Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection: Cochrane systematic review
Assessed as up to date: 2010/11/17
Vulvovaginal candidiasis (VVC) is one of the most common fungal infections that recur frequently in HIV infected women. Symptoms of VVC are pruritis, discomfort, dyspareunia, and dysuria. Vulval infection presents as a morbiliform rash that may extend to the thighs. Vaginal infection is associated with white discharge, and plaques are seen on erythematous vaginal walls.
Even though rarely or never resulting in systemic fungal infection or mortality, left untreated these lesions contribute considerably to the morbidity associated with HIV infection. Prevention and treatment of this condition is an essential part of maintaining the quality of life for these individuals.Objectives
-To compare the efficacy of various antifungals given vaginally or orally for the treatment and prophylaxis of VVC in HIV-infected women and to evaluate the risks of the same.Search methods
The search strategy was comprehensive, iterative and based on that of the HIV/AIDS Cochrane Review Group. The aim was to locate all relevant trials, irrespective of publication status or language. Electronic databases :CENTRAL, Medline, EMBASE, LILACS and CINAHL were searched for randomised controlled trials for the years 1980 to 1st October 2010. WHO ICTRP site and other relevant web sites were also searched for conference abstracts.Selection criteria
Randomised controlled trials (RCTs) of palliative, preventative or curative therapy were considered. Participants were HIV positive women receiving one or more of the following:treatment / prophylaxis for VVC or HAART(Highly Active Antiretroviral Therapy).Data collection and analysis
Three authors independently assessed the methodological quality of the trials and extracted data. The quality of the evidence generated was graded using the GRADE approach.Main results
Our search did not yield any trial investigating treatment of VVC in HIV positive women.
Two trials dealing with prophylaxis were eligible for inclusion.One trial (n= 323) favoured the use of weekly Fluconazole as compared to placebo (RR 0.68; 95% CI 0.47 to 0.97).
The second trial with three arms of comparison; Clotrimazole, Lactobacillus and Placebo gave no definitive results in preventing an episode of VVC. Clotrimazole against placebo (RR 0.49; 95% CI 0.22 to 1.09), Clotrimazole against lactobacillus (RR 1.11; 95% CI 0.45 to 2.76) and lactobacillus against placebo (RR 0.54 ;95% CI 0.26 to 1.13).Authors' conclusions
Implications for practice
No trials were found addressing treatment of VVC in HIV positive women.In comparison to placebo,Fluconazole was found to be an effective preventative intervention. However, the potential for resistant Candida organisms to develop might impact the feasibility of implementation.
Direction of findings suggests that Clotrimazole and Lactobacillus improved the prophylactic outcomes when compared to placebo.
Implications for research There is a need to evaluate drugs and drug regimens for VVC treatment and prophylaxis in HIV positive women through randomised clinical trials. Development of resistance to azoles remains under-studied and more work must be done in this area, so as to determine whether routine prophylaxis for VVC is at all needed or whether adequate ART would be sufficient to prevent recurrent VVC. The viral load in vaginal secretions with or without treatment or prophylaxis has not been studied, this is very relevant to the spread of HIV.
Ray Amita, Ray Sujoy, George Aneesh Thomas, Swaminathan Narasimman
Interventions for the prevention and management of vaginal thrush in HIV positive women
Vulvovaginal candidiasis (VVC) / thrush is one of the most common fungal infections and recurs frequently in women with human immunodeficiency virus (HIV) infection. Even though rarely or never resulting in systemic fungal infection or mortality, interventions for prevention and treatment of this condition is an essential part of maintaining the quality of life of such individuals.This review was aimed at evaluating such interventions.
The treatment aspect could not be evaluated as our search yielded no trials.
The search yielded two studies dealing with the preventive aspect of the condition. The first trial found weekly fluconazole significantly effective in preventing clinical episodes from occurring as compared to placebo. However,this regimen lead to emergence of species resistant to azoles.
The second trial with three arms of comparison; Clotrimazole, Lactobacillus and placebo gave no definitive results in preventing an episode of VVC.
