Search

Background: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). Methods: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. Results: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. Conclusions: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. Trial registration number: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019). [ABSTRACT FROM AUTHOR]

Background: Older People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings. Methods: We performed a cross-sectional, comparative study including patients living with HIV aged ≥50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both. Results: We organized 680 participants data by location (Center and South America [CSA], Western Europe [WE], Africa, Eastern Europe and Israel [EEI]) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life. Conclusions: Patients' opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIV/AIDS. This is crucial for improving health-related quality of life and patient's satisfaction. [ABSTRACT FROM AUTHOR]

Introduction: Entry inhibitors are a relatively new class of antiretroviral therapy and are typically indicated in heavily treatment experienced individuals living with HIV. Despite this, there is no formal definition of 'heavily treatment experienced'. Interpretation of this term generally includes acknowledgement of multidrug resistance and reflects the fact that patients in need of further treatment options may have experienced multiple lines of therapy. However, it fails to recognize treatment limiting factors including contraindications, age‐associated comorbidities, and difficulty adhering to regimens. Methods: This manuscript follows a roundtable discussion and aims to identify the unmet needs of those living with HIV who are in need of further treatment options, to broaden the definition of heavily treatment experienced and to clarify the use of newer agents, with an emphasis on the potential role of entry inhibitors, in this population. Results/Conclusions: Within the entry inhibitor class, mechanisms of action differ between agents; resistance to one subclass does not confer resistance to others. Combinations of entry inhibitors should be considered in the same regimen, and if lack of response is seen to one entry inhibitor another can be tried. When selecting an entry inhibitor, physicians should account for patient preferences and needs as well as agent‐specific clinical characteristics. Absence of documented multidrug resistance should not exclude an individual from treatment with an entry inhibitor; entry inhibitors are a valuable treatment option for all individuals who are treatment limited or treatment exhausted. We should advocate for additional clinical trials that help define the role of entry inhibitors in people with exhausted/limited ART options other than drug resistance. [ABSTRACT FROM AUTHOR]

Background: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described.Methods: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation.Results: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20).Conclusions: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America. [ABSTRACT FROM AUTHOR]

Aging, a time-dependent loss of physiological function, and its drivers are turning into a significant topic of research as the population’s mean age increases. Epigenetic alterations, telomere shortening or dysfunction, mitogenic stress, oxidative stress, or accumulation of DNA damage can drive the cell to senescence: a permanent cell cycle arrest sometimes associated with a secretory phenotype and inflammatory consequences in the surrounding tissue. The amount of senescent cells grows over time in older organisms and may induce tissue inflammation and threaten overall tissue homeostasis, favoring aging. Senolytic and senomorphic therapeutics are an emerging approach to eliminate senescent cells or to block their secretory phenotypes respectively. Given that people living with HIV suffer non-AIDS comorbidities in a higher prevalence than the general population, aging is accentuated among them. Inflammation biomarkers may be helpful to assess prognosis or act as surrogate endpoints for studies of strategies focused on reversal of HIV-associated accelerated aging. This review summarizes the latest findings in aging and its major drivers, under the light of HIV infection. Since the number of older PLWH is currently rising, it will be of great importance to address and treat their age-related conditions, as well as to better decipher their biological mechanisms. [ABSTRACT FROM AUTHOR]

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field's longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives. [ABSTRACT FROM AUTHOR]

