collected around six, twelve and twenty‐four months after PrEP initiation. We assessed the proportion of days with condomless anal sex (CAS) acts that were protected by PrEP, per partner type (i.e. steady partners, known casual partners, unknown casual partners), and the proportion of three‐month periods during which PrEP was correctly used. Intracellular TFV‐diphosphate (TFV‐DP) concentrations were determined from DBS. Good adherence was defined as at least one tablet before and one tablet within 48 hours after a CAS act. Results: Between 11 September 2015 and 6 October 2019, 182 of 376 MSM (48.4%) used edPrEP for at least one three‐month period. Of the 8224 CAS days that were reported in the app during edPrEP‐use, we observed good protection for most CAS days involving steady partners (n = 1625/2455, 66.9%), known casual partners (n = 3216/3472, 92.6%) and unknown casual partners (n = 2074/2297, 90.3%). Men reported consistently correct PrEP‐use in 851 (81.4%) of the 1046 three‐month periods of edPrEP‐use. The median TFV‐DP concentration was 591 fmol/sample (interquartile range = 270 to 896). Conclusions: Adherence to edPrEP was high as determined from the online app and questionnaire. DBS measurements were consistent with two to three tablets per week on average., INTRODUCTION Pre‐exposure prophylaxis (PrEP) has been proven to be highly effective against the acquisition of human immunodeficiency virus (HIV) [1,2]. The World Health Organization has therefore recommended that PrEP be [...]

: Introduction: Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) is used for HIV pre‐exposure prophylaxis (PrEP). TDF may affect bone mineral density (BMD), particularly in youth who are at a stage of peak bone mass accrual. The objective of this study was to evaluate the effect of vitamin D and calcium supplementation on BMD among Thai youth receiving daily oral PrEP. Methods: This open‐label randomized trial was conducted in male youth aged between 15 and 24 years. Participants were randomized to Arm A who received once‐daily TDF/FTC plus vitamin D3 and calcium supplementation with meals twice daily (400 units of vitamin D3 and 1200 mg of elemental calcium/day) or Arm B who received once‐daily TDF/FTC only. PrEP users were defined as taking at least two tablets/week (tenofovir‐diphosphate level of >350 fmol/punch). Adherence to vitamin D/calcium supplementation was defined as self‐reported adherence of >50%. Lumbar spine (L2‐L4) BMD (LSBMD) was evaluated by dual‐energy X‐ray absorptiometry scan zero and six months after PrEP initiation. Results: From March 2019 to March 2020, 100 youth were enrolled. Baseline characteristics between the two arms were similar. Median (IQR) age was 18 (17 to 20) years. At entry, median (IQR) LSBMD z‐score was −0.8 (−1.5 to −0.3), 17% had low LSBMD (Z‐score < −2). The median amount of calcium intake from nutritional three‐day recall was 167 (IQR 94 to 272) mg/day, 39% of participants had vitamin D deficiency, defined as 25(OH)D levels 3% increase in LSBMD at month 6 compared to baseline (67.6% vs. 42.9% respectively; p = 0.03). There were significantly higher increases in LSBMD among youth with vitamin D deficiency who were supplemented; arm A + 0.05 (0 to 0.05) compared to arm B + 0.03 (−0.1 to 0.03), p = 0.04. Conclusions: Increases in LSBMD over six months among youth using PrEP who received vitamin D/calcium supplementation was greater than those not supplemented. Long‐term follow‐up should be considered to explore long‐term outcomes., INTRODUCTION Men who have sex with men (MSM) make up the largest population receiving new HIV diagnoses in the United States (87%) [1], a trend also seen in Thailand where [...]

