Human Immunodeficiency virus (HIV) infection causes acquired immuno deficiency syndrome (AIDS).[27
] It is a newly found disease consisting various clinical presentations, which are primarily stemmed from profound immunodeficiency caused by the selective depletion of CD4 +
] Ayurvedic texts lack the reference to the disease owing to its recent emergence. Fortunately, one can find several disease entities described in ayurvedic literature similar to the HIV/AIDS disease, but still they are different. The various clinical presentations of the advanced HIV disease or AIDS are the phenomenon of Vyadhi Samkaratwa
] At the end, it is the profound immuno deficiency, which causes all the disorders, thus the state of immuno deficiency could be well correlated with the loss of both the aspects of Vyadhi Kshamatwa
(Vyadhi utpada pratibandhakatwa avum vyadhi bala virodhitwa
] and its communicability and prognosis (the prognosis of HIV infection has recently changed from a fatal condition to a manageable chronic illness)[32
] with yapya aupasargika roga
To counteract the associated destructive control mechanisms[34
] and AIDS-related wasting syndrome[35
] in the progression of HIV infection, ayurvedic therapeutic modalities such as Santarpana
] and Vrishya
] therapies are indicated. Not only that, it was also postulated to exploit especially Yuktikrita bala
] thereby preventing or delaying Aparirakshanaja vyadhi
, e.g., jara
or metabolic derangement (seven types of aging damage[43
]) associated with aging, etc. To modulate the psycho-neuro-endocrine-immune (PNI) axis,[44
] medhya rasayana, achara rasayana
] and Sattvavajaya
] therapy are indicated.[47
] By the treatment with Ranahamsa Rasayanaya
(RR), the same purposes have been hoped for along with anti-HIV properties of its ingredients, such as ajoene, caffeic-acid, diallyl-disulfide, quercetin,[48
] selenium (Se), zinc (Zn),[49
] coriandrin (Singh et al
] apigenin, glycyrrhisoflavone, glycyrrhizin, licochalcone-A, lignin,[51
] caffeic acid, chlorogenic acid, ellagic acid, epicatechin, gallic acid, myricetin, procyanidins,[52
] etc. Besides that, the test drug contained renowned medhya rasayana
drugs, i.e., Guduchi
] Go ghrita (butter oil, anhydrous),[55
] etc., which help in modulating the PNI axis. In general, it has been expected that, advantageous PNI modulation, anti-HIV properties, plus weakening of destructive control mechanisms would have produced a favorable homeostatic balance and restoration of wellness in the patient.
Age: Reported large numbers of HIV positive participants were young. An increased incidence of HIV in young age groups reflects the sexual activeness during this age, and maximum number of transmission through sexual route.
: Majority of the patients registered for the present study were males with a frequency of 70.4%, and females belonged to 29.6%. High risk sexual practices reported among MSM (i.e., unprotected receptive anal sex – kothis
, multiple partners, violent sex,[56
] etc.) are also high in frequency, thus making them more vulnerable to contract the disease. However, in the developing countries, major transmission route is unprotected heterosexual contact. Even though, the disease burden among MSM should not be overlooked.
: Majority (85.2%) having either or primary education is a welcoming fact, because by educating the masses, this dreaded disease only can be prevented. Another alarming fact is that, this finding does not reveal the truth. In India and in Gujarat state, the literacy rate is not higher like that among the population.[57
Habitations of the patients: Every participant (100%) was reported from an urban setting. This finding also does not show the reality, as higher percentage of the population belong to rural areas.
Risk level of the patients
: Most of the patients (70.4%) were found to have an increased level risk in their life style. It is possible because many of them engage in same sex relationships with multiple partners. Both come under high risk activities.[58
] Another finding showed that, despite the high risk sexual activities, the participants did not use intravenous drug use (IDU).[59
] This may be due to the legal restrictions of alcohol and other drugs in Gujarat state.
Probable transmission route of HIV infection
: More than half of the participants (55.6%) believed that, they got infected with HIV via
unprotected homosexual contact. This figure is attributed largely to the sample contained MSM. Over one third of the patients (37.0%) believed that, they contracted the disease through unprotected heterosexual contact. There was one minor, it may be attributed to the contaminated injection caused the disease. Apart from that, one patient reported that, she does not have a clue about contracting the disease. These findings confirm that, the major route of HIV transmission in developing countries is via
sexual route, and at the same time, it contradicts the major role of unprotected heterosexual contact, reporting 55.6% cases of unprotected homosexual contacts. Reporting more than 96.3%, from unprotected sexual contact and unsafe injections, the present findings were in accordance with the established theories of HIV transmission.[60
History of exposure to injections
: All of the patients (100%) admitted to have got injections in one time or the other in their life. This may be a possible way in the case of a single patient who reported to have no idea about how she contracted the disease. Even though many had casual sexual encounters, we could not rule out the possibility of transmitting HIV infection by this route. The recycling of medical waste in developing countries like India thrives in. Recent outbreak of hepatitis B infection was caused by the usage of recycled medical waste by the physicians, thus causing iatrogenic epidemics.[61
] History of casual sexual encounters found among the patients. Many (85.2%) reported that, they had had casual sex apart from their regular partner either with a stranger or a known person. The remaining patients denied having casual sex, including a minor. As it is a well documented fact that the major route of HIV transmission is through unprotected sexual contact regardless of its nature.[62
History of foreign travel: No patient travelled abroad, who came under the present study.
