Eosinophilic Ascites-Rarest Presentation of a Rare Disease, Eosinophilic Gastroenteritis.

Eosinophilic gastroenteritis (EGE) is an uncommon disease of unknown etiology reported in both adult and pediatric age group. Here we report a case of a 46-year-old HIV positive female who presented to us with ascites and abdominal distension with peripheral eosinophilia and diagnosed as EGE.

Idiopathic Pyoderma Gangrenosum as a Novel Manifestation of the HIV Immune Reconstitution Inflammatory Syndrome: A Report of Three Cases.

The initiation of antiretroviral treatment for individuals with HIV may be accompanied by a paradoxical flare of underlying inflammatory diseases, the recurrence of dormant infections, or worsening of prior treated opportunistic infections, termed the immune reconstitution inflammatory syndrome (IRIS). Cutaneous manifestations of IRIS are common. Pyoderma gangrenosum is a neutrophilic dermatosis postulated to reflect disrupted innate immune regulation causing altered neutrophil chemotaxis. It is uncommonly reported in association with HIV. In this case series, we present three cases of IRIS manifesting with pyoderma gangrenosum in individuals with HIV from India and the United States to raise awareness of this previously undescribed presentation and discuss the treatment challenges in the management of these patients.

Primary HIV-1 infection--a "window of opportunity" for healthcare providers.

The diagnosis of primary HIV-1 infection (PHI) is often missed and requires a high index of suspicion and a thorough knowledge of laboratory methods. We report the case of a young promiscuous male who presented with fever, rash and neurological symptoms 8 weeks after unprotected sexual exposure. Clinical and laboratory investigations showed the presence of leucopenia and thrombocytopenia with elevated transaminases, and a normal cerebrospinal fluid analysis, while CNS imaging revealed a vasculitis-like involvement of the corpus callosum. Symptoms resolved spontaneously over 3 weeks. Fourth generation ELISA with p24 antigen assay was positive with high HIV-1 RNA load while Western-Blot was negative, thus confirming the diagnosis of PHI. The patient was subsequently started on antiretroviral therapy (ART) and showed undetectable viral load after 8 weeks of therapy. We present the differential diagnoses which need to be entertained as well as the pros and cons of very early ART intervention.

Nevirapine-induced fulminant hepatitis.

Nevirapine induced hepatotoxicity is known but fatality is rare. We report a case of a young individual who developed nevirapine (NVP) induced fatal hepatitis without apparent risk factors or preceding rash. Exacerbation of underlying silent chronic liver dysfunction possibly contributed to the fatal outcome. This case stresses the need for careful evaluation, regular monitoring and prompt omission of drug on suspicion of hepatotoxicity.

Neural network-longitudinal assessment of the Electronic Anti-Retroviral THerapy (EARTH) cohort to follow response to HIV-treatment.

HIV infection is for the most part a chronic and asymptomatic disease. To properly monitor the health status of infected individuals it is important to use host and viral surrogate markers as well as pharmacokinetic parameters. Disease progression, assessment of the antiviral potency of the drugs and response to therapy can only be monitored by repetitive measures of viral and host parameters. To prevent the emergence of antiviral drug-resistance, long term side effects and to decide on the appropriate treatment choices, a comprehensive assessment of all contributing factors, medical and non-medical, is necessary. However, the relationship between treatment outcomes with disease markers and other contributing factors is not simple. To date, a model that accurately predicts the likelihood of disease progression or treatment failure in HIV infected patients does not exist. Extending our previous work in this area, we developed temporal Artificial Intelligence models based on Jordan-Elman networks to longitudinally follow viral surrogate markers together with demographics, biochemical and laboratory data to describe the drug-virus-host interactions in over 4000 HIV adult patients. In an international (multi-continent) study of HIV clinical and laboratory data, the profiles of drug-naïve as well as treated patients were evaluated during a 20 year follow-up. Validation of models on a subset of this cohort (n=595) estimated the sensitivity and specificity of treatment success/failure, under different management modalities for individual patients. ROC-curves predicted: virologic success from baseline (ROC=0.871) in drug-naïve previously non-treated patients, switch from virologic success/ failure to failure/success if ever and when (ROC=0.625), switch to virologic success/failure from failure/success within 6 months (ROC=0.722) following a previous switch. This tool may be helpful in the design of longitudinal clinical trials.

