HIV Protease Inhibitors, Indinavir or Nelfinavir, Augment Antimalarial Action of Artemisinin in vitro

Mishra, Lokesh C.; Bhattacharya, Amit; Sharma, Manish; Bhasin, Veena

doi:10.4269/ajtmh.2010.09-0427

Cited by 22 publications

(15 citation statements)

References 18 publications

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“…It is unclear whether differences in results between our groups are due to the different protease inhibitors studied, differences in methodology, or other factors. Other groups have reported synergy (29) or antagonism (16) between HIV protease inhibitors and artemisinins, although only older protease inhibitors and not lopinavir were studied; we found additive effects between lopinavir and dihydroartemisinin.…”

Section: Discussionmentioning

confidence: 60%

“…Indeed, in normal volunteers, exposure to the antimalarial lumefantrine, a component of the ACT artemether-lumefantrine, was markedly enhanced by coadministration of lopinavirritonavir (12), and exposure to a number of other antimalarial drugs may be affected by ritonavir or other agents (41). Considering antimalarial efficacy, HIV protease inhibitors have been shown to potentiate the activity of chloroquine (14,15,23) and to either augment (29) or antagonize (16) the activity of artemisinins. To help clarify the impacts of antiretroviral therapy on malaria, we systematically evaluated the activity of representatives of all currently used classes of antiretroviral drugs against two strains of P. falciparum.…”

mentioning

confidence: 99%

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In Vitro Activity of Antiretroviral Drugs against Plasmodium falciparum

Nsanzabana

Rosenthal

2011

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 99%

In Vitro Activity of Antiretroviral Drugs against Plasmodium falciparum

Nsanzabana

Rosenthal

2011

Antimicrob Agents Chemother

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“…Malaria infection was more prevalent in women on nevirapine‐based therapy than those on nelfinavir‐based therapy. This difference may have been due to nelfinavir, a protease inhibitor known to have antimalarial properties , given that there was no difference in malaria prevalence before and after the introduction of bed nets. Again, there was no difference in prevalence of malaria in women with CD4 < 250, all on nevirapine‐based therapy, before and after bed net introduction, supporting the antimalarial effect of nelfinavir.…”

Section: Discussionmentioning

confidence: 99%

Anaemia in HIV‐infected pregnant women receiving triple antiretroviral combination therapy for prevention of mother‐to‐child transmission: a secondary analysis of the Kisumu breastfeeding study (KiBS)

Odhiambo

Zeh

Angira

et al. 2016

Tropical Med Int Health

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Abstractobjective The prevalence of anaemia during pregnancy is estimated to be 35-75% in sub-Saharan Africa and is associated with an increased risk of maternal mortality. We evaluated the frequency and factors associated with anaemia in HIV-infected women undergoing antiretroviral (ARV) therapy for prevention of mother-to-child transmission (PMTCT) enrolled in The Kisumu Breastfeeding Study 2003-2009. methods Maternal haematological parameters were monitored from 32 to 34 weeks of gestation to 2 years post-delivery among 522 enrolled women. Clinical and laboratory assessments for causes of anaemia were performed, and appropriate management was initiated. Anaemia was graded using the National Institutes of Health Division of AIDS 1994 Adult Toxicity Tables. Data were analysed using SAS software, v 9.2. The Wilcoxon two-sample rank test was used to compare groups. A logistic regression model was fitted to describe the trend in anaemia over time.results At enrolment, the prevalence of any grade anaemia (Hb < 9.4 g/dl) was 61.8%, but fell during ARV therapy, reaching a nadir (7.4%) by 6 months post-partum. A total of 41 women (8%) developed severe anaemia (Hb < 7 g/dl) during follow-up; 2 (4.9%) were hospitalised for blood transfusion, whereas 3 (7.3%) were transfused while hospitalised (for delivery). The greatest proportion of severe anaemia events occurred around delivery (48.8%; n = 20). Anaemia (Hb ≥ 7 and < 9.4 g/dl) at enrolment was associated with severe anaemia at delivery (OR 5.87; 95% CI: 4.48, 7.68, P < 0.01). Few cases of severe anaemia coincided with clinical malaria (24.4%; n = 10) and helminth (7.3%; n = 3) infections.

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“…In addition to studies in adults that are designed to directly address whether PIs have a beneficial effect on malaria in regions where malaria is endemic and the prevalence of HIV-1 is high, further research is warranted to determine the effects of HIV PIs on malaria in children and pregnant women, two groups that are at greater risk for clinical malaria. In addition, since laboratory evidence suggests that the coadministration of HIV PIs with additional antimalarial agents, including chloroquine or mefloquine, may enhance the antimalarial activity of these drugs (16,23,31), the utility of such combinations also warrants further research. In conclusion, the results from our analyses, which were not consistent with large a decreased hazard of clinical malaria in subjects receiving LPV/r-based ART, provide evidence, albeit preliminary and imperfect, that supports the possibility of no or little effect of LPV/r-based therapy on clinical malaria.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Protease Inhibitors and Clinical Malaria: a Secondary Analysis of the AIDS Clinical Trials Group A5208 Study

Porter

Cole

Eron

et al. 2012

Antimicrob Agents Chemother

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HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n ‫؍‬ 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio ‫؍‬ 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIVinfected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted.

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HIV Protease Inhibitors, Indinavir or Nelfinavir, Augment Antimalarial Action of Artemisinin in vitro

Cited by 22 publications

References 18 publications

In Vitro Activity of Antiretroviral Drugs against Plasmodium falciparum

In Vitro Activity of Antiretroviral Drugs against Plasmodium falciparum

Anaemia in HIV‐infected pregnant women receiving triple antiretroviral combination therapy for prevention of mother‐to‐child transmission: a secondary analysis of the Kisumu breastfeeding study (KiBS)

HIV-1 Protease Inhibitors and Clinical Malaria: a Secondary Analysis of the AIDS Clinical Trials Group A5208 Study

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