Background: Cumulative burden of multiple mental health conditions may worsen physical health outcomes in vulnerable populations. Accordingly, identifying cumulative burdens of mental health conditions that may affect HIV treatment and care can guide public health strategies to reduce their impact on HIV-related health outcomes. This study examined the relationship between the cumulative burden of mental health conditions and factors associated with engagement in HIV care in Argentina. Method: Data for this study was obtained at baseline from Conexiones y Opciones Positivas en la Argentina 2 (COPA2). Participants (N = 360) were cisgender patients living with HIV who were lost to care, recruited from seven clinics serving people living with HIV in four Argentine urban centers. Cumulative burden of mental health conditions (i.e., depressive symptoms, problematic substance use, unhealthy alcohol use, and psychotic symptoms) was assessed. Results: Every one-point increase in the number of mental health conditions present was associated with a decrement in patient-provider communication (b = − 0.22, p <.001), self-efficacy (b = − 0.13, p =.012), and motivation for adherence (b = − 0.11, p =.039). Conclusion: This study found cumulative burden of depression, problematic substance use, unhealthy alcohol use, and psychotic symptoms to be negatively associated with factors related to engagement in HIV care. Results highlight the importance of identification and treatment of challenges to mental health, in order to ameliorate their influence on engagement in HIV care. [ABSTRACT FROM AUTHOR]

Background A prespecified integrated safety analysis was conducted for 3 doravirine (DOR) double-blind trials (Phase IIb: P007 [NCT01632345]; Phase III: DRIVE-FORWARD [NCT02275780] and DRIVE-AHEAD [NCT02403674]). Methods DOR (100 mg) arms from these trials were compared with darunavir plus ritonavir (DRV+r) in DRIVE-FORWARD and efavirenz (EFV) in P007 and DRIVE-AHEAD. Background therapies were emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in P007; abacavir/lamivudine (ABC/3TC) or FTC/TDF in DRIVE-FORWARD; and 3TC/TDF for DOR and FTC/TDF for EFV in DRIVE-AHEAD. The primary endpoint was the proportion of participants discontinuing due to adverse events (AEs) through Week 48. Results Discontinuation rates due to AEs were similar for participants on DOR and DRV+r (2.5% vs 3.1%, respectively) and lower for those on DOR than for those on EFV (2.5% vs 6.6%, respectively). Rates of drug-related AEs for DOR, DRV+r, and EFV were 30.9%, 32.1%, and 61.4%, respectively. In an analysis of DOR versus EFV, the treatment difference for discontinuations due to AEs was −3.4%, favoring DOR (95% confidence interval −6.2 to −0.8; P =.012). Fewer participants experienced neuropsychiatric AEs on DOR than on EFV (25.0% vs 55.9%, respectively), and fewer experienced diarrhea on DOR than on DRV+r (12.4% vs 22.5%, respectively). Changes from baseline in most lipid parameters also favored DOR. Conclusions At Week 48, DOR at 100 mg had a favorable safety profile compared with EFV or DRV+r and a favorable tolerability profile compared with EFV. Clinical Trials Registration NCT01632345; NCT02275780 and NCT02403674. [ABSTRACT FROM AUTHOR]

Objectives To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults. Methods In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400–900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015. Results We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30–43) years. Baseline CD4 count was 592 (491–694) cells/mm3 and VL was 4.04 (3.5–4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3/year in the valaciclovir arm versus 58 cells/mm3/year in the placebo arm (P  =   0.65). No differences were seen in the rate of change in CD4 percentage (−1.2%/year versus −1.7%/year, P  =   0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P <0.001). Placebo participants had more HSV recurrences (62 versus 21/100 person-years, P  <   0.0001) but similar rates of grade ≥2 drug-related adverse events. Conclusions Unlike prior trials using aciclovir, we found that valaciclovir did not slow CD4 count decline in cART-untreated adults, although power was limited due to premature study discontinuation. Valaciclovir modestly lowered HIV VL. [ABSTRACT FROM AUTHOR]