Background: To realize the promise of ending the global epidemic, long-lasting HIV protection is needed through sustained release of antiretroviral drugs for months to years. Leveraging promising exploratory pharmacokinetics (PK) showing high TFV-diphosphate (TFV-DP) levels in PBMCs and dose escalation in rhesus macaques, we investigated the PK and efficacy of a polycaprolactone implant releasing tenofovir alafenamide (TAF) in pigtail macaques for preventing vaginal SHIV infection. Methods: Implants were administered subcutaneously in the arm using a contraceptive trocar. The PK profile of implants releasing 0.35 mg/day of TAF was evaluated in 3 pigtailed macaques. Efficacy was evaluated in 6 macaques that received two TAF implants (one per arm; total release-rate = 0.7 mg/day). Macaques were exposed vaginally to SHIV162p3 twice-weekly for 6 weeks. Infection outcome was compared to 8 untreated controls. SHIV RNA was monitored in plasma by RT-PCR. TFV-DP in PBMCs and vaginal lymphocytes was measured by LC-MS/MS. Skin biopsies near implantation were assessed by H&E staining. Results: Median TFV-DP levels in PBMCs over 84 days with a single TAF implant were 954 [range 398 to 2080] fmols/106 cells. TFV-DP was consistently detected in vaginal lymphocytes 24 h post implant removal (50.7 [range 29.3 to 67.9] fmol/106 cells). Median TFV-DP levels in PBMCs during the challenge phase were 1.6-fold higher (1,519 [range 1068 to 1897] fmols/106 cells), which was consistent with the use of 2 TAF implants per animal. All macaques receiving TAF implants were SHIV RNA negative following 12 virus exposures and remained negative for 16 weeks after implant removal. In contrast, 7/8 controls were infected after median of 4 SHIV exposures (Wilcoxon p-value = 0.0037). Despite slight to no skin reactions, H&E revealed marked deep dermal necrosis and inflammation by 7 weeks post-implantation. Recovered implants maintained a high degree of drug purity (>96%) and showed a strong correlation with in vitro release-rates (median per animal = 0.77 mg/d). Conclusions: TAF implants releasing 0.7 mg/d resulted in high TFV-DP levels in PBMCs that provided complete protection against vaginal SHIV infection. Findings define benchmarks needed for full protection against vaginal infection with single agent TAF. Improved TAF implants that maintain high efficacy while reducing local toxicity have the potential to provide long-lasting protection against vaginal HIV infection., OA04.02 I. Massud Centers for Disease Control and Prevention, Laboratory Branch, Division of HIV/AIDS Prevention, Atlanta, United States https://doi.org/10.1002/jia2.25659 Please Note: Illustration(s) are not available due to copyright [...]

Few data exist on the safety of tenofovir (TDF) in HIV-infected patients with preexisting renal dysfunction. We report 12-month changes in renal profiles among 19 such patients (6 patients with history of and 13 patients with current renal disease) in the HIV Outpatient Study (HOPS) who initiated TDF-containing highly active antiretroviral therapy (HAART) during 2001-2005 with TDF dosed mostly at 300 mg once daily. At baseline, the median estimated glomerular filtration rate (GFR) was 49 mL/min/1.73 [m.sup.2] and the median [CD4.sup.+] cell count was 322 cells/[mm.sup.3]. Patients had a median 12-month change in estimated creatinine clearance from baseline of -0.3 mL/min (range, -32.2 to +23.6) and the median change in GFR of -0.1 mL/min/1.73 [m.sup.2] (range, -49.8 to +29.5). We observed confirmed worsening of kidney disease stage in 5 of the 19 patients during follow-up. TDF use can be considered in patients with preexisting or current renal dysfunction who have limited antiretroviral treatment options, require TDF for fully active antiretroviral regimen, and can be closely monitored for incident worsening of renal function.

We report two cases of tenofovir (TDF)-associated nephrotoxicity in perinatally HIV-infected adolescents. The first case, a 16-year-old African American male with an absolute [CD4.sup.+] cell count of 314 cells/[mm.sup.3], presented with an abrupt rise in serum creatinine leading to irreversible renal failure while on TDF-containing highly active antiretroviral therapy (HAART). While the patient had evidence of underlying kidney disease, the timing of his renal failure indicates that TDF played a central role. The second case, a 16-year-old African-American male with an absolute [CD4.sup.+] cell count of 895 cells/[mm.sup.3], presented with rickets and hypophosphatemia while receiving FDF-based HAART. To our knowledge, these cases represent the first reports of TDF-associated irreversible renal failure and rickets in pediatric patients. We believe these cases highlight important and potentially irreversible side effects of this agent and emphasize the need for further studies of the renal safety of TDF in pediatric patients.