History of sexually transmitted infection (STI)
: Only 14.8% patients admitted that, they had suffered from an STI earlier. Majority claimed they were free from an STI in the past. Anyhow, this finding not exactly back the transmission of HIV infection, but still it credited the theory of facilitating the HIV transmission due to the presence of inflammation in the genital organs or where the contact occur.[64
Sexual orientation and sexual practices
: Majority (51.9%) reported that, they were bisexually orientated. Exclusively homosexual patients found to be 11.1% and 33.3% heterosexually oriented patients were also found during the present study. Apart from them, there was a child obviously without sexual activity. Under broad term of MSM or men-having-sex-with-men, the above mentioned both the categories, i.e., bisexually and exclusively homosexually oriented can be included. Then there were 63.0% of patients, can be categorized under MSM. Majority of the patients (85.2%) admitted to have vaginal intercourse. Around 60% patients admitted to have anal sex. This finding is in accordance with the sexual orientation finding, where both heterosexually and bisexually oriented patients were found in the same proportions. Anal sex is considered to be a high risk factor in the transmission of HIV infection. Compared to anal sex and vaginal sex, oral sex is considered to be less riskier,[65
] but still there is a considerable chance of contracting the disease, if the ejaculation occurs in the mouth or if vaginal secretion gets swallowed.
Positive family history for HIV
: The findings of positive family history for HIV showed 22.2% of the patients had one or more HIV positive members in the family. This figure included the three widows, whose husbands died due to AIDS. It is most of the husband. But there was an isolation case of wife is HIV positive and the husband is negative. This indicates the “bridging population
”, who links the gap between the high risk population (who practice unwise sexual choices) and the low risk populations, i.e., housewives, etc. Risk associated with this intimate act makes it a burden. This is evident from the quote “Who ever having sex is in risk
”. This phenomenon is named as “Silda Spitzer syndrome”, New York Governor Eliot Spitzer, who involved in a prostitution scandal, was reluctant to use condoms. So his wife never thought she is in risk. At the same time, many Indian gay men get married to escape from the social stigmatization[66
] and thereby exposing their spouses to a greater risk.
: It was found that HIV-1 was responsible for the most of the infections reported among the participants with 92.6%, the same is the most common cause of HIV disease throughout the world.[67
] Also there were two patients, in whom the strain of HIV was not specified in their laboratory result form. It is well established, HIV-1 has a rapid pathogenesis compared to HIV-2.[68
Clinical stages and CD4+ T-cell Categories found among the patients
: Around 75% of the patients belonged to the Clinical Stage 2 of WHO classification, while 18.5% were in Clinical Stage 1 and followed by Clinical stage 3 (7.4%). No patient was reported from Clinical Stage 4 for the present study. This had happened due to the exclusion of such patients from the study. There were 33.3% of the patients reported with CD4+
T-cell count between 200 and 499 cells per microliter and another 33.3% of the patients reported with CD4+
T-cell count below 200 cells per microliter. The latter group (CD4+
T-cell <200 cells per microliter) were well categorized under AIDS, according to the 1993 revised CDC classification system for HIV infection and expanded AIDS surveillance case definition for adolescents and adults.[69
] And normal CD4+
T-cell count was reported among 18.5% of the patients, while 14.8% patients were reported without such laboratory investigation.
Chronicity of the infection: It was found many patients became aware of their seroreactivity for HIV during the last 12 months. That may be due to the aggressive media campaigns and screening methods implemented by the Indian government in the recent past. Even though, they were recently diagnosed as HIV positive, that is not a reliable measure to decide the chronicity, because the disease itself is chronic in nature.
Effect of the test drug on major and minor signs: The treatment produced statistically significant reduction only in diarrhea and cough. Ranahamsa Rasayanaya contains Tala, Brahmi, Bhanga, Twak, Narikela, Karavi, Parpati, these all have antidiarrheal, anti-dysenteric and antibacterial properties. Besides that, opium is reported to have astringent properties, thereby arresting diarrhea. This may be the cause for 100% relief of diarrhea. Not only that, some patients sought the treatment with modern drugs, while continuing the test drug. That may be another reason for this antidiarrheal effect.