Background: Globally, Latin America ranks third among regions with most cases of AIDS related cryptococcal meningitis. In 2009, a lateral flow immunoassay (LFA) for the detection of cryptococcal antigen (CrAg) was developed as a potential point-of-care test for diagnosis of cryptococcal infection. In 2011 World Health Organizations recommended on CrAg screening for HIV positive persons with CD4 below 100 cells/μL, followed by preemptive fluconazole treatment. However, in Argentina no formal recommendations for CrAg screening have been issued. Methods: HIV positive patients > = 18 years with advanced immunosuppression (CD4 counts ≤100 cells/μL within 3 months or WHO stage III/IV), who visited the hospital between April 1, 2014 and January 31, 2015, were included. The LFA was performed according to the manufacturer’s instructions on all serum samples. When CrAg detection was positive, a lumbar puncture was performed to rule out cryptococcal meningitis. Patients without evidence of meningeal involvement were treated with preemptive oral fluconazole in ambulatory care. Results: We included 123 patients. Prevalence of CrAg-positivity was 8.1%. Among the 10 CrAg-positive patients, 6 had meningeal involvement detected through the CSF analysis (CSF India-ink testing, CSF CrAg and culture). The remaining 4 patients with positive CrAg received targeted preemptive treatment with oral fluconazole and were free of cryptococcal disease during the follow-up period. None of the 113 patients with a negative CrAg test result developed cryptococcal disease. Conclusions: This is the first study in Argentina, to our knowledge, describing the prevalence of cryptococcosis and usefulness of CrAg screening. LFA provided early diagnosis to determine a high prevalence of CrAg in our hospital, and that screening for subclinical infection with preemptive antifungal treatment, prevented a substantial proportion of meningeal disease. [ABSTRACT FROM AUTHOR]

Challenging HIV-infected patients, those neither adherent nor actively engaged in care, represent an important opportunity for intervention if the HIV epidemic is to be contained. This pilot study assessed the feasibility and acceptability of an adapted patient adherence intervention and a motivational interview-based provider intervention in urban Buenos Aires, Argentina, in order to optimize health benefits in challenging HIV-infected patients. To maximize implementation and uptake of both strategies, interventions were adapted to the local setting. Qualitative data and a short quantitative assessment from patients, staff, fellows, residents and physicians (n = 84) were examined to establish the feasibility and acceptability of offering patient and provider evidencebased interventions in both public and private health-care settings. Results identified key themes on provision of information, use of specialized communication techniques and group support in the utilization of the interventions. Both providers (n = 12) and patients (n = 120) endorsed the acceptability and value of the interventions, and the feasibility of their delivery. Findings support the use of both intervention modalities with challenging patients in diverse urban health-care settings. [ABSTRACT FROM AUTHOR]

Objective: We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. Methods: A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Results: Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. Conclusions: The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy. [ABSTRACT FROM AUTHOR]

HIV guidelines increasingly recommend antiretroviral therapy (ART) initiation at a higher CD4 levels. The extent to which these evolving standards are translated into routine clinical care has not been evaluated in Argentina. During October 2012, we conducted an online survey among Argentinean HIV clinicians to assess their attitudes and practices toward ART initiation and its potential use for HIV prevention. Of the 280 physicians included, 61% would prescribe ART at CD4 ≤500 cells/µL for asymptomatic patients. Although, only 11% would recommend ART irrespective of CD4 cell count, 72% would do it for serodiscordant couples, and 75% for sex workers. Most participants agreed that they would consider earlier initiation of ART if transmission risk exists, and that expansion of ART could help decrease HIV incidence. These results suggest that a large proportion of Argentinean HIV care providers are willing to adopt the recently updated Argentinean guidelines recommending earlier ART, especially when high HIV transmission risk exists. [ABSTRACT FROM AUTHOR]

Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46-6.14; p=0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00-1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34-6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users. [ABSTRACT FROM AUTHOR]

The article focuses on the 2012 recommendations of the Intemational Antiviral Society for the antiretroviral treatment (ART) of adult HIV infection. It states that the new recommendations for HIV patient care include providing ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing. It also recommends providing ART irrespective of the choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis. It also states that the concentration of HIV in both blood and seminal plasma is related to the probability of transmission of HIV to a sexual partner.

