Faculty
Joseph Harwell
Associate Professor of Medicine:
Bio Med Medicine
Phone: +1 401 793 4713
Joseph_Harwell_MD@Brown.EDU
Read Joseph Harwell's full Faculty Research Profile.
HIV in women, prevention of mother-to-child transmission of HIV, clinical care of HIV in resource-poor settings, sexually transmitted infections
Interests
Worldwide, most adults with HIV have been infected through sexual exposure to HIV-infected seminal fluid or cervicovaginal secretions. In addition, most perinatal HIV transmission occurs following exposure to infected maternal cervicovaginal secretions. Several studies have shown that antiretroviral therapy can decrease HIV-1 RNA levels in the female genital tract. Studies have also shown a good correlation between blood plasma viral load and male and female genital tract viral load. It is postulated that reducing genital tract HIV-1 viral load should lead to reductions in sexual and mother to child HIV transmission.
Several factors have been associated with genital tract HIV-1 shedding. From these studies, the strongest indicators of genital tract HIV-1 shedding include plasma HIV-1 RNA level, CD4 cell count, and genital tract infection. However, studies evaluating the factors associated with HIV-1 shedding among women in resource-poor setting who are often taking generic antiretroviral therapy are lacking. Plasma HIV RNA level is closely related to long-term survival and disease progression. Plasma HIV RNA however, is not always predictive of tissue-specific HIV activity and disease, and HIV replication may in fact be compartmentalized. Several studies have noted that genital tract HIV-1 RNA may be genotypically distinct from or present in higher copy numbers than that found in plasma. These data show that assessment of plasma HIV RNA, while important prognostically, may not be representative of the virus' activity in other body compartments. This is important when sexual and vertical exposures account for the majority of new infections, and our understanding of the biology of HIV in the genital tract is not well understood.
Several factors have been shown to be associated with genital tract HIV shedding, including contraceptive pill use, genital infections, cervical ectopy, and pregnancy. One study of genital tract infections in Nairobi, Kenya found that HIV infected women diagnosed with acute gonococcal cervicitis or pelvic inflammatory disease experienced a significant rise in plasma HIV RNA level and a fall in CD4 cell counts at the time of infection. Viral RNA levels and CD4 cell counts returned to normal following treatment of STDs. This is important, because it suggests that aggressive screening and treatment of genital infections may alter the natural history of HIV infection by maintaining lower viral loads and preserving immune function.
We are interested in understanding the determinants of sexual and mother to child HIV transmission and to identifying ways to intervene to help prevent this transmission. One way we are doing this is through the study of cervicovaginal HIV RNA levels, particularly among women receiving antiretroviral therapy. Because the bulk of HIV infections occur outside of the United States, we have been developing programs to study these factors in clinical settings where HIV is highly endemic. In addition, to improve the quality of the care delivered, we have been studying some of the basic epidemiology of HIV-infected populations in these settings, including the spectrum of opportunistic infections and barriers to care.
Degrees
MD
