Background. Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). Methods. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. Results. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (？77.6？cells/μL, 95% CI: ？125.2, ？30.1) and not receiving antiretrovirals (？33.7？cells/μL, 95% CI: ？58.6, ？8.8). Conclusions. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination. 1. Introduction Cotrimoxazole prophylaxis has been shown to reduce morbidity and mortality in HIV-infected adults and children [1–5]. The World Health Organization (WHO) guidelines issued in 2006 recommend daily cotrimoxazole prophylactic treatment (CPT) for HIV-infected adults and HIV-infected pregnant women with CD4 cell counts of less than 350？cells/μL or WHO clinical stage III or IV [6]. The WHO guidelines advised adapting the CD4-based CPT eligibility cut points based on availability of CD4 testing and country-specific resources. Data on CPT in HIV-infected pregnant women are scarce, though there is some evidence suggesting that CPT may reduce the risk of poor birth outcomes in women with CD4 cell counts of less than 200？cells/μL in addition to reducing morbidity and mortality due to opportunistic infections [7]. CPT in HIV-infected adults has been associated with reduced malaria incidence [1, 3, 8]. HIV-infected pregnant women may have greater benefit from malaria prophylaxis, as these women experience more peripheral and placental malaria compared with HIV-uninfected pregnant women [9]. Due to similarities between cotrimoxazole
References
[1]
X. Anglaret, G. Chêne, A. Attia et al., “Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial,” The Lancet, vol. 353, no. 9163, pp. 1463–1468, 1999.
[2]
J. Mermin, J. Lule, J. P. Ekwaru et al., “Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda,” The Lancet, vol. 364, no. 9443, pp. 1428–1434, 2004.
[3]
J. D. Campbell, D. Moore, R. Degerman et al., “HIV-infected ugandan adults taking antiretroviral therapy with CD4 counts >200 cells/μL who discontinue cotrimoxazole prophylaxis have increased risk of malaria and diarrhea,” Clinical Infectious Diseases, vol. 54, no. 8, pp. 1204–1211, 2012.
[4]
D. Lowrance, S. Makombe, A. Harries et al., “Lower early mortality rates among patients receiving antiretroviral treatment at clinics offering cotrimoxazole prophylaxis in Malawi,” Journal of Acquired Immune Deficiency Syndromes, vol. 46, no. 1, pp. 56–61, 2007.
[5]
S. Z. Wiktor, M. Sassan-Morokro, A. D. Grant, et al., “Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d'Ivoire: a randomised controlled trial,” The Lancet, vol. 353, no. 9163, p. 1469, 1999.
[6]
WHO, “Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults in resource-limited settings,” Geneva, Switzerland, 2006.
[7]
J. Walter, M. Mwiya, N. Scott et al., “Reduction in preterm delivery and neonatal mortality after the introduction of antenatal cotrimoxazole prophylaxis among HIV-infected women with low CD4 cell counts,” Journal of Infectious Diseases, vol. 194, no. 11, pp. 1510–1518, 2006.
[8]
J. Mermin, J. P. Ekwaru, C. A. Liechty et al., “Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study,” The Lancet, vol. 367, no. 9518, pp. 1256–1261, 2006.
[9]
F. O. ter Kuile, M. E. Parise, F. H. Verhoeff et al., “The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-Saharan Africa,” American Journal of Tropical Medicine and Hygiene, vol. 71, no. 2, pp. 41–54, 2004.
[10]
A. Kapito-Tembo, S. R. Meshnick, M. B. Van Hensbroek, K. Phiri, M. Fitzgerald, and V. Mwapasa, “Marked reduction in prevalence of malaria parasitemia and anemia in HIV-infected pregnant women taking cotrimoxazole with or without sulfadoxine-pyrimethamine intermittent preventive therapy during pregnancy in Malawi,” Journal of Infectious Diseases, vol. 203, no. 4, pp. 464–472, 2011.
[11]
C. van der Horst, C. Chasela, Y. Ahmed et al., “Modifications of a large HIV prevention clinical trial to fit changing realities: a case study of the Breastfeeding, Antiretroviral, and Nutrition (BAN) protocol in Lilongwe, Malawi,” Contemporary Clinical Trials, vol. 30, no. 1, pp. 24–33, 2009.
