Human Immunodeficiency Virus (HIV)-1 Transmission Among Persons With Acute HIV-1 Infection in Malawi: Demographic, Behavioral, and Phylogenetic Relationships.

BACKGROUND: Understanding sexual networks involving acute human immunodeficiency virus (HIV)-1 infections (AHI) may lead to prevention opportunities to mitigate high rates of onward transmission. We evaluated HIV-1 phylogenetic and behavioral characteristics among persons with AHI and their referred partners. METHODS: Between 2012 and 2014, 46 persons with AHI in Malawi participated in a combined behavioral and biomedical intervention. Participants referred sexual partners by passive referral. Demographics and sexual behaviors were collected through interviews and HIV-1 genetic relationships were assessed with phylogenetics. RESULTS: Among 45 AHI participants with HIV-1 sequences, none was phylogenetically-linked with another AHI index. There were 19 (42%) AHI participants who referred a single partner that returned for testing. Most partners (n = 17) were HIV-infected, with 15 (88%) presenting with an established infection. There were 14 index-partner pairs that had sequences available; 13 (93%) pairs were phylogenetically-linked dyads. The AHI index was female in 7/13 (54%) dyads. Age-disparate relationships among dyads were common (≥5-year age difference in 67% of dyads), including 3/6 dyads involving a male index and a younger woman. Index participants with a referred partner were more likely to report no casual partners and to be living with their current partner than participants not in dyads. CONCLUSIONS: Passive-partner referral successfully identified partners with genetically-similar HIV infections-the likely source of infection-but only 40% of index cases referred partners who presented for HIV-1 testing. Future work evaluating assisted partner notification may help reach susceptible partners or more people with untreated HIV-1 infections connected to acute transmission. CLINICAL TRIALS REGISTRATION: NCT01450189.

Sustained Sexual Behavior Change After Acute HIV Diagnosis in Malawi.

BACKGROUND: Identification of acute HIV infection (AHI) allows for important opportunities for HIV prevention through behavior change and biomedical intervention. Here, we evaluate changes in sexual risk behaviors among persons with AHI enrolled in a combined behavioral and biomedical intervention designed to reduce onward transmission of HIV. METHODS: Participants were randomized to standard HIV counseling, a multisession behavioral intervention, or a multisession behavioral intervention plus antiretrovirals. Sexual behaviors were assessed periodically over 1 year. RESULTS: Four weeks after diagnosis, the predicted probability of reporting multiple sexual partners decreased from 24% to 9%, and the probability of reporting unprotected sex decreased from 71% to 27%. These declines in sexual risk behaviors were sustained over follow-up irrespective of study arm. CONCLUSIONS: Diagnosis of AHI alone may be sufficient to achieve immediate and sustained behavior change during this highly infectious period.

The prevalence of renal impairment in individuals seeking HIV testing in Urban Malawi.

BACKGROUND: Chronic kidney disease (CKD) poses a major health threat to people living in low- and middle-income countries, especially when it is combined with HIV, antiretroviral treatment (ART) or communicable and non-communicable diseases. Data about the prevalence of CKD and its association with other diseases is scarce, particularly in HIV-negative individuals. This study estimated the prevalence of CKD in individuals who were either HIV-positive (and ART-naïve) or HIV-negative in an urban Malawian population. METHODS: This cross-sectional study was conducted at a HIV Testing and Counselling Centre in Lilongwe, Malawi. Consecutive clients who were ≥18 years and consented to participate were enrolled over a 3-month period. Clients were screened for potential renal disease and other conditions. Their blood pressure was measured, urine examined via dipstick and albumin/creatinine ratio and blood drawn for creatinine, cystatin C and sero-markers for schistosomiasis. Estimated glomerular filtration (eGFR) rate was calculated using a cystatin C-based formula and classified according to the matching CKD stages by K/DOQI (The National Kidney Foundation Kidney Disease Outcome Quality Initiative). We performed a descriptive analysis and compared differences between HIV-positive (and ART naïve) and -negative participants. RESULTS: Out of 381 consecutive clients who were approached between January and March 2012, 366 consented and 363 (48% female; 32% HIV-positive) were included in the analysis. Reasons for exclusion were missing samples or previous use of ART. HIV-positive and negative clients did not differ significantly with regard to age, sex or medical history, but they did differ for BMI-21.3 (±3.4) vs. 24 (±5.1), respectively (p < 0.001). Participants also differed with regard to serum cystatin C levels, but not creatinine. Reduced kidney function (according to CKD stages 2-5) was significantly more frequent 15.5 vs. 3.6%, respectively (p < 0.001) among HIV-positive clients compared to the HIV-negative group. Differences in renal function were most pronounced in the eGFR range 60-89 ml/min/1.73 m2 accompanied by proteinuria with results as 11.2% vs. 1.2%, respectively for clients who were HIV-positive vs. HIV-negative (p = 0.001). CONCLUSIONS: Reduced glomerular filtration and/or proteinuria occurred in 15.5% of HIV-positive, and 3.6% of HIV-negative patients in this urban Malawian cohort. Since generalized renal monitoring is not feasible in Malawi or other resource-limited countries, strategies to identify patients at risk for higher stages of CKD and appropriate preventive measures are needed for both HIV-positive and HIV-negative patients.

