Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial.

Background: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT).

1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis.

Background: Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups.

Methods: We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year.

Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group.

Background: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.

Methods: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio.

Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349).

Background: Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 noninferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the prespecified subgroup of people with human immunodeficiency virus (HIV) (PWH).

Methods: PWH and CD4+ counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART).

Correlates and Timing of Reproductive Aging Transitions in a Global Cohort of Midlife Women With Human Immunodeficiency Virus: Insights From the REPRIEVE Trial.

Background: Reproductive aging may contribute to cardiometabolic comorbid conditions. We integrated data on gynecologic history with levels of an ovarian reserve marker (anti-müllerian hormone [AMH)] to interrogate reproductive aging patterns and associated factors among a subset of cisgender women with human immunodeficiency virus (WWH) enrolled in the REPRIEVE trial.

Methods: A total of 1449 WWH were classified as premenopausal (n = 482) (menses within 12 months; AMH level ≥20 pg/mL; group 1), premenopausal with reduced ovarian reserve (n = 224) (menses within 12 months; AMH <20 pg/mL; group 2), or postmenopausal (n = 743) (no menses within12 months; AMH <20 pg/mL; group 3).

Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease.

Background: We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial.

Methods: We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing.

Quality of life improvement in resource-limited settings after one year of second-line antiretroviral therapy use among adult men and women.

Objective: We evaluated improvement of quality of life (QoL) after 1 year of second-line antiretroviral therapy (ART) use in resource-limited settings (RLS) among adult men and women, comparing two randomized treatment arms.

Design: The AIDS Clinical Trial Group A5273 was a randomized clinical trial of second-line ART comparing lopinavir/ritonavir (LPV/r) + raltegravir with LPV/r + nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in participants failing a non-NRTI-containing regimen at 15 sites in nine RLS. Participants completed the AIDS Clinical Trial Group short-form-21 which has eight QoL domains with a standard score ranging from 0 (worst) to 100 (best).

Recommendations for the management of idiopathic pulmonary fibrosis in South Africa: a position statement of the South African Thoracic Society.

Idiopathic pulmonary fibrosis (IPF) is a very specific form of a chronic, progressive fibroproliferative interstitial pneumonia of unknown aetiology. The disease is generally associated with a poor prognosis. Several international evidence-based guidelines on the diagnosis and management of IPF and other interstitial lung diseases (ILDs) have been published and updated in the last decade, and while the body of evidence for the use of some treatment modalities has grown, others have been shown to be futile and even harmful to patients.

TB/HIV pleurisy reduces Th17 lymphocyte proportion independent of the cytokine microenvironment.

T-helper (Th) 17 cells are a pro-inflammatory subset of CD4(+) effector T-cells critical in mucosal immunity. Imbalances in Th17 cell proportion have been implicated in the pathogenesis of several diseases; however, this has not been adequately explored in tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Since Th17 cells are predominantly mucosally associated, we assessed Th17 proportion and associated microenvironment in pleural effusions from patients co-infected with TB/HIV.

HIV and COPD: a conspiracy of risk factors.

Chronic obstructive pulmonary disease (COPD) is an under recognized complication of HIV infection. It is estimated that up to 25% of HIV infected people may have COPD. HIV is associated with COPD as a result of a complex interplay of multiple factors such as pulmonary inflammation, recurrent pulmonary infections especially tuberculosis (TB), increased cigarette smoking, socio-economic status, childhood respiratory illnesses and industrial and environmental exposures; each of which are risk factors for COPD in their own right.

Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks.

Objectives: To explore factors associated with short and long-term hepatitis B virus (HBV) DNA suppression in a multinational cohort of HIV-HBV co-infected patients receiving HBV-active antiretrovirals.

Methods: One hundred and fifteen HIV-HBV co-infected patients participating in one of the two global randomized clinical trials conducted by the Adult AIDS Clinical Trials Group of different antiretroviral regimens received either HBV monotherapy with either lamivudine or emtricitabine (N = 56), or HBV dual therapy with tenofovir disoproxil fumarate (TDF) + lamivudine or emtricitabine (N = 59). Associations of pretreatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression.

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

Background: Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators.

Methods: A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4 T-cell count <300 cells/mm; 9 countries) was conducted.

Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial.

Background: Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites.

Methods: Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group).

Psychosocial predictors of non-adherence and treatment failure in a large scale multi-national trial of antiretroviral therapy for HIV: data from the ACTG A5175/PEARLS trial.

Background: PEARLS, a large scale trial of antiretroviral therapy (ART) for HIV (n = 1,571, 9 countries, 4 continents), found that a once-daily protease inhibitor (PI) based regimen (ATV+DDI+FTC), but not a once-daily non-nucleoside reverse transcriptase inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) regimen (EFV+FTC/TDF), had inferior efficacy compared to a standard of care twice-daily NNRTI/NRTI regimen (EFV+3TC/ZDV). The present study examined non-adherence in PEARLS.

