Suniti Solomon

Comorbidities among HIV-infected injection drug users in Chennai, India.

Objectives: To document the natural history of herpes simplex virus type 2 (HSV-2) in relation to HIV and highly active antiretroviral therapy (HAART) in Africa, a longitudinal study was conducted of women in the placebo arms of two randomised controlled trials of HSV-suppressive therapy in Burkina Faso. Methods: 22 HIV-uninfected women (group 1), 30 HIV-1-infected women taking HAART (group 2), and 68 HIV-1-infected women not eligible for HAART (group 3) were followed over 24 weeks. HSV-2 DNA was detected on alternate weeks using real-time PCR from cervicovaginal lavages. Plasma HIV-1 RNA was measured every month. CD4 cell counts were measured at enrolment. Results: Ulcers occurred on 1.9%, 3.1% and 7.2% of visits in groups 1, 2 and 3 (p = 0.02). Cervicovaginal HSV-2 DNA was detected in 45.5%, 63.3% and 67.6% of women (p = 0.11), and on 4.3%, 9.7% and 15.5% of visits in the three groups (p<0.001). Among HIV-infected women, cervicovaginal HSV-2 DNA was detected more frequently during ulcer episodes (adjusted risk ratio (aRR) 2.79, 95% CI 2.01 to 3.86) and less frequently among women practising vaginal douching (aRR 0.60, 95% CI 0.40 to 0.91). Compared with women not taking HAART and with CD4 cell counts of 500 cells/μl or greater, women on HAART had a similar risk of HSV-2 shedding (aRR 0.95, 95% CI 0.52 to 1.73), whereas women with CD4 cell counts of 200–500 cells/μl were more likely to shed HSV-2 (aRR 1.71, 95% CI 1.02 to 2.86). Conclusions: HSV-2 reactivations occur more frequently among HIV-infected women, particularly those with low CD4 cell counts, and are only partly reduced by HAART. HSV therapy may benefit HIV-infected individuals during HAART.

Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV Transmission

BACKGROUND Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed. METHODS We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site. RESULTS A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08). CONCLUSIONS Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.)

Natural History of Human Immunodeficiency Virus Disease in Southern India

There are few reports of the natural history of human immunodeficiency virus (HIV) infection from Asia. In a retrospective analysis of 594 patients (72.9% male; baseline CD4 cell count, 216 cells/microL) receiving care at YRG Center for AIDS Research and Education, a tertiary HIV referral center in southern India, the mean duration of survival from serodiagnosis was 92 months. Ninety-three percent of the patients acquired infection through heterosexual contact. The most common acquired immune deficiency syndrome-defining illnesses were pulmonary tuberculosis (49%; median duration of survival, 45 months), Pneumocystis carinii pneumonia (6%; median duration of survival, 24 months), cryptococcal meningitis (5%; median duration of survival, 22 months), and central nervous system toxoplasmosis (3%; median duration of survival, 28 months). Persons with a CD4 lymphocyte count of <200 cells/microL were 19 times (95% confidence interval [CI], 5.56-64.77) more likely to die than were those with CD4 cell count of >350 cells/microL. Patients who had > or =1 opportunistic infection were 2.6 times more likely to die (95% CI, 0.95-7.09) than were those who did not have an opportunistic infection. Antiretroviral therapy for patients with low CD4 lymphocyte counts improved the odds of survival (odds ratio, 5.37; 95% CI, 1.82-15.83).

Incidence of immune reconstitution syndrome in HIV/tuberculosis-coinfected patients after initiation of generic antiretroviral therapy in India.

This paper describes the incidence of immune reconstitution syndrome (IRS) from the developing world and implications for clinicians. Eleven of 144 HIVand tuberculosis (TB)-coinfected individuals followed for 72 person-years developed IRS within 6 months of initiating generic highly active antiretroviral therapy (HAART). All of the IRS patients were male, with a median age of 29 years; median CD4 at HAART initiation was 123 cells/mm3, and 6-month median CD4 rise was 124 cells/mm3. There was no statistical difference in CD4 rise or CD4 count and duration of TB treatment at HAART initiation between those who did and those who did not develop IRS (P = 0.8380). The median time to development of clinical IRS was 42 days (range 10-89 days). The incidence of IRS in this cohort is 15.2 cases per 100 patient-years. With increased coprevalence of opportunistic infections, especially TB, and increasing access to antiretroviral therapy in the developing world, clinicians in these countries must be able to identify IRS and relieve symptoms without compromising clinical care.