Detection of acute HIV infection: a field evaluation of the determine® HIV-1/2 Ag/Ab combo test.

BACKGROUND: Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies (Ab) but not p24 antigen (Ag) or RNA. In the absence of antibodies, p24 antigen and RNA typically indicate acute HIV infection. We conducted a field evaluation of the Determine® HIV-1/2 Ag/Ab Combo rapid test (Combo RT). METHODS: The antigen portion of the Combo RT (for acute HIV infection) was compared with a Roche Monitor HIV RNA polymerase chain reaction assay. The antibody portion of Combo RT (for established HIV infection) was compared with rapid test algorithms. Participants were enrolled at a sexually transmitted infection clinic and HIV testing and counseling center in Lilongwe, Malawi. Rapid testing was conducted with parallel testing in the clinic and serial testing in the center. The Combo RT was performed in clinic participants with negative or discordant antibody results and in all center participants. RESULTS: Of the participants 838 were HIV negative, 163 had established HIV infection, and 8 had acute HIV infection. For detecting acute HIV infection, the antigen portion had a sensitivity of 0.000 and a specificity of 0.983. For detecting established HIV infection, the antibody portion had a sensitivity of 0.994 and a specificity of 0.992. CONCLUSIONS: Combo RT displayed excellent performance for detecting established HIV infection and poor performance for detecting acute HIV infection. In this setting, Combo RT is no more useful than current algorithms.

Randomized Controlled Pilot Study of Antiretrovirals and a Behavioral Intervention for Persons With Acute HIV Infection: Opportunity for Interrupting Transmission.

BACKGROUND: Persons with acute HIV infection (AHI) have heightened transmission risk. We evaluated potential transmission reduction using behavioral and biomedical interventions in a randomized controlled pilot study in Malawi. METHODS: Persons were randomized 1:2:2 to standard counseling (SC), 5-session behavioral intervention (BI), or behavioral intervention plus 12 weeks of antiretrovirals (ARVs; BIA). All were followed for 26-52 weeks and, regardless of arm, referred for treatment according to Malawi-ARV guidelines. Participants were asked to refer partners for testing. RESULTS: Among 46 persons (9 SC, 18 BI, 19 BIA), the average age was 28; 61% were male. The median viral load (VL) was 5.9 log copies/mL at enrollment. 67% (10/15) of BIA participants were suppressed (<1000 copies/mL) at week 12 vs 25% BI and 50% SC (P = .07). Although the mean number of reported condomless sexual acts in the past week decreased from baseline across all arms (1.5 vs 0.3 acts), 36% experienced incident sexually transmitted infection by 52 weeks (12% SC, 28% BI, 18% BIA). Forty-one percent (19/46) of participants referred partners (44% SC, 44% BI, 37% BIA); 15 of the partners were HIV-infected. CONCLUSIONS: Diagnosis of AHI facilitates behavioral and biomedical risk reduction strategies during a high-transmission period that begins years before people are typically identified and started on ARVs. Sexually transmitted infection incidence in this cohort suggests ongoing risk behaviors, reinforcing the importance of early intervention with ARVs to reduce transmission. Early diagnosis coupled with standard AHI counseling and early ARV referral quickly suppresses viremia, may effectively change behavior, and could have tremendous public health benefit in reducing onward transmission.