Tenofovir disoproxil fumarate (TDF) is a commonly used HIV antiretroviral. A relatively uncommon adverse effect of this drug is Fanconi syndrome. What is known about this toxicity, especially in regards to concomitant medication use and outcomes, is limited to isolated case reports and small case series. Therefore, a retrospective review of the FDA Adverse Event Reporting System from 2001 through 2006 was conducted to examine demographics, concomitant medication use, outcomes, and temporal trends in reporting of Fanconi syndrome associated with TDF use. In this large case series of 164 subjects who met the case definition for Fanconi syndrome, the majority (83%) of the subjects received protease inhibitors (PI) with TDF; specifically, 74% of the total received a ritonavir-boosted PI. Didanosine was the most commonly (43%) prescribed nucleoside reverse transcriptase inhibitor (NRTI). The combination of didanosine with boosted PI was frequently observed (34%), and in particular, didanosine plus lopinavir/ritonavir was documented for 22%. Nearly half (46%) of the total were hospitalized. Fracture (2%) and requirement for dialysis (2%) were infrequent while Fanconi syndrome contributed to death in 2% of these subjects. Patients receiving ritonavir-boosted protease inhibitors or didanosine with tenofovir should be closely monitored for development of nephrotoxicity. Although reporting biases and the exclusion of reports with serious confounding conditions likely affected the estimation of outcomes in this case series, severe complications of tenofovir-associated Fanconi syndrome were uncommon.

: Introduction: HIV prevention during pregnancy and lactation is critical for both maternal and child health. Pregnancy provides a critical opportunity for clinicians to elicit women's vulnerabilities to HIV and offer HIV testing, treatment and referral and/or comprehensive HIV prevention options for the current pregnancy, the postpartum period and safer conception options for future pregnancies. In this commentary, we review the safety of oral pre‐exposure prophylaxis with tenofovir/emtricitabine in pregnant and lactating women and suggest opportunities to identify pregnant and postpartum women at substantial risk of HIV. We then describe a clinical approach to caring for women who both choose and decline pre‐exposure prophylaxis during pregnancy and postpartum, highlighting areas for future research. Discussion: Evidence suggests that pre‐exposure prophylaxis with tenofovir/emtricitabine is safe in pregnancy and lactation. Identifying women vulnerable to HIV and eligible for pre‐exposure prophylaxis is challenging in light of the myriad of individual, community, and structural forces impacting HIV acquisition. Validated risk calculators exist for specific populations but have not been used to screen and offer HIV prevention methods. Partner testing and engagement of men living with HIV are additional means of reaching at‐risk women. However, women's vulnerabilities to HIV change over time. Combining screening for HIV vulnerability with HIV and/or STI testing at standard intervals during pregnancy is a practical way to prompt providers to incorporate HIV screening and prevention counselling. We suggest using shared decision‐making to offer women pre‐exposure prophylaxis as one of multiple HIV prevention strategies during pregnancy and postpartum, facilitating open conversations about HIV vulnerabilities, preferences about HIV prevention strategies, and choosing a method that best meets the needs of each woman. Conclusion: Growing evidence suggests that pre‐exposure prophylaxis with tenofovir/emtricitabine during pregnancy and lactation is safe and effective. Shared decision‐making provides one approach to identify at‐risk women and offers pre‐exposure prophylaxis but requires implementation research in diverse clinical settings. Including pregnant and breastfeeding women in future HIV prevention research is critical for the creation of evidence‐driven public health policies and clinical guidelines., Introduction While a growing body of literature describes safer conception for HIV serodifferent couples [1–3], relatively little focuses on HIV prevention strategies during pregnancy and postpartum. Many women miss opportunities [...]

Regimens containing abacavir (ABC), tenofovir (TDF), and lamivudine (3TC) have recently been demonstrated to have high failure rates. This poses a clinical dilemma of how to manage patients currently being treated with other regimens containing tenofovir/abacavir. We evaluated the outcomes of tenofovir/abacavir regimens in our clinical practice through a retrospective review of 2655 charts. Two hundred patients (7%) were on a tenofovir/abacavircontaining regimen. Fifty-nine patients met the criteria for analysis and were grouped into three groups: (1) antiretroviral naive, (2) virally suppressed patients switched to TDF/ABC, and (3) patients with failure of their first antiretroviral regimen. Rates of viral suppression in the naive, switch, and first-failure groups were 95%, 86%, and 46%, respectively. In the first-failure group, viral suppression was 66% without and 18% with a preexisting M184V. A composite analysis of the groups revealed a success rate of 86% when the regimen contained zidovudine (ZDV) and 62% when it did not. No K65R mutations were noted. These findings support continued caution in the use of TDF/ABC in combination. However, these data suggest that this combination may be successfully used in selected situations such as in combination with ZDV. In patients already virally suppressed on a TDF/ABC-containing regimen, considerations include continuing the regimen or adding zidovudine, in the attempt to protect against the development of a K65R mutation and/or virologic failure, versus changing a stable regimen.

