Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial

Laurens, Matthew B.; Mungwira, Randy G.; Nampota, Nginache; Nyirenda, Osward; Divala, Titus; Kanjala, Maxwell; Mkandawire, Felix A.; Galileya, Lufina Tsirizani; Nyangulu, Wongani; Mwinjiwa, Edson; Downs, Matthew; Tillman, Amy; Taylor, Terrie E.; Mallewa, Jane; Plowe, Christopher V.; Oosterhout, Joep J. van; Laufer, Miriam K.

doi:10.1093/cid/ciab252

Cited by 10 publications

(16 citation statements)

References 24 publications

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“…We conducted a clinical trial evaluating the impact of TS prophylaxis vs. chloroquine (CQ) prophylaxis vs. no prophylaxis on overall morbidity and mortality caused by malaria and HIV-associated opportunistic infections and on HIV disease progression in Malawi. The primary results showed that TS and CQ effectively prevented malaria, as described previously [16], and consistent with findings in other high malaria burden settings [17][18][19].…”

Section: Introductionsupporting

confidence: 88%

High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis

Mungwira¹,

Laurens

Nyangulu

et al. 2022

Aids

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Objective:Many individuals living with the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy (ART) reside in areas at high risk for malaria but how malaria affects clinical outcomes is not well described in this population. We evaluated the burden of malaria infection and clinical malaria, and impact on HIV viral load and CD4+ cell count among adults on ART.Design:We recruited Malawian adults on ART who had an undetectable viral load and ≥250 CD4+ cells/μl to participate in this randomized trial to continue daily trimethoprim-sulfamethoxazole (TS), discontinue daily co-trimoxazole, or switch to weekly chloroquine (CQ).Methods:We defined clinical malaria as symptoms consistent with malaria and positive blood smear, and malaria infection as Plasmodium falciparum DNA detected from dried blood spots (collected every 4–12 weeks). CD4+ cell count and viral load were measured every 24 weeks. We used Poisson regression and survival analysis to compare the incidence of malaria infection and clinical malaria. Clinicaltrials.gov NCT01650558.Results:Among 1499 participants enrolled, clinical malaria incidence was 21.4/100 person-years of observation (PYO), 2.4/100 PYO and 1.9/100 PYO in the no prophylaxis, TS, and CQ arms, respectively. We identified twelve cases of malaria that led to hospitalization and all individuals recovered. The preventive effect of staying on prophylaxis was approximately 90% compared to no prophylaxis (TS: incidence rate ratio [IRR] 0.11, 95% confidence interval [CI] 0.08, 0.15 and CQ: IRR 0.09, 95% CI 0.06, 0.13). P. falciparum infection prevalence among all visits was 187/1475 (12.7%), 48/1563 (3.1%), and 29/1561 (1.9%) in the no prophylaxis, TS, and CQ arms, respectively. Malaria infection and clinical malaria were not associated with changes in CD4+ cell count or viral load.Conclusion:In clinically stable adults living with HIV on ART, clinical malaria was common after chemoprophylaxis stopped. However, neither malaria infection nor clinical illness appeared to affect HIV disease progression.

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Section: Introductionsupporting

confidence: 88%

High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis

Mungwira¹,

Laurens

Nyangulu

et al. 2022

Aids

Self Cite

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“…Daily co-trimoxazole is recommended for African adults living with HIV, irrespective of antiretroviral treatment, immune status, or disease stage [ 28 ]. The CD4 + cell count test, early identification and treatment of AIDS patients, together with co-trimoxazole prevention and treatment programs were important approaches in extending the survival time and reducing the death rates from AIDS-related illnesses [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China

Lei

Jin

et al. 2022

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Objective. CD4+ cell recovery is hampered in some human immunodeficiency virus (HIV)-infected patients, despite a successful highly active antiretroviral therapy (HAART) with suppressed viral replication. We investigated the factors that might have hindered the CD4+ cell recovery in these patients. Methods. In this retrospective study, we collected the data of all immune nonresponders (INRs) in Wuhan, China, until the end of 2020. A linear model was constructed based on the data from 220 patients with baseline and follow-up records. The response variables in this study were the CD4+ cell count increase. The predictor variables considered in this study were those factors likely to affect the CD4+ cell recovery. Results. Our findings revealed that the plasma HIV-1 viral load of all patients was suppressed and 87.3% patients’ CD4+ cells was increased after more than one year of the HAART treatment. In addition, their last follow-up showed a significant reduction in complications. In our results, the body mass index (BMI), number of months since HIV diagnosis to HAART start, and nonuse of co-trimoxazole were negatively correlated with the increase in CD4+ cells ( P < 0.05 ). However, there were positive associations between serum creatinine levels and CD4+ cell recovery ( P < 0.05 ). Further stratified analyses indicated that the associations between HAART replacement or creatinine usage and CD4+ cell growth were only observed in those participants with a BMI <18.5 ( P < 0.05 ). Conclusions. An early initiation of HAART and co-trimoxazole preventive therapy (CPT) can promote immune reconstitution. BMI and serum creatinine can serve as monitoring indicators of immune reconstitution prognosis after the HAART.

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“…Symptomatic cases of Whipple’s diseases are commonly treated with short-term parenteral ceftriaxone or penicillin, followed by oral co-trimoxazole for one year [ 1 ]. At the same time, daily co-trimoxazole is recommended for African adults living with HIV, irrespective of antiretroviral treatment, immune status, or disease change [ 13 ]. As T. whipplei is susceptible to co-trimoxazole, potential long-term prophylaxis has to be accounted for when interpreting prevalence rates in HIV positive African populations.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Colonization with Tropheryma whipplei—Clinical and Immunological Implications for HIV Positive Adults in Ghana

et al. 2021

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Background: Recent studies demonstrated higher prevalence rates of Tropheryma whipplei (T. whipplei) in HIV positive than in HIV negative subjects. However, associations with the immune status in HIV positive participants were conflicting. Methods: For this cross-sectional study, stool samples of 906 HIV positive and 98 HIV negative individuals in Ghana were tested for T. whipplei. Additionally, sociodemographic parameters, clinical symptoms, medical drug intake, and laboratory parameters were assessed. Results: The prevalence of T. whipplei was 5.85% in HIV positive and 2.04% in HIV negative participants. Within the group of HIV positive participants, the prevalence reached 7.18% in patients without co-trimoxazole prophylaxis, 10.26% in subjects with ART intake, and 12.31% in obese participants. Frequencies of clinical symptoms were not found to be higher in HIV positive T. whipplei carriers compared to T. whipplei negative participants. Markers of immune activation were lower in patients colonized with T. whipplei. Multivariate regression models demonstrated an independent relationship of a high CD4+ T cell count, a low HIV-1 viral load, and an obese body weight with the presence of T. whipplei. Conclusions: Among HIV positive individuals, T. whipplei colonization was associated with a better immune status but not with clinical consequences. Our data suggest that the withdrawal of co-trimoxazole chemoprophylaxis among people living with HIV on stable cART regimen may inadvertently increase the propensity towards colonization with T. whipplei.

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Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial

Cited by 10 publications

References 24 publications

High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis

High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China

Intestinal Colonization with Tropheryma whipplei—Clinical and Immunological Implications for HIV Positive Adults in Ghana

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