Inpatient mortality rates during an era of increased access to HIV testing and ART: A prospective observational study in Lilongwe, Malawi.

BACKGROUND: In the era of increased access to HIV testing and antiretroviral treatment (ART), the impact of HIV and ART status on inpatient mortality in Malawi is unknown. METHODS: We prospectively followed adult inpatients at Kamuzu Central Hospital medical wards in Lilongwe, Malawi, between 2011 and 2012, to evaluate causes of mortality, and the impact of HIV and ART status on mortality. We divided the study population into five categories: HIV-negative, new HIV-positive, ART-naïve patients, new ART-initiators, and ART-experienced. We used multivariate binomial regression models to compare risk of death between categories. RESULTS: Among 2911 admitted patients the mean age was 38.5 years, and 50% were women. Eighty-one percent (81%) of patients had a known HIV status at the time of discharge or death. Mortality was 19.4% and varied between 13.9% (HIV-negative patients) and 32.9% (HIV-positive patients on ART ≤1 year). In multivariable analyses adjusted for age, sex and leading causes of mortality, being new HIV-positive (RR = 1.64 95% CI: 1.16-2.32), ART-naive (RR = 2.28 95% CI: 1.66-2.32) or being a new ART-initiator (RR = 2.41 95% CI: 1.85-3.14) were associated with elevated risk of mortality compared to HIV-negative patients. ART-experienced patients had comparable mortality (RR = 1.33 95% CI: 0.94-1.88) to HIV-negative patients. CONCLUSION: HIV related mortality remains high among medical inpatients, especially among HIV-positive patients who recently initiated ART or have not started ART yet.

Incorporating Acute HIV Screening into Routine HIV Testing at Sexually Transmitted Infection Clinics, and HIV Testing and Counseling Centers in Lilongwe, Malawi.

BACKGROUND AND OBJECTIVES: Integrating acute HIV-infection (AHI) testing into clinical settings is critical to prevent transmission, and realize potential treatment-as-prevention benefits. We evaluated acceptability of AHI testing and compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV testing and counseling (HTC) clinics in Lilongwe, Malawi. METHODS: We conducted HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI was defined as positive RNA and negative/discordant rapid antibody tests. We evaluated demographic, behavioral, and transmission-risk differences between STI and HTC patients and assessed performance of a risk-score for targeted screening. RESULTS: Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)-a 0.9% case-identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs 0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25% (15/59) had VL ≥ 10,000,000 copies per milliliter. Median VL was higher at STI (1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among persons with AHI, those tested at STI clinics were more likely to report genital sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The risk score algorithm performed well in identifying persons with AHI at HTC clinics (sensitivity = 73%, specificity = 89%). CONCLUSIONS: The majority of patients consented to AHI testing. AHI prevalence was substantially higher in STI clinics than HTC clinics. Remarkably high VLs and concomitant genital scores demonstrate the potential for transmission. Universal AHI screening at STI clinics, and targeted screening at HTC centers, should be considered.

Implementation and Operational Research: Implementation of Routine Counselor-Initiated Opt-Out HIV Testing on the Adult Medical Ward at Kamuzu Central Hospital, Lilongwe, Malawi.

The optimal approach of provider-initiated HIV testing and counseling (PITC) for inpatients in high-burden settings is unknown. We prospectively evaluated the implementation of task shifting from clinician-referral to counselor-initiated PITC on the medical wards of Kamuzu Central Hospital, Malawi. Most of patients (1905/3154, 60.4%) had an unknown admission HIV status. Counselors offered testing to 66.6% (1268/1905). HIV prevalence was 39.3%. Counselor-initiated PITC significantly increased HIV testing by 79% (643/2957 vs. 1228/3154), resulting in an almost 2-fold increase in patients with known HIV status (2447/3154 vs. 1249/3154) (both P < 0.0001), with 18.4% of those tested receiving a new diagnosis of HIV.