In an international multicenter study, HIV patients from nine countries showed significant improvement in health by the use of antiretroviral therapy (ART). The study also found that HIV patients who were on ART had a reduced likelihood to transmit the disease in their HIV negative sex partners.
Led by Myron Cohen, MD, Director, Institute for Global Health & Infectious Disease, University of North Carolina School of Medicine, an international team of experts unified their efforts to highlight the pivotal role of ART to prevent sexually transmitted HIV. The study results were published in the New England Journal of Medicine (NEJM) on 18th July, 2016.
This crucial longitudinal study was funded by the National Institute of Allergy and Infectious Disease, while the drugs were sponsored by pharmaceutical giants GalxoSmithKline, Merck, Bristol-Myers Squibb, Gilead Science and others.
Will The Use Of Antiretroviral Therapy Change The Global Trend Of HIV Prevalence?
Earlier this month, Recommendations of the International Antiviral Society were released which also endorsed the use of ART in all the patients of HIV as soon as a diagnosis is made. Often, switching to ART is followed by a reduced CD4 T count, at which time the virus has progressed to advanced stages. However, now experts recommend to switch to ART right after the first trace of virus is reported in the blood test. The recommendation analyzed the present knowledge of ART amongst populations and the future implications of the drug to not only improve the HIV progression but also help HIV patients who suffer from opportunistic infections.
Regular use of ART has also been studied in relation with transmission of HIV through condomless sex. To the relief of HIV patients, the study showed that people who are on ART are highly unlikely to transmit the disease to their sex partners.
Amongst these advancements, the use of ART is currently in the forefront. In this particular study, the participants hailed from Zimbabwe, South Africa, Botswana, Kenya, Malawi, Thailand, India, Brazil, and the United States and their clinical trials were carried out at 13 sites. The study ran from April 2005 to May 2010 and follow-ups continued till 2015.
It is worth noting that ART is a combination of nucleoside reserve transcriptase inhibitors (NRTIs), protease inhibitors and integrase stand transfer inhibitor (InSTI) that help restrict viral cell proliferations and subsequent spread of the disease.
At the time of enrollment to the trial, 1,763 serodiscordant couples were monitored (it means in these couples one partner was HIV positive and the other partner was HIV negative). From there onwards, the index participants, who had not been previously using ART, were treated by ART and the drug efficacy was periodically monitored.
At the beginning of this trial, the index participants i.e., HIV positive patients went through standardized blood tests to see the progression of the disease. In the context of HIV, the CD4 count was conducted which is reliable laboratory indicator for HIV progression. The test measures the count of CD4 T lymphocytes that reflect upon the state of immune system. In an HIV patient, the virus attacks the CD4 cells leaving in bad health. Therefore, a standardized threshold CD4 cell count can help with the detection of the disease. In an uninfected adult, the cell count ranges between 500 cells/mm3 and 1,600 cells/mm3. On the contrary, for an HIV patient who have reached stage 3 of the infection can have a cell count of as low as less than 200 cells/mm3 of sample.
The index participants showed a CD4 count of 350 cells/mm3 to 550 cells/mm3. These participants were assigned two groups in a randomized assortment process: early-ART group and delayed-ART group. As it suggests, in early-ART group the index participants were given ART right from the beginning. On the other hand, index participants were given ART when two consecutive CD4 count values fell below 250 cells/mm3.
The HIV negative partners were also offered laboratory and clinical checkups regularly to detect any possible virus contraction in a timely manner.
After a median follow up of 1.7 years from the start of the study, it was observed that early ART group showed 96% lower risk of sexual transmission of the virus than in delayed-ART group. However, after a follow-up time of 5 years the delayed-ART group begins to show improved immune response against the viral intrusion. By the conclusion of the study, the difference of sexual transmission of HIV was slightly reduced to 93% between the groups.
However, it was found that 78 previously HIV negative partners contracted the virus. To know if the contracted virus came from the HIV positive partner, assessment of genetic linkage was carried out by phylogenetic analysis of the polymerase region sequences from related pairs, non-related participants and reference sequence. Furthermore, HIV virus envelop genome was also sequenced through Next Generation Sequencing techniques.
Out of these 78 cases, genetic linkage was determined in 72 cases. Amongst them, 26 cases showed no genetic linkage which suggested that HIV was not contracted from the partners. Out of them, 14 unrelated viral contractions were recorded in early ART group and 12 were recorded in delayed-ART group. Supporting the hypothesis further, in the related viral contractions only 3 cases were found in early-ART group while in delayed-ART group 43 cases were observed.
In recent years, advancements in the treatment of human immunodeficiency virus type 1 (HIV-1) have helped improve health of millions of HIV patients worldwide. The morbidity and mortality rates have also been effectively curbed to reduced levels for this global epidemic. Despite these encouraging figures, the sexual transmission of HIV remains at a high rate, contributing about 2 million new cases per annum.
With the increasingly encouraging results of ART, it is likely that the use of ART will be adapted at a global level to fight off HIV and promote healthy living.