Neither of the included studies investigated the effects of HAART(Highly Active Antiretroviral Therapy) or any other form of antiretroviral treatment on VVC nor did they explore difference in quality of life, viral shedding in vaginal secretions (infectivity) ,patient preference for route of administration or the cost.
Implications for practice
Practice for treatment of VVC in HIV positive: No trials were found addressing treatment of VVC in HIV positive women so no comments can be made on the treatment aspect.
Practice for prevention of VVC in HIV positive Prophylaxis was addressed by two trials.The finding of these indicated that in comparison to placebo,fluconazole is an effective preventative intervention. No studies were found comparing fluconazole with other interventions.The downside of this regime would be as per the study emergence of non albicans species. As regards resistance C albicans did not show significant resistance to this regime but that was not the case in the non albicans species which did show resistance.The cost of maintaining this prophylaxis has not been looked into.
Both Clotrimazole and Lactobacillus acidophilus when used pro phylactically reduced the relative risk of an episode of VVC, however the 95% confidence intervals do not suggest any definitive evidence to favour the use of either of these two interventions.
The decision to use prophylaxis should take into account the effect of recurrences on the patient’s well-being and quality of life; the need for prophylaxis for other fungal infections;the regime to be used, cost, toxicities, risk of development of resistance and drug interactions.
Implications for research
Research for treatment of VVC in HIV positive There is need for drugs and drug regimes for VVC treatment in HIV positive women to be evaluated in randomised clinical trials.
Research for prophylaxis of VVC in HIV positive: There is also a strong need for more research to be done on the various aspects of prevention of VVC in HIV positive. Development of resistance to azoles remains under-studied and more work must be done in this area so as to determine whether routine prophylaxis for VVC is at all needed or whether adequate ART would be sufficient to prevent recurrent VVC.CDC does not recommend routine prophylaxis.Studies that follow subgroups that are well defined in terms of disease stage,CD4 counts,ART use and azole use to estimate the risk of resistance need to be done. All the included studies have dealt with weekly prophylaxis ,no other regime has been studied. Randomised trials to obtain estimates of Relative Risks for resistance that are associated with different regimes for prophylaxis need to be undertaken.
Lactobacillus as an intervention for prophylaxis of VVC in HIV positive women would be free of resistance problems and would be cost effective too. However two important aspects of this intervention needs to be evaluated in randomised trials namely the regime to be used and the storage or refrigeration. In the included study which investigated the effect of Lactobacillus weekly on prevention of VVC, the authors have stated that they did not confirm the presence of viable Lactobacillus in the vaginas of women on Lactobacillus treatment arm, as this was a self care evaluation the applicability of the results showing that Lactobacillus helps prevent VVC in HIV positive women would entirely depend on patient compliance and proper storage .Other studies and reviews on the efficacy of probiotics in preventing VVC in HIV negative women have concluded that further research is needed to prove the effectiveness of probiotics in preventing the recurrences of VVC and to allow their wide use for this indication.
More well designed trials need to be done to target the risk populations namely sex workers regarding two important aspects of spread HIV in relation to VVC. Vaginal infection including VVC would increase the viral load in vaginal secretions making the women more liable to pass on infection to her partner.Besides it would make her more susceptible to acquire new and possibly more virulent strains from an infected partner. Trials need to assess whether prophylaxis is more relevant to this group of women
Similarly vertical transmission would be more when vaginal infections are present and C-Section is either not possible , acceptable or affordable.The question therefore would be whether there is need for prophylaxis for pregnant women with HIV to minimize such transmission keeping in mind that pregnancy per se is a risk factor for VVC.Topical therapy is preferred for treatment of vaginal candidiasis in pregnancy when possible. Single-dose, episodic treatment with fluconazole has not been associated with birth defects in humans. However, with chronic use of doses of fluconazole of 400 mg or higher in pregnancy, five cases of a syndrome of craniosynostosis, characteristic facies, digital synostosis, and limb contractures have been reported (“fluconazole embryo pathy”).Get full text at The Cochrane Library
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