HIV/AIDS in India - Indigenous evidence through operational research

In clinical medicine, a clinical paradigm is taught to all medical students that ‘Time is muscle’ in a patient of acute coronary syndrome. It is well known that after an acute coronary event, if the reperfusion of the occluded coronary vessel is done early, it protects the potentially compromised myocardium from permanent ischaemic damage and hence reduces morbidity and mortality. The same analogy has been shown to be beneficial in ischaemic cerebrovascular events where ‘Time is brain’!

Logically, this phrase ‘Time is life’ is true for all communicable or non-communicable diseases, when early diagnosis followed by appropriate therapy is the key to reduce morbidity and mortality. In the subspecialty of infectious diseases, especially in a resource-limited setting like India, the problem of early diagnosis and compliance to therapy in diseases like tuberculosis and people living with HIV/AIDS (PLHA) is compounded due to a lot of myths associated with these two diseases in the general population. At times, these two diseases are also perceived as a ‘social stigma’, wherein the patients and their families tend to keep the ‘diagnosis under wraps’ to ‘prevent’ social isolation.

In this issue, Chakravarty et al1 in an observational study done in eastern Uttar Pradesh, included treatment naive HIV patients and assessed outcome after two years of antiretroviral therapy (ART). The patients were enrolled as per 2009 National AIDS Control Organization (NACO) guidelines1. The study observed that survival was poor in first six months of initiation of ART. The factors resulting in poor survival in their study included CD+ T-cell count less than 100/μl, anaemia and low body weight. Low CD4+ T-cell count reflecting severe immunosuppression associated with undernutrition obviously makes a deadly synergism for PLHA. The authors have emphasized an early enrolment of HIV patients for initiation of ART. It is pertinent to note that the authors used the enrolment criteria for initiation of ART in their study as per 2009 NACO guidelines. The enrolment period in their study was from May 2009 to May 2010.

In a randomized open-label trial in a resource-limited setting in Haiti, it was observed that ART initiated when the CD4+ count was between 200 and 350 cell/μl resulted in a 75 per cent reduction in death and a 50 per cent decrease in incidence of tuberculosis, when compared to standard ART initiated when CD4+ count fell to less than 200/μl an AIDS defining illness2.

In fact, the guidelines for initiation of ART in adults have been modified by NACO in 2011. The revised 2011 NACO guidelines recommend the initiation of ART in World Health Organization (WHO) clinical stage 1 and 2 if CD4+ count is less than 350 cells/μl. In WHO clinical stages 3 and 4, the modified guidelines recommend that all patients should be treated irrespective of the CD4+ count3. Obviously, the modified criteria reiterate the fact that early diagnosis and treatment is the sheet anchor for success in PLHA.

In HIV, going a step further, there is a debate about the initiation of ART even in patients with CD4+ counts between 351 to 500 cells/μl or more than 500. In United States and Canada, among patients with a 351 to 500 CD4+ cells/μl, the deferral of ART till CD4+ count is less than 350 cells/μl was associated with an increase in death of 69 per cent. In patients with > 500 CD4+ cells/μl, there was a 94 per cent increase in risk of death in patients where ART was deferred till CD4+ count was < 350 cells/μl. Though this was an observational study, it postulated the benefits of very early versus deferred therapy for patients with HIV4. The cost for a resource-limited country like India and the rigorous follow up for drug side effects need to be taken into consideration before the potential implementation of such early ART strategies can be considered in our country.

The other important observation made by Chakravarty et al1 is the high rate of lost to follow up (LFU) of patients occurring in the first six months after initiation of ART. Consequently, the authors have also highlighted the need to build an efficient patient retrieval system in the national ART programme. The factors in LFU patients were almost the same as the risk factors for poor survival patients in their study. Though the authors have not dwelled into the reasons of this high rate of LFU, it can be hypothesized that socio-cultural factors and economic considerations like lack of employment and undernutrition in critically ill HIV patients in the absence of social security in our country may be leading to this scenario.

However, it needs to be recalled that the tuberculosis (TB) control programme in our country also faced a similar dilemma of LFU, till Directly Observed Therapy, Short Course (DOTS) was launched as Revised National Tuberculosis Programme in 19975. In DOTS, the patients are given the antituberculosis therapy under the direct supervision of a provider and the responsibility of ensuring regular and completion of treatment lies with the programme. Perhaps the same analogy for PLHA may not be feasible in a resource-limited setting like India as logistically it is easy to keep a track of TB patients for six months in DOTS, whereas in AIDS this kind of strategy would require a lifelong approach. Chakravarty et al1 advocate that a proactive approach of tracing the LFU patients needs to be evolved at the national level.

Last but not the least, we should not forget that the age-old dictum “Prevention is better than cure” is most relevant for HIV/AIDS. The core strategy for controlling this epidemic has to be two fold giving equal emphasis to increase public awareness regarding prevention of HIV, besides a continuous appraisal of recommendations for initiation and compliance of ART to improve outcome in HIV/AIDS patients. Obviously, indigenous operational research to generate and validate evidence regarding appropriate ART for our country is the need of the hour to facilitate the policy makers in drafting national guidelines.