Penicillium marneffei infection: an AIDS-defining illness.

A 29-year-old HIV seropositive male patient from Manipur presented with fever, cough, weight loss and asymptomatic papules and nodules all over the body. Differential diagnoses of secondary syphilis, histoplasmosis, cryptococcosis and penicilliosis were considered. Histopathological and mycological study of the skin biopsy tissue, and blood culture confirmed the diagnosis of penicilliosis. Although penicilliosis, an AIDS-defining illness, is restricted to Southeast Asia, more and more cases are being recognized in non-endemic countries.

Parasitic diarrhoea in patients with AIDS.

BACKGROUND: Diarrhoea is a common clinical manifestation of HIV infection regardless of whether or not patients have AIDS. Two newly recognized opportunistic coccidial protozoa are parasitic pathogens in AIDS patients. We attempted to determine the common parasites in Indian patients with AIDS. METHODS: Between October 1994 and December 1996, a total of 110 stool specimens from 94 AIDS patients with acute or chronic diarrhoea were examined by microscopy of wet mounts and smears stained by a modified Ziehl-Neelsen's (cold) staining method. RESULTS: Isospora belli was the most frequently encountered parasite in 17% of patients, followed by Entamoeba histolytica in 14.9% and Cryptosporidium in 8.5%. Strongyloides stercoralis and Giardia lamblia were detected in 5.3% and 4.3% of patients, respectively. CONCLUSION: The presence of different parasites in 56.4% of stool specimens of patients with AIDS indicates that their specific diagnosis is essential. This will help initiate therapy to reduce the morbidity and mortality among such patients due to these pathogens.

Increased promoter diversity reveals a complex phylogeny of human immunodeficiency virus type 1 subtype C in India.

OBJECTIVE: To evaluate human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) sequence diversity among distinct populations within India and to determine the prevalent subtype. STUDY DESIGN/METHODS: Analysis of the 3'LTR was conducted from 28 HIV-1-positive samples: 1992-1993 (Pune, New Delhi) and 1995-1996 (Pune, Mumbai and Vellore). Genomic DNA was extracted from cocultivated peripheral blood mononuclear cells (PBMCs) and used for polymerase chain reaction (PCR) amplification and sequencing using dye terminator chemistry. Sequences were edited, aligned, and analyzed phylogenetically utilizing gap-stripped and bootstrapping parameters. Mobility shift assays were used to confirm binding activity. RESULTS: All nucleotide sequences were HWV-1 subtype C based on phylogenetic analysis. The isolates from Pune/Delhi formed subclusters when analyzed separately, irrespective of time or sample source. However, no significant subclustering was observed with isolates from Mumbai or Vellore or with the entire sample set when analyzed collectively. Subtype-specific enhancer analysis revealed an expected third NF-kappaB site but also revealed six isolates with insertions and deletions not previously described, one of which resembles an AP-1 binding site. CONCLUSIONS: The results confirm the prevalence of HIV-1C and suggest increasingly complex phylogeny of HIV-1C within India, such that the previously observed subclustering may no longer adequately reflect the diversity of isolates currently circulating throughout India.

Seronegative HIV-2 carriers in India.

The discordant cases of seronegative, but culture and proviral HIV-2 DNA positive were found in Mumbai, India. This was corroborated by the successful isolation of HIV-2-RNA in culture medium, HIV-2 cDNA sequence determination and the detection of the antigen. The sequence of the isolated HIV-2 genomic RNA does not seem to be altered to the extent that the change will alter antibody binding. Furthermore, antibody from the same individual (even at 8 months from initial sampling) from whom HIV-2 was isolated did not react with the antigen of this strain. Those evidences imply that extremely low or non-production of the antibody may be due to suboptimal immune stimulation due to extremely slow HIV-2 replication. This low virus-load may be responsible for the negative antibody results in the HIV-2 carriers.

PIP: This paper describes the characteristics of HIV-2 seropositive and seronegative cases in Mumbai, India, and characterizes the differences between HIV-1 and HIV-2. More than 200 outpatients considered to be at high risk of HIV infection were screened for HIV-1 and HIV-2 antibody and proviral DNA. The study found 11 cases that were discordant for antibody test and HIV proviral DNA (i.e., negative for anti-HIV but positive for HIV-2 proviral DNA). The presence of this provirus was further corroborated by the detection of HIV-2 RNA in the culture medium upon HIV isolation, HIV-2 cDNA sequencing, and antigen detection. The sequence of the isolated HIV-2 genomic RNA did not seem to be altered to the extent that the change would affect antibody binding. Moreover, antibody from the same person in whom HIV-2 was detected did not react with the antigen of this strain even 8 months after the initial sampling. These findings indicate that extremely low production or non-production of the antibody may be brought about by suboptimal immune stimulation due to very low HIV-2 replication speed. This low virus load may account for the negative antibody results in the HIV-2 carriers in India.

Cyclospora infection in acquired immunodeficiency syndrome.

BACKGROUND: Diarrhea is a common clinical manifestation of human immunodeficiency virus (HIV) infection. The important protozoan pathogens causing diarrhea include cryptosporidium, microsporidium, Isospora belli and cyclospora besides giardia lamblia and entamoeba histolytica. OBJECTIVE: The objective of the present study was to determine the incidence of cyclospora (a coccidian protozoan) infection in HIV infected patients. METHODOLOGY: Faecal smears were stained by modified acid fast staining method to demonstrate oocysts of cyclospora. RESULTS: Out of 334 faecal specimens which were studied, cyclospora were identified in 22 cases (6.6 percent); and in 50 percent of the patients, there was a mixed infection with another protozoan parasite namely cryptosporidium. CONCLUSION: Identification of this parasite is important because cyclosporiasis can be treated with trimethoprim-sulfamethoxazole. Outbreaks of cyclospora infection have been linked to waterborne transmission. Though adequately chlorinated water is free of coliforms, it can still contain cyclospora.

Interleukin-9 receptor alpha chain mRNA formation in CD8+ T cells producing anti-human immunodeficiency virus type 1 substance(s).

A search for gene(s) associated with anti-human immunodeficiency virus type 1 (HIV-1) activity of CD8+ T cells was attempted using molecular cloning and the relation between the anti-HIV activity of CD8+ T cells and the interleukin-9 receptor alpha chain (IL-9R-alpha) mRNA expression from the cDNA clones obtained was examined. The anti-HIV-1 activity of CD8+ T cell culture supernatants was assessed by measuring the level of HIV-1 replication of a CD4+ T cell line transfected with an infectious HIV-1 DNA clone. IL-9R-alpha mRNA was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high level of anti-HIV-1 activity (more than 80% suppression of HIV-1 replication), the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-1 activity (less than 80% suppression of HIV-1 replication), the mRNA was detected in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress HIV-1 replication at a concentration of 1 microgram/ml. These data suggest that the IL-9R-alpha mRNA formation in CD8+ T cells may correlate with and play some role in the anti-HIV-1 activity of CD8+ T cells from HIV-1-infected individuals.

HIV-1 variants in South and South-East Asia.

HIV spread in South and South-East Asia is most alarming, and genetic variability of HIV-1 is an important consideration in vaccine development. In this study, we examined the third variable (V3) region of env gene of HIV-1 variants prevalent in Thailand, Malaysia, India, and the Philippines. By phylogenetic tree analyses, an HIV-1 variant from an injecting drug user (IDU) in Thailand belonged to subtype B, and HIV-1 variants from 2 IDUs in Malaysia were classified into 2 subtypes, B and E. One HIV-1 variant from a male homosexual in the Philippines belonged to subtype B. Out of 8 HIV-1 variants from sexually transmitted disease patients in India, 7 belonged to subtype C, and one to subtype A. Although the total number of individuals examined in this study was limited, 4 HIV-1 subtypes were found in South and South-East Asia and large international movements of HIV-1-infected individuals in this region could induce global dissemination of these HIV-1 variants.

The epidemiology of HIV in India.

India is the first country outside Africa where an HIV-2 epidemic is running in parallel to an HIV-1 epidemic, resulting in a significant proportion of double infections. HIV is spreading rapidly, mainly by heterosexual contact, but also among intravenous drug users. Genetic analyses of the HIV variants circulating in India point towards HIV-1 and HIV-2 having been introduced into the country recently.

PIP: The genetic strains of HIV which have been uncovered in India have a different origin from those present in Thailand. Also, both HIV-1 and HIV-2 have been detected in India. In a 1991-93 study of clients of a sexually transmitted disease clinic in Bombay, it was found that seroprevalence of HIV in 241 clients was 39%, the 78.5% positive for HIV-1, 6.5% for HIV-2, and 15% for both. Distribution was even for males and females, reflecting heterosexual transmission. HIV-2 has also been detected in other parts of India, and HIV-1 is spreading throughout the country. HIV in children is a sequelae to blood transfusion. The prevalence of HIV in areas where IV drug use is rampant is increasing rapidly and is spreading to the general population. Genetic analysis revealed that the most closely related genetic sequence to the Indian HIV-1 from Bombay occurs in a strain of the virus from South Africa. One subtype of HIV-2 and several subtypes of HIV-1 have been found, with HIV-1 subtype C and HIV-2 subtype A the most frequently encountered. An examination of phylogenetic trees shows the relationships among these different strains. The close genetic relationship between isolates of HIV-1 and HIV-2 from patients in different parts of the country reflects the recent introduction of these strains. Thus, India is an ideal site for studying the efficacy of a vaccine designed specifically for a population of highly similar strains (the high similarity among HIV-2 isolates is unique in India). Since HIV-2 strains are diverging at a rate of 1% per year, any such research would have to occur soon.

Genetic analysis of human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) mixed infections in India reveals a recent spread of HIV-1 and HIV-2 from a single ancestor for each of these viruses.

DNA sequences encoding the surface envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) were amplified by PCR from uncultured peripheral blood mononuclear cells obtained from patients with serologically defined HIV-1/HIV-2 mixed infections from Bombay, India. HIV-1-specific PCR products were obtained in seven of seven randomly chosen doubly reactive cases, while HIV-2-specific sequences were detected in five of seven cases (71%). DNA sequence analysis showed that the HIV-1 gp120 coding sequences were closely related to each other (nucleotide sequence divergence of between 3.1 and 6.8%). Phylogenetic tree analysis placed the Indian strains within the C subtype of HIV-1, being most similar to sequences previously found in East and South Africa. The HIV-2 sequences were also closely related to each other, with an overall sequence divergence of between 5.6 and 10.5%. The low level of nucleotide divergence among Indian HIV-1 and HIV-2 sequences suggests a fairly recent introduction of each virus into this population from a single point of entry in each case. The HIV-2 sequences reported here represent the first analysis of Asian HIV-2 strains and confirm the serological pattern previously detected in India. These data show that a substantial spread of HIV-2, together with HIV-1, has appeared outside Africa in a population hitherto unexposed to HIV. These findings imply that further spread of HIV-2 worldwide is to be expected and have important implications for future vaccine and therapy development.

Sequence analysis of V3 loop region of HIV-1 strains prevalent in India.

The third variable (V3) domain of human immunodeficiency virus type 1 (HIV-1) env gene has been found to elicit type-specific neutralizing antibodies as well as a cytotoxic and helper T-cell response in both humans and animals. We analyzed the V3 domain of 8 HIV-1 isolates from India by using polymerase chain reactions. The V3 loops of 7 Indian isolates contained the apical tetra peptide GPGQ, while the V3 loop of one Indian isolate carried the apical tetra peptide GPGK. The amino acid sequences of the seven Indian isolates were closely related to each other, with an average of the nucleotide sequence homology of 96.0% (94.6 to 97.6%). The marked relatedness of the amino acid sequences among the seven Indian HIV-1 isolates indicated a recent and very rapid spread of this HIV-1 variant in Bombay. The amino acid sequence of the C2/V3 region of env gene of the 7 Indian isolates were homologous to the C subtype reported by Meyers et al. These findings could be useful in assessing the sources of infection and developing an AIDS vaccine.