When HIV-Prevention Messages and Gender Norms Clash: The Impact of Domestic Violence on Women's HIV Risk in Slums of Chennai, India

This paper examines how marital violence affects womens ability to protect themselves from HIV/AIDS. In-depth interviews (n = 48) and focus groups (n = 84, 3–7 per group) were conducted among men and women in two randomly selected slums of Chennai, India. The study showed that community gender norms tacitly sanction domestic violence that interferes with adopting HIV-preventive behaviors. Given the choice between the immediate threat of violence and the relatively hypothetical specter of HIV, women often resign themselves to sexual demands and indiscretions that may increase their risk of HIV acquisition. In conclusion, AIDS-prevention interventions must incorporate gender-related social contexts in settings where husbands strictly enforce their locus of control. HIV-prevention messages targeting men may effectively reduce womens exposure to HIV/AIDS.

The changing natural history of HIV disease: before and after the introduction of generic antiretroviral therapy in southern India.

The number of individuals seeking treatment for infection with human immunodeficiency virus increased as the cost of highly active antiretroviral therapy (HAART) decreased 20-fold after the introduction of generic HAART in India in the year 2000. The incidence of tuberculosis and opportunistic infections decreased to <2 cases per 100 person-years. Death rates decreased from 25 to 5 deaths per 100 person-years between 1997 and 2003.

total Lymphocyte Count (tlc) Is a Useful Tool for the Timing of Opportunistic Infection Prophylaxis in India and Other Resource-constrained Countries

Background: In most resource‐constrained countries, CD4 cell count testing is prohibitively expensive for routine clinical use and is not widely available. As a result, physicians are often required to make decisions about opportunistic infection (OI) chemoprophylaxis without a laboratory evaluation of HIV stage and level of immunosuppression. Objectives: To evaluate the correlation of total lymphocyte count (TLC), an inexpensive and widely available parameter, to CD4 count. To determine a range of TLC cutoffs for the initiation of OI prophylaxis that is appropriate for resource‐constrained settings. Methods: Spearman correlation between CD4 count and TLC was assessed in patients attending an HIV/AIDS clinic in South India. Positive predictive value (PPV), negative predictive value (NPV), and sensitivity and specificity of various TLC cutoffs were computed for CD4 count <200 cells/mm3 and <350 cells/mm3. Correlation and statistical indices computed for all patients and for patients dually infected with HIV and active tuberculosis. Results: High degree of correlation was noted between 650 paired CD4 and TLC counts (r = 0.744). TLC <1400 cells/mm3 had a 76% PPV, 86% NPV, and was 73% sensitive, 88% specific for CD4 count <200 cells/mm3. TLC <1700 cells/mm3 had a 86% PPV, 69% NPV, and was 70% sensitive, 86% specific for CD4 count <350 cells/mm3. The cost of a single CD4 count in India is approximately US

Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India.

30, whereas the cost of a single TLC is US

High Prevalence of Hiv, Hiv/hepatitis C Virus Coinfection, and Risk Behaviors Among Injection Drug Users in Chennai, India: A Cause for Concern

0.80. Conclusion: TLC could serve as a low‐cost tool for determining both a patient’s risk of OI and when to initiate prophylaxis in resource‐constrained settings. PPV, NPV, sensitivity, and specificity maximally aggregated at TLC <1400 cells/mm3 for CD4 <200 cell/mm3 and TLC <1700 cells/mm3 for CD4 <350 cells/mm3. Selection of appropriate TLC cutoffs for prophylaxis administration should be made on a regional basis depending on OI incidence, antimicrobial resistance patterns, and availability of the antimicrobials.

Risk factors for HIV infection in injection drug users and evidence for onward transmission of HIV to their sexual partners in Chennai India.

Objective:To describe reasons for modification and discontinuation of antiretroviral regimens in association with adverse events (AEs), treatment failure, and cost among patients in southern India. Methods:Secular trends of patients initiating highly active antiretroviral therapy (HAART) between January 1996 and October 2004 at a tertiary HIV referral center in India were analyzed using a previously validated natural history database. Results:All previously antiretroviral therapy-naive patients who initiated HAART (N = 1443) and had at least 1 follow-up visit were evaluated. The median CD4 count at the time of initiating HAART was 108 cells/μL The most common first-line regimens were stavudine (d4T) plus lamivudine (3TC) plus nevirapine (NVP) (63%), zidovudine (AZT) plus 3TC plus NVP (19%), d4T plus 3TC plus efavirenz (EFV) (9%), and AZT plus 3TC plus EFV (4%). Twenty percent of patients modified their first-line regimen. The most common reason for modifying therapy was the development of an AE (64%), followed by cost (19%) and treatment failure (14%), with median times to modify therapy being 40, 151, and 406 days, respectively. Common AEs were itching and/or skin rash (66%), hepatotoxicity (27%), and anemia (23%). Nine percent of patients discontinued therapy entirely after a median duration of 124 days, primarily because of cost (64%). Conclusion:The most common reason for modifying therapy was the occurrence of AEs, whereas cost was the most common reason for discontinuing therapy. Despite increasing access to lower cost generic HAART in India, even less expensive and more tolerable first-line regimens and cost-effective treatment monitoring tools need to be introduced to achieve better treatment outcomes and access in resource-constrained settings.