Background: Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation. Methods and Findings: Using a prospective cohort of HIV-infected patients (n = 1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4+ T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4+ T cell count of 200 or 350 cells/μl). The algorithm correctly classified 90% (cross-validation estimate = 91.5%, standard deviation [SD] = 4.5%) of CD4 count measurements, 200 cells/μl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/μl threshold, we estimate a potential savings of 54.3% (SD = 4.2%) in CD4 testing capacity. A capacity savings of 34% (SD = 3.9%) is predicted using a CD4 threshold of 350 cells/ml. Similar results were obtained over the 3 y of follow-up available (n = 619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold. Conclusions: Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4+ T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEAsuphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. Methods: This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). Results: Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/ r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200copies/mL (P = 0.61). Time-tovirologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/ r;3:HAART) patients. Conclusion: At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in virologically-suppressed patients merits further prospective long-term evaluation. [ABSTRACT FROM AUTHOR]

The article presents a comparative study on the effectiveness of rilpivirine and efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 in Ireland. The study intends to assess the efficacy, safety and tolerability of rilpivirine versus efavirenz wherein each are combined with tenofovir-disoproxil-fumarate and emtricitabine. The findings reveal the safety and tolerability profile of rilpivirine.

Background: The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs. Methods: We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed. Findings: We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load 50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference 20.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity = 0.08, I2 = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p,0.001; risk difference 20.07 (95%CI 20.10 to 20.03) p,0.001, p for heterogeneity = 0.44, I2 = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression. Interpretation: Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors. [ABSTRACT FROM AUTHOR]

Background: HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%-70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. Methodology: Antiretroviral-naïve patients .= 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. Principal Findings: Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31-44), and median CD4 count was 105 cells/uL (IQR, 38-200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15-17%) and 28% (95% CI 27-29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1-2.6) and 2.1 (95% CI 1.7-2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1-1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens. Conclusions: Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation. [ABSTRACT FROM AUTHOR]

Apricitabine is a novel deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI) currently in clinical development for the treatment of HIV infection. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. Resistance to apricitabine is slow to develop in vitro and there has been little evidence of development of resistance to apricitabine in clinical use thus far, including patients receiving apricitabine for up to 48 weeks. The resistance profile of apricitabine suggests there is a low potential for cross-resistance with the currently available NRTIs and, thus, apricitabine may provide a treatment option for treatment-experienced HIV-1-infected patients with resistance to other NRTIs. In particular, the activity of apricitabine in the presence of the M184V mutation, which confers high-level resistance to lamivudine and emtricitabine, lends it to being used as a replacement for deoxycytidine analogues in patients who have failed treatment with lamivudine or emtricitabine. [ABSTRACT FROM PUBLISHER]

Background: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. Methodology/Principal Findings: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. Conclusions: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted in an effort to summarize new data in the field of antiretroviral treatment of adult HIV infection and to provide current recommendations for antiretroviral management and monitoring of HIV infection. Researchers found that new data and considerations support initiating therapy before CD4 cell counts decline to less than 350/ul. They also determined that the initial treatment regimen for patients must be individualized, particularly in the presence of comorbid conditions. Their findings on treatment failure are discussed.