Methods: Outcomes: non-adherence assessed by pill count and by self-report, and time to treatment failure.

A strategy for developing future academic leaders for South Africa in a resource-constrained environment.

A key challenge in addressing the shortage of health care workers in resource-constrained environments is ensuring that there is optimal academic capacity for their training. South Africa's University of KwaZulu-Natal has placed academic and research capacity building at the heart of its program with the Medical Education Partnership Initiative in a program called ENhancing Training and REsearch capacity and Expertise (ENTREE). The program aims to increase the quantity, quality, and retention of health care graduates.

Outcomes among HIV-1 infected individuals first starting antiretroviral therapy with concurrent active TB or other AIDS-defining disease.

Background: Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the "Prospective Evaluation of Antiretrovirals in Resource-Limited Settings" (PEARLS) study.

Methods: PARTICIPANTS WERE CATEGORIZED RETROSPECTIVELY INTO THREE GROUPS ACCORDING TO PRESENCE OF ACTIVE CONFIRMED OR PRESUMPTIVE DISEASE AT ART INITIATION: those with pulmonary and/or extrapulmonary TB ("TB" group), those with other non-TB AIDS-defining disease ("other disease"), or those without concurrent TB or other AIDS-defining disease ("no disease").

HIV transmission risk behavior among HIV-positive patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa.

The aim of this investigation was to identify factors associated with HIV transmission risk behavior among HIV-positive women and men receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. Across 16 clinics, 1,890 HIV+ patients on ART completed a risk-focused audio computer-assisted self-interview upon enrolling in a prevention-with-positives intervention trial. Results demonstrated that 62 % of HIV-positive patients' recent unprotected sexual acts involved HIV-negative or HIV status unknown partners.

Adverse events in an integrated home-based treatment program for MDR-TB and HIV in KwaZulu-Natal, South Africa.

Most patients with multidrug-resistant tuberculosis (MDR-TB) in South Africa are HIV-infected, but the safety and tolerability of cotreatment are unknown. The authors reviewed all adverse events (AEs) for patients with MDR-TB in a home-based treatment program in rural KwaZulu-Natal. Of 91 MDR-TB patients, 74 (81%) were HIV-positive and receiving antiretroviral therapy.

Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort.

Objective: To understand the HIV-hepatitis B virus (HBV) epidemic from a global perspective by clinically and virologically characterizing these viruses at the time of antiretroviral therapy (ART) initiation in a multinational cohort.

Methods And Design: HIV-infected patients enrolled in two international studies were classified as HIV-HBV coinfected or HIV monoinfected prior to ART. HIV-HBV coinfected patients were tested for HBV characteristics, hepatitis D virus (HDV), a novel noninvasive marker of liver disease, and drug-resistant HBV.

Counsellor-delivered HIV risk reduction intervention addresses safer sex barriers of people living with HIV in KwaZulu-Natal, South Africa.

This study developed an HIV risk reduction intervention for people living with HIV (PLWH) obtaining care at primary healthcare clinics in KwaZulu-Natal, South Africa by (1) conducting elicitation research to understand the dynamics of risk behaviour among PLWH, (2) modifying an existing HIV risk reduction intervention based on research findings and (3) conducting a pilot study to evaluate feasibility, acceptability and fidelity of the modified intervention implemented by trained lay counsellors at a rural clinic in KwaZulu-Natal. A total of 61 healthcare providers and 77 HIV+ patients from four primary healthcare clinics participated in 14 focus groups and 20 individual interviews to identify informational, motivational and behavioural skills (IMB) factors contributing to PLWH's sexual risk behaviour. Elicitation research findings were incorporated into a revised version of Options for Health, an evidence-based risk reduction intervention for PLWH in clinical care.

Occupational exposures and chronic obstructive pulmonary disease: a hospital based case-control study.

Background: Occupational exposures are associated with chronic obstructive pulmonary disease (COPD). This study investigated this association among a population with a high prevalence of tuberculosis and smoking.

Methods: Cases (n=110) diagnosed by pulmonologists were selected from specialist respiratory clinics.

Culture conversion among HIV co-infected multidrug-resistant tuberculosis patients in Tugela Ferry, South Africa.

Background: Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting.

Methods: Patients with culture-proven MDR-TB were treated with a standardized second-line regimen.

New antituberculous drugs in development.

There have been no new antituberculous drugs since the introduction of rifampin in 1952. The collision of the HIV and tuberculosis (TB) epidemics in developing regions of the world together with the emergence of multidrug resistance and extensively drug-resistant strains of TB has emphasized the urgent need for newer antituberculous drugs. There is a need for drugs that are safe, effective against resistant strains, are able to shorten the course of treatment, are effective for latent TB infection, and that have minimal interactions with antiretroviral drugs.