[12]
C. S. Chasela, M. G. Hudgens, D. J. Jamieson et al., “Maternal or infant antiretroviral drugs to reduce HIV-1 transmission,” The New England Journal of Medicine, vol. 362, no. 24, pp. 2271–2281, 2010.
[13]
World Health Organization, “Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults in resource-limited settings,” Geneva, Switzerland, 2006.
[14]
National Statistical Office (NSO) and ICF Macro, “Malawi demographic and health survey 2010,” Zomba, Malawi and Calverton, MD: NSO and ICF Macro, 2011.
[15]
J. Gutman, D. Mwandama, R. E. Wiegand, D. Ali, D. P. Mathanga, and J. Skarbinski, “Effectiveness of intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy on maternal and birth outcomes in machinga district, Malawi,” The Journal of Infectious Diseases, vol. 208, pp. 907–916, 2013.
[16]
M. E. Stokes, C. S. Davis, and G. G. Koch, Categorical Data Analysis Using the SAS System, SAS Institute, Cary, NC, USA, 2nd edition, 2000.
[17]
P. D. Allison, Survival Analysis Using SAS, SAS Institute, Cary, NC, USA, 1995.
[18]
K. J. Rothman and S. Greenland, Modern Epidemiology, Lippincott-Raven, Philadelphia, Pa, USA, 1998.
[19]
G. Maldonado and S. Greenland, “Simulation study of confounder-selection strategies,” American Journal of Epidemiology, vol. 138, no. 11, pp. 923–936, 1993.
[20]
L.-A. McNutt, C. Wu, X. Xue, and J. P. Hafner, “Estimating the relative risk in cohort studies and clinical trials of common outcomes,” American Journal of Epidemiology, vol. 157, no. 10, pp. 940–943, 2003.
[21]
M. Kutner, C. Nachtsheim, J. Neter, and W. Li, Applied Linear Statistical Models, McGraw-Hill Irwin, New York, NY, USA, 5th edition, 2005.
[22]
J. Mermin, J. Lule, J. P. Ekwaru et al., “Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members,” AIDS, vol. 19, no. 10, pp. 1035–1042, 2005.
[23]
C. Chintu, G. J. Bhat, A. S. Walker et al., “Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial,” The Lancet, vol. 364, no. 9448, pp. 1865–1871, 2004.
[24]
A. J. Nunn, P. Mwaba, C. Chintu, A. Mwinga, J. H. Darbyshire, and A. Zumla, “Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial,” BMJ, vol. 337, p. a257, 2008.
[25]
C. Watera, J. Todd, R. Muwonge et al., “Feasibility and effectiveness of cotrimoxazole prophylaxis for HIV-1-infected adults attending an HIV/AIDS clinic in Uganda,” Journal of Acquired Immune Deficiency Syndromes, vol. 42, no. 3, pp. 373–378, 2006.
[26]
M. A. Thera, P. S. Sehdev, D. Coulibaly et al., “Impact of trimethoprim-sulfemethoxazole prophylaxis on falciparum malaria infection and disease,” Journal of Infectious Diseases, vol. 192, no. 10, pp. 1823–1829, 2005.
[27]
M.-L. Newell, C. Rudin, D. Dunn, and C. Peckham, “Immunological markers in HIV-infected pregnant women,” AIDS, vol. 11, no. 15, pp. 1859–1865, 1997.
[28]
D. K. Ekouevi, A. Inwoley, B. Tonwe-Gold et al., “Variation of CD4 count and percentage during pregnancy and after delivery: implications for HAART initiation in resource-limited settings,” AIDS Research and Human Retroviruses, vol. 23, no. 12, pp. 1469–1473, 2007.
[29]
C. Watera, J. Todd, G. Mutonyi et al., “Effects of cotrimoxazole on hematologic parameters in HIV-infected adults in a community-based clinic in entebbe, Uganda,” Journal of Acquired Immune Deficiency Syndromes, vol. 46, no. 3, pp. 369–371, 2007.