Background. Tipranavir, a novel protease inhibitor, has demonstrated antiviral activity against protease inhibitor- resistant human immunodeficiency virus type 1 (HIV-1) isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-2) trial is an ongoing, open-label, phase III trial comparing ritonavir-boosted tipranavir (TPV/r) plus an optimized background regimen with an individually optimized, ritonavir-boosted protease inhibitor in treatment-experienced, HIV-1–infected patients. Methods. Patients at 171 sites in Europe and Latin America who had received ≥2 previous protease inhibitor regimens, had triple-antiretroviral class experience, had an HIV-1 RNA level ≥1000 copies/mL, and had genotypically demonstrated primary protease inhibitor resistance were eligible. After genotypic resistance tests were performed, a protease inhibitor and optimized background regimen were selected before randomization. Patients were randomized to receive either TPV/r or comparator protease inhibitor-ritonavir (CPI/r) and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed HIV-1 load reduction ≥1 log10 less than the baseline value without a treatment change at week 24. Results. A total of 863 patients were randomized and treated. At baseline, the mean HIV-1 load was 4.73 log10 copies/mL, and the mean CD4+ cell count was 218 cells/mm³. The preplanned 24-week efficacy analyses of 539 patients demonstrated treatment response rates of 41% in the TPV/r arm and 14.9% in the CPI/r arm (intent-to-treat analysis; P<.0001). The mean CD4+ cell count increased by 51 cells/mm³ in the TPV/r arm and by 18 cells/mm³ in the CPI/r arm. The most common adverse events were mild-to-moderate diarrhea, nausea, and headache. Grade 3 or greater elevations in serum transaminase, cholesterol, and triglyceride levels were more frequent in the TPV/r arm. Conclusions. TPV/r had superior antiviral activity and increased immunologic benefits, compared with CPI/ r, at week 24 among treatment-experienced patients infected with multidrug-resistant HIV-1. [ABSTRACT FROM AUTHOR]

Background Patients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV). Methods and Findings Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n =417), or EFV (n =289) in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5%) than for patients receiving EFV (33.7%; p =0.036), while the increase in TC was lower (26.9% and 31.1%, respectively; p =0.073), resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP ( 4.1%) and an increase for patients receiving EFV ( p 5.9%; p < 0.001). The increase of non-HDL-c was smaller for patients receiving NVP (24.7%) than for patients receiving EFV (33.6%; p =0.007), as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001) and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p =0.378). These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4 p cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs. Conclusion NVP-containing ART shows larger ... [ABSTRACT FROM AUTHOR]

Discusses the clinical presentations of tuberculosis (TB) in relation to HIV and HIV-associated immune deficiency from the perspective of clinical diagnosis and treatment in patient care. Recommended treatment regimens for TB; Immune reconstitution inflammatory syndrome; Management of latent TB infection; Monitoring and management of adverse events; Risk factors for nosocomial transmission.

Presents a randomized, controlled phase II trial comparing escalating doses of subcutaneous interleukin-2 (IL-2) plus antiretrovirals versus antiretroviral alone in HIV-infected patients with CD4[sup +] cell counts of 350 per cubic millimeter. Effects of the T cell-derived cytokine IL-2 on the immune system; Efficacy of the treatment groups; Side effects of subcutaneous IL-2 administration.

10.1007/s12529-020-09921-5 [ABSTRACT FROM AUTHOR]

