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Abstract Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

It is very exceptional that a new disease becomes a true pandemic. Since its emergence in Wuhan, China, in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has spread to nearly all countries of the world in only a few months. However, in different countries, the COVID-19 epidemic takes variable shapes and forms in how it affects communities. Until now, the insights gained on COVID-19 have been largely dominated by the COVID-19 epidemics and the lockdowns in China, Europe and the USA. But this variety of global trajectories is little described, analysed or understood. In only a few months, an enormous amount of scientific evidence on SARS-CoV-2 and COVID-19 has been uncovered (knowns). But important knowledge gaps remain (unknowns). Learning from the variety of ways the COVID-19 epidemic is unfolding across the globe can potentially contribute to solving the COVID-19 puzzle. This paper tries to make sense of this variability-by exploring the important role that context plays in these different COVID-19 epidemics; by comparing COVID-19 epidemics with other respiratory diseases, including other coronaviruses that circulate continuously; and by highlighting the critical unknowns and uncertainties that remain. These unknowns and uncertainties require a deeper understanding of the variable trajectories of COVID-19. Unravelling them will be important for discerning potential future scenarios, such as the first wave in virgin territories still untouched by COVID-19 and for future waves elsewhere., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In 2001, an international beverage company implemented an HIV workplace programme providing free antiretroviral treatment (ART) for employees and dependents in sub-Saharan Africa, at a time when ART, cost assessments of ART programmes and related public funding was hardly available. This study describes the outcomes of this programme with respect to achieving the UNAIDS 90-90-90 targets in five African countries and analyses trends over the past 15 years., Methods: Anonymous human resource data were analysed in three cohorts of participants (those enrolling in 2001-2005, 2006-2010 and 2011-2015)., Results: Over 15 years, 42,490 unique individuals in five African countries were tested for HIV in this programme and 746 (1.8%) were found to be HIV-infected. Between 2002 and 2015, the proportion of HIV-positive participants on ART increased from 42% to 94% and the proportion of participants on ART who achieved virological suppression increased from 38% to 87%., Conclusions: This study shows that in one of the earliest HIV treatment programmes in Africa long-term success has been achieved, approaching the current UNAIDS 90-90-90 targets, demonstrating that the treatment of HIV in developing countries is possible with superior results at low costs (45 US dollars/employee). Reasons for this success include continuous access to on-site quality care and ART and the assistance of an independent NGO with experience in HIV treatment. This provides an argument to continue private sector involvement in international efforts to combat HIV/AIDS, particularly in light of increased ART targets, under-capacity in the public sector and stagnating international funding.

High uptake of HIV voluntary counseling and testing (VCT) services is important for the success of HIV workplace programs in sub-Saharan Africa. From 2001 onwards, Heineken, a multinational brewing company, implemented a comprehensive HIV prevention and treatment program for employees and their dependents of its African subsidiaries. Confidential in-house VCT is part of this program. VCT uptake dynamics over time, and factors associated with early uptake were studied. Between September 2001 and December 2007, 9723 adult beneficiaries were tested for HIV in 14 company sites in five African countries. Three hundred and seventy (3.8%) of tested persons were infected with HIV-1. During the first 12 months 1412 tests were done, compared to 8311 tests in the subsequent years. The annual average uptake of testing among eligible persons varied between 15 and 32%. The coverage was higher among female compared to male employees, and higher among female compared to male spouses. Distinct peaks in uptake were linked to specific local events. HIV-1 infected persons were significantly more likely to be tested in the early period. The proportion of HIV-1 infected persons among testees was 8.8% in the first 12 months compared to 3.0% in the subsequent period (p<0.001). HIV-1 infected persons diagnosed in the early period were in a more advanced clinical stage, and had a significantly lower CD4 count than those tested later (median CD4 count 227 vs. 314 cells/microl; p=0.002). In this workplace program, HIV-1 infected individuals came earlier for an HIV test than uninfected people, and people with advanced infection came earlier than those with less advanced disease. Employees' spouses are harder to reach than employees and extra efforts should be undertaken to reach them as well. Uptake of HIV testing can be actively influenced by educational or promotional activities.

Background: This study aimed to evaluate the effectiveness of an HIV workplace programme in sub-Saharan Africa., Methods: The international brewing company, Heineken, introduced an HIV workplace programme in its African subsidiaries in 2001. Beneficiaries from 16 sites in 5 countries were eligible. HIV type-1 (HIV-1)-infected individuals were assessed clinically and immunologically, and started highly active antiretroviral therapy (HAART) if they had AIDS or had a CD4+ T-cell count <300 cells/microl. In this cohort, study patients were followed-up for vital status, new AIDS events, CD4+ T-cell count and haemoglobin., Results: Over the first 5 years of the programme, 431 adults were found to be HIV-1-infected. The mortality rate among those not yet taking HAART was 2.6 per 100 person-years of observation (pyo). By October 2006, 249 patients had started HAART at a median CD4+ T-cell count of 170 cells/microl; 59 (23.7%) patients were in CDC stage C. Among patients on HAART, 25 died and 7 were lost to follow-up. The mortality rate was 3.7 per 100 pyo overall, 14 per 100 pyo in the first 16 weeks and 2.5 per 100 pyo thereafter (P < 0.0001). At 4 years after start of treatment, 89% of patients were known to be alive. The CD4+ T-cell count increased by a median of 153 and 238 cells/microl after 1 and 4 years of HAART, respectively., Conclusions: In this HIV workplace programme in sub-Saharan Africa, long-term high survival was achieved.

We examined the incidence of and risk factors for tuberculosis during the first year of highly active antiretroviral therapy in low-income (4540 patients) and high-income (22,217 patients) countries. Although incidence was much higher in low-income countries, the reduction in the incidence of tuberculosis associated with highly active antiretroviral therapy was similar: the rate ratio for months 7-12 versus months 1-3 was 0.48 (95% confidence interval, 0.36-0.64) in low-income countries and 0.36 (95% confidence interval, 0.26-0.50) in high-income countries. A low CD4 cell count at the start of therapy was the most important risk factor in both settings.

Heineken Breweries launched a workplace HIV/AIDS program at its Rwanda subsidiary in September 2001. By January 25, 2005, 736/2,595 eligible individuals had reported for counseling and HIV testing: 380/521 employees (72.9%), 254/412 spouses (61.7%), 99/1,517 children (6.5%), and 3/145 retired (2.0%). As a result, 109 HIV+ individuals were identified: 62 employees, 34 spouses, 12 children, and 1 retired. In September 2003 an anonymous HIV seroprevalence survey was performed with participation rates of 69.4% for employees, 58.2% for spouses, and 79.7% for adolescents. Using the survey result, the expected number of HIV+ employees was 71, which implies a program uptake of 87.1% (62/71) in this group. Of the identified 109 HIV+ beneficiaries, 42 were on highly active antiretroviral treatment (HAART). In November 2003 a qualitative study of awareness and health-seeking behavior of the Heineken Rwanda beneficiaries identified key principles contributing to the success of this program.