The steady-state pharmacokinetics of lopinavir/ritonavir (LPV/r) and tenofovir during multiple-dose administration relative to administration of LPV/r and tenofovir disoproxil fumarate (TDF) is discussed. It was seen that higher tenofovir exposures did not result in any evidence of alterations in the safety profile for TDF and in the pharmacokinetic study.

Three cases of primary adefovir (a reverse transcriptase inhibitor used in the treatment of hepatitis B virus) resistance that were sensitive to tenofovir are described. All three cases involved a rare hepatitis B virus (HBV) variant which displayed resistance to adefovir and sensitivity to tenofovir in vitro.

A study to compare the efficacy and safety of the fixed-dose combination group to the separate entities group, in combination with tenofovir and a new protease inhibitor or nonnucleoside reverse transcription inhibitor in antiretroviral-experienced adults experiencing virologic failure is illustrated. Combination antiretroviral therapy has dramatically reduced the morbidity and mortality associated with HIV infection and a one-tablet, once-daily abacavir/lamivudine (FDC) has been recently approved to treat HIV-1 infection.

Coadministration of didanosine (ddI) and tenofovir (TDF) results in increased ddI serum concentrations, which may lead to increased risk of ddI-associated toxicities. To evaluate the safety and tolerability of ddI/TDF, we performed a retrospective cohort analysis of patients seen in the HIV Outpatient Study, an ongoing dynamic cohort study of HIV-infected persons in clinical care. Study subjects were those who received at least 14 days of combined ddI/TDF before October 2003. Of 260 subjects who received ddI/TDF-based antiretroviral therapy, 155 (60%) received high-dose ddI (400 mg daily dose) and 105 (40%) received low-dose ddI (100--250 mg daily). Forty-two of the high-dose ddI recipients were later switched to low-dose ddI. The median time of observation for those on high-dose ddI only was 5 months, high-dose ddI switched to low-dose ddI was 16 months, and low-dose ddI only was 5 months (p < 0.05). Discontinuations because of toxicity were more frequent on high-dose ddI regimens (34/155, 22%) than on low-dose ddI regimens (9/105, 9%) (unadjusted odds ratio [[OR.sub.unadj]] 3.0, 95% confidence interval [95% CI] 1.30-7.09; p = 0.007). Among subjects without preexisting peripheral neuropathy, 12 (12%) of 101 subjects ever on high-dose ddI regimens had treatment-emergent peripheral neuropathy compared to 2 (4%) of 55 subjects on low-dose ddI regimens ([OR.sub.unadj] 3.57; 95% CI, 0.72--24.1; p = 0.14). Among patients without a history of pancreatitis, 6 (4%) of 153 subjects developed pancreatitis after starting high-dose ddI regimens, compared to none of the 103 subjects on low-dose ddI regimens ([OR.sub.adj] and 95% CIs undefined; p = 0.08). Severe laboratory abnormalities of creatinine, phosphorous, and bicarbonate were not different between the groups. A summary variable for any event--discontinuation for toxicity, treatment-emergent adverse event or abnormal laboratory values--indicated that 44 (28%) of 155 of those on high-dose ddI versus 13 (12%) of 105 on low-dose ddI developed any event ([OR.sub.unadj] 2.81; 95% CI, 1.36-5.86; p = 0.004). In conclusion, high-dose ddI/TDF-based therapy was more frequently associated with drug-related toxicity, adverse events, and treatment discontinuation than low-dose ddI/TDF regimens; low-dose ddI with TDF was generally well tolerated in these HIV-infected persons.

A prospective, randomized, multicenter noninferiority study comparing the regiments of tenofovir DF, emtricitabine and efavirenz and a fixed dose of zidovudine and lamivudine plus efavirenz were conducted. Results revealed that the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs.

A study is conducted to assess the interactions between the drugs, namely tenofovir disoproxil fumarate (TDF) and the two nonnucleoside reverse inhibitors, nevirapine and efavirenz, which are used in the treatment of HIV-infected patients. The data obtained from the study demonstrates that these drugs, which can be co-administered without any need for dose adjustments, do not affect the plasma levels of the inhibitors.