Background: "Challenging" HIV-infected patients, those not retained in treatment, represent a critical focus for positive prevention, as linkage to care, early initiation of antiretroviral therapy, adherence and retention in treatment facilitate viral suppression, thus optimizing health and reducing HIV transmission. Argentina was one of the first Latin American countries to guarantee HIV prevention, diagnosis and comprehensive care services, including antiretroviral medication, which removed cost and access as barriers. Yet, dropout occurs at every stage of the HIV continuum. An estimated 110,000 individuals are HIV-infected in Argentina; of these, 70% have been diagnosed and 54% were linked to care. However, only 36% have achieved viral suppression and 31% of those diagnosed delayed entry to care. To achieve meaningful reductions in HIV infection at the community level, innovative strategies must be developed to re-engage patients. Motivational Interviewing (MI) is a patient-centered approach and has been used by therapists in Central and South America to enhance motivation and commitment in substance use and risk reduction. Our pilot feasibility study utilized culturally tailored MI in physicians to target patients not retained in treatment in public and private clinics in Buenos Aires, Argentina. Results demonstrated that a physician-based MI intervention was feasible and effective in enhanced and sustained patient adherence, viral suppression, and patient-physician communication and attitudes about treatment among these patients at 6 and 9 months post baseline.Methods/design: This clinical trial seeks to extend these findings in public and private clinics in four urban population centers in Argentina, in which clinics (n = 6 clinics, six MDs per clinic site) are randomized to experimental (physician MI Intervention) (n = 3) or control (physician Standard of Care) (n = 3) conditions in a 3:3 ratio. Using a cluster randomized clinical trial design, the study will test the effectiveness of a physician-based MI intervention to improve and sustain retention, adherence, persistence, and viral suppression among "challenging" patients (n = 420) over 24 months.Discussion: Results are anticipated to have significant public health implications for the implementation of MI to re-engage and retain patients in HIV treatment and care and improve viral suppression through high levels of medication adherence.Trial Registration: ClinicalTrials.gov, ID: NCT02846350 . Registered on 1 July 2016. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. Methods: Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC). The association of mortality with cancer- and HIV-related factors was assessed using Kaplan-Meier curves and Cox proportional hazards models stratified by clinic site and cancer type. Results: Among 15,869 patients, 783 had an eligible cancer diagnosis; 82% were male and median age at cancer diagnosis was 39 years (interquartile range [IQR]: 32–47). Patients were from Brazil (36.5%), Argentina (19.9%), Chile (19.7%), Mexico (19.3%), and Honduras (4.6%). A total of 564 ADC and 219 NADC were diagnosed. Patients with NADC had similar survival probabilities as those with ADC at one year (81% vs. 79%) but lower survival at five years (60% vs. 69%). In the adjusted analysis, risk of mortality increased with detectable viral load (adjusted hazard ratio [aHR] = 1.63, p = 0.02), age (aHR = 1.02 per year, p = 0.002) and time between HIV and cancer diagnoses (aHR = 1.03 per year, p = 0.01). Conclusion: ADC remain the most frequent cancers in the region. Overall mortality was related to detectable viral load and age. Longer-term survival was lower after diagnosis of NADC than for ADC, which may be due to factors unrelated to HIV. [ABSTRACT FROM AUTHOR]

The article reports on the clinical development of raltegravir, an integrase inhibitor that can be used in the treatment of HIV. The author focuses on the evolution of salvage therapies since the year 2004. Protease inhibitors including darunavir and tipranavir have aided in the reestablishment of virological suppression in HIV patients. Integrase inhibitors are antiretroviral drugs that stop the HIV-1 enzyme from speeding up the insertion of HIV-1 DNA into the patient's own DNA. Side-effects participants experienced were generally mild to moderate.

Introduction Treatment with ritonavir-boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study. Materials and Methods The GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in fixed-dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms. Results Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94 mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL-C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC. Conclusion Changes in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL-C) in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction []. So, the DT strategy, even missing the lipid-lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy. [ABSTRACT FROM AUTHOR]

Presents a correction to the article "Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral-Therapy-Naive Patients Infected With HIV-1," by Frank van Leth, Prahpan Phanuphak, Erik Stroes, Brian Gazzard, Pedro Cahn, et al. that was previously published in the October 19, 2004 issue of the journal "PLoS Medicine."

Acquired immune deficiency syndrome has been one of the most devastating epidemics of the last century. The current estimate for people living with the HIV is 36.9 million. Today, despite availability of potent and safe drugs for effective treatment, lifelong therapy is required for preventing HIV re-emergence from a pool of latently infected cells. However, recent evidence show the importance to expand HIV testing, to offer antiretroviral treatment to all infected individuals, and to ensure retention through all the cascade of care. In addition, circumcision, pre-exposure prophylaxis, and other biomedical tools are now available for included in a comprehensive preventive package. Use of all the available tools might allow cutting the HIV transmission in 2030. In this article, we review the status of the epidemic, the latest advances in prevention and treatment, the concept of treatment as prevention and the challenges and opportunities for the HIV cure agenda. [ABSTRACT FROM AUTHOR]

Examines the administration of abacavir in combination with lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infected adults. Dosage level; Efficacy of the treatment in comparison with single therapy; Safety profile in terms of general adverse events.

Background Recent studies indicate that there is selection bias for transmission of viral polymorphisms associated with higher viral fitness. Furthermore, after transmission and before a specific immune response is mounted in the recipient, the virus undergoes a number of reversions which allow an increase in their replicative capacity. These aspects, and others, affect the viral population characteristic of early acute infection. Methods 160 single gag-gene amplifications were obtained by limiting-dilution RT-PCR from plasma samples of 8 ARV-naïve patients with early acute infection (<30 days, 22 days average) and 8 ARV-naive patients with approximately a year of infection (10 amplicons per patient). Sanger sequencing and NGS SMRT technology (Pacific Biosciences) were implemented to sequence the amplicons. Phylogenetic analysis was performed by using MEGA 6.06. HLA-I (A and B) typing was performed by SSOP-PCR method. The chromatograms were analyzed with Sequencher 4.10. Epitopes and immune-proteosomal cleavages prediction was performed with CBS prediction server for the 30 HLA-A and -B alleles most prevalent in our population with peptide lengths from 8 to 14 mer. Cytotoxic response prediction was performed by using IEDB Analysis Resource. Results After implementing epitope prediction analysis, we identified a total number of 325 possible viral epitopes present in two or more acute or chronic patients. 60.3% (n = 196) of them were present only in acute infection (prevalent acute epitopes) while 39.7% (n = 129) were present only in chronic infection (prevalent chronic epitopes). Within p24, the difference was equally dramatic with 59.4% (79/133) being acute epitopes (p < 0.05). This is consistent with progressive viral adaptation to immune response in time and further supported by the fact that cytotoxic responses prediction showed that acute epitopes are more likely to generate immune response than chronic epitopes. Interestingly, only 27.5% of acute epitopes match the population-level consensus sequence of the virus. Conclusions Our results indicate that certain non-consensus viral residues might be transmitted more frequently than consensus-residues when located in immunological relevant positions (epitopes). This observation might be relevant to the rationale behind development of an effective vaccine to reduce viral reservoir and induce functional cure of HIV infection based in prevalent acute epitopes. [ABSTRACT FROM AUTHOR]

Elucidating the factors that modulate HIV-specific antibody-dependent cellular cytotoxicity (ADCC) will help in understanding its role in HIV immunity. The aim of this study was to determine whether IgA could modify the magnitude of ADCC in HIV infection, abrogating its protective role. Plasma samples from 20 HIV-positive (HIV) subjects enrolled during primary HIV infection (PHI), 10 chronically infected subjects (chronic), and 7 elite controllers (EC) were used. ADCC was determined by using a fluorometric ADCC assay, before and after removal of plasma IgA. Data were analyzed by using nonparametric statistics. ADCC was documented in 80% of PHI enrollment samples and in 100% of PHI 12-month, chronic, and EC samples; it peaked after acute infection, reached a plateau in chronic infection, and decreased after initiation of antiretroviral treatment (ART). Significant associations between ADCC and disease progression were found only after removal of plasma IgA from 12-month PHI samples: the magnitude of ADCC not only increased after IgA removal but also correlated with CD4+ T-cell preservation. This work provides evidence that gp120-specific IgA was capable of modifying ADCC responses during natural HIV infection for the first time and adds to similar evidence provided in other settings. Furthermore, it underscores the complexity of the ADCC phenomenon and will help in an understanding of its underlying mechanisms. [ABSTRACT FROM AUTHOR]

The article presents a study which examines first-year mortality rates in HIV-1-infected patients after the initiation of highly active antiretroviral therapy (HAART) in Latin America and the Caribbean region. The study observed 5,152 HIV-infected persons from 1996-2007 and assessed their demographics, regimen, baseline cluster of differentiation 4 (CD4), and clinical stage. Results of the study indicate that mortality rates during HAART initiation are associated with limited resources.

A letter to the editor is presented which examines the association of abnormal alanine aminotransferase (ALT) with uncommon hepatitis B virus (HBV) or hepatitis C virus (HCV) occult infection in HIV-positive patients.