HIV and host immunogenetics: unraveling the role of HLA-C.

Host genetic factors play a major role in determining the outcome of many infections including human immunodeficiency virus (HIV). Multiple host factors have been studied till date showing their varied role in susceptibility or resistance to HIV infection. HLA-C, however, has been recently started gaining interest in researchers mind revealing its polymorphisms to have an important effect on viral load set-points, disease progression as well as transmission. In this review report, we have compiled these significant findings of HLA-C in HIV infection, in an attempt to highlight the need for further research in the area in different ethnic population to establish its role in the infection.

Antiretroviral treatment, viral load of mothers & perinatal HIV transmission in Mumbai, India.

BACKGROUND & OBJECTIVES: Mother-to-child transmission (MTCT) is the most significant route of HIV transmission in children below the age of 15 yr. In India, perinatal HIV transmission, even after treatment, accounts for 5.4 per cent of HIV cases. The present study was conducted to evaluate the efficacy of anti-retro viral therapy (ART) or prophylactic treatment (PT) to control maternal viral load in HIV positive women, and its effect on vertical HIV transmission to their infants. METHODS: A total of 58 HIV positive women were enrolled at the time of delivery and their plasma samples were obtained within 24 h of delivery for estimation of viral load. Viral load analysis was completed in 38 women. Infants received single dose nevirapine within 2 h of birth and zidovudine for 6 wk. At the end of 18 month follow up, HIV positive or negative status was available in 28 infants. RESULTS: Results revealed undetectable levels of viral load in 58.3 per cent of women with ART compared to 30.7 per cent of women with PT. No women on ART had viral load more than 10,000 copies/ml, whereas seven (26.9%, P=0.07) women receiving PT had this viral load. Median CD4 count of women on PT (483 cells/µl) was high compared to the women on ART (289 cells/ µl). At the end of 18 months follow up, only two children were HIV positive, whose mothers were on PT. One had in utero transmission; infection detected within 48 h of delivery, while the other child was infected post partum as HIV was detected at six months follow up. INTERPRETATION & CONCLUSIONS: Women who received a single dose of nevirapine during delivery had higher levels of viral load than women on ART. Combination drug therapy for pregnant women is now a standard of care in most of the western countries; use of nevirapine monotherapy at the time of delivery in our settings is not effective in controlling viral load. This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit mother to child HIV transmission.

Polymorphisms in major cytokine genes: a study among human immunodeficiency Virus-1 serodiscordant couples in Mumbai, India.

PURPOSE: Polymorphism in cytokine genes may affect its production, which play an important role in modulation of human immunodeficiency virus (HIV) infection. Evaluation of these polymorphisms might help to understand why some individuals remain uninfected in spite of several exposures to HIV infection, such as the negative spouses of discordant couples. The aim of this study was to evaluate the association of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes and their receptors with HIV infection in serodiscordant couples, attending the Integrated Counselling and Testing Centre of a Municipality Hospital. MATERIALS AND METHODS: At the end of at least 2 years of follow up, 42 couples were confirmed as being serodiscordant. Genotyping was carried out in blood samples of these couples using the polymerase chain reaction-sequence-specific amplification method. RESULTS: Significantly high frequency of interleukin-1 receptor antagonist IL-1RA mspa 11100 CC (P=0.04), tumor necrosis factor-alpha TNF-α -238 AG (P=0.01) and IL-4 -33 TT (P=0.01) was observed in HIV seropositives (HSP) while frequency of TNF-α -238 GG (P=0.02) was significantly high among the exposed uninfected (EU). However, application of Bonferroni correction identified only two SNPs i.e., TNF-α -238 AG and IL-4 -33 TT to be significantly associated with the acquisition of HIV. In remaining cytokine genes, no significant association was observed. CONCLUSION: Our study highlighted possible association of certain specific polymorphisms with HIV transmission, whereas presence or absence of certain other polymorphism in EU individuals might be offering protection from HIV infection. These variations at the genetic level might help to explore new insights into treatment and HIV prevention strategies.

Bacterial vaginosis: a cause of infertility?

Bacterial vaginosis (BV) is a common disorder of the genital tract in women characterized by an alteration of the normal acidic lactobacilli-predominant vaginal ecosystem to a vaginal environment dominated by Gardnerella vaginalis, mycoplasma species and anaerobes, with an increase in pH. The present study evaluated whether BV is associated with reproductive complications in women. BV was screened with a Gram stain of vaginal smear and interpretation was done using the Nugent score. Wet mount and polymerase chain reaction were used to screen other infections. Among 510 enrolled women, 72 (14.1%) had BV. Statistical analysis between the BV negative and positive population revealed a significant association (P = 0.0001) with infertility. In pregnant women, the infection rate was low (P = 0.01). Multiple infections such as Candida, Chlamydia and human papilloma virus were observed in 4.2%, 15.3% and 8.3% of BV-infected women, respectively. Results suggest that BV infection is associated with infertility and its absence leads to pregnancy, emphasizing its screening and treatment.

Use of polymerase chain reaction (PCR) for detection of Chlamydia trachomatis infection in cervical swab samples.

A polymerase chain reaction (PCR) based method has been set up for detection of Chlamydia trachomatis (C. trachomatis) infection in single cervical swab samples. A primer pair specific to the major outer membrane protein (MOMP) gene common to all serotypes of C. trachomatis was used. This method was validated for its sensitivity as well as specificity. A minimum Ing of DNA could be used for detection of the infection. Specificity of the method was confirmed by carrying out a sample dilution curve. The cervical swab samples analysed in the present study were in coded form for validation of the PCR with an established commercial ELISA (Chlamydiazyme). Both the sensitivity and specificity of PCR was 100% when the ELISA results of these samples were decoded. Thus, this PCR technique could be used for better diagnosis of C. trachomatis infection in comparison to the commercially available ELISA technique.

Chlamydia trachomatis infection among asymptomatic males in an infertility clinic.

Chlamydia trachomatis can lead to a variety of complications including tubal infertility. Similarly asymptomatic infection in male partner can also hinder conception. The prevalence of this infection among the infertile female in the Institute's Infertility Clinic was observed to be 34%. Hence the present study was undertaken to find out these infection among the asymptomatic male partners of these infected women. Fifteen asymptomatic males who were not treated with any antibiotics in recent past were enrolled. First voided urine, semen and blood were collected from each individual for diagnosis of this infection. Chlamydia antigen was detected in 33.3% while Chlamydia antibody was detected in seven (46.7%) of these cases. Of these seven, three cases were positive for antigen. This preliminary observation suggests that amongst the infertile couple a sizable percentage (60%) of asymptomatic male partners remain infected with Chlamydia trachomatis.

Lactoferrin in cervical mucus as a biochemical marker for inflammation.

Lactoferrin, an iron-binding protein, has been proposed to act as an anti-infective agent and has been used as a diagnostic marker in several inflammatory disorders. A sensitive enzyme-linked immunosorbent assay developed earlier was used for lactoferrin estimation in cervical mucus. A brief study was undertaken to observe if lactoferrin is detectable in cervical mucus and to correlate its level with reproductive tract infection, if present. One hundred and twelve cervical mucus samples were collected from healthy as well as infected females. Some of these females were using CuT-200 intrauterine copper devices for contraception. Women were at different phases of their menstrual cycle. The presence of detectable amount of lactoferrin in cervical mucus was confirmed. The average level of lactoferrin in cases either with clinical symptoms of cervicitis or with proven infection by PAP smear was significantly (t=7.6, P<0.01) higher than the normal controls. CuT users have higher (P<0.01) mean level of lactoferrin than corresponding non-users.