Concern exists about the risk of nephrotoxicity using tenofovir (TDF) in HIV-infected patients. We performed a retrospective case-control study including 122 consecutive TDF-na

The patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil are studied. The intensification with once daily tenofovir DF therapy resulted in a sustained reduction in HIV-1 viral load and a low risk for development of the K65R mutation in this treatment experienced patient population.

A study focusing on a subset of infant macaques that were infected with highly virulent simian immunodeficiency (SIV) mac25, and for which prolonged tenofovir treatment failed to significantly suppress viral RNA levels in plasma is presented. It is further found that these tenofovir-treated animals have improved survival while untreated animals with similarly high viremia developed fatal immunodeficiency within 3-6 months.

Tenofovir disoproxil fumarate (DF) is the first nucleotide analog reverse transcriptase inhibitor approved for treatment of human immunodeficiency virus (HIV) and a test was conducted to assess its efficacy and safety compared with stavudine in antiretroviral-naive patients. It was found, over a period 144 weeks, that combination of tenofovir DF, lamivudine and efavirenz was highly effective and also comparable with a combination of stavudine, lamivudine and efavirenz in antiretroviral-naive patients.

Seven cases of renal tubular injury in HIV infected patients receiving an antiretroviral regimen containing tenofovir were examined. It was found that proximal tubulopathy appears to be a rare adverse effect of long-term tenofovir therapy, in patients with low weight or mild preexisting renal impairment and that, regular monitoring of tubulopathy markers could lead to early detection of this dysfunction.

Introduction: Despite progress in scaling up antiretroviral treatment, HIV prevention strategies have not been successful in significantly curbing HIV incidence in Latin America. HIV prevention interventions need to be expanded to target the most affected key populations with a combination approach, including new high impact technologies. Oral pre- exposure prophylaxis (PrEP) is recommended as additional prevention choice for individuals at higher risk of infection and could become a cost-effective prevention tool. We discuss the barriers and solutions for a fair consideration of PrEP as part of combination HIV prevention strategies in Latin America. Discussion: Although demonstration projects are ongoing or being planned in a number of countries, to date no Latin American country has implemented a public PrEP programme. The knowledge of policymakers about PrEP implementation needs to be strengthened, and programmatic guidance and cost estimate tools need to be developed to support adequate planning. Despite high levels of awareness among health providers, especially if engaged in HIV or key population care, willingness to prescribe PrEP is still low due to the lack of national policies and guidelines. Key populations, especially men who have sex with men, transgender women and sex workers, have been engaged in demonstration projects, and qualitative research shows high awareness and willingness to use PrEP, especially if accessible in the public sector for free or at affordable price. Concerns of safety, adherence, effectiveness and risk compensation need to be addressed through targeted social communication strategies to improve PrEP knowledge and stimulate demand. Alliance among policymakers, civil society and representatives from key populations, healthcare providers and researchers will be critical for the design and successful implementation of PrEP demonstration projects of locally adapted delivery models. The use of mechanisms of joint negotiation and procurement of antiretrovirals could reduce costs and significantly increase the cost-effectiveness of PrEP. Conclusions: PrEP is an additional prevention tool and should be implemented in combination and synergy with other prevention interventions. PrEP programmes should target high-risk individuals from key populations for higher cost- effectiveness. Demonstration projects may generate strategic information for and lead to the implementation of full- scale PrEP programmes. Keywords: pre-exposure prophylaxis; HIV; prevention; antiretrovirals; Latin America., Introduction By the end of 2014, Latin America had achieved substantial results in expanding antiretroviral treatment (ART) coverage to 47% of estimated people living with HIV [1]. However, progress in [...]

Introduction: HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Discussion: Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility-and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Conclusions: Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes. Keywords: pre-exposure prophylaxis; the Asia-Pacific region; implementation; demonstration studies; PrEP policy; PrEP awareness; PrEP use; MSM., Introduction In 2014, the Asia-Pacific region was home to more than half of the world's population and 15.2% of the estimated 36.9 million people living with HIV globally [1]. Most [...]

Abstract Tenofovir-related tubule damage characterized by Fanconi syndrome, renal insufficiency and nephrogenic diabetes insipidus has been reported in the adult HIV-infected population. To our knowledge there has been no reported [...]