Effect of the test drug on nonspecific constitutional symptoms: The following statistically significant results were observed; reduction of debility by 41.18%, relieving of headache (75.0%), relieving of muscular aching (66.67%), reduction of loss of appetite (44.44%) and increasing the ingestive capacity by 100.0%. Talispatra, Jatipatri, Kumkuma, Bhanga and Pippali known to stimulate appetite. Opium and Bhanga are reported to have analgesic properties. During the experimental studies, it was observed that, the test drug produced statistically significant anabolic effects in the body weight and statistically significant reduction in forced swimming induced hypothermia in rats. Therefore, it can be inferred based on these results, the test drug had an apparent adaptogenic activity. The same adaptogenic activity of the test drug may be beneficial in the treatment of HIV associated nonspecific constitutional symptoms.
Effect of the test drug on 7-item Hamilton scale for depression (HAMD-7) for evaluation of mental health: Following statistically significant effects were observed; reduction in loss of interest, pleasure, level of activities by 37.50%, loss of energy level by 33.33% and total HAMD-7 score by 18.09%. This may be due to the presence of many medhya rasayana drugs, i.e. Tala, Brahmi, Narikela,Guduchi, Yashtimadhu, Nilotpala, etc.
Effect of the test drug on hematological and biochemical parameters: It was observed that, absolute CD4+ T-cell count was increased by 41.36%, which is statistically significant. Besides that, it was also observed reduction of neutrophil count by 11.33% and increment of hemoglobin levels by 11.31%, both were statistically significant. All other parameters such as CD4+ T-cell percentage, absolute CD8+ T-cell count, CD8+ T-cell percentage, CD4/CD8 ratio, total lymphocyte count and lymphocyte percentage were increased, but failed to reach a statistically significant level. Even the ALT (Alanine aminotransferase) level also was reduced without being statistically significant. This shows the probable hepatoprotective activity of the test drug. This may be attributed to the presence of hepatoprotective dugs like Guduchi, Yashtimadhu, Pippali, Chitraka, etc.
Adverse drug reactions reported among the patient treated with the test drug: It is worthwhile to report, three side effects were reported during the clinical trial. First two symptoms (e.g., mild burning sensation and transient mouth ulceration) were reported among women and mild drowsiness was reported among two male patients. Both burning sensation and mouth ulceration were mild in nature. That may be due to the presence of Bhallataka bija in the test drug. Mild drowsiness may be caused due to mdaka properties of opium and hemp. It must be noted that, not any other adverse effect was observed during the study and no life-threatening condition was occurred during the trial period of the test drug. Even during the pharmacological study, not any kind of adverse effect was observed.
Comparison of the results of Group A with Group B
Statistical evaluation of the test drug's effect with the control group using unpaired Student's t test: It was observed that, the test drug has produced only one statistically significant (P<0.05) result in relieving diarrhea (by 67.27%) compared to the control group. All the remaining effects on symptoms were statistically nonsignificant compared to the control group.
Comparison of the overall effect of the therapy
In Group A, no patient showed marked improvement. Moderate improvement was recorded in 7.4% of the participants, followed by mild improvement in 25.9% of the patients and unchange in 22.2% of the patients.
In Group B, similarly no patient showed marked improvement, while 7.4% of the patients showed moderate improvement and 14.8% of the patients showed mild improvement.
The management of HIV/AIDS disease is complicated owing to its complex clinical manifestations along with deep-rooted pathogenesis. The defense mechanism of the body becomes vulnerable for this infection, which resulted in a profound immunodeficiency. The state of susceptibility to disease, due to profound immunodeficiency, could be well correlated with the loss of both the aspects of Vyadhi kshamatwa
(Vyadhi utpada pratibandhakatva
and vyadhi bala virodhikatva
). This leads to the occurrence of Vyadhi samkaratva
, the ayurvedic technical term for the syndrome (a group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms).[70
HIV type 1 (HIV-1) is the most common causative agent in HIV infection worldwide, the same was found in this study also. The most common transmission route of HIV infection is the unprotected sexual contact. The findings of the present study confirm that adverse drug reactions were observed among four participants, but they were mild and no life threatening condition was reported. Mild burning sensation was reported among two female participants and one out of them also complained of transient and mild mouth ulceration. That may be due to the presence of Bhallataka bija in the test drug. Mild drowsiness, which was found among two male participants, may be caused due to madaka properties of opium and hemp. This finding is important from the pharmacovigilance point of view.
Even though, the overall effect of the test drug does not show better results compared to modern medicine, it increased absolute CD4+
T-cell count by 41.36% (P
<0.05) in nine participants. Absolute CD4+
T-cell count is the laboratory test generally accepted as the best indicator of the immediate state of immunologic competence of the patient with HIV infection.[71
] Recovery of the absolute CD4+
T-cell count by 41.36% shows the test drug's ability to improve the deteriorated immunocompetence of a HIV infected patient, who receives the test drug. The same effect testifies to its powerful immunomodulatory properties.