Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa

Background: A subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/μL were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir. Methods: This analysis includes the 625 women who remained on-study through 48 weeks without experiencing protocol-defined virologic failure. We defined SCR as < 100 CD4 cells/μL increase from baseline and absolute CD4 cell count < 350 cells/μL, both at 48 weeks after HAART initiation. Results: The baseline characteristics for the 625 women prior to HAART initiation were: median age 33 years, screening CD4 count 134 cells/μL, and HIV-1 RNA 5.1 log10 copies/mL; 184 (29%) were WHO Stage 3 or 4. Seventy one (11%) of these 625 women experienced SCR. Baseline factors independently associated with increased odds of SCR included older age, lower HIV-1 RNA, positive Hepatitis B surface antigen, and site location. At 96 weeks, only 6% of the SCR group had CD4 ≥ 350 cells/μL compared with 67% in the non SCR group. Conclusion: After starting HAART, 11% of women with virologic suppression through 48 weeks experienced SCR. These patients were also less likely to achieve CD4 ≥ 350 cells/μL by 96 weeks. The underlying causes and long term clinical implications of SCR deserve further investigation. Trial registration Clinicaltrials.gov Identifier: NCT0008950

Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants

Background: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, −0.69% (95% confidence interval [CI] −2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI −1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. ClinicalTrials.gov Registration Numbers NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296)

HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log10) and cART-initiating cohorts (5.1–5.3 log10) by about one log10. The proportion of individuals with high (≥50,000 (4.7 log10) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log10) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities

Nevirapine- Versus Lopinavir/Ritonavir-Based Initial Therapy for HIV-1 Infection among Women in Africa: A Randomized Trial

In a randomized control trial, Shahin Lockman and colleagues compare nevirapine-based therapy with lopinavir/ritonavir-based therapy for HIV-infected women without previous exposure to antiretroviral treatment

Immunohaematological reference values for HIV-negative healthy adults in Botswana

BACKGROUND: Clinical laboratories in Botswana have relied entirely on the reference intervals for normal immunohaematological values provided by manufacturers' kits and textbooks. OBJECTIVES: The aim of this study was to determine the means, medians, 2.5th and 97.5th percentile reference intervals, for normal immunohaematological values in healthy adults in Botswana. METHOD: A total of 261 healthy participants comprising 126 men (48%) and 135 (52%) women were enrolled in the southern part of Botswana, and immunological and haematological laboratory parameters were measured. RESULTS: The mean age was 28.8 (95% Confidence Interval [CI] 27.7-29.8) years, with a median of 27 years and a range 18-66 years. The mean haemoglobin level was significantly lower for women (12.4 g/dL; 95% CI 12.1% - 12.7%) than men (15.1 g/dL; 95% CI 14.9% - 15.3%). The women's haemoglobin reference values (9.0 g/dL - 15.0 g/dL) levels were lower than observed in predominantly White populations (12.0 g/dL - 16.0 g/dL), but comparable with regional consensus reference intervals (9.5 g/dL - 15.8 g/dL) recently defined for East and Southern Africa. CONCLUSION: The established values provide an important tool for patient management and could influence decisions on inclusion of participants and adverse events in clinical trials conducted locally

Willingness to take multidrug-resistant tuberculosis (MDR-TB) preventive therapy among adult and adolescent household contacts of MDR-TB index cases : an international multisite cross-sectional study

CITATION: Suryavanshi, N. et al. 2020. Willingness to Take Multidrug-resistant Tuberculosis (MDR-TB) Preventive Therapy Among Adult and Adolescent Household Contacts of MDR-TB Index Cases: An International Multisite Cross-sectional Study. Clinical Infectious Diseases, 70(3): 436–445. doi:10.1093/cid/ciz254The original publication is available at https://academic.oup.com/cid/Background. Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. Methods. In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. Results. From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). Conclusions. The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.https://academic.oup.com/cid/article/70/3/436/5421246?login=truePublishers versio

Feasibility of identifying household contacts of rifampin-and multidrug-resistant tuberculosis cases at high risk of progression to tuberculosis disease

CITATION: Gupta, A. et al. 2020. Feasibility of identifying household contacts of rifampin-and multidrug-resistant tuberculosis cases at high risk of progression to tuberculosis disease. Clinical infectious diseases, 70(3): 425–435. doi:10.1093/cid/ciz235The original publication is available at https://academic.oup.com/cid/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. Results: From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. Conclusions: The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.https://academic.oup.com/cid/article/70/3/425/5426963?login=truePublishers versio

BOTSWANA HAS A MORAL DUTY TO EXPAND ACCESS TO ANTIRETROVIRAL THERAPY TO SURVIVAL MIGRANTS

Social, political and economic problems since Zimbabwe’s post-independence period have resulted in the creation of survival migrants that flock to neighboring countries for a better life. In the same period, HIV/AIDS had become a global epidemic affecting Botswana and Zimbabwe severely. While Botswana has become a beacon of success in controlling the epidemic by having the political will and international collaborations to provide preventative and therapeutic care to its citizens, the government has overlooked the survival migrants that are residing in Botswana. This population does not receive any HIV/AIDS preventative or therapeutic care from the Botswana national Antiretroviral Therapy (ART) program. In this paper, I argue that Botswana’s national ART program should be broadened to include survival migrants with HIV/AIDS. In doing so, I seek justification for the argument from 1) Utilitarian Moral Theory Perspective; and 2